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+"Guinea pigs have been an important source of protein in the Andean region since ancient times (Aliaga-Rodrigues, Moncayo-Galliani, Rico-Numbela, & Caycedo-Vallejo, [@cit0001]). Currently, 12 million guinea pigs are reared in Peru for meat consumption (Food and Agriculture Organization of the United States, [@cit0014]; Instituto Nacional de Estadistica e Informatica, [@cit0026]). Guinea pigs are adapted to high altitudes where other small livestock species, such as chickens and turkeys, have substantial health and production issues associated with the altitude. Recently guinea pig production has spread to other regions of the globe (Herman et al., [@cit0025]; Kouakou, Speybroeck, Assidjo, Grongnet, & Thys, [@cit0027]; Maass, Katung-Musale, Chiuri, Zozo, & Peters, [@cit0031]), where guinea pigs have been promoted as an affordable source of nonhuman animal protein and income for impoverished communities at high altitudes (Lammers, Carlson, Zdorkowski, & Honeyman, [@cit0028]).\n\nTraditionally, slaughter by exsanguination is performed without stunning and with or without cervical neck dislocation. Cervical neck dislocation is a recommended and routinely used method for dispatching species in laboratories (American Veterinary Medical Association \\[AVMA\\] Members of the Panel on Euthanasia, [@cit0002]; *Code of practice,* [@cit0007]). However, studies on decapitation, puntilla, captive-bolt shooting into the spinal cord, and cervical neck dislocation in a range of"
+"Introduction {#Sec1}\n============\n\nMixed-species groups (MSG) can be observed in a number of vertebrate taxa including fish (Ehrlich and Ehrlich [@CR10]; Semeniuk and Dill [@CR49]), birds (Morse [@CR39]; Thompson and Barnard [@CR60]; Metcalfe [@CR38]; Munn [@CR40]) and mammals (Struhsaker [@CR57]; Cords [@CR9]; Fitzgibbon [@CR12]; Shelden et al. [@CR51]; Herzing and Johnson [@CR22]; Heymann and Buchanan-Smith [@CR27]). Benefits of forming such associations are considered in terms of predator detection and avoidance, increased foraging efficiency, and reproductive advantages (reviewed in Stensland et al. [@CR55]). However, antipredator benefits are most often considered as the ultimate cause leading to the evolution of MSG (Thompson and Barnard [@CR60]; Munn [@CR40]; Fitzgibbon [@CR12]; No\u00eb and Bshary [@CR41]; Semeniuk and Dill [@CR49]), and in primates strong predation pressure may even be one of the preconditions for MSG formation (Struhsaker [@CR57]; Gautier-Hion et al. [@CR17]; Terborgh [@CR59]). Larger single-species groups (SSG) are supposed to be safer due to both the detection (Pulliam [@CR45]) and dilution effects (Hamilton [@CR19]). Individuals in MSG have the same antipredator advantages as animals forming SSG, while avoiding increased intraspecific competition for food and mates, which poses a limitation on how large SSG can be (Terborgh [@CR59]; Caine [@CR6]; Hardie and Buchanan-Smith [@CR20]).\n\nBesides"
+"Introduction {#s1}\n============\n\nRoadless wilderness is widely recognised for its high conservation value in terrestrial ecosystems [@pone.0003546-Strittholt1], and therefore its preservation is frequently a primary goal of conservationists [@pone.0003546-Wilkie1]. Conversely, developers and economists value roads as a cornerstone of efficient natural resource exploitation, and a prerequisite of economic development and poverty alleviation [@pone.0003546-Anon1]. Roads improve access which facilitates resource extraction, human settlement and habitat degradation [@pone.0003546-Laurance1]. They fragment once contiguous habitats into smaller, isolated patches triggering numerous negative ecological consequences [@pone.0003546-Forman1]. As road developments expand across the globe, understanding their impacts on ecosystems, populations, and individuals is increasingly important if ecologists, economists, and developers are to mitigate their negative ecological impacts while maintaining their socio-economic importance [@pone.0003546-Wilkie1], [@pone.0003546-Forman2].\n\nThe Congo Basin is among the world\\'s great wilderness areas [@pone.0003546-Sanderson1] containing the second largest rainforest block on earth, outstanding biological diversity, and its full complement of post-Pleistocene megafauna, including great apes and the forest elephant (*Loxodonta africana cyclotis*) [@pone.0003546-KamdemToham1]. It also contains globally important reserves of high quality timber, minerals, and other natural resources, critical to the economies of central African states [@pone.0003546-KamdemToham1]. Industrial-scale commercial exploitation of these natural resources is expanding dramatically and access to them relies on the proliferation"
+"Introduction\n============\n\nWhen the *RV Knorr* set sail for the Galapagos Rift in 1977, the geologists aboard eagerly anticipated observing a deep-sea hydrothermal vent field for the first time. What they did not expect to find was life---abundant and unlike anything ever seen before. A series of dives aboard the *HOV Alvin* during that expedition revealed not only deep-sea hydrothermal vents but fields of clams and the towering, bright red tubeworms that would become icons of the deep sea. So unexpected was the discovery of these vibrant ecosystems that the ship carried no biological preservatives. The first specimens from the vent field that would soon be named \"Garden of Eden\" were fixed in vodka from the scientists' private reserves ([@ref-4]).\n\nSince that first discovery, deep-sea hydrothermal vents have been found throughout the world's oceans at mid-ocean ridges, volcanic arcs, and back-arc spreading centers ([@ref-7]). As more geographic regions are explored, newly discovered vent fields present the potential for entirely new ecosystems as well as species. Vents can range from black smokers to shimmering diffuse flow, can exist on ultra-slow to ultra-fast spreading centers, can be talc-hosted, serpentinite-hosted, or any of several other geologic conditions ([@ref-82]). Just as \"forest\" can describe"
+"Background {#Sec1}\n==========\n\nThe Bengal cat breed found its origin in the USA as the result of crossing the Asian Leopard Cat (*Prionailurus bengalensis*) with a domestic cat breed (Felis Sylvestris catus), the purpose being to combine its unique physical appearance with the amenable character of a domesticated breed. The Bengal cat is now generally recognised as a very popular feline breed worldwide and it is enjoying its relatively recent introduction into Poland, with 4475 Bengal registrations being recorded in 2018 by the Polish Federation Felis Polonia (FPL).\n\nA number of genetically determined ocular diseases have been recognized in several feline breeds, the most common of which are the lysosomal storage diseases, retinal dysplasia, progressive retinal atrophy and glaucoma \\[[@CR1]--[@CR6]\\]. Hereditary cataract would appear to be rare in cats, most reports describing mainly posterior nuclear and cortical lesions thought to be congenital or early onset in origin. Several breeds are involved including the Birman, the British Shorthair, the Himalayan, the Persian and the Russian Blue \\[[@CR7]--[@CR12]\\]. Cataract secondary to uveitis, trauma, neoplasia, nutritional deficiency or metabolic disease is more commonplace in this species \\[[@CR13]--[@CR21]\\]. A congenital cataract has also been noted in the feline Chediak-Higashi syndrome \\[[@CR22]\\].\n\nThere are few"
+"Faecal microbiota transplantation (FMT) has revolutionised the management of patients with recurrent *Clostridioides (Clostridium) difficile* infection (rCDI) [@bib0001]. With resolution rates exceeding 90%, the use of FMT has surged in clinical practice. FMT is now a recommended treatment for rCDI and reduces mortality and hospital costs alike [@bib0002]. The application of viable intestinal microbiota obtained from healthy donors requires strict compliance with acknowledged safety standards to minimise risks. A technical guide issued by the European Council [@bib0003] and a recent international consensus conference describe in detail how safety and quality measures may be applied according to tissue and cells standards [@bib0004]. In a recent report, published in EClinicalMedicine, McCune and co-workers describe how a hospital-based stool bank using FMT to treat rCDI may be adapted to comply with national drug legislation [@bib0005]. The two competing approaches reveal a regulatory struggle challenging the development of FMT as an integral service in modern healthcare.\n\nClassification of minimally manipulated donor faeces as a drug paves the way for an unethical commercialisation of human material. Donated material is in essence diverse, and the process of obtaining human material and the precautionary measures needed are not covered by current drug legislation. The English stool bank,"
+"Introduction {#Sec1}\n============\n\nScreening for previously unrecognized contaminants in (surface) waters may be done by non-target screening or suspect screening involving liquid chromatography--high-resolution mass spectrometry (LC-HRMS). While non-target screening makes use of the entity of mass spectrometric data collected over a chromatographic run, its data processing effort is extremely high and its success often limited by the need to effectively reduce the data set and by the difficulty to identify unknown compounds based solely on their mass spectrometric data.\n\nIn comparison, suspect screening is more straightforward as it makes use of existing (chemical) knowledge, such as on compounds that may be expected to be of relevance for the environmental compartment being studied, e.g., because they have already been detected in such settings previously. Suspect screening may even account for transformation products (TPs), as long as those are formed along known transformation pathways. Correspondingly, it was concluded recently in a study on pesticide metabolites in groundwater that suspect screening was more successful than non-target screening \\[[@CR1]\\].\n\nIn Europe, most chemicals sold by industry, whether to the consumer or for use in further production, have to be registered under REACH. Parts of the information provided by industry in the registration process are"
+"Introduction {#s1}\n============\n\nThe development of a novel vaccine is a highly complex and demanding process that, from the initial concept to a licensed product, can take up to decades. Once a candidate has evolved in the laboratory, it undergoes vast series of pre-clinical *in vitro* and *in vivo* examination and optimization procedures. Evidently, only a minority of candidates passes all these obstacles, is permitted to clinical trials, accepted by regulatory agencies, and converted into a commercial product. The development of allergy vaccines faces additional problems, because unlike prophylactic vaccination, allergen-specific immunotherapy (SIT) attempts to counteract an already established pathological immune response [@pone.0017278-Rolland1]. Severe anaphylactic side effects can result from interactions between the administered vaccine and allergen-specific IgE antibodies of the atopic patient. Moreover, the current use of extracts of undefined contents can lead to sensitizations against new allergens during conventional immunotherapy [@pone.0017278-Egger1]. Thus, allergy research today focuses on strategies to improve both, safety and clinical efficacy of SIT.\n\nOthers and we have proposed the substitution of allergen extracts in immunotherapy by molecule-based vaccines in order to implement safer and patient-tailored treatment [@pone.0017278-Egger1], [@pone.0017278-Valenta1]. However, in contrast to infectious disease antigens, many allergens have been reported to be weak immunogens"
+"Introduction\n============\n\nEver since the BOLD effect was described, fMRI has dominated neuroscience as a mean to evaluate brain activity ([@B32],[@B31], [@B33]). It allows mapping of signal changes generated by the mismatch between oxygen delivery and consumption upon neuronal activation. While providing significant insight into brain function, a major limitation of BOLD is that it is an indirect measure and is affected by subject-specific haemodynamic factors. Thus, an approach that could directly measure neuronal activity in humans *in vivo*, non-invasively, would have a major advantage over BOLD-fMRI.\n\nIn this paper, we propose that, thanks to sodium MRI technology, we are within reach of measuring directly a local transient change of sodium ions (23Na) concentration in the intracellular space. During activity, neuronal action potentials cause a transient 23Na flux from the extracellular to intracellular space over a temporal scale of several milliseconds. If sodium imaging, dynamically repeated, was successful in detecting 23Na concentration changes evoked by specific tasks, it would open up a new way of investigating human brain function, complementing BOLD-fMRI.\n\nImaging aspects of the brain electrical activity, other than BOLD, related to transmembrane sodium-potassium ion exchange during depolarization could provide a direct access to primary brain function everywhere. Although"
+"Mate choice can generate sexual selection ([@zoy089-B21]; [@zoy089-B73]), but mate choice can only proceed if choosers can detect signalers. So understanding the basic mechanisms of signal detection is crucial to understanding the tempo and mode of sexual selection. Acoustic communication is an ideal system for such studies; it is a requisite for social behavior across a diversity of taxonomic groups as it mediates interactions such as mate choice and territory defense ([@zoy089-B77]; [@zoy089-B32]; [@zoy089-B36]). Hearing threshold, the lowest sound pressure level (SPL) detectable by a receiver, is an important factor for all functions of acoustic communication because a receiver must first detect an auditory signal prior to responding. It is especially critical for mate choice because if an animal is calling or singing for mates but receivers do not hear it, we can ask rhetorically, is the sender even sending a signal?\n\nHearing threshold is also a critical variable for determining a signal's active space, the distance over which receivers can detect a signal ([@zoy089-B59]; [@zoy089-B14]; [@zoy089-B53]; [@zoy089-B10]). Active space can vary substantially depending on the amplitude at the source, receiver sensitivity, ambient noise, competing acoustic signals, and attenuation due to habitat structure ([@zoy089-B94]; [@zoy089-B23]; [@zoy089-B4]). Measuring hearing threshold relative"
+"Natural materials have remarkable functional properties and ambient processability: threads with high strength, glues that cure underwater, and ceramics that resist fracture. Multiple functions emerge when materials evolve under harsh conditions, for instance, many natural marine glues exhibit added bond toughness to withstand dynamic ocean currents or wave action at the seashore. For sessile marine organisms such as barnacles, oysters and tubeworms, the adhesive is required to function for a lifetime and persists long afterwards. Such permanent adhesives use inventive adaptations to achieve durability, such as hierarchical structuring and chemical modification at the molecular and supramolecular level[@b1][@b2]. Despite inspiring scientific inquiry for more than a century[@b3] and impeding maritime operations even today[@b4], the permanent bond of adult barnacles is among the least understood. In contrast to marine organisms that use glues to fabricate protective shelters (e.g., sand-castle worm tubes[@b5], case-maker fly larva retreats[@b2], and amphipod tubes[@b6][@b7]) or tie themselves to rocks, (e.g., mussel byssus threads[@b8][@b9]) adult barnacles produce their adhesive interface in a sequential process hidden under their base as a part of their normal growth cycle[@b10][@b11]. The recent finding that barnacle adhesive is nanostructured and held together as an amyloid-like material[@b12][@b13][@b14] further distinguishes it from archetypal marine adhesives processed"
+"Introduction {#s1}\n============\n\nNow that Cone Beam Computed Tomography (CBCT) is a regular diagnostic tool in oral- and maxillofacial surgery, clinical interests are shifting to digital planning and eventually robotic surgery for orthognathic cases. With 3D planning software surgery can be planned digitally and then transferred to the patient. However, 3D virtual planning of orthognathic surgery still suffers from the disadvantages CBCT imaging has. For orthognathic surgery a good representation of the dental surfaces as well as the occlusion is needed for the 3D planning to properly position the jaws and to reach a stable occlusion. In CBCT imaging visualization of the dentition is still difficult. Loubelle and co-workers and Schulze and co-workers showed that the density of enamel is so high, that it gives rise to artefacts around the teeth [@pone.0059130-Loubele1], [@pone.0059130-Schulze1]. Besides that, brackets will always be present in orthognathic patients, since treatment continues into the postsurgical phase. This means that the dentition is poorly visible on CBCT scans of these patients, since scattering (from the brackets) and other artefacts occur at the occlusal level [@pone.0059130-Gateno1], [@pone.0059130-Uechi1]. Integration of digital dental casts into CBCT scans, could increase the accuracy of the orthognathic procedure.\n\nSeveral methods have been proposed"
+"The shaping of light using spatial light modulators (SLMs) is an established technology for advanced three-dimensional (3D) displays[@b1] and micro-manipulation[@b2]. In the SLM an incident beam of coherent light is transformed via amplitude and phase manipulation into a wide range of reflected or transmitted optical distributions. Crucially the SLM is computer controlled and it is possible to reconfigure the optical field produced in almost real-time.\n\nThe acoustic equivalent of an SLM does not exist. Traditionally, the control of an acoustic field distribution was achieved by using fixed lenses[@b3], which perform a single function, or phased arrays[@b4][@b5], where the amplitudes and phases of the individual array elements are independently controlled. However, phased arrays are often bulky and expensive, with cost and complexity scaling linearly with the number of channels. Despite these limitations, phased arrays are in widespread use. In High Frequency Focused Ultrasound (HIFU), for example, sparse arrays of transducers are used to treat a variety of tumours[@b6] or functional brain disorders[@b7], inducing a localized heating effect, even behind the ribs[@b8]. In industrial applications, focusing and steering of ultrasonic waves is required to find small cracks in metallic components, which can be complex in geometry and highly anisotropic[@b9]. New applications that"
+"INTRODUCTION\n============\n\nMouse hepatitis virus (MHV) collectively designates corona viruses of a wide range of virulence. The strains that are endemic in most mouse colonies over the world show relatively low virulence and animals from infected colonies do not present overt signs of illness. Nevertheless, although tolerated by many researchers, evidence has accumulated over the years that results from several investigation areas can be compromised by concomitant MHV infections. In particular, the study of immunological parameters that determine resistance to infections can be seriously affected by MHV infection (reviewed in refs 1,2). There are few studies on the effects of infection by natural-low-virulence enzootic MHV strains on immune responses and on their interference with experimental models of infection. Most reports deal with virulent laboratory strains, although more recently, attenuated MHV laboratory strains have been used in an attempt to mimic the prevalent strains.[@b2] The objective of this study was to investigate the effects of a natural acute outbreak of MHV due to accidental exposure, in our otherwise specific-pathogen-free (SPF) inbred mouse colonies, and of enzootic chronic MHV infection on cytokine production and resistance to the intracellular pathogen *Trypanosoma cruzi*.\n\n*Trypanosoma cruzi* is a dygenetic protozoan that infects several kinds of"
+"Introduction {#Sec1}\n============\n\nCreative approaches to healthcare are needed to cope with ageing populations and increasing economic pressure. Commercially available gaming systems, which provide advanced technology made available for the mass market at low cost, have thus received growing interest. Systems such as Microsoft Kinect are significantly less expensive than most medical sensing devices, but have the potential to provide accuracy sufficient for clinical practice.\n\nKinect is an input device designed for computer gaming with the XBox^\u00ae^ video game console. The sensor enables the user to interact in virtual reality by means of body movement, hand gestures, and spoken commands \\[[@CR1]\\]. It uses a color camera, infrared (IR) emitter, and IR sensor to compose a three-dimensional (3D) image comprising a \"cloud\" of over 200,000 points describing object position and surface as x, y, z coordinates. Besides its original application in gaming, this sensor has found use in retail, education, and training, with healthcare and therapy applications under evaluation \\[[@CR2]\\]. In the summer of 2014, the second generation of Kinect (Kinect II) was released, but to date most publications describe the first-generation device (Kinect I).\n\nThis paper gives a brief overview of the latest research on healthcare imaging using Kinect. A"
+"Nearly every profession or trade has its own technical language or jargon, and science is no exception. Scientists in every discipline rely on a specific vocabulary of well-defined words and phrases to communicate efficiently with their peers. In fact, this vocabulary, combined with a formal way of writing, means that precise statements can be made in only a few words. Yet this kind of economy also comes at a cost; it can prevent people from outside of the field understanding what is written or said.\n\nConsider the word \\\"trogocytosis\\\", for example. Put simply, those 12 letters describe a process whereby certain types of white blood cell briefly fuse with another cell so that some proteins are transferred between the membranes of the two cells. However, even if you know that \\\"*trogo*\\\" is essentially Greek for gnaw or nibble, and that \\\"*cytosis*\\\" refers to the transport of molecules into or out of cells, the exact meaning of the word is still far from obvious. You either know its meaning or you don't.\n\nPlain-language summaries are one way to combat this exact issue, and eLife has included such summaries -- called eLife digests -- in research articles since it first started publishing"
+"Ehlers--Danlos Syndrome (EDS) affects collagen synthesis, resulting in pathologic connective tissue and joint hypermobility that clinically present as joint subluxations and dislocations.[@bib1] Recurrent instability of the hip limits the quality of life of patients due to constant apprehension and chronic pain, and it may predispose them to early joint degeneration.[@bib2] Conservative management is the initial treatment; however, in refractory cases, surgical intervention should be considered. Arthroscopic and open capsular plication techniques can be attempted; however, the native pathologic connective tissue increases risk of recurrence. Previously described by our institution, an open caspsuloligamentous reconstruction technique using Achilles tendon allograft has been successful for post-hip arthroscopy instability.[@bib3]\n\nWe present a surgical technique demonstrating an open anterior capsule reconstruction using an Achilles tendon allograft for native hip instability in EDS. We used an allograft to ensure normal collagen is used, as diseased connective tissue of EDS can subsequently stretch and instability can recur. This technique is unique as it is performed on a native hip and shows how the Achilles tendon allograft is fashioned to adopt the dynamic and static stabilizing features of the native iliofemoral ligament. Furthermore, this may be useful for hip arthroscopy surgeons, as it demonstrates a stabilization procedure for"
+"Introduction {#Sec1}\n============\n\nDermatophytosis, the commonest cutaneous fungal infection has drawn attention in recent years in India due to a change in the clinical profile and an upsurge in the number of chronic/recurrent/recalcitrant dermatophytosis cases^[@CR1]^. Extensive infection, atypical presentation, poor response or non-responsiveness to the recommended antifungals has made dermatologists perplexed about management and control of the disease. Although antifungal resistance has been proposed as one of the causes for treatment unresponsiveness, there may be other reasons as well, as treatment failure cases outnumber the number of resistant cases. The current guidelines for management of the chronic/recurrent/recalcitrant cases recommend accurate dermatophyte identification and antifungal susceptibility testing^[@CR2]^. Terbinafine being a fungicidal drug, is recommended for systemic therapy. However, recent reports from the subcontinent has revealed an emerging trend of terbinafine resistance in *Trichophyton* species. A recent study from India demonstrated low cure rates of 2% at 2 weeks duration and 30.6% at 4 weeks in patients treated with terbinafine^[@CR3]^. Terbinafine resistance in *Trichophyton mentagrophytes* complex and *Trichophyton rubrum* has been ascribed to point mutation in the squalene epoxidase (*SE*) gene, the gene essential for the ergosterol biosynthesis^[@CR4]--[@CR6]^.\n\nWith the advent of the molecular techniques, identification of the dermatophytes to the species"
+"Ritschl PV, Nevermann N, Wiering L, et al. Solid organ transplantation programs facing lack of empiric evidence in the COVID\u201019 pandemic: A By\u2010proxy Society Recommendation Consensus approach. Am J Transplant. 2020;00:1--11. 10.1111/ajt.15933\n\nMoritz Schmelzle and Johann Pratschke contributed equally as senior authors.\n\nPaul Viktor Ritschl and Nora Nevermann contributed equally as first authors.\n\nABTO\n\n:   Brazilian Association of Organ Transplantation\n\nAST\n\n:   American Society of Transplantation\n\nBAL\n\n:   bronchoalveolar lavage\n\nCMS\n\n:   Centers for Medicare & Medicaid Services\n\nCNT\n\n:   Italian National Transplant Center\n\nCOVID\u201019\n\n:   Coronavirus disease 2019\n\nDTG\n\n:   German Transplant Society\n\nIPST\n\n:   Portuguese Institute of Blood and Transplantation\n\nKTS\n\n:   Korean Transplant Society\n\nNAT\n\n:   Nucleoid acid testing\n\nNTS\n\n:   The Dutch Transplant Society\n\nONT\n\n:   Organizaci\u00f3n Nacional de Trasplantes\n\nSARS\u2010CoV\u20102\n\n:   Severe acute respiratory syndrome coronavirus 2\n\nSEIMC\n\n:   Spanish Society of Infectious Diseases and Clinical Microbiology\n\nSET\n\n:   Spanish Society of Transplantation\n\nSRC\n\n:   Society recommendation consensus\n\nTTS\n\n:   The Transplantation Society\n\n1. INTRODUCTION {#ajt15933-sec-0001}\n===============\n\nCurrently, the global public health sector is facing an unprecedented challenge in dealing with the severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102) pandemic. Readjustments in the sector of organ transplantation are critically important for several reasons. All stages"
+"The 1918 influenza pandemic offers the worst-case planning scenario for public health officials because it resulted in unparalleled numbers of deaths. The virus, an A(H1N1) subtype, may have infected half the world's population ([@kwy165C1], [@kwy165C2]) and caused at least 50 million deaths, according to estimates ([@kwy165C3]); 675,000 deaths are thought to have occurred in the United States ([@kwy165C4]). The source of the 1918 H1N1 virus is unknown; avian and swine origins have been proposed ([@kwy165C5], [@kwy165C6]). Although 3 later pandemics, in 1957, 1968, and 2009, resulted in much lower estimated rates of morbidity and death, the threat of a 1918-like severity pandemic remains, because reports of human infections with novel influenza A viruses (generally of avian or swine origin) that pose pandemic potential have increased in recent years. In particular, Asian lineage avian influenza A (H7N9) viruses caused 1,557 reported human infections and at least 605 deaths during 5 epidemics in China during 2013--2017 ([@kwy165C7]). Now, 100 years after the 1918 pandemic, is an important time to recall the significant impact of the pandemic and to reflect on the current state of readiness to respond to the next influenza pandemic.\n\nTHE PANDEMIC IN 1918 {#kwy165s2}\n====================\n\nThe world situation in"
+"INTRODUCTION\n============\n\nThe acetabular labrum provides a significant functional role and may be important in overall hip preservation \\[[@hnv001-B1]\\]. Labral tears often occur in the setting of bony dysmorphisms such as dysplasia and femoroacetabular impingement (FAI). Arthroscopic surgery for FAI is a less invasive option that typically addresses bony deformities and chondrolabral pathology \\[[@hnv001-B5], [@hnv001-B6]\\]. Patients undergoing labral refixation have better outcomes than those undergoing labral debridement \\[[@hnv001-B7]\\]. When the labrum is deficient and/or irreparable, labral reconstruction has been performed with early successful outcomes \\[[@hnv001-B11]\\]. Current labral repair and reconstruction techniques utilize suture anchor fixation.\n\nSuture anchors provide a common method for fixation of soft tissues to bone. In order to restore labral function including the labral fluid seal effect, the fixation device should be placed on the acetabular rim close to but not violating the articular cartilage or joint \\[[@hnv001-B16], [@hnv001-B17]\\]. Suture anchors placed too far from the articular cartilage can evert or medialize the labrum, compromising its function; anchors placed too close to the articular cartilage can cause iatrogenic cartilage injury. Complications related to suture anchors have been documented, mainly in the shoulder literature including chondrolysis, osteolysis, synovitis, articular cartilage damage and fixation failure \\[[@hnv001-B18]\\]. Consequences from anchor-induced"
+"INTRODUCTION {#sec1-1}\n============\n\nWound infection was once a major cause of disability and mortality. However, the introduction of antiseptic techniques and antibiotics has dramatically changed the course of wound healing. Today, however, wound healing is of even greater global medical and financial significance because of advancements in technologies, high-speed traffic accidents, modern weaponry\\'s destructive capacity, the extension of life-expectancy, the increase in chronic diseases and the surging worldwide prevalence of diabetes, as well as the problem of antibiotic resistance. Any substantial progress in wound healing is expected to lead to a considerable improvement in health on a global scale.\n\nRNPT utilizes subatmospheric pressure (vacuum, negative pressure) to optimize the wound\\'s microenvironment to promote the healing process. This unique, physical, nonpharmaceutical technology applies regulated subatmospheric pressure to a wound, inflicting a variety of phenomena with the desired end-point of improved healing of simple and hard-to-cure, acute and chronic wounds. Through multiple publications on its advantages in various clinical applications during the last decade, RNPT has been established as an important technology, yet the full scope of the basic science and its associated mechanism of action, modes of application, and safe use need to be explored further.\\[[@ref1]\\]\n\nAt the core of RNPT"
+"Introduction {#s1}\n============\n\nRNA silencing pathways are critical regulators of gene expression in organisms ranging from yeast to humans. RNA silencing is initiated by the action of RNase III enzymes, which target RNAs with dsRNA character to generate small RNA duplexes [@pone.0055458-Kim1]. Following biogenesis, small RNA sorting directs the selection of one strand of the duplex to be retained and stabilized by an Argonaute family member in RISC [@pone.0055458-Czech1]. The RNA silencing pathways of *Drosophila melanogaster* have been extensively characterized and allow for detailed dissection of the mechanisms governing RNAi-mediated gene silencing. The siRNA silencing pathway is responsible for controlling the expression of both endogenous and exogenous targets in somatic cells. siRNA biogenesis is carried out by Dicer-2 (Dcr-2), which generates predominantly 21 nucleotide (nt) products from several types of precursors [@pone.0055458-Kim2]. Endogenous siRNAs (esiRNAs) are generated from long hairpins, retrotransposons or convergent transcription units and regulate endogenous gene expression, while exogenous siRNAs (exo-siRNAs) are processed from long dsRNAs, a process commonly manipulated in molecular biology to achieve targeted gene silencing [@pone.0055458-Kim1]. In addition, virus-derived siRNAs (vsiRNAs) are cleaved from viral RNAs produced during infection [@pone.0055458-Ding1]. The miRNA pathway generates mature miRNAs from stem-loop structures within pri-miRNA transcripts through a"
+"Introduction {#Sec1}\n============\n\nFermentation of plant materials causes a significant change in bioactive volatile and non-volatile components^[@CR1]^. Moreover, the concentrations of both flavonoids and the unsaturated fatty acid esters, as well, increase due to the fermentation of soybean. Extracts of fermented soybean\u00a0have shown strong antioxidant, anti-breast cancer and antiviral activities^[@CR2]^. A growing major objective interest is to develop special catalytic systems (one-pot tandem), that integrate both the reactivity of a chemical catalyst and a selected active site of an enzyme^[@CR3]^. Fungi (as yeasts, moulds), bacteria and several microorganisms are known to produce lipases that digest lipids. Moreover, fungal lipases are used as industrial catalysts to resolve racemic alcohols used for preparing some prostaglandins, steroids, and carboxylic nucleoside analogues. Such lipases also catalyse the hydrolysis of short chain triglycerides, which represent very good substrates for lipases. In addition, proteases and amylases, which catalyse the hydrolysis of proteins and carbohydrates respectively, are widely used in different industries. Recently, the biocatalytic potential of microbial lipases, in both aqueous and non-aqueous media, have encourage many industries to utilize these enzymes in a variety of great important reactions, especially organic synthesis reactions. The region selective nature of lipases are used for different purposes such"
+"INTRODUCTION\n============\n\nChronic constipation is a symptom-based disorder of unsatisfactory defecation. Patients complain of mainly infrequent stools and/or difficult stool passage. There are two principal etiologies for such symptoms: delayed transit through the colon and impaired evacuation of the rectum. Impaired rectal evacuation can result from mechanical or structural obstruction, but the more common cause are functional pelvic outlet obstructions, which include paradoxical contraction or inadequate relaxation of pelvic floor muscle during defecation (pelvic floor dyssynergia, PFD) and failure to increase intrarectal pressure during evacuation \\[[@B1],[@B2]\\].\n\nDynamic defecography is a fluoroscopic procedure used to observe rectal evacuation of contrast paste, in order to assess changing anatomic relationships of the pelvic floor and associated organs. Thus, it is particularly relevant in those patients who complain of difficult stool passage and usually performed to diagnose functional pelvic outlet obstruction. This test is generally known to be sensitive and specific for PFD, and recommended in situations when other anorectal physiologic test results differ from clinical impression \\[[@B2]-[@B4]\\]. However, even in defecography, standardized parameters for diagnostic analysis is still incomplete, and there are some controversies about what kind of defecographic finding is necessary for diagnosing PFD \\[[@B5]-[@B7]\\].\n\nIn this study, we tried to determine"
+"As of April 27, altogether 629 coronavirus disease 2019 (COVID-19) cases have been diagnosed in Seoul, two of whom have died (fatality rate, 0.32%) since the first COVID-19 patient in Seoul was confirmed on January 24, 2020. There were 65.7 patients and 0.2 deaths per 1 million population, which is an exceptional result compared to that in other major metropolitan cities in the world (e.g., fatality rate of New York is 7.6% and Tokyo is 2.7%).[@B1][@B2]\n\nDuring this period, in total, 111,987 tests were conducted. Some people may judge that these relatively good results have been obtained due to massive, large-scale testing in Seoul.[@B3][@B4] However, the proportion of screening is only 1.1% of 9.776 million Seoul citizens. We believe that the favorable results were possible because we tried to minimize the time from first symptom onset to hospitalization (TFSH) as well as conduct massive testing. Alternatively, detecting symptom expression (D)---COVID-19 test (T)---reporting examination results (R)---hospitalization (H) was considered one chain reaction. We focused on avoiding bottlenecks at each stage and completing this D-T-R-H process ([Fig. 1](#F1){ref-type=\"fig\"}) at the earliest.\n\nTo achieve this goal, the Seoul Metropolitan Government (SMG) launched the SMG COVID-19 Rapid Response Team (SCoRR team) ([Fig. 2](#F2){ref-type=\"fig\"}), which"
+"Introduction {#s1}\n============\n\nBurkitt lymphoma (BL) is a human tumor of B cell origin whose pathogenesis involves complementation between a defined cellular genetic change, translocation of the c-myc oncogene into an active immunoglobulin (Ig) locus, and a B cell-transforming virus, Epstein-Barr virus (EBV) [@ppat.1000341-Brady1],[@ppat.1000341-Kelly1]. C-myc deregulation appears to be the crucial lymphomagenic event, since all BLs worldwide carry a c-myc/Ig translocation, and in model systems, expression of c-myc from such a construct converts B cells to the proliferating BL phenotype [@ppat.1000341-Polack1]--[@ppat.1000341-Zhu1]. There is, nevertheless, strong selection for EBV as a complementing agent. Thus all cases of BL in its high incidence (endemic) form are EBV genome-positive, as are 15--85% of the low/intermediate incidence (sporadic) BLs seen elsewhere in the world [@ppat.1000341-Magrath1]. However, the virus\\' role in BL pathogenesis has remained obscure, not least because EBV gene expression in tumor cells does not mirror that of a typical growth-transforming infection.\n\nTo illustrate the point, [Figure 1 (bottom line)](#ppat-1000341-g001){ref-type=\"fig\"} shows the pattern of latent gene expression established when EBV transforms normal B cells into permanent lymphoblastoid cell lines (LCLs) *in vitro*. This entails expression of the non-coding EBER RNAs, the *Bam*HIA rightward transcripts (BARTs) from which most of the EBV micro(mi)-RNAs are"
+"Nanoscale science has been in the research labs of industry and academia for over 20 years. Consumers increasingly confront an abundance of products that contain nanoparticles or that claim to be a result of nanotechnology, including skin-care products, wrinkle- and stain-resistant fabrics, and sports items like golf clubs and baseball bats \\[[@pbio-0050283-b001]\\]. Yet as recently as late 2006, over 80% of the American public reported that they had heard nothing or next to nothing about nanotechnology \\[[@pbio-0050283-b002]\\].\n\nThe Nanoscale Informal Science Education Network (NISE Net) is an ambitious initiative funded by the National Science Foundation (NSF) to engage families, schoolchildren, and adults in nanoscale science, engineering, and technology through informal learning experiences in science centers and museums across the United States. NISE Net has designed exhibits and public programs about nanoscience and plans to disseminate these to 100 science centers and museums by the year 2010. Two years into this multi-year project, the team has reached an inflection point---a time to assess critically the status of our work, re-evaluate our original assumptions, and redouble our efforts to support the collective vision that has emerged from this period of intensive collaboration.\n\nNanoscale Science {#s2}\n=================\n\nThe prefix \"nano\" derives from the"
+"Widespread concern exists among policymakers and the public about the potential effects of alcohol advertising on alcohol consumption and problems, especially among children and adolescents. It is especially important to counter the potential effects of advertising on young people because these age groups may be more susceptible to those effects. Children are less able to discriminate between advertising and other media content and are less critical of commercial messages than are adults ([@b3-15-21]). Moreover, recent studies of children and adolescents (e.g., [@b8-15-21]; [@b16-15-21]; [@b39-15-21]) have shown that attention to and liking of alcohol advertising are related to (1) greater knowledge about alcohol slogans and beer brands, (2) more favorable beliefs about drinking, (3) increased intentions to drink as an adult, and (4) increased drinking. Similarly, it may be important to counter the potential effects of alcohol advertising on young adults, and especially college students, who frequently are at risk for heavy and problematic drinking ([@b38-15-21]).\n\nA recent national survey indicates that 67 percent of adults in the United States support banning liquor advertisements on television and 61 percent favor banning beer and wine advertisements in this medium ([@b37-15-21]). Similarly, public health advocates routinely call for the strict regulation or even"
+"Introduction {#s1}\n============\n\nIn the catalogue of behavioral laboratory tasks that have generated considerable research interest the past centennial is the relative simple task of moving a finger or hand to an auditory sequence consisting of clicks or tones (e.g., finger tapping). It was introduced in early experimental psychology studies [@pone.0069353-Stevens1], [@pone.0069353-Dunlap1], and the defining feature is repetitive movements alternating back and forth from a single contact point or between different contact points. These points consist of a period of negligible movements, and the goal of the task is to arrive at these points in accordance with the isochronous (repetitive) metronome signal. The task can be divided into two distinct phases: Synchronization that consists of actively moving in accordance with the metronome, or continuation where the metronome is turned off and the participant attempts to maintain a previously provided metronome rhythm for a given period [@pone.0069353-Wing1], [@pone.0069353-Aschersleben1]. In the first case (synchronization phase), the task involves temporally coordinating motor responses with predictable external events. Hence, it falls under the term sensorimotor synchronization which is typically defined as the rhythmic coordination of perception and action [@pone.0069353-Repp1], [@pone.0069353-Repp2].\n\nPerhaps for their apparent simplicity, synchronization tasks form one of the backbones in the"
+"Background {#Sec1}\n==========\n\nIn the frame of the sterile insect technique (SIT) \\[[@CR1]\\] and its application towards the management of medically important mosquito species, it is essential to standardize methods for the evaluation of radiation induced sterility in the males produced for releases. Consistent, reproducible and reliable irradiation methods are required to ensure that the target sterility level is reached for millions of male mosquitoes over time, so that no unknown levels of residual fertility can compromise the beneficial effects of the sterile males. It is also essential to balance the high sterility levels targeted, with optimal irradiation and handling protocols in efforts to improve male biological quality to minimize fitness costs and therefore maintain effectiveness in the field.\n\nThe first step for improvement for the irradiation procedures for mosquitoes is to harmonize materials and methods used and to find the causes for largely varying dose-response data currently found in the literature. Differences in radiosensitivity can be expected between families and even genera within the families of insects \\[[@CR2]\\]; however, such variations in irradiation doses and resulting sterility within the same species beyond a \"reasonable range\" infers the effects of internal or external variables and these require evaluation and standardization"
+"Introduction {#s1}\n============\n\nMurine lung development is initiated at embryonic day 9 (E9) by separation of the lung primordium from the anterior foregut endoderm [@pone.0044871-Cardoso1], [@pone.0044871-Morrisey1]. During the pseudoglandular stage from E10.5-16.5, the bronchiolar tree is established by branching morphogenesis [@pone.0044871-Metzger1] providing the foundation of the developing lung. Moreover, the epithelium begins to differentiate into secretory (Clara), neuroendocrine (NE), or ciliated cells. During the canalicular stage (E16.5-17.5), the undifferentiated distal epithelium continues to branch and gives rise to terminal sacs. During the terminal sac stage \\[E17.5-postnatal day (P) 5\\], the sacs increase in number and type 1 and 2 alveolar epithelial cells begin to differentiate. During the alveolar stage (P5-30), the terminal sacs develop into mature alveoli [@pone.0044871-Minoo1].\n\nMolecularly, the pseudoglandular stage is marked by the expression of the transcription factor Nkx2.1 [@pone.0044871-Minoo1], [@pone.0044871-Monaghan1] and the surfactant gene, surfactant protein-c (Sftpc) in the progenitor cells of the distal epithelium. In conjunction with other transcription factors such as Gata6, Nkx2.1 appears to control transcriptional programs of the respiratory system [@pone.0044871-Morrisey1]. In the mouse lung, complete loss of either Gata6 or Nkx2-1 results in severe defects in branching morphogenesis and cell lineage differentiation [@pone.0044871-Kimura1], [@pone.0044871-Zhang1], [@pone.0044871-Que1]. As the distal progenitor epithelium grows"
+"The London plague epidemic of 1665 occupies an unusually prominent place in disease history, and for that reason alone the revisiting of its sources undertaken by A Lloyd Moote and Dorothy C Moote is welcome. The authors hope to recreate a narrative picture of individual experiences and responses to a cataclysm that may have taken 100,000 lives, and they have produced a readable and reasonable account that should now be the first choice of readers who want to know the story.\n\nThe narrative is structured around several individuals who left extensive accounts of their own experiences: the apothecary William Boghurst, the physician Nathaniel Hodges, the clergyman Symon Patrick, the bureaucrat Samuel Pepys, and the merchant William Turner. Also contributing are the gentleman John Evelyn, the Southwark medical practitioner and preacher John Allin, the Essex clergyman Ralph Josselin, Lucy Hastings (Lady Huntingdon), and her London agent Gervase Jacques. The authors, well aware that such testimony represents only the successful minority, must allow poorer London to speak collectively, relying particularly on records from such stricken parishes as St Giles' Cripplegate, St Margaret\\'s Westminster, and St Botolph\\'s Bishopsgate. Vivid details from the sources bring home the realities of the epidemic: powdered unicorn horns"
+"Epithelial herpes simplex keratitis is the most common form of the recurrent disease, typically presents mild clinical course, mostly which heals without any sequelae. Conversely, recurrent herpetic stromal keratitis is an immunopathologic process, can lead to stromal scarring, neovascularization, stromal thinning, and/or endothelial dysfunction and resultant astigmatism leading to visual impairment.\\[[@ref1]\\] Anecdotally, various trigger factors have been implicated in the causation of herpetic reactivation, namely, immunosuppression, febrile condition, exposures to ultraviolet light, cold wind, systemic illness, surgery, menstruation, emotional stress, and minor local trauma; many patients can clearly foresee recurrent disease following a given event. Nevertheless, the HEDS epidemiological study did not show such a statistical correlation with above-stated risk factors. In published literature, the herpetic recurrence documented in the following circumstances use of topical medications such as steroids, prostaglandin analogs, intravitreal injections of anti-vascular endothelial growth factor agents, corneal-based laser procedures, laser iridectomy or trabeculoplasty, or any corneal interventions such as partial or full thickness keratoplasty particularly in those who had an active herpetic eye diseases in the past.\\[[@ref2][@ref3]\\]\n\nIn this context, we intend to present a case of unusual reactivation of herpetic necrotizing stromal keratitis 1 week after the periocular injection of botulinum toxin for the management of"
+"1 INTRODUCTION\n==============\n\nMost cellular processes require a large number of proteins to assemble into functional complexes to perform their activity. Therefore, describing functional protein complexes taking part in given processes is critical to the underlying molecular mechanism understanding. Experimental protocols such as Affinity Purification followed by Mass-Spectrometry (AP-MS) have been devised to *pull down* a protein of interest (*bait*) together with all the interacting proteins within the same protein complex (*preys*). However, these sets of *preys* may contain both false positives, proteins detected despite not actually interacting with the *bait*, and omit false negatives ([@btu517-B4]), proteins interacting in the cellular context studied but not detected. Effective control experiments and usage of contaminants repositories can remove some false positives. However, false negative interacting partners identification, thereby the definition of the entire protein complex, remains challenging. Protein--Protein Interaction (PPI) data represents abundant information that can be used for this purpose.\n\nProtein complexes extraction from PPI networks is a very active area of research and many methodologies have been developed to tackle this problem. These computational methods generally model protein complexes as dense subnetworks within the complete set of PPIs and thus try to solve a graph clustering problem or to identify"
+"1 Introduction\n==============\n\nAutomatic gene function annotation is an important first step to interpret genomic data. Kyoto Encyclopedia of Genes and Genomes (KEGG) is a widely used reference knowledge base, which helps investigate genomic functions by linking genes to biological knowledge such as metabolic pathways and molecular networks ([@btz859-B4]). In KEGG, the KEGG Orthology (KO) database---a manually curated large collection of protein families (i.e. KO families)---serves as a baseline reference to link genes with other KEGG resources such as metabolic maps through *K* number identifiers. Currently, KOs are assigned to 12\u00a0934\u00a0525 (48%) protein sequences in the KEGG GENES database (27\u00a0173\u00a0868 proteins). Three existing tools, BlastKOALA, GhostKOALA ([@btz859-B5]) and KAAS ([@btz859-B7]), are available to assign KOs to protein sequences. These tools use homology search software such as BLAST ([@btz859-B1]) and GHOSTX ([@btz859-B8]) to search amino acid sequences against GENES. To reduce the lengthy computational times required for multiple pairwise sequence comparisons, these tools use selected representative sequences from GENES to build their target database. In this study, we propose to employ profile hidden Markov model (pHMM) to compress the database and to define adaptive thresholds for similarity scores, which can be used for reliable KO assignments.\n\n2"
+"I. Introduction\n===============\n\nMost of the medical records we have today are either in unstructured or semi-structured form. Documents from the domain of laboratory reports, for example, consist of attributes from a closed set of attribute types and their respective measurements, and they are already in the desired structured form. However, data in documents like doctor\\'s notes, discharge statements, etc. is mostly unstructured, and very difficult to analyse.\n\nHealthcare Data Extraction and Analysis (HEDEA) is a system to extract information from clinical reports, including prescriptions, blood and urine test reports, and medical notes. The system stores this information and retrieves it as a single-page anamnesis of the patient, with all past records displayed in a comprehensive tabular form. This can help a physician to thoroughly analyse the patient\\'s medical history without sifting through years of paperwork, some of which go missing.\n\nAnother area in which a structured information system can be useful is biomedical research. Epidemiological research is highly dependent on the statistical evaluation of medical data; hence, it requires data available in a structured form \\[[@B1]\\]. Obtaining such structured medical data through study-specific tests on a carefully selected subgroup of patients is both time and cost-intensive. Another way to"
+"The dynamics of an influenza epidemic are difficult to determine because they vary for each circulating influenza subtype. We evaluated the epidemiology of influenza A subtypes at Oshima Medical Center and Maeda Internal Medicine Clinic on Izu-Oshima Island, Japan. The island is a semiclosed community, which facilitates population-based surveillance. Access to the island is limited; \u224818,000 persons travel to and from the island each month, primarily to and from Tokyo ([@R1]). Izu-Oshima Island is 120 km southwest of Tokyo; population was 8,856 in January 2009.\n\nThe Study\n=========\n\nClinical information was collected retrospectively for January 1 through July 31, 2009, and prospectively from August 1, 2009 through April 30, 2011. Retrospectively, we identified patients who had been tested for influenza by use of a rapid test kit and extracted personal and clinical information from medical records. Prospectively, we collected the same information from patients tested for influenza by rapid test kit and used nasopharyngeal swab extracts from rapid test kits for virus typing. Typing was performed by reverse transcription nested-PCR (RT-nPCR): multiplex for seasonal influenza virus (subtypes A/H1, A/H3, B-, and A/H5) and simplex for influenza A(H1N1)pdm09 virus ([Technical Appendix](#SD1){ref-type=\"local-data\"}[Table 1](#T1){ref-type=\"table\"}). By amplifying product exclusively for influenza A(H1N1)pdm09 and for"
+"World demand for oil and fat is on yearly increase and as a consequence, the area planted with oil palm in Malaysia tremendously increased from 0.3 million hectares (ha) to 4.49 million ha in 1970 and 2008, respectively ([@b14-ppj-32-396]). In Southeast Asia, basal stem rot (BSR) disease has remained one of the major obstacles in oil palm cultivation. It is caused by the white-rot fungus, *Ganoderma boninense* which cuts down the oil palm yield in most production areas in Malaysia as well as Indonesia. To date, BSR is controlled by using cultural practices, biological control agents such as *Tricoderma* spp. and selected systemic chemical fungicides. However, till now, no single control proven to effectively control BSR in the field was reported ([@b32-ppj-32-396]). The difficulty managing this disease is due to not exhibiting any external symptoms on mature palms until advanced stage. When it comes to this stage, the infected trees may not be able to respond to any treatment given. Therefore, enhanced nutritional programmes (ENPs) by using mineral nutrients and plant hormone, appropriate dosage application at seedling stage should be done, in order to make them resistant towards BSR disease when they are transplanted in the field.\n\nNutritional status of"
+"Between 1999 and 2016, more than 630\u2009000 persons in the United States died from drug overdoses---most of these drug-related deaths were due to opioids prescribed for pain.^[@bibr1-1178632918819440]^ From 1999 to 2010, overdose deaths due to opioid pain relievers increased continuously, a time known as the first wave of the opioid epidemic. After this wave, the second and the third waves of opioid overdose deaths due to heroin and illicitly manufactured fentanyl (IMF), respectively, affected the United States significantly.^[@bibr1-1178632918819440][@bibr2-1178632918819440][@bibr3-1178632918819440][@bibr4-1178632918819440][@bibr5-1178632918819440]-[@bibr6-1178632918819440]^ There was an increase in deaths from 52\u2009404 in 2015 to 72\u2009000 deaths (provisional) by 2017.^[@bibr7-1178632918819440][@bibr8-1178632918819440]-[@bibr9-1178632918819440]^ A recent suggested revision to the classification of prescription opioid-related deaths removes synthetic opioids (such as fentanyl) from this category to better characterize those deaths as, increasingly, from illicit opioids. This reclassification has important implications for strategies to address the problem as we discuss under possible solutions.^[@bibr10-1178632918819440]^ This article reviews the evolution of the understanding of pain and the impact of pain (initially with disability of WW II veterans as the proxy for the subjective symptom of pain) on the political, legal, and regulatory systems in the United States as a template for the increase in use of opioids in the past 2"
+"Over the last few years, Orthopaedics has been inundated with Open Access journals, the continued quality and survivorship of which is uncertain. SICOT, the only international society of Orthopaedics and Traumatology has therefore decided to participate and take a lead in this rapidly evolving field. *SICOT-J* has now been launched. It is backed by an internationally renowned Editorial Board and we seek quality publications.\n\n*SICOT-J* is an Open Access journal which publishes original clinical, basic and translational research in orthopaedic surgery and traumatology. SICOT-J will accept, subject to peer review, review articles, original articles, research articles, surgical techniques, case reports, congress proceedings, editorials and letters to the Editor.\n\nAs *SICOT-J* is published under Open Access conditions, all the articles will also be published quickly by the Open Access Repository (OAR) of publicly accessible scientific articles, in Biomedical and Life Science journals and by PubMed Central which is hosted by the US National Institute of health's National Library of Medicine (NIH/NLM).\n\nWe invite you to submit your articles to *SICOT-J* by visiting the website of the journal at [www.sicot-j.org](http://www.sicot-j.org). We hope that many of you will support the Journal as it is with your quality articles that the journal's impact in"
+"The past decade has seen big changes in the field of genomics, not only in terms of advances in technology, but also with regard to the views on sharing the data generated \\[[@B1],[@B2]\\]. Open data has become the buzzword of this age. No one can deny that this openness and willingness to share genomic data, both published and (perhaps more importantly) unpublished, has resulted in remarkable progress. However, when it comes to unpublished genomic data, this openness can also leave the data generators vulnerable. The community needs to balance the benefits of data sharing against the interests of the data owners, and usually the process works well.\n\nThe genomics community has measures in place to protect the data owners--data are often released under embargoes (of varying lengths, but usually not longer than 24 months) and data owners can also publish a 'statement of intent', i.e. outline the specific analyses they plan to undertake, when they release the data. There are also community norms--specifically the Bermuda rules \\[[@B3]\\], and the Fort Lauderdale \\[[@B4]\\] and Toronto \\[[@B5]\\] agreements--to help researchers navigate this rather sensitive issue. However, embargoes are not indefinite and neither does it seem fair to indefinitely prohibit specific analyses. It"
+"The conscious perception of spatial or temporal changes in the environment is limited by the visual system's ability to perceptually resolve high spatial and temporal frequencies. This limit is approximately 60 cycles per degree of visual angle when discriminating the orientation of fine grids ([@bibr7-2041669520925111]), 30 to 60\u2009Hz when observing flickering patches ([@bibr4-2041669520925111]; [@bibr5-2041669520925111]; [@bibr10-2041669520925111]), and approximately 30\u2009Hz when detecting the direction of sinusoidally moving gratings ([@bibr3-2041669520925111]). These limits, however, apply to conscious perception. Some studies suggest that information can unconsciously be encoded even when these limits are exceeded. [@bibr8-2041669520925111], for example, demonstrated that gratings indistinguishable from a uniform field can affect the magnitude of the tilt aftereffect, and [@bibr15-2041669520925111] showed that temporal frequency modulations above the critical flicker fusion frequency (CFF) can influence the sensitivity to subsequent flickering patches.\n\nIn 2010, Mattler and Fendrich published a study that indicated the human visual system can process motions so rapid they are not visually perceptible as motion. On an analog oscilloscope with an effective frame rate of 1000\u2009Hz, they presented a 16-point ring (the *inducing ring*^[1](#fn1-2041669520925111){ref-type=\"fn\"}^) that rotated at angular velocities of up to 2,250\u00b0/s. These high velocities were achieved by advancing the points around the ring circumference"
+"A telessa\u00fade consiste na utiliza\u00e7\u00e3o de tecnologias de informa\u00e7\u00e3o e comunica\u00e7\u00e3o (TIC) para prestar servi\u00e7os de sa\u00fade a dist\u00e2ncia e para compartilhar informa\u00e7\u00f5es e conhecimento. Na literatura, os termos telessa\u00fade, telemedicina e eHealth s\u00e3o frequentemente utilizados; eles expressam estrat\u00e9gias de resposta para problemas de sa\u00fade socialmente constru\u00eddos, como escassez de profissionais em \u00e1reas remotas e aumento da longevidade da popula\u00e7\u00e3o ([@B1]--[@B3]).\n\nNo s\u00e9culo XIX, o desenvolvimento dos servi\u00e7os postais, o uso do tel\u00e9grafo e, posteriormente, o uso do telefone facilitaram a troca de informa\u00e7\u00f5es e a divulga\u00e7\u00e3o das pr\u00e1ticas m\u00e9dicas. No s\u00e9culo XX, o uso da televis\u00e3o e da radiocomunica\u00e7\u00e3o permitiram maior troca de informa\u00e7\u00f5es de sa\u00fade. Com o advento da Internet, a partir da d\u00e9cada de 1990, cresceu a integra\u00e7\u00e3o da telecomunica\u00e7\u00e3o \u00e0s necessidades de sa\u00fade ([@B4]). Atualmente, a telessa\u00fade utiliza os mais diversos mecanismos, inclusive palestras por videoconfer\u00eancia para educa\u00e7\u00e3o permanente e interconsultas, telefone, mensagens via celular, plataformas de mensagens via Internet, v\u00eddeos ou mensagens via sat\u00e9lite ([@B1]--[@B10]).\n\nDiante desse hist\u00f3rico, tornou-se evidente a possibilidade de resultados nas a\u00e7\u00f5es de telessa\u00fade para preven\u00e7\u00e3o de doen\u00e7as, promo\u00e7\u00e3o da sa\u00fade e tratamento de morbidades, justificando investimentos por parte dos governos. Levando em considera\u00e7\u00e3o esses aspectos, fizemos a seguinte pergunta de"
+"Case description {#section3-2055116917733642}\n================\n\nA 6.3 kg, 11-year-old, spayed female domestic shorthair cat presented with periodontal disease for dental evaluation and treatment. The cat had a history of chronic kidney disease (evaluated as IRIS stage 1) and had been prescribed a commercial renal diet. The cat was also receiving fluoxetine (1 mg/kg q24h PO) and trazodone (3 mg/kg q12h PO) to manage anxiety and aggression.\n\nInitial examination of the oral cavity revealed significant gingivitis and mild calculus, which warranted closer examination under general anesthesia. The owners provided written informed consent for anesthesia and the procedure.\n\nThe cat had been anesthetized twice before for dental procedures at the hospital. In both instances a standard orotracheal intubation protocol was followed: pre-oxygenation with a face mask for 3--5 mins, intravenous induction of general anesthesia, topical lidocaine applied to arytenoid cartilages, and attempted orotracheal intubation no sooner than 30 s after lidocaine application. Laryngospasm was reported at the induction of both anesthetics. In the second case, orotracheal intubation was achieved, with a documented delay of 7 mins between the induction of anesthesia and placement of the endotracheal tube (duration of intubation not noted in the first case). Other than laryngospasm, the anesthetic procedures and"
+"Quantum information science promises powerful and unconventional capabilities across a broad range of technologies. An important example relates to the imaging technology, optical coherence tomography (OCT). OCT can noninvasively reconstruct the 3-dimensional structure of tissue with micron resolution[@b1]; it is emerging as an important clinical tool with diverse medical applications. OCT can diagnose retinal diseases such as glaucoma, analyze artherosclerotic tissues within arteries, and detect early-stage cancerous lesions in breast tissue[@b2][@b3]. In addition, OCT has found application in precision laser machining[@b4]. Since OCT relies on low-coherence interferometry, its axial resolution is limited by the coherence length of the light, inversely proportional to the bandwidth. The coherence length determines ultimate resolution, however, material dispersion can limit the practical one.\n\nFundamental studies in quantum optics showed that interference with energy-time entangled photon pairs[@b5] exhibits inherent robustness against unbalanced dispersion[@b6][@b7]. Even-order effects of dispersion, including the dominant group-velocity dispersion, are automatically cancelled, effectively solving the dispersion problem. This dispersion cancellation is automatic since one does not need to precisely measure and compensate the dispersion. When energy-time entanglement is strong, but not perfect, the effect is more accurately described as automatic even-order dispersion reduction since the dispersion is dramatically reduced, not cancelled[@b8]. OCT based"
+"Microcephaly is a neurodevelopmental disorder characterized by small brain and mental retardation. A significant number of proteins implicated in microcephaly, including ASPM (abnormal spindle-like microcephaly associated) participate in organizing mitotic spindle poles[@R1]. The function of a spindle pole depends on microtubule nucleation as well as stabilization, disassembly and bundling of microtubule minus ends. Microtubule minus ends can grow and shrink in vitro[@R2], however, it is generally believed that within mitotic spindles, minus ends are either stable or slowly depolymerize, resulting in poleward microtubule flux[@R3]. The molecular mechanisms controlling microtubule minus-end behavior in the spindle are poorly understood.\n\nPrevious work indicated that ASPM (known as Asp in fly and ASPM-1 in worm) is an excellent candidate for being a mitotic microtubule minus-end regulator[@R4]--[@R13]. It is encoded by the gene that is most frequently mutated in microcephaly[@R14], but the molecular mechanism underlying ASPM activity is not understood. Katanin, a conserved microtubule-severing protein complex, which consists of the AAA ATPase containing enzymatic subunit p60 and the regulatory subunit p80[@R15]--[@R17], is also linked to microcephaly[@R18],[@R19]. Formation of the katanin p60/p80 heterodimer is mediated by the N-terminal Microtubule Interacting and Trafficking domain of p60 and a conserved C-terminal domain of p80[@R20]. Katanin localizes to spindle"
+"The possibility of risks specific for pregnant women and their fetuses became immediate concerns at the outbreak of the COVID-19 pandemic. In contrast to the 2015 Zika virus epidemic, when unique birth defects were identified early in the course of the spread, no novel fetal or maternal risks have yet been confirmed[@R1]. However, the limited extant data regarding the maternal and fetal effects of COVID-19 infection especially for the first trimester provide little reassurance. The pandemic posed an immediate dilemma for centers actively treating infertile couple with medically assisted reproduction (MAR) and assisted reproductive technology (ART), including in vitro fertilization.\n\nOut of caution, several professional societies around the world recommended suspending therapy for infertility services initially on March 18, 2020, 1 week after the World Health Organization declared COVID-19 infection to be a pandemic[@R2]--[@R4]. All guidelines published by reproductive medicine societies at this time endorsed cessation of infertility services although some granted exemptions for exceptional circumstances, such as oocyte or sperm cryopreservation procedures in patients about to undergo chemotherapy or radiation, that would likely deplete their gamete number. Reasons cited for these extraordinary measures included preventing possible complications of ART and MAR, possible virus induced complications of pregnancy and concerns"
+"Research in contextEvidence before this studyA non-consanguineous white European pedigree with three affected male patients, presented with severe recurrent hypoglycaemia, short stature with GH and TSH deficiencies, an unusual form of glucose dysregulation, and mild learning difficulties. This combination of phenotypes has, to date, not been reported in the literature. There were no publications linking these phenotypes in any online journal listed on Pubmed or elsewhere.Added value of this studyExome sequencing of the X-chromosome revealed a novel missense variant c.1294C\u202f\\>\u202fT in *EIF2S3* (p.Pro432Ser), encoding a subunit of the eukaryotic translation initiation factor 2, eIF2\u03b3, in all three male patients and in the heterozygous mothers. Mutations in *EIF2S3* have been described in patients with MEHMO syndrome, characterized by severe intellectual disability, microcephaly, short stature, epilepsy and accompanying midline and facial abnormalities. The functional and expression data in our study show a moderate but significant eIF2\u03b3 impairment, which relates to the milder phenotype in our three male patients.Implications of all the available evidenceThis milder loss of function compared with previous *EIF2S3* mutations gives rise to a phenotype that is distinct from the classical spectrum of MEHMO syndrome. Untreated hypoglycaemia in the previously published cases may have contributed to their more"
+"**PURPOSE:** In the clinical care of patients with burn injuries requiring grafting, skin graft donor site pain significantly affects pain management, narcotic use, and hospital length of stay. We proposed to evaluate the efficacy of regional anesthesia to decrease narcotic consumption, and to assess the impact on hospitalization costs via meta-analysis. We hypothesized that regional anesthesia at donor sites would significantly decrease pain and narcotic consumption, as well as decrease total hospital costs compared to non-regional pain management.\n\n**METHODS:** Using PRISMA criteria, PubMed/MEDLINE, Embase and ScienceDirect were searched with the following inclusion criteria: comparative studies, adult populations, burn patients, autologous skin grafting, regional nerve blocks and traditional narcotic regimens. MINORS criteria assessed methodological rigor of included studies. Outcomes assessed included narcotic consumption, pain scores, and opioid side effects. Meta-analysis obtained pooled values for morphine consumption and side effects. Cost analysis was performed using published data in the literature.\n\n**RESULTS:** Final analysis included 101 patients. Cumulative morphine consumption at 72 hours was lower for patients treated with regional anesthesia (fascia iliaca compartment block) versus patient-controlled analgesia (single shot regional 25\u2009\u00b1\u200912mg; continuous regional 23\u2009\u00b1\u200916mg; control 91.5\u2009\u00b1\u200924.5mg; p\\<0.05). Regional anesthesia decreased nausea/vomiting (p\\<0.05), and lowered subjective pain"
+"We are pleased to launch Volume 8 of *Molecules* with a special issue containing a selection of lectures and papers presented at the ISFMS 2002 conference, co-sponsored by MDPI and hosted by the Ocean University of China last July 2002 at Qingdao, P.R China \\[[@B1-molecules-08-00001]\\]. We are especially honoured to present the text of the Science and Society Lecture given by the 1991 Nobel Laureate in Chemistry, Professor Dr. Richard Ernst (ETH, Switzerland).\n\nThe other 21 papers in this issue are expanded, peer-reviewed versions of some of the presentations given at the conference, which represent a cross-section of current research taking place on the frontiers of molecular science.\n\nReference\n========="
+"Introduction {#s1}\n============\n\nMetazoans, or multicellular animals, represent the epitome of biological complexity. Prerequisite for generating this complexity was the development of a multicellular lifestyle, and the ability to coordinate cell division, migration and differentiation to optimize the overall fitness of the organism [@pgen.1003804-Michod1]. Multicellularity emerged several times during evolution (in algae, plants, fungi and metazoans); however, the one that emerged in metazoans is notable in terms of the extreme diversity of body plans and differentiated cell types that subsequently evolved [@pgen.1003804-Rokas1].\n\nMetazoans form a monophyletic group within the opisthokont lineage, a large taxonomic unit containing fungi and several groups of single-celled organisms, including choanoflagellates, ichthyosporea, filasterea and nucleariids [@pgen.1003804-ShalchianTabrizi1] ([Figure 1A](#pgen-1003804-g001){ref-type=\"fig\"}). The properties of the last common ancestor of metazoans and identity of its closest relatives has been the subject of much debate, due to a lack of fossils and sequence data from a broad range of relevant species. This is currently being addressed by genome sequencing efforts such as the UNICORN project [@pgen.1003804-RuizTrillo1]. The release of the complete genome sequence of *Monosiga brevicollis*, now widely recognized as the closest known unicellular ancestor of metazoans, as well as the genomes of several early branching metazoan species---including *Amphimedon queenslandica*, *Trichoplax"
+"Introduction\n============\n\nThe Lives Saved Tool (*LiST*) can use baseline coverage data, programme targets and a demographic projection to model the magnitude of mortality reduction expected from planned programme activities, as described earlier in this issue[@B1]. As a validation exercise, we modelled data from a recently completed, retrospective evaluation of a child survival programme in West Africa and compared the results with estimates of mortality measured through demographic surveys as part of the evaluation. Using this large-scale, 'real life' evaluation to validate *LiST* will help current and future users understand the strengths and limitations of mortality-modelling tools.\n\nThe United Nations Children's Fund (UNICEF) implemented the Accelerated Child Survival and Development (ACSD) programme in 11 countries from 2001 to 2005, supported by the Canadian International Development Agency (CIDA). UNICEF focused efforts on several 'high-impact' countries, including Benin, Ghana, Mali and Senegal, working closely with country governments and other partners to implement ACSD with the ultimate goal of reducing under-5 mortality. Focus districts within these countries implemented three intervention packages. The 'EPI+' package included vaccinations, vitamin A supplementation and distribution of insecticide-treated nets (ITN). The 'ANC+' package targeted pregnant women and included improved access to antenatal care and skilled delivery along with"
+"Introduction {#Sec1}\n============\n\nWeaning from mechanical ventilation (MV) is a challenging decision, it means complete transition from mechanical breathing support to patient's own respiratory drive support. This transition is very critical and needs accurate, intense, confident decision based on trusted validated clinical, radiological and laboratory parameters to avoid the risk of weaning failure \\[[@CR1]\\].\n\nThe patient's failure to accomplish this or to withstand 48\u00a0h of spontaneous breathing is defined as a weaning failure. Weaning failure is a disappointing event that, in relation to the comorbidities and other reported complications, impacts all ICU staff and patient families and costs patient exposure to reintubation risk \\[[@CR2]\\].\n\nThe readiness of the patient for weaning depends globally on the respiratory muscles' power that faces the burden of breathing. Unbalance between the power and the burden leads to weaning failure, including any factor that impairs the respiratory muscle function as ICU acquired neuromuscular dysfunction which is either due to prolonged mechanical ventilation, prolonged sedation or any other potential cause \\[[@CR3]\\].\n\nAlthough the validated respiratory parameters which are assessed during weaning process are appropriate for weaning, however, the proficiency of these parameters to detect the power of the respiratory muscles to carry on the burden"
+"1. Introduction {#sec1}\n===============\n\nAn amelanotic or slightly pigmented iris mass is an uncommon finding, but usually indicates a benign or malignant tumor. In adult/elderly patients, differential diagnosis chiefly involves an iris melanoma versus rarer forms such as: secondary cysts (which may result from anterior segment surgery, prolonged use of miotics, metastasis, or parasites); leiomyoma, a benign smooth muscle tumor often located in the pupillary margin; inflammatory granulomas.[@bib1], [@bib2], [@bib3] Iris melanoma is a slow-growing tumor that typically presents during the fifth decade of life. Regarding pigmentation, amelanotic forms have been widely reported, although some residual pigmentation is usually present.[@bib4]\n\nA so-called morgagnian cataract, named after the Italian anatomist Giovanni B. Morgagni, is a form of hypermature cataract in which the brown sclerosed nucleus is present in a capsular bag filled by milky white, liquefied cortex. Quite common in the past, it is presently exceptionally rare in developed countries. We report a case of morgagnian cataract that involved clinical and instrumental differentiation from the abovementioned iris lesions.\n\n2. Case report {#sec2}\n==============\n\nA 60-year-old Caucasian male was referred to the eye clinic of the University Hospital of Parma for bilateral painless worsening of his vision that lasted for several months."
+"Upper respiratory tract complaints are among the leading causes of admission into emergency service. Upper urinary tract infections are the most frequently seen cause of morbidity. They are the most frequently observed diseases which threaten community health, and result in labour loss. These infections can have viral or bacterial origins, and their incidence increases markedly during winter months \\[[@ref1]\\]. Since these diseases spread by droplets, they are more frequently seen among crowded places. In the treatment of the patients analgesics, antipyretics, decongestants, antitussive drugs, and antibiotics have been used. As indicated in many guidelines, for these diseases with frequently viral etiology, prescription of antibiotics under certain indications has been recommended \\[[@ref2], [@ref3]\\]. As a known fact antibiotic use has been frequently abused by both the physicians, and the patients which results in increasingly prevalent antibiotic resistance.\n\nDevelopment of resistance against antibiotics is a global problem. Centers for Disease Control (CDC) reports that \u0131n the United States of America every year 2 million people are infected with antibiotic-resistant bacteria, and at least 23,000 individuals die from these diseases \\[[@ref4]\\]. World Health Organization has prepared a report based on data gathered from 114 countries in order to attract attention to this subject,"
+"Conventionally, assessment of childhood obsessive compulsive disorder (OCD) in research settings has focused on systematic categorization of diagnosis and symptoms using a barrage of interviews and questionnaires whereas community-based evaluations have been generally based on of unstructured clinical interviews. Nevertheless, there is an increasing movement towards evidence-based assessment in child psychiatry, and assessment techniques from clinical research are becoming more commonplace in practice settings. This article summarizes critical content areas (e.g., pre-visit screening, establishment of the diagnosis, differential diagnosis, identifying comorbidity, tracking symptom severity, determining psychosocial functioning, and evaluating outcome/clinical improvement) for any assessment of childhood OCD. Throughout this review, similarities and differences between assessment approaches geared towards clinical and research settings are discussed. The aim of this article is to provide an overview of research-supported approaches for the assessment of youth with OCD relevant to both research and clinical applications.\n\nPre-Visit Screening {#Sec1}\n===================\n\nPrescreening prior, to a comprehensive assessment or intake, can be an important tool in both clinical and research settings. Childhood OCD treatment and research is often conducted in specialty treatment programs. Consequently, pre-office visit screenings are commonplace to maximize effective use of examiner's and patient's time. In many settings, the screening is the first assessment"
+"Introduction {#s1}\n============\n\nPhenotype MicroArrays (PM) technology provides a simple tool for testing microbial cells [@pone.0056545-Bochner1], [@pone.0056545-Bochner2], [@pone.0056545-Bochner3] as well as mammalian cells [@pone.0056545-Bochner4] under hundreds or thousands of culture conditions. In 2009, Gardiner and colleagues [@pone.0056545-Gardiner1] reported on the use of PM to examine the effect of many culture condition variables on toxin production by the pathogenic fungus, *Fusarium graminearum*. This fungus is a major pathogen on wheat, with severe agricultural and commercial impact. Over many decades of study, no one was able to find *in vitro* culture conditions that would turn on synthesis of the *F. graminearum* trichothecene mycotoxin. However, the use of PM technology provided the breakthrough, indicating that strong toxin induction could be obtained *in vitro* by simply culturing the fungus with arginine, putrescine, agmatine, or guanine as the nitrogen source. Secondarily they found and confirmed that pH 4.5 produced additional induction [@pone.0056545-Gardiner2].\n\nA different novel approach was taken by Singh [@pone.0056545-Singh1] from the Natural Products Discovery Group at Wyeth Pharmaceuticals, who studied substrate utilization effects on secondary metabolite production in fungal strains with promising commercial potential. He used the 95 substrates of the FF MicroPlate combined with scaled-down LC-MS to quantitatively profile the secondary metabolites"
+"Microstructure engineering is a persistently vigorous technique in altering material's properties through tailoring geometrical features of structural units at multiple length scales and modifying three-dimensional arrangements of structural units. Structural units can be classified into three, two, one, or zero dimensions, such as three-dimensional volumes[@b1][@b2] (phases, grains, particles/precipitates), two-dimensional surfaces[@b3][@b4] (boundaries, interphases), one-dimensional lines (triple lines, edges, dislocations) or zero-dimensional points (quadruple points, vertices on polyhedral particles)[@b5]. In advancing the material's performance resulted from these structural units, arranging their distribution provides different strategies in addition to regulating the dimensions and shapes of these structural units. To realize specific microstructure, heat treatment, mechanical deformation, and/or their combinations can be applied while adjusting chemical compositions of a material.\n\nRare-earth (RE) elements[@b6] has a demonstrated significance in tuning the microstructure of Mg alloys, such as weakening basal texture of Mg alloys[@b7][@b8], refining grain sizes, forming long-period stacking-ordered structure[@b4], etc. RE solutes can also be trapped in twin boundaries, and in turn, impeding migration of twin boundaries[@b9][@b10]. In addition, the elastic interactions between solutes and dislocations lead to solute segregation and depletion around dislocation cores. Such a solute atmosphere, which can maintain their confined structural and chemical states over a range of evaluated temperatures[@b11],"
+"The tumor suppressor p53 can act as a transcription factor, but only a few p53-activated genes have been found, and the biochemical basis of p53-mediated apoptosis has been especially difficult to probe. Now, Bourdon et al. describe the discovery and characterization of a novel p53-inducible proapoptotic gene (page 235).\n\nFigureThe location of Scotin (green) suggests a function for the ER in apoptosis.\n\nBy comparing gene expression in normal and p53-knockout mice exposed to ionizing radiation, the authors identified *Scotin*, a novel gene that is directly trans-activated when p53 binds to a specific site in its promoter. Mouse *Scotin* and its human homologue appear to induce apoptosis in a caspase-dependent manner.\n\n*Scotin* has the structure of a type I transmembrane receptor, but is located in the endoplasmic reticulum and the nuclear membrane, not in the Golgi apparatus, mitochondria, or plasma membrane. The authors are now trying to determine whether this localization pattern is required for *Scotin* activity, and whether the protein can promote apoptosis in response to endoplasmic reticulum stress as well as DNA damage.\n\nThe chromosomal location of the human *Scotin* gene, 3p21.3, is also tantalizing, as this region is rearranged or deleted in a wide range of human tumor"
+"G-protein coupled receptors constitute the largest protein family in the human proteome (over 800 members). Their diversity and central role in cellular signaling makes them important drug targets. Indeed, GPCRs are the targets of about 40% of all therapeutic drugs, including 25% of the top-selling ones[@b1]. Understanding molecular mechanisms of GPCR signaling is of both fundamental scientific impact and high medical potential. Biophysical studies on these receptors are particularly challenging because they are transmembrane proteins that require the appropriate hydrophobic lipid environment for proper function. Following their isolation from cellular membranes using detergents that preserve their function, reconstitution in lipid membranes is necessary to maintain their stability. Their reconstitution from a detergent-stabilized state into a well-defined artificial lipid model system of controlled lipid composition for *in vitro* studies[@b2][@b3] can be achieved by dilution or detergent removal using dialysis, gel filtration, hydrophobic absorption using Bio-beads, or complexation by cyclodextrins. Regardless of the method used, the process itself remains most often intractable (with the exception of an indirect Isothermal Titration Calorimetry approach reported by S. Keller and coworkers based on phase transition monitoring[@b4]). Herein we demonstrate that Plasmon Waveguide Resonance (PWR) spectroscopy can be used to directly follow the reconstitution of a"
+"Dear Sirs,\n\nResearch serves a vital purpose in furthering the knowledge base on which medicine is practised. Furthermore it may be defined as the method to which we *inform our action*. In order for us to practice evidence-based medicine, we must be informing our action, which is reliant on robust and rigorous research.\n\nTomorrow's Doctors 2009 relates to three domains: the scholar, the scientist and the practitioner. All three domains are intrinsically linked and responsible for consistently increasing the knowledge base \\[[@CR1]\\] and hence require consistent, thorough and accurate research \\[[@CR2], [@CR3]\\]. Thus it is only logical that the authors of Tomorrow's Doctors, the General Medical Council, expect these graduates to have the skills to perform this task.\n\nAnecdotal evidence, however, suggests research is often seen by medical students as something only students who intercalate or come from previous academic backgrounds can achieve. Research techniques and methodologies are practically absent from the busy curriculum facing medical undergraduates. Furthermore, anecdotal evidence and conference presentations suggest many students do not feel they have any research skills teaching throughout their undergraduate course. The absence of research skills in the general undergraduate curriculum therefore jeopardizes the furthering of each domain, but also the ability"
+"In this work, we investigate the fundamental question of how aromatic reactivity can be directed with high precision from above and below the planes of aromatic rings. By advancing towards this general goal, we aim to add a new dimension of control to the large class of electrophilic aromatic substitution (SEAr) reactions. While synthetic chemists still rely[@b1] largely on traditional covalent electron-donating and -withdrawing groups to direct SEAr reactions, nature has already mastered the third dimension in this regard. Enzymes, for instance, make heavy use of the areas above and underneath aromatic rings to (i) align electrophiles above/underneath a desired position of attack and (ii) stabilize reactive SEAr intermediates through space with protein residues. This three-dimensional approach provides exquisite reaction selectivities and has enabled evolution to tailor enzymatic pockets to form different products selectively from the same starting materials. Different orthologs of dimethylallyl tryptophan synthase (DMATS) catalyse, for example, Friedel-Crafts alkylations of *L*-tryptophan with dimethylallyl diphosphate with varying regioselectivities[@b2][@b3]. This family of enzymes is involved in the biosynthesis of ergot alkaloids, which find use in a variety of pharmaceuticals currently on the market[@b4]. On the basis of high-resolution X-ray crystal structures, it was proposed[@b5][@b6] that DMATS from *Aspergillus fumigatus* achieves"
+"Dear Sir,\n\nIt is widely recognized that 3-dimensional computed tomography (3D-CT) is useful for diagnosing facial bone fractures.[@B1] However, it can be sometimes difficult to obtain such specialized 3D-CT images from radiologists because of the unusual and specific nature of the request. Moreover, it sometimes takes a long time before the 3D photographs are received. Consequently, we have developed a system by which plastic surgeons themselves can immediately and precisely determine the details of a facial fracture. This system involves the use of a personal laptop computer on which a Digital Imaging and Communications (DICOM) viewer has been preinstalled.\n\nThis viewer is used as follows. When a patient with suspected facial bone fractures comes to the emergency outpatient clinic, the \"volumetric data\" of the fractures are captured by the multidetector-row CT with either 8-, 16-, 32-, 64-, or 256-row scanners. The CT images can be reconstructed with the maximum intensity projection and the volume rendering technique. This reconstructed DICOM data can then be analyzed by the plastic surgeon by using the software \"OsiriX\" (<http://www.osirix-viewer.com/>), which will work on a personal laptop computer. The author employs a Macintosh OS X for this purpose.\n\nThere are several advantages of using this portable"
+"*Sr. Editor:*\n\nCOVID-19 es la enfermedad infecciosa causada por el coronavirus SARS-CoV-2, descubierto recientemente. Tanto el virus como la enfermedad eran desconocidos hasta diciembre de 2019, cuando se inici\u00f3 el brote en Wuhan (China), habi\u00e9ndose propagado por todo el mundo[@bib0020]. La afectaci\u00f3n de la infecci\u00f3n a nivel respiratorio est\u00e1 claramente establecida. Sin embargo, sus manifestaciones neurol\u00f3gicas son menos conocidas[@bib0025]. Presentamos un caso de s\u00edndrome de Guillain-Barr\u00e9 (SGB) asociado a COVID-19.\n\nPaciente var\u00f3n de 43 a\u00f1os de edad, que consulta por debilidad sim\u00e9trica y global de las 4 extremidades de intensidad progresiva con imposibilidad para la deambulaci\u00f3n, as\u00ed como alteraci\u00f3n en la sensibilidad de los 4 miembros a nivel distal. Diez d\u00edas antes hab\u00eda presentado un episodio autolimitado de diarrea, seguido de sintomatolog\u00eda de infecci\u00f3n de v\u00edas respiratorias superiores.\n\nEn la exploraci\u00f3n neurol\u00f3gica se objetiva debilidad de las 4 extremidades con balance muscular 3/5 a nivel proximal, 4/5 distal y arreflexia universal. En la radiograf\u00eda de t\u00f3rax se objetivan alteraciones sugerentes de neumon\u00eda incipiente por COVID-19 ([fig. 1](#fig0005){ref-type=\"fig\"} ). Se obtiene positividad en la PCR deL SARS-CoV-2. En el estudio EMG de conducci\u00f3n se registra aumento de las latencias distales motoras y disminuci\u00f3n de las velocidades de conducci\u00f3n sensitivas en los"
+"Specifications TableSubject areaComputer scienceMore specific subject areaComputer Vision and Image ProcessingType of dataImage, graph, video and spreadsheetHow data was acquiredMicrosoft Kinect RGB-D (Infrared and RGB camera) matricesData formateps, pdf, avi, xlsExperimental factorsData from the infrared and RGB sensor were converted into appropriate matrices with RGB channels.Experimental featuresImages produced for Detection and Tracking of Dynamic Objects and figures that detail the applied methodology in order to calculate effectiveness.Data source locationIndoor environment (SP-Brazil)Data accessibilityImage, video and spreadsheet (Supplementary files)Related research articleNatal Henrique Cordeiro, Emerson Carlos Pedrino,\\\nA new methodology applied to dynamic object detection and tracking systems for visually impaired people, Computers & Electrical Engineering, Volume 77, 2019, Pages 61--71,\\\nISSN 0045--7906, <https://doi.org/10.1016/j.compeleceng.2019.05.003>.**Value of the data**\u2022The data enable visually identifying which detections were effectively mapped using dynamic object detection and tracking techniques.\u2022The data allows (researcher) the chance of measuring the and effectiveness of each technique used for detection and tracking of dynamic objects.\u2022The data allow to understand how the detection of a dynamic object and error identification is performed by each technique.\u2022These data demonstrate how the positions of the detected dynamic objects can be mapped in millimeters.\u2022The quality of segmentation performed by each technique can be understood visually.\n\n1. Data {#sec1}\n======="
+"Introduction\n============\n\nHuman urine is mainly composed of shed cells, debris, and secreted components from the urinary tract as well as blood components that have passed through glomerular filtration and renal tubule reabsorption. Therefore, urine contains useful information not only regarding the kidney and urinary tract, but also about more distant organs. Analysis of the urinary proteome could aid the discovery of biomarkers for both urogenital and systemic diseases. Moreover, compared to serum, human urine is relatively simple and easy to collect, which makes urinary proteome analysis an attractive approach in clinical proteomics research.\n\nBecause inherent and environmental factors may influence the components of the urinary proteome, the biological and technical variations are important issues for urinary proteome research. Many groups \\[[@B1]-[@B6]\\] have contributed data regarding this issue and found that (1) a considerable degree of variation can be found in intra-day (collection from one volunteer at different daily time points), intra-individual (collection from one volunteer on different days), and inter-individual (collection from different volunteers) samples; (2) the variation of five intra-day samples (first morning, second morning, 24 h, random, and water loading void) was similar; (3) the variation of intra-individual samples was less than that of inter-individual samples; and"
+"**PURPOSE:** There have been many advancements in the field of neuroprosthetics for functional restoration following limb loss. However, devices that provide prosthetic users with intuitive, simultaneous motor control and somatosensory feedback have not yet been realized. Critical to the evolution of this ideal bioprosthetic device is the development of a reliable, biologic human-machine interface that facilitates transmission of both efferent motor signals for device control, and afferent somatosensory information. The Composite Regenerative Peripheral Nerve Interface (C-RPNI) is a novel biologic interface that demonstrates promise in this role. The C-RPNI is a surgical construct composed of a transected, mixed peripheral nerve implanted between a composite free graft consisting of de-epithelialized glaborous skin and skeletal muscle. The purpose of the present study was to investigate the viability and bidirectional signal transduction capabilities of the C-RPNI.\n\n**METHODS:** C-RPNIs were surgically implanted on the end of transected common peroneal nerves of thirty F344 rats using de-epithelialized dermal grafts harvested from glaborous skin of isogenic donor rat hindpaws and free skeletal muscle grafts from the animal's contralateral limb. Thirty animals underwent endpoint testing at three months (n=15) and at six months (n=15). Electrophysiologic testing was performed to determine both the *in vivo* efferent and afferent"
+"INTRODUCTION {#s01}\n============\n\nAs one of the oldest and most important predatory arthropods, the centipede has a fossil record that extends back 420 million years ([@bUndheim2011]). Approximately 3 300--3 500 centipede species have been found, with distribution worldwide and in most provinces of China ([@bRong2015]). Centipede venom, which is secreted from venom glands in the first pair of limbs ([@bEdgecombe2007]), is essential for survival, not only for subduing and killing prey but also for defense against predators.\n\nAnimal venom has long been considered a rich source of pharmacological and novel therapeutics ([@bKalia2015]; [@bSmith2013]; [@bZhang2015]). Furthermore, dried centipedes have been used medicinally for centuries, as shown in ancient Chinese medical records. Recently, an increasing number of studies have shown that centipede venom contains various functional components, including a rich reservoir of structural and pharmacological peptides ([@bHakim2015]; [@bUndheim2015], [@bUndheim2016]). In addition, because of their excellent chemical and pharmacological activities, particularly as neurotoxins and ion channel inhibitors, centipede toxins have received further attention ([@bLiu2012]; [@bYang2012], [@bYang2013], [@bYang2015]). Several antimicrobial peptides and specific toxins have also been identified in centipede venom ([@bChen2014]; [@bHou2013]; [@bPeng2010]; [@bYang2012]). Interestingly, centipede toxins are expressed outside the venom gland and are involved in gene recruitment processes ([@bZhao2018a]). These venom"
+"Introduction {#s1}\n============\n\nIntravenous medication administration is complex, and data suggest that errors are common. For example, a systematic review of nine studies across various stages of intravenous medication preparation and administration reported errors in 73% of intravenous doses.[@R1] However, published error rates vary widely, from 18% to 173% of intravenous doses in studies using structured observation of medication administration.[@R2]\n\nAmidst concerns over safety, technologies such as 'smart pumps' have been advocated. These incorporate dose error reduction software to check programmed infusion rates against preset limits within a customisable drug library. However, dose limits can be over-ridden, and evidence regarding their impact is mixed.[@R3] While unintended infusion overdoses represent a major safety concern, there are many factors that affect infusion administration, and smart pumps are just one possible solution.\n\nA recent multisite US study using structured observation reported a high prevalence of intravenous infusion administration errors and procedural failures, even with the use of smart pumps, yet few potentially harmful errors.[@R4] Building on this and an earlier US study,[@R5] we therefore wanted to conduct a similar study in the UK with a larger sample size[@R6] to confirm or refute these findings in a different context in which smart pumps are"
+"Background\n==========\n\nDespite significant improvements in care and health system strengthening for children who are living with Congenital Adrenal Hyperplasia (CAH) in Vietnam in recent years, consultation with families has confirmed that financial burdens continue to present urgent and pressing challenges for many. As part of its strategic framework for action and \"5 Pillar\" approach to helping children who are living in resource poor countries enjoy the highest quality of life possible, CLAN (Caring & Living As Neighbours) is committed to helping families achieve financial independence, and overcome any financial barriers to providing their children with the best care they can.\n\nAim\n===\n\nThis project sought to understand the financial burdens affecting CAH families in Vietnam and potential opportunities for the development of income generating activities.\n\nMethod\n======\n\nThe project concentrated on the most vulnerable and impoverished families. With support from members and staff connected with the CAH Club of NHP, willing families in rural areas of North Vietnam were identified for participation in face-to-face interviews in their homes in the month of July 2012. Families' financial situation and possible avenues to improve same were discussed.\n\nResults\n=======\n\nApproximately 50% of all 650 CAH families attending NHP for care live"
+"Introduction {#Sec1}\n============\n\nIn cases where re-intubation is likely to be difficult, an airway-exchange catheter (AEC) can be placed through the endotracheal tube (ETT) prior to extubation.[@CR1] Should re-intubation prove necessary, an ETT can be advanced over the AEC. In case of a difficult intubation, a similar strategy of \"railroading\" an ETT over an intubating catheter (IC) is a basic principle of securing the airway. In addition to functioning as a guide for the ETT, some AECs and ICs have a central lumen through which oxygen can be delivered.\n\nFlow resistance in a small-bore AEC or IC is high, however, so oxygen must be insufflated at high pressure. With conventional high-pressure (i.e., jet) ventilation devices that are used to inject oxygen through such catheters, the injected gas volume cannot be estimated. Also, because of its flow resistance, exhalation through small-bore catheters is limited. Thus, the absence of a patent airway allowing egress of air around the AEC/IC is a relative contraindication for oxygen injection into the lungs. Despite this contraindication, these catheters are still typically used in patients whose airways may become compromised due to obstruction (e.g., tissue swelling or hematoma).[@CR2] In such patients, expiration time is prolonged, and complete"
+"Research on vertebrate species has shown that it is beneficial to have a lateralized brain so that information can be processed differently and simultaneously on the left and right sides. For example, chicks with lateralized processing of visual information can attend to two tasks at the same time (viz., searching for grains of food while monitoring overhead for a potential predator), whereas chicks not lateralized in this way perform poorly on both aspects of the task[@b1]. A similar result has also been found in a comparison of lateralized and non-lateralized fish[@b2]. Pigeons, also, are more efficient at finding grain amongst non-food items (grit) if they are more strongly lateralized[@b3]. Hence, cognitive/behavioural efficiency can be enhanced by having a lateralized brain.\n\nIt remains less clear, however, what advantage might ensue from the majority of individuals in a population or a species displaying the same direction of lateralization when increased neural efficiency and capacity could be achieved by lateralization at the individual level alone. Indeed, since the left eye detects predators and controls escape and attack responses, it seems disadvantageous for the majority of individuals to have the same direction of lateralization: predators could take advantage of this bias by approaching their"
+"Image en medicine {#S0001}\n=================\n\nIl s\\'agit d\\'une patiente de 17 ans qui se plaignait depuis un mois d\\'une h\u00e9micr\u00e2nie gauche positionnelle paroxystique, rebelle aux antalgiques simples, associ\u00e9e \u00e0 des naus\u00e9es, des vomissements et une diplopie d\\'instalation brutale apparue 48 heure avant son hospitalisation. L\\'examen Clinique a trouv\u00e9 une paralysie de la 6^\u00e8me^ paire cr\u00e2nienne gauche et le fond d\\'\u0153il a objectiv\u00e9 un \u0153d\u00e8me papillaire bilat\u00e9ral stade III. Le bilan biologique \u00e9tait sans particularit\u00e9s. Une imagerie par r\u00e9sonance magn\u00e9tique c\u00e9r\u00e9brale (IRM) a montr\u00e9 une hydroc\u00e9phalie aigue obstructive biventriculaire et un processus l\u00e9sionnel arrondi bien limit\u00e9 suspendu \u00e0 la partie ant\u00e9ro-sup\u00e9rieure du troisi\u00e8me ventricule (V3), directement en arri\u00e8re des trous de Monro, correspondant \u00e0 un kyste collo\u00efde. La patiente fut alors orient\u00e9e en urgence en neuro-chirurgie pour prise en charge. Le kyste collo\u00efde du V3 est une tumeur b\u00e9nigne rare (0,5 \u00e0 2% des tumeurs c\u00e9r\u00e9brales), naissant du neuro-\u00e9pith\u00e9lium primitif de la toile choro\u00efdienne et survient habituellement entre 30 et 50 ans. Il si\u00e8ge toujours en arri\u00e8re des trous de Monro, o\u00f9 il est appendu \u00e0 la paroi ant\u00e9ro-sup\u00e9rieure du V3. Son \u00e9ventualit\u00e9 doit \u00eatre \u00e9voqu\u00e9e chez les patients pr\u00e9sentant typiquement des pouss\u00e9es d\\'hypertension intracr\u00e2nienne paroxystique (par un m\u00e9canisme de clapet)"
+"More than 170 years after the discovery of skeletal remains of giant vertebrates preserved in Australian caves[@b1], and later in dry lakebeds[@b2], the cause of their demise is still debated. Most scientific studies are directed at evaluating the two dominant explanations for extinction: human impact or climate change[@b3]. As dating methods have improved, chronologies for human dispersal across Australia and for the last surviving megafauna have become more accurate and more precise[@b4][@b5][@b6]. Although the date of initial human arrival on mainland Australia remains uncertain, populations were established over most of the continent by at least 47\u2009ka (refs [@b6], [@b7]). Although many elements of the Australian megafauna (those animals \\>45\u2009kg body mass) lack firm extinction timelines, last appearance dates for taxa that occur most frequently in the fossil record are between 50 and 40\u2009ka (refs [@b4], [@b5], [@b8]), indicating a temporal overlap between humans and megafauna[@b9]. The climate of Australia was drying gradually between 60 and 40\u2009ka, but neither the rate nor magnitude of change were more severe than during earlier Pleistocene climate shifts[@b10][@b11]. The lack of evidence for unprecedented climate change between 60 and 40\u2009ka and survival of megafauna during earlier more extreme climate fluctuations[@b12]"
+"Arthroscopic hip surgery has revolutionized the treatment of hip injuries, and with these treatments, injuries that could have ended careers of professional athletes in the past can now be treated. Among these athletes are professional golfers. As a noncontact and low-impact sport, the injury profile of golfers is different from many other sports. The injury pattern is influenced by repetition, muscle coordination, and a well-described range of motion required for the golf swing.^[@bibr7-2325967116643532],[@bibr16-2325967116643532]^ Dynamic hip motion is accentuated in professional golfers, whose careers hinge on both finesse and power and for whom small kinematic aberrations correlate with decreased performance. The extensors and abductors of the hip are of critical importance when initiating the forward motion of the golf swing and are responsible for creating the energy that is ultimately transferred through the upper extremities to the ball at impact.^[@bibr2-2325967116643532]^ Novice and professional golfers have differences in hip rotation, with increased rotation in professionals contributing to increased speed and power throughout the swing.^[@bibr9-2325967116643532]^ With repeated rotations, the labrum may become bruised or detached. The damaged labrum can no longer maintain the seal with the femoral head, resulting in increased femoral head translation. With the loss of the seal and increased translation,"
+"Introduction {#s1}\n============\n\nThe acquisition of optimal tube dimensions during development is critical for the function of organs like the lung, renal and vascular systems. This is reflected by the high incidence of human pathologies associated with tube size defects. For example, cystic overgrowth in the collecting ducts is a landmark of polycystic kidney disease, whereas stenotic tubes cause obstructions of blood vessels and other organs [@pone.0001964-Sadler1], [@pone.0001964-Lubarsky1]. We use the *Drosophila* respiratory network as a genetic model to understand the determinants of tube size expansion. The tracheal system derives from twenty metameric cell clusters that undergo their last cell division as they invaginate from the epidermis. Cell migration and a series of coordinated tracheal cell rearrangements generate a tubular network that sends branches to all developing tissues [@pone.0001964-Ghabrial1]--[@pone.0001964-Uv1]. Branching is followed by three precise morphological events transforming the nascent tubes into mature airways. First, a secretory burst of luminal proteins drives the diametric expansion of the tubes. Later the luminal proteins are cleared and finally, the luminal liquid is replaced by gas to generate a functional respiratory network [@pone.0001964-Tsarouhas1]. Tube diameter expansion occurs within a defined time interval without changes in the number or shape of the constituent cells"
+"Introduction {#s1}\n============\n\nAt elite performance levels, such as in high-level sports, expertise is expressed by individuals achieving consistent performance outcomes, often in highly dynamic performance environments. According to Ericsson and Lehman [@pone.0089865-Ericsson1], an expert is defined as an individual with at least ten years or 10000 hours of deliberate practice. They argued that expertise results from repeated, motivated engagement in an activity requiring effort and concentration, both of which have little to do with talent [@pone.0089865-Ericsson1]. In cognitivist approaches, a high level of expertise results in the capacity to reproduce a movement like an automatism, with movement variability considered as a dysfunctional aspect of motor control, representing the amount of noise to be reduced for achievement of successful performance [@pone.0089865-Davids1]--[@pone.0089865-VanEmmerik1].\n\nAlternatively, in an ecological dynamics approach [@pone.0089865-Beek1], [@pone.0089865-Davids2], it has been suggested that the nature of performer-environment relationship and the coupling of perception and action is not the same for beginners and experts. This is because the expert is more capable of exploiting information about environmental and task-related constraints to functionally (re)organize the multiple degrees of freedom of the body to achieve consistent performance outcomes. Thus, the greater adaptability of the experts to a variety of interacting constraints, categorised"
+"I read with great interest the article by Toyota and colleagues published in PLOS ONE entitled, \"Short versus prolonged dual antiplatelet therapy (DAPT) duration after coronary stent implantation: A comparison between the DAPT study and 9 other trials evaluating DAPT duration\".\\[[@pone.0184513.ref001]\\] The authors compare results of the Dual Antiplatelet Therapy Study (DAPT Study) to pooled results of 9 other randomized trials evaluating duration of DAPT. The analysis concludes that the beneficial effects of prolonged DAPT in reducing rates of myocardial infarction (MI) and stent thrombosis (ST) seen within the DAPT Study were greater than in the other pooled trials, yet the magnitude of excess risk associated with prolonged DAPT was consistent across studies. In part, the authors suggest that this discrepancy may be due to higher rates of MI and ST within the control arm of the DAPT Study compared to the control arms of the other studies.\n\nWhile the desire to further understand the risks and benefits of prolonged DAPT holds merit, several points need to be considered when interpreting the presented results. First and foremost, the DAPT Study is a large, international, multicenter, randomized, double-blinded, placebo-controlled trial powered specifically to detect the impact of prolonged DAPT on the"
+"To the Editor,\n\nCardiac dysfunction with electrocardiographic (ECG), echocardiographic (ECHO) changes and sudden cardiac death following acute neurological injury has been well reported. Here, we describe the occurrence of recurrent ventricular tachycardia (VT) following traumatic brain injury (TBI) which reverted following surgical evacuation of extradural haematoma (EDH).\n\nA 58-year-old hypertensive, diabetic male presented in triage after road side accident with score on Glasgow Coma Scale of E3V2M5. During examination, bilateral pupils were 2 mm in size and were reacting to light. A non-contrast computed tomographic scan of head revealed right sided frontotemporal EDH with midline shift of 5.5 mm. In the triage, he had a cardiac arrest following VT for which cardiopulmonary resuscitation (CPR) was done. His trachea was intubated and 200 joules of direct biphasic synchronous shock was delivered thrice for subsequent ventricular tachycardia without pulse. Thereafter, the sinus rhythm was restored and the patient was shifted to intensive care unit (ICU). Surgical evacuation of haematoma was planned immediately. However, the relatives refused to give consent for surgery. Supportive care with aim to prevent raised intracranial pressure (ICP) was initiated i.e. head up, sedation, mechanical ventilation, constant monitoring of GCS, pupils and vitals. Twelve lead-ECG, ECHO and baseline investigations"
+"Introduction {#S0001}\n============\n\nHip and knee arthroplasty continue to be among the most common surgical procedures performed in the United States with an expected increase in utilization as indications expand and an aging population lives longer with an increased demand for more active, pain-free lifestyles.[@CIT0001] As a result, the likelihood of patients having ipsilateral hip and knee prostheses increases, as does the risk of periprosthetic complications, specifically, interprosthetic femur fractures (IFF), defined by a fracture of the femur between an ipsilateral hip and knee prostheses. Early reports on the treatment of these fractures were presented with significant reservation. The earliest report by Dave et al described successful treatment of a single patient who sustained an interprosthetic femur shaft fracture around a stemmed total knee and total hip implant with the use of a Mennan plate, iliac crest bone grafting, and a 3-month period of restricted weight-bearing.[@CIT0002] However, subsequent reports by Kenny et al demonstrated poor outcomes in treating similar fractures, with all four patients in that series failing initial treatment, two of whom required either above knee amputation or hip disarticulation.[@CIT0003] Since these early reports advancement in treatment strategies, namely implant choice and understanding and classifying the fracture pattern have"
+"If we know John is taller than David, and David is taller than Eric, then we can deduce Eric must be shortest of all three, that John is tallest and also that David is intermediate in height. This thought process is often termed relational reasoning, linear syllogistic reasoning or transitive reasoning (Bonnefond, Castelain, Cheylus, & Van der Henst, [@CIT0006]; Clark, [@CIT0016]; Guez & Audley, [@CIT0027]; Piaget, [@CIT0047]; Sternberg, [@CIT0056]; Wright, [@CIT0063]). In more abstract terms, we can say \"if *A*\u2009\\>\u2009*B*, and *B*\u2009\\>\u2009*C*, it then follows that *A*\u2009\\>\u2009*C*\". This kind of deductive reasoning is basic to the development and normal functioning of many socio-cognitive processes---from mathematical and text-processing skills, through friendships and the trusting of other people, to generalisations of racial prejudice (Coleman et al., [@CIT0017]; Favrel & Barrouillet, [@CIT0025]; Kim & Song, [@CIT0035]; Markovits, Dumas, & Malfait, [@CIT0041]; Ragni & Knauff, [@CIT0051]; Sedek, Piber-Dabrowska, Maio, & Von Hecker, [@CIT0054]). For example, one might generally trust Mary more than Sally, but might trust Sally more than Trudy. Applying what Halford and Andrews ([@CIT0028]) have called \"the transitivity principle\", it follows that in a choice between Mary and Trudy, one should generally trust Mary.\n\nThree-term problems"
+"*Academic journalism* is a competitive and complex realm. It is a world of unrelenting struggle for recognition, reputability and acceptance where promoted research is constantly exposed to criticism over quality and relevance to bolster journal metrics.\n\nThere are three main aspects of scholarly metrics: impact, speed and reach. Impact factors are based on the number of journal citations, usually over a 2-year period. Speed is related to review turnaround time and time to publication. Reach pertains to global authorship and readership.^[@CIT0001],[@CIT0002]^\n\n*Indexing* on the other hand reflects on the journal's scientific quality. It places the journal on a database, allowing increased visibility, accessibility and readership, and ultimately reputability as a respectable and reliable source in the field of research. The prestige associated with indexing holds relevance for several reasons. Firstly, several academic institutions only recognise indexed publications, particularly for teaching and medical colleagues. Thus, an indexed journal is likely to receive more manuscripts than a non-indexed journal. Secondly, not all indexers are considered equal, despite the availability of several established, well-known databases.^[@CIT0003]^ As such, indexing services worldwide have strict inclusion criteria and stringent evaluations prior to acceptance. The difficulty faced by authors and journals is deciding on which indexers to"
+"Lower extremity injuries are common in high school sports and are associated with posttraumatic osteoarthritis and \u2009high costs. Fernandez et al^[@bibr7-1941738117733981]^ estimate that 807,222 lower extremity injuries occur in high school athletes each year, or 1.3 injuries per 1000 athlete-exposures. Posttraumatic osteoarthritis can be observed in up to 70% of individuals 15 years after a serious sports-related lower extremity injury,^[@bibr16-1941738117733981],[@bibr20-1941738117733981]^ and the associated costs are high. For example, the estimated cost of providing health care for athletic injuries in North Carolina was \\$9.9 million in medical costs, \\$44.7 million in capital costs, and \\$144.6 million in comprehensive costs.^[@bibr14-1941738117733981]^\n\nWarm-up exercises are performed before engaging in physical activity to decrease injury risk and increase athletic performance.^[@bibr4-1941738117733981],[@bibr6-1941738117733981],[@bibr31-1941738117733981]^ The importance of performing preactivity warm-up exercises lies in the ability to increase muscle temperature and the muscle's ability to stretch, as well as to activate other physiological responses.^[@bibr4-1941738117733981],[@bibr6-1941738117733981],[@bibr11-1941738117733981],[@bibr24-1941738117733981],[@bibr31-1941738117733981]^ The need for a preactivity warm-up has been established; however, the particular components of warm-up protocols have continued to change over time.\n\nControversy exists in determining whether dynamic or static stretching exercises should be performed during a preathletic event. Recently, research has supported the use of dynamic over static stretching because of the benefits of increased"
+"Introduction {#s1}\n============\n\nAn efficient strategy employed by nature to sequester unstable intermediates along various biosynthetic pathways is by evolving separate enzymes with coupled reactions that are only active in consort as multiprotein complexes [@pone.0077781-Kappock1], [@pone.0077781-Baker1]. On the other hand, in some instances analogous systems have emerged that retain these activities together via synthesis of the enzymes as a single polypeptide chain [@pone.0077781-Huang1], [@pone.0077781-Arentson1]. However, conjoining various domains with multiple activities not only leads to complex folding and unfolding profiles, but also results in creation of interfaces that play a critical role in coordinating function of spatially distant active centers. As a consequence of these complexities caused by domain interactions, there are very few multi-domain proteins for which stability, unfolding mechanism and allosteric regulation have been investigated in detail [@pone.0077781-Batey1], [@pone.0077781-Han1]. An analysis of genomes and present protein sequence databases suggests that 40--60% of proteins exist in multidomain format highlighting the importance of studying such systems [@pone.0077781-Han1], [@pone.0077781-Vogel1]. Efforts to understand and mimic such systems have been also pursued for optimizing the production of molecules important from the perspective of industry and medicine [@pone.0077781-Schoffelen1], [@pone.0077781-Conrado1].\n\nIn order to understand multidomain proteins, it is important to understand various aspects of its"
+"Introduction\n============\n\nTwitter \\[[@ref1]\\] is a mobile microblogging and social networking service through which its subscribers can send and read small text-based messages known as *tweets*. Tweets have a message size limit of 140 characters based on the size of the Short Message Service (SMS) messages used on mobile phones at the time of Twitter's creation in 2006. Twitter is a technology that still has to be adopted by much of the anesthetic community. Twitter is easily accessed through a number of platforms: the Twitter website, applications (apps) developed for smartphones and tablets, and through SMS from mobile phones (in certain countries). Less than half of the tweets posted are through the Twitter website; most users prefer to use mobile apps on their smartphones or tablets \\[[@ref2]\\].\n\nAlthough most consider Twitter primarily a method of personal communication, it is gaining traction in business and is beginning to be used in academia for many purposes, including rapid sharing and dissemination of information and for citing articles \\[[@ref3]\\]. Organizers, delegates, and speakers at meetings and conferences have found tweeting to be beneficial in their own domains and as a tool for online discussion \\[[@ref4]\\]. This function of Twitter is achieved by the"
+"Introduction {#s1}\n============\n\nSuppose that a researcher wants to study individual differences in how children respond to a training program. The predictor is a continuous measure of some individual property P. The dependent variable is improvement in ability, measured by a pre-training test and a post-training test. However, test scores are not perfect measures of ability. The same improvement in test scores from different pretest scores may therefore reflect different changes in ability. To control for this possibility the researcher may include the pretest score as a covariate in a regression analysis, thereby investigating whether property P predicts test score improvement *among children with equal pretest scores*. The topic of our paper is how this statistical adjustment may lead to incorrect conclusions because of regression artifacts arising from biased regression to the mean.\n\nIn 1999, Campbell and Kenny [@pone.0095949-Campbell1] devoted an entire book to warning about the dangers of statistical adjustments in comparisons of treatment effects between non-randomized groups. The basic problem was pointed out already thirty years earlier in a classic paper by Campbell and Erlebacher [@pone.0095949-Campbell2]. The problem has continued to attract attention, see [@pone.0095949-vanBreukelen1] for a review of the literature and a novel analysis. One reason to"
+"Introduction {#sec1-1}\n============\n\nIn Ayurveda, *Dosha-Dhatu-Mala* concept is important to understand the body functions. *Malas* are the metabolic end products those are to be excreted. *Malas* are divided into two major parts that is *Sharirika Mala* (body wastes) and *Dhatu Mala* (metabolic wastes). *Sharirika Mala* is further classified into three parts that is *Mutra* (urine), *Purisha* (stool), and *Sweda* (sweat); and *Dhatu Malas* are further classified into seven types.\\[[@ref1]\\] *Purisha* comes under *Sharirika Mala*. Both *Purisha* and *Mutra* are formed from the food.\\[[@ref2]\\] After digestion, the *Sarabhaga* (nutrient portion) gets absorbed and the remaining undigested part becomes solid and that is called as *Purisha*. If *Malas* are not excreted from the body, the metabolic process will be impaired and this will ultimately lead to the formation of malformed tissues and diseases. *Purisha Pariksha* (stool examination) is included in *Ashtasthana Pariksha*.\\[[@ref3]\\] In Ayurvedic texts, examination of stool is limited mainly up to the examination of physical characteristics such as color, quantity, odor, froth, and consistency. Besides these, a specialized technique of stool examination, i.e., *Jala Nimajjana Purisha Pariksha* has been described to detect the presence of *Ama* thereby inferring the status of *Agni* in the body.\\[[@ref4][@ref5][@ref6]\\]\n\nAll the three classics of"
+"AD\n\n:   adrenal\n\nAO\n\n:   aorta\n\nC2\n\n:   the second cervical vertebra\n\nCA\n\n:   celiac artery\n\nCIA\n\n:   common iliac artery\n\nDC\n\n:   descending colon\n\nGL\n\n:   celiac sympathetic ganglia\n\nIVC\n\n:   inferior vena cava\n\nJ\n\n:   jejunum\n\nK\n\n:   kidney\n\nL1, L2, L3, L4, L5\n\n:   the first, second, third, fourth, and fifth lumbar vertebrae, respectively\n\nM\n\n:   mesonephros\n\nMA\n\n:   mesonephric artery\n\nMD\n\n:   mesonephric duct\n\nMSN\n\n:   major splanchnic nerve\n\nOV\n\n:   ovary\n\nOA\n\n:   ovarian artery\n\nOD\n\n:   ovarian duct\n\nP\n\n:   pancreas\n\nRA\n\n:   definite renal artery\n\nSMA\n\n:   superior mesenteric artery\n\nSCV\n\n:   subcardinal vein\n\nST\n\n:   stomach\n\nT\n\n:   testis\n\nTA\n\n:   testicular artery\n\nT1, T2, T11\n\n:   the first, second, and eleventh thoracic vertebrae, respectively\n\nUA\n\n:   umbilical artery\n\nUR\n\n:   ureter\n\nVAS\n\n:   vas deferens\n\nINTRODUCTION {#ar23930-sec-0001}\n============\n\nThe ascent of the embryonic kidney from the level of the sacral vertebrae to that of the first lumbar vertebra is well established. One driving force underlying this ascent is the straightening of the body, which involves the rapid longitudinal growth of the lumbosacral vertebrae and a reduction of the flexion at the lumbar level (Hamilton et al., [1976](#ar23930-bib-0001){ref-type=\"ref\"}; Parrott et al., [1994](#ar23930-bib-0007){ref-type=\"ref\"};"
+"**Related research article** Adler CE, Seidel CW, McKinney SA, S\u00e1nchez Alvarado AS. 2014. Selective amputation of the pharynx identifies a FoxA-dependent regeneration program in planaria. *eLife* **3**:e02238. doi: [10.7554/eLife.02238](http://dx.doi.org/10.7554/eLife.02238)\n\n**Image** A planarian with its pharynx extended\n\n![](elife02517inf001.jpg)\n\nPlanarian flatworms are well known for their amazing regenerative capacity. In a manner reminiscent of the Sorcerer's Apprentice, chopping one worm into little pieces will result in a dish full of tiny worms regenerated from the fragments in just a few days. In recent years this system has been rediscovered as an experimental model for probing how and why tissues regenerate, with the hope that this will help us to improve tissue repair in our own bodies.\n\nRegeneration in planarians depends on the presence of stem cells called neoblasts. These cells are distributed throughout the body and, when part of the worm has been amputated, they are activated to reform the tissues that have been removed ([@bib10]). It is still not entirely clear how the stem cells regenerate specific organs. Are there different types of stem cell that form different tissues? Do signals produced by nearby cells cause specific tissues to form? Or is a combination of both stem cell bias and local"
+"At the beginning of the recording, atrial tachycardia (AT) can be observed with 1:1 conduction at ventricular rate 140\u00a0bpm (upper track). At the spontaneous termination of the tachycardia, atrial-ventricular pacing at 45\u00a0bpm (lower rate) and after two cycles atrial-ventricular pacing at 100 beats/min (upper track) can be observed.\n\nThe rate drop response was activated: drop size 25\u00a0ppm, drop rate 50\u00a0ppm, detection beat 2, detection window 1\u00a0min, intervention rate 100\u00a0ppm, intervention duration 2\u00a0min (Fig.\u00a0[1](#Fig1){ref-type=\"fig\"}).Fig. 1Holter recording of rate drop response induced by paroxysmal atrial tachycardia\n\nThe termination of atrial tachycardia is followed by 45\u00a0bpm pacing, which is lower than the drop rate (50\u00a0bpm) while the rate drop is higher than the drop size (25\u00a0bpm). These two parameters can activate rate drop response separately and in combination, resulting in 100\u00a0bpm pacing.\n\nThe upper track was reduced to 100\u00a0bpm and AT ablation was suggested.\n\nConflict of interest {#FPar1}\n====================\n\nNone."
+"![](jove-139-58023-thumb)\n\nIntroduction\n============\n\nRLN is a common pathology of the upper airway in horses characterized by varying degrees of arytenoid paralysis. The left side of the larynx is most commonly affected. The prevalence of the disease can reach up to 35% in certain horse populations. Although several hypotheses tried to explain the etiology and pathogenesis of this disease, the exact cause of RLN remains uncertain. The pathology is described as a distal axonopathy of the recurrent laryngeal nerve with lesions of demyelination but also some degree of remyelination. This axonopathy leads to the denervation of intrinsic laryngeal muscles and concomitant atrophy[@B0][@B1]. This pathology is often slowly progressive and may lead to a total loss of the arytenoid abduction of the affected side[@B2].\n\nAffected horses emit abnormal respiratory sounds during exercise and, sometimes, show exercise intolerance in more severe cases. The definitive diagnosis is made by the endoscopic examination on a non-sedated standing horse where a partial or total loss of laryngeal abduction is observed[@B0][@B1][@B3]. Currently, the most common treatment is laryngoplasty (also known as \\\"tie-back\\\"), which is sometimes associated with a ventriculo-cordectomy. Although the overall success rate of these surgeries is considered as good to excellent[@B4], post-operative complications are very"
+"Background/introduction\n=======================\n\nHistotripsy ablation of liver tumors is a non-invasive surgery that uses high-intensity acoustic pulses to control an inertial cavitation cloud. Repeated exposure to the cavitation cloud renders a target tissue into a homogenous slurry which is then gradually absorbed by the body. Like other non-invasive surgeries, histotripsy requires a feedback system that can estimate therapy location and dose in real-time. Because the time-average power output of histotripsy is very small, the treatment region does not express a significant rise in temperature, making MRI thermometry an ineffective method to actively monitor therapy. Previous work has shown that MRI pulse sequences can be made sensitive to the chaotic water flow present during inertial cavitation. This is done by synchronizing the timing of the histotripsy pulses with the timing of the sequence's gradient waveforms. Incoherent water flow caused by cavitation attenuates the MR signal through a process similar to that used in diffusion-weighted MRI. It was shown that these sequences can give localized contrast specific to histotripsy bubble clouds. However, the MR images could only be acquired in a piecemeal fashion over several minutes such that a single image represented the influence of many cavitation events. Here, we introduce a single-shot"
+"In this manual, the World Health Organization (WHO) updates its guidance for governments in preparing for a possible terrorist attack with biological or chemical weapons. The book has something for virtually everyone who may have an interest in this topic, from government officials to clinicians, including information about the history of biological and chemical warfare, applicable international treaties, procedures for requesting WHO technical consultation, fundamentals of public health emergency response, basics of infectious disease treatment, treatment of patients with specific infectious or toxic exposures, physical properties of various agents, utility of reconnaissance satellites for detecting weapons development, management of food and water safety programs, etc.\n\nAnd it is this ubiquity and ambitiousness that underlie the manual's limitations and strengths. At times the guidance is so general that is almost an inventory of truisms (e.g., \"If it is found that the \\[emergency\\] control measures are not effective, they must be changed or modified.\"); elsewhere, the manual is a detailed resource. Its utility for different users will depend on their backgrounds and information needs. The core chapter, Public Health Preparedness and Response, may disappoint those seeking more than general principles. Yet these principles merit articulation as the foundation for prevention and response."
+"Knockout mouse lines that show embryonic and perinatal lethality are valuable models to investigate the genetic pathways that are associated with human congenital diseases. To elucidate the relationship between a specific gene and a developmental defect, detailed screening of knockout phenotypes is pivotal. Here, Wolfgang Weninger and colleagues used high-resolution episcopic microscopy (HREM) to screen the morphological phenotypes of embryonic day 14.5 (E14.5) embryos of 34 mouse strains that produce prenatally lethal offspring. The authors developed a reliable and ergonomic screening protocol to efficiently and comprehensively score structural abnormalities in those embryos. Their approach enabled them to detect a total of 58 defects that might be missed by employing alternative three-dimensional imaging methods and scoring systems. Many of these defects might be causal to embryonic or perinatal mortality. The results demonstrate that HREM combined with a systematic screening protocol enables more efficient phenotyping of E14.5 mouse embryos than any alternative approach. Such a method will contribute to advancing our knowledge of normal tissue and organ development, and of the causality of congenital diseases. **Page 1143**\n\n![](dmm-07-10-e1002-f01){#f1-007e1002}"
+"INTRODUCTION\n============\n\nIndustrial development and population growth have led to a surge in global energy consumption over recent decades. To address the increasing scarcity of fossil fuels, there are extensive research efforts focusing on sustainable and renewable energy substitutes. Among the wide array of renewable energy resources, abundant solar energy can be converted into electric power through photovoltaic (PV) technologies without inducing substantial environmental burden. To meet the stringent requirements of efficient deployment of PVs on a global scale, low manufacturing costs and enhanced power conversion efficiency (PCE) are urgently needed.\n\nThe emerging metal halide perovskite family has demonstrated great potential as light-harvesting active materials by virtue of excellent light absorption and charge-carrier mobilities ([@R1]). Despite record-breaking PCEs (up to 25.2%) ([@R2]), single-junction perovskite solar cells stand little chance to outcompete the current benchmark of crystalline silicon (PCE of 27.6%) that dominates the marketplace ([@R2], [@R3]). There are already several commercial (nonperovskite) multi-junction technologies including tandems and triple- and quadruple-junction modules that typically use III to V semiconductors, with promising PCEs that rival and even outperform the benchmark silicon PVs ([@R4]). Nevertheless, triple and quadruple junctions are prohibitively expensive for manufacture and terrestrial deployment ([@R5]) and thus, to date, are"
+"Cell identity in *Saccharomyces cerevisiae* is determined by a set of master regulatory transcription factors that dictate cellular phenotype by regulating mating-type-specific gene expression programs [@R4]. These regulators, and the gene expression states they control, must be labile since transitions between the two haploid mating-types occur readily and are evident phenotypically within the span of a single cell cycle[@R5]. For example, the \u03b12 regulator represses the transcription of one cell type-specific gene set to help define the \u03b1 cell phenotype. Upon the genetic switch of mating-type information, \u03b12 expression is lost; the existing pool of the \u03b12 repressor is rapidly turned over (\u03b12 half-life is \\~5 min[@R6]--[@R8]) and its regulatory targets are de-repressed, allowing the transition to a new cellular phenotype[@R3]. This rapid destruction of \u03b12 is governed by the ubiquitin (Ub)-proteasome pathway[@R7], [@R9], [@R10], and if this process is impaired, phenotypic switching is delayed[@R3].\n\nSince \u03b12 promoter occupancy is critical for its functions, it is the elimination of this promoter-bound pool of \u03b12 that is of paramount importance to the mating-type transition. To explore the role of ubiquitination in directing mating-type switching, we first determined how long the DNA operator-bound fraction of \u03b12 occupies its binding sites by chromatin"
+"In December 2015, the World Health Organization (WHO) released estimates of the burden of human disease attributable to consumption of food contaminated with 31 infectious agents or chemicals.[@R1] The report concluded that exposure to contaminated food worldwide in 2010 resulted in 600 million episodes of illness (95% uncertainty interval, UI: 420--960 million), 420\u2009000 deaths (95% UI: 310\u2009000--600\u2009000) and 33 million disability-adjusted life years (DALYs) (95% UI: 25--46 million).[@R1] The numbers were based on 4.6 billion cases of diarrhoea (95% UI: 3.5--6.5 billion) and 1.6 million deaths due to diarrhoea (95% UI: 1.3--1.9 million) that occurred worldwide in 2010, similar to numbers occurring in later years.[@R2]\n\nA key element of the estimation was attributing a proportion of the diarrhoea deaths to foodborne transmission of infections. A structured expert judgement was used to apportion transmission modes for individual pathogens, by estimating that 29% (95% UI: 22--36%) of 11 key bacterial, viral and protozoal causes of diarrhoea were foodborne.[@R3] Food contaminated with these 11 agents resulted in 548 million episodes of diarrhoea (95% UI: 370--888 million) and 200\u2009000 deaths (95% UI: 137\u2009000--287\u2009000) in 2010. Of these, 217 million infections (39%; 95% UI: 29--38%) were in children younger"
+"Introduction {#S1}\n============\n\nAging organisms exhibit functional declines at many levels of biological organization. These declines ultimately conspire to kill the organism and determine its lifespan. Because lifespans vary remarkably^[@R1]^ even within isogenic populations, useful information about aging mechanisms can be obtained by identifying their statistical signature in the response of lifespan distributions to genetic, chemical and physical interventions\n\n*C. elegans* individuals live as self-fertile adults for a few weeks, producing large numbers of isogenic offspring. Early investigations revealed single point mutations in insulin/IGF-1 pathway components capable of doubling average lifespan^[@R2]-[@R5]^. These findings subsequently generalized to other organisms, including fruit flies and mice^[@R5]^, establishing *C. elegans* as a metazoan model for studying the genetics of aging. The acquisition of survival curves in *C. elegans* thus became an essential part of aging research. In routine practice, survival curves of animals cultured on solid agar in a Petri dish, fed by a bacterial lawn of *E. coli*, are acquired manually through daily observation with a low-power dissecting microscope^[@R6],\\ [@R7]^. Death is recognized by the failure of an individual to react by motion to prodding with a wire, requiring labor-intensive, repetitive, and subjective observation. This protocol provides strong incentives to keep population sizes"
+"Introduction\n============\n\nCarotenoids have been investigated due to the importance of their diverse biological functions, since the beginning of the 19th century ([@bax004-B1]). Investigations of their molecular structures were triggered by the successful determination of the structures of lycopene and \u03b2-carotene by Paul Karrer *et al.* in 1930 ([@bax004-B2]). The number of compiled carotenoid structures can be estimated to have risen almost linearly with time since 1948, that is, at about 15 structures per year on average (see [Figure 1](#bax004-F1){ref-type=\"fig\"}). The growth curve shows no saturation yet, implying the existence of many carotenoids yet to be identified. According to Carotenoids Handbook ([@bax004-B3]), about 30 well-assigned natural carotenoids plus another 30--40 non-fully characterized carotenoids were compiled by Paul Karrer and Ernst Jucker in 1948. In 1971, 273 carotenoids were compiled by Otto Isler *et al.* in the book 'Carotenoids' ([@bax004-B4]) and by Otto Straub in the book 'Key to Carotenoids' ([@bax004-B5]). In 1987, 563 carotenoids were compiled in the 'Key to Carotenoids, second edition' by Hanspeter Pfander ([@bax004-B6]). In 1995, D. Kull and H. Pfander added 54 new carotenoids as 'Appendix' ([@bax004-B7]).\n\n![Growth curve of compiled carotenoid structures.](bax004f1){#bax004-F1}\n\nIn 2004, 750 carotenoids were compiled by George Britton, Synn\u03c6ve Liaaen-Jensen and Hanspeter"
+"Recently, due to increasing demand for inactivated poliovirus vaccine (IPV) and yellow fever vaccine (YFV) for routine immunization and outbreak response, limited availability of these important vaccines has resulted in a shortage of both products in many countries. On the basis of clinical data, the World Health Organization (WHO) Strategic Advisory Group of Experts on Immunization has recommended use of fractional doses of IPV (fIPV; one-fifth of dose delivered intradermally) and YFV (fYFV; one-fifth of dose delivered subcutaneously) to permit introduction and higher coverage for areas in need.[@cit0001] A full dose of each vaccine is 0.5\u00a0mL, and the recommended fractional dose is 0.1\u00a0mL, which increases the potential number of doses that can be obtained from existing 5- or 10-dose vials to approximately 25 or 50 doses. In 2016, fYFV was used in outbreak response campaigns in the Democratic Republic of Congo, and fIPV was implemented in India, Sri Lanka, and Pakistan and is planned for use in Bangladesh. It is likely that more countries will adopt fractional dosing, because vaccine supplies remain limited.[@cit0003][@cit0005]\n\nAdministering fractional doses increases the number of piercings of IPV and YFV vial stoppers compared with what they were validated for, and this off-label practice"
+"Sir,\n\nThe testing for HIV, early diagnosis and access to treatment are important factors for controlling the HIV/AIDS epidemic[@ref1]. The theme of \"Getting to Zero\" adopted by UNAIDS for the period 2011-2015 clearly reflected optimism regarding global response to HIV[@ref2]. The impact of various interventions under the National AIDS Control Programme (NACP) can be seen from an overall reduction of 57 per cent in the annual new HIV infections among adult population from 2.74 lakh in 2000 to 1.16 lakh in 20113. After the encouraging results of NACP Phase III, the NACP Phase-IV (2012-2017) aims to accelerate the process of reversal and further strengthen the HIV epidemic response in India[@ref4].\n\nTo understand the HIV/AIDS epidemiology in a particular region with reference to various socio-demographic factors, awareness, high risk behaviour, *etc*. The HIV reporting trends in the Integrated Counselling and Testing Centres (ICTC) provide an important clue to assess the effectiveness of the preventive strategies undertaken[@ref5]. Therefore, a retrospective analysis of data from available records of all individuals who attended ICTC of Government Medical College, Nagpur, Maharashtra, India, between January 2004 and December 2013 was carried out. The present study included 60,181 ICTC attendees. The NACO guidelines of pre-test counselling, written"
+"1.. Introduction {#s1}\n================\n\nBiological interactions are far more complex than the interpretations we make from the one-time 'screen-shots' we usually use to portray them and the simplistic classification in which we force them. This is even truer when humans come into action. Humans have been part of the interaction networks characterizing most natural ecosystems for thousands of years \\[[@RSOS171456C1]\\]. However, ever since human populations began to increase exponentially, and especially, since humans started gathering in societies and using new technologies, ecosystem overexploitation and disruption of ecological interactions began \\[[@RSOS171456C2]--[@RSOS171456C4]\\]. In the last decades, the recognition of widespread human--nature interactions and human intrinsic need of intensive resource consumption have changed conservation practices, from the preservation of biodiversity by creating protected areas free of people to the inclusion of the humans in the design of conservation strategies.\n\nDespite these efforts, humans have been proved to be drivers of manifold negative impacts on species interactions worldwide through activities that lead to global change \\[[@RSOS171456C5]\\]. For instance, habitat fragmentation, a consequence of man-driven land use conversion, disrupts species interactions by altering species and gene movements and differentially contributing to the mortality of interacting species \\[[@RSOS171456C6]\\]. Global anthropogenic warming and plant invasions break plant--pollinator"
+"Background\n==========\n\nAs we move into the post-genome era, bioinformatics tools provide a powerful means of organizing and integrating information related to hereditary diseases. We present here a prototype study of this approach. Using a database of all identifiable proteins that contribute to the structure and/or biosynthesis of yeast (*Saccharomyces cerevisiae*) mitochondria, we have generated a library of protein profiles \\[[@B1]\\] that enables us to identify homologs in a wide range of genomes, including human. As a result, we have available sets of highly accurate amino-acid sequence alignments over the conserved regions that correspond to these profiles. By mapping known human disease-related mutations onto these alignments we can investigate the relationships to sequence conservation - and to sequence variations. In the cases where one or more of the identified homologs has a determined structure, these mutations can be interpreted in structural terms, allowing us to draw mechanistic inferences.\n\nWe have used profile analysis based on Bayesian priors, conditional probabilities that allow the estimation of the likelihood of an event on the basis of prior occurrences of similar events, to make this library of sequence profiles. The strength of prior-based profile analysis lies in its ability to capture homologous protein domains"
+"Introduction {#s1}\n============\n\nMore often than not, the study of problem solving is approached from the perspective of logical and rational thinking. In an early study, Weitzenfeld \\[[@B1]\\] defined the *isomorphic structure* of a task in terms of its elements and the relationship between those elements. Weitzenfeld further claimed that the isomorphic structure defines the strategy for accomplishing the task. However, Weitzenfeld ignored the significant impact presentation style can have on problem solving even when the isomorphic structure is preserved. Weitzenfeld took two games as an example of structure preservation: Tic-Tac-Toe and Number Scrabble. In Number Scrabble, players select in turn one of the remaining numbers from a pile that contains the numbers from 1 to 9. A player who is first to collect a triad of numbers adding up to 15 wins the game. Tic-Tac-Toe and Number Scrabble are valid isomorphic tasks. Isomorphism is obvious if numbers in Number Scrabble are arranged into a magic square where each column and row adds up to 15. Although it is highly likely that the two games require the same strategy, they are fundamentally different in terms of cognitive processes applied due to differences in visual presentation. While Number Scrabble requires top-down"
+"Introduction {#s1}\n============\n\nIn spite of optimal medical therapy, heart failure (HF) may progress with unpredictable episodes of worsening. Fluid retention (hypervolaemia) is a major cause of worsening HF.[@R1] Haemodynamic disturbances leading to acute decompensated HF may start weeks before the actual onset of typical HF.[@R1] In the early stages of decompensation effective and more aggressive therapy could potentially prevent deterioration and hospitalisation.[@R4] Estimation of volume status is crucial because achieving euvolaemia in HF patients is an important goal of therapy.[@R1] Diuretics are superior for achieving and maintaining euvolaemia but frequently there is a very narrow window of optimal volume status.[@R5] [@R6] Hyper- and hypovolaemia may lead to decompensated HF and organ failure caused by inadequate perfusion.[@R2]\n\nTraditionally, the cornerstone of the patient's volume status assessment in the outpatient HF clinic is the evaluation of symptoms, monitoring of weight and peripheral oedema, and blood tests including creatinine and natriuretic peptides, but these are neither sensitive nor specific with respect to detecting volume status.[@R3] [@R7] Ultrasound (US) is a sensitive and specific tool to estimate volume status, by assessment of the inferior vena cava (IVC) and the pleural cavities, and may have a crucial influence.[@R10] The development of high quality, low"
+"Sport academies are the vehicle by which clubs and governing bodies often develop and nurture talented sports people, with their demographic predominately adolescent. Conceptualized initially within Western mass participation sports, academies are now seen across the globe, with a diversity of nationalities, ethnicities, religions, and cultures, encompassing a broad variety of sports.\n\nSubstantial prospective capital investment is typically required by academies, balanced by potential future \"on-field\" (e.g., Olympic Gold Medal, League Champions, etc) and/or \"financial\" reward (e.g., transfer fee received for a soccer academy graduate). To contextualize, a successful English Premier League soccer academy runs at a cost of \\~\u00a32.3 (\\~\\$3.3) million per year and has produced graduates worth \\< \u00a3100 (\\>\\$143) million since inception, with several players representing their senior national team. The small probability of success within this paradigm, which is mirrored to varying degrees within other sports, has led to a change of ethos within academies. Early academies suffered social and political pressure due to low salaries and \"token\" educational offerings. Emphasis is now placed on genuine academic and athletic development, in an attempt to ensure that if a successful athletic career is not realized, then employment prospects away from an athletic career are viable. For example,"
+"Myelomeningocele (MMC) is the most common and most severe congenital anomaly of the CNS that is compatible with life, occurring between the 25th and 27th post ovulatory days.[@ref1] Myelomeningocele can be associated with other dysraphic malformations, with split cord malformation (SCM) being the most common association. The incidence of type I SCM in patients with MMC who had MRI performed ranges from 5-40%.[@ref2] The most common location of SCM is one or 2 levels above the MMC, and is thus hidden from the surgical field during closure of the MMC. Usually, the MMC is repaired in the initial operation, and the SCM is dealt with in a later setting either following the symptoms of tethered cord later in childhood, or after routine MRI. This case highlights the importance of recognizing the rare combination of MMC and distal SCM to avoid inadvertent injury to the distal conus, and avoid the possibility of missing the SCM, which may require an additional operation in the future.\n\nCase Report {#sec1-2}\n===========\n\nA 28-year-old Yemeni female presented to the obstetric service in labor. Obstetric ultrasound showed the fetus to have severe hydrocephalus. A mid-lumbar MMC and a Chiari II malformation were also evident. The baby"
+"Introduction {#sec1}\n============\n\n*Nocardia* is a soil-dwelling, aerobic, facultative intracellular bacteria with a challenging growth pattern to discern when sampled from cutaneous infections.[@bib1], [@bib2] This difficulty is partly attributed to similarity with the *Actinomyces* species, slow growth rate, and low incidence.[@bib3] Although considered opportunistic, immunocompetent hosts may become infected with a primary cutaneous infection following penetrative trauma.[@bib4] *Nocardia* causes localized destruction or systemic infection, with a particular affinity for the pulmonary and central nervous systems once disseminated. More prevalent in tropical countries, *Nocardia* has various cutaneous presentations, belonging with differential diagnoses including *Actinomyces*, sporotrichosis, and tuberculosis because of similarity in presentation.[@bib2] Cutaneous infections left untreated can progress into a mycetoma, a chronic subcutaneous, granulomatous infection with fistulous tracts leading to invasion of the musculoskeletal system, lymphatics, or the central nervous system.[@bib3], [@bib5]\n\nCase report {#sec2}\n===========\n\nThis patient is an immunocompetent 56-year-old Hispanic man with no significant medical history, presenting with painful posterior cervicothoracic skin lesions ([Fig 1](#fig1){ref-type=\"fig\"}).Fig 1Prior to laminectomy.\n\nOnset was estimated to be 20\u00a0years ago; however, in the last 6\u00a0months, pain and purulent drainage from fistulous tracts had progressively increased. Evaluations and laboratory analysis by previous institutions\\' dermatology and infectious disease departments were nonrevealing. Earlier"
+"In India, breast and cervix uteri cancers are two of the leading causes of neoplasia for women, while neoplasia of lung and gastroenteric tract are a cause of mortality in men. It appears that lifestyle, exposition to carcinogenic substances and diet can greatly influence the incidence of cancer[@ref1][@ref2][@ref3]. Data reported from several agencies should be carefully analyzed as several confounding elements can be present. India is a vast country with diverse cultures, habits, and living conditions and the Population Based Cancer Registries cover a small percentage of the total population leaving several States uncovered[@ref1][@ref2][@ref3]. Besides the conventional therapy targeted molecular therapies are becoming popular for treatment of neoplasia. These therapies hit neoplasia focusing on an essential biochemical pathway blocking mainly phosphokinases with specific inhibitors or targeting tumour cells with humanized monoclonal antibodies. Usually, monoclonal antibodies interfere with soluble growth factors or trigger complement and cellular dependent tumour cytotoxicity[@ref4][@ref5]. In addition, it is becoming more prominent to use antibodies which favour autoimmune reactivity by relieving the brake of host immune system[@ref6][@ref7][@ref8]. Further, it is also relevant to point out that the infiltration of neoplasia as breast and gastrointestinal tract cancer with lymphocytes could identify patients with a better outcome[@ref9][@ref10]. Thus, a"
+"INTRODUCTION\n============\n\nThe term 'complex trauma of the foot and ankle' is reserved for fractures that involve severe soft tissue damage associated with neurovascular lesions and joint involvement, which entail a high risk for complications.[@B1] These injuries can also be called: mutilating injuries to the lower extremity, mangled extremity injuries and high-energy lower extremity trauma.[@B2]\n\nCourt-Brown and Caesar observed fractures involving the foot and ankle of approximately 12% of a total group of approximately 6000 patients over the period of one year, of which toe and metatarsal fractures represented 85%.[@B3] In a supplementary study, the authors noticed that foot fractures corresponded to 10.5% of all open fractures in almost 2400 open fractures over 15 years.[@B4]\n\nThe most common mechanism of injury involved in complex fractures of the foot and ankle is traffic accidents, which represent 49% of causes, followed by falls from heights and work-related trauma.[@B5] The general distribution of foot and ankle fractures, observed by Shibuya et al., reveals 56% ankle, 17% hindfoot, 9% midfoot and 18% forefoot fractures.[@B6]\n\nThe World Health Organization reports that every year 1.2 million people die in traffic accidents and more than 50 million are injured.[@B7] The literature shows a high rate of association"
+"The repair capacity of articular cartilage is limited and large cartilage defects generally fail to heal spontaneously, making intervention necessary in order to avoid the progression of osteoarthritis[@b1]. Nevertheless, the therapeutic effect for large cartilage damage is not satisfactory, as autografts suffer from the inadequate tissue availability and the associated morbidity of the donor site, and allografts are limited by transplant rejection[@b2][@b3]. The tissue engineering for the treatment of articular cartilage defects presents a promising strategy[@b4], however, many problems remain. For instance, natural materials suffer from the limitation of immunogenicity, potential risks of transmitting animal-originated pathogens, and weak mechanical properties[@b5]; synthetic materials lack natural sites for cell adhesion and may cause a local reduction in pH and potential inflammation due to the degradation through hydrolysis[@b6]. Moreover, scaffolds combining natural and synthetic materials barely show good results in *in vivo* studies[@b7]. Much attention has been paid to the biological safety and efficacy of the scaffolds[@b8]. It is safe and reliable when the scaffolds are obtained from the patient's own tissue.\n\nPlatelet-rich plasma (PRP) is an autologous blood product containing concentrated platelets. After activation by thrombin or calcium chloride, the platelets in PRP release platelet-derived growth factor (PDGF), transforming growth factor (TGF),"
+"Introduction {#s1}\n============\n\nHabitat loss is one of the greatest threats to global biodiversity ([@COV047C47]). For this reason, estimating habitat suitability is an integral part of wildlife management and conservation, allowing for better-informed decisions about what habitats must be preserved to maintain species of conservation concern ([@COV047C39]). Traditionally, habitat suitability has been estimated via presence--absence or abundance data in various habitats ([@COV047C21]). Abundance may not always be a good metric of habitat suitability ([@COV047C52]); animals are not always most abundant where the population growth rate (the ultimate measure of population success) is the highest. Moreover, habitat occupancy does not always imply habitat quality ([@COV047C29]).\n\nIdeal despotic distributions ([@COV047C56]) are a clear example of a mismatch between abundance and population success. Under an ideal despotic distribution, dominant individuals occupy high-quality habitats and exclude subordinates from such habitats. Therefore, a few dominant individuals experience high fitness in high-quality habitats, whereas many subordinates experience low fitness in lower-quality habitats. For example, dominant European jays live in high-quality older forests at low densities and achieve high fitness, whereas subordinate jays live in poorer-quality habitats at high densities and have lower fitness owing to higher predation ([@COV047C1]). Likewise, a few large, dominant brook trout occupy"
+"Madam,\n\nNasotracheal intubation, first described by Kuhn\\[[@ref1]\\] in 1902, popularized by Magill\\[[@ref2]\\] in 1920s, finds its place in various head and neck surgeries. It offers the benefit of more surgical manoeuver ability in such surgeries. It\\'s use is also beset with a number of complications. such as bleeding through the Kisselbach\\'s plexus\\[[@ref3]\\] lacerations, turbinate avulsion, nasal polyp or tumor avulsion, bacteremia, and retropharyngeal mucosa dissection/laceration. Complications may also lead to death due to excessive hemorrhage or choking due to an avulsed turbinate.\n\nNasotracheal intubation remains one of the established techniques of securing the airway. Careful assessment and preparation of the patient before the procedure are important. Various complications such as epistaxis, polypectomy, adenoidectomy, and turbinectomy have all been described. The incidence of these complications is variable. Tintinalli and Claffey, with nasotracheal intubations, demonstrated a hemorrhage rate of 17%.\\[[@ref4]\\] Nasal anatomy aberrations such as septal deviations and septal spurs are common. Studies have shown that eliciting proper history and evaluation of nasal patency clinically, though recommended, might be misleading.\\[[@ref5]\\] Septal spurs might provide obstacle while intubating \\[[Figure 1](#F1){ref-type=\"fig\"}\\] and can lead to complications like bleeding. The use of anterior rhinoscopy has not shown to be of much benefit.\\[[@ref6]\\] Flexible fiberoptic bronchoscopy"
+"Research in contextEvidence before this studyApoptosis and cytoskeleton played an important role in regulating cardiac remodeling, and the detailed mechanism was elusive. Microtubule associated protein 4 (MAP4) was found an important factor in regulating cardiomyocyte apoptosis and microtubule dynamics, however, whether MAP4 was involved in cardiac remodeling was still unknown.Added value of this studyIncreased cardiac phosphorylation of MAP4 (S737 and S760) was detected in tetralogy of Fallot patients, myocardial infarction and transverse aortic constriction mouse models. And age-dependent cardiac remodeling was observed in MAP4 (S667A, S737E and S760E) knock in (MAP4 KI) mouse. In addition, increased cardiomyocyte apoptosis together with microtubule disassembly and mitochondrial translocation of phosphorylated MAP4 was detected prior to the onset of cardiac remodeling, and p38/MAPK was found to be the possible signaling pathway that mediated MAP4 (S737 and S760) phosphorylation.Implications of all the available evidenceOur findings reveal that MAP4 phosphorylation may serve as a springboard for the pathogenesis of multiple cardiomyopathies including cardiac hypertrophy, fibrosis, diastolic and systolic dysfunction, suggesting its therapeutic potentials in these comorbidities.Alt-text: Unlabelled Box\n\n1. Introduction {#s0020}\n===============\n\nCardiac remodeling is a cellular response to a variety of stimuli, characterized by cardiac hypertrophy and fibrosis. Pathological cardiac remodeling is a major risk"
+"Introduction\n============\n\nTwenty years ago, Milton Roemer and Max Shain raised the possibility that hospital use increases along with the number of hospital beds available in an area ([@b15-hcfr-5-1-87]). This relationship, commonly referred to as \"Roemer\\'s law,\" became a major conceptual basis for health planning. If additions to bed capacity caused an increase in utilization, then market forces might not result in the optimal number of beds. Further, because excess beds would generate additional demand, their cost would be greater than the cost of maintaining empty facilities. Regulatory constraints on hospital construction could be justified by this relationship.\n\nA decade later, Martin Feldstein pointed out that Roemer had in mind something different than the usual workings of markets---where an increase in supply raises the quantity sold via the price mechanism ([@b7-hcfr-5-1-87]). Feldstein instead conceptualized the Roemer phenomenon as a shift in supply (the change in bed capacity) inducing a shift in the demand function. To test this hypothesis, he estimated a demand with both price and the number of beds *per capita* as independent variables. The elasticity of hospital days with respect to hospital beds was found to be 0.53, which was statistically significant. That is, an increase of 1"
+"Introduction {#s1}\n============\n\nAdult hippocampal neurogenesis is a complex multi-stage process. An ever increasing number of publications deal with the role of single genes in the control and regulation of adult neurogenesis. A crucial question becomes how this information can be integrated to form coherent concepts about the molecular bases of adult neurogenesis [@pone.0048527-Kempermann1]. As they stand, the data fail to provide a comprehensive picture because they often either use different nomenclatures or the same nomenclature with a different understanding. Similar problems across biology have led to initiatives to develop defined standardized vocabularies (i.e. ontologies) that allow the integration of large amounts of data across studies and fields of research [@pone.0048527-Kempermann1]--[@pone.0048527-Rubin1]. In the end, useful ontologies are community efforts that need to integrate with existing related initiatives and respect a growing set of rules that evolve to accomplish such tasks [@pone.0048527-Noy1].\n\nThe best known initiative of this type is the Gene Ontology (GO) [@pone.0048527-Lomax1]--[@pone.0048527-Rhee1]. GO provides a \"controlled vocabulary to describe gene and gene product attributes in any organism\" ([www.geneontology.org](http://www.geneontology.org)). The immense scope of the GO project means that very specialist terms, particularly those only applicable to a subset of organisms, may not be present in the ontologies. This is"
+"Introduction {#s1}\n============\n\nLegged locomotion involves coordination of limb swing and stance phases with distinct yet tightly coupled dynamics. Studies of legged locomotion often focus primarily on the dynamics of the stance phase, during which an animal\\'s legs experience the greatest demands for force and power [@pone.0100399-Cavagna1]--[@pone.0100399-Rubenson1]. Yet, recent research highlights the critical role of swing-leg trajectory on locomotor dynamics---experimental evidence shows that leg loading is critically sensitive to the initial landing conditions (leg angle, leg length and body velocity) at the swing-stance transition [@pone.0100399-Moritz1]--[@pone.0100399-Daley2], which are influenced by swing-leg trajectory. Running animals must effectively coordinate the interplay of swing-leg trajectory, landing conditions and stance leg loading [@pone.0100399-Daley3]--[@pone.0100399-Blum2]. For example, when running guinea fowl encounter an unexpected pothole, late-swing leg retraction leads to variation in leg contact angle, which explains 80% of the variance in stance leg impulse [@pone.0100399-Daley4]. Thus, the swing-leg trajectory is a critical factor in the dynamics of legged locomotion, particularly during movement over uneven terrain.\n\nRecent theoretical studies have highlighted inherent trade-offs in swing-leg trajectory for walking and running in uneven terrain. Simple walking and running models have revealed that swing-leg velocity just before the stance transition influences numerous aspects of locomotor dynamics, including stability [@pone.0100399-Seyfarth1]--[@pone.0100399-Blum2],"
+"Study HighlightsWHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?\u2611\u2009 The psychosis phenotype in Alzheimer\\'s disease (AD) predicts an accelerated speed of cognitive and functional declines, but it is unclear if phenomenological differences in psychosis subtypes have distinct disease trajectories.WHAT QUESTION DID THIS STUDY ADDRESS?\u2611\u2009 Does the presence of paranoid (persecutory delusions) or misidentification (misperceptions and/or hallucinations) subtypes of psychosis have an impact on the speed of cognitive decline in early AD?WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?\u2611\u2009 The misidentification subtype (alone or in conjunction with paranoid delusions) is associated with a faster speed of AD progression. These findings may reflect additional AD (or other) pathology in functional networks that are involved in the perception and contextual association of visual stimuli.HOW MIGHT THIS CHANGE DRUG DISCOVERY, DEVELOPMENT, AND/OR THERAPEUTICS?\u2611\u2009 These findings suggest that treatment approaches addressed to AD patients with misidentification psychotic subtype should aim to target functional networks involved in the processing of sensory stimuli to improve psychotic symptoms and to slow down the rate of disease progression.\n\n {#psp412389-sec-0006}\n\nPsychosis symptoms (delusions, hallucinations) are common in Alzheimer\\'s disease (AD)[1](#psp412389-bib-0001){ref-type=\"ref\"} and manifest early in the illness course. They are associated with an accelerated speed of cognitive and functional declines and"
+"Introduction {#s1}\n============\n\nHumans are an extraordinarily cooperative species. Yet, unless exercised with caution, the tendency to act on behalf of others is risky. Specifically, individuals who are indiscriminately cooperative can be exploited by 'free riders', those who reap the benefits of cooperation without ever bearing the costs, thus undermining the success of cooperative individuals [@pone.0061804-Nowak1]. This observation has led to great interest, across many fields of inquiry, in identifying the factors that support human cooperation. Indeed, an impressive body of research in the fields of behavioral and biological sciences suggests that individuals have many ways to exploit the benefits of cooperation while mitigating the risks. Specifically, mechanisms for maintaining cooperation between unrelated individuals can be divided into at least two categories of evolutionarily stable strategies that support reciprocity, one set involving partner fidelity (partner control) and another involving partner choice [@pone.0061804-Bull1], [@pone.0061804-Baumard1].\n\nIn partner control models, the same two individuals engage in an iterated, indefinite, series of interactions. Because individuals are locked into cooperative partnerships, negative feedback enforces cooperation through the punishment of defection. The classic example of a partner-fidelity model is Trivers' [@pone.0061804-Trivers1] theory of reciprocity in which individuals protect against exploitation by tracking another's past behaviors and"
+"Introduction {#s1}\n============\n\nAdherent cells exert mechanical forces on the extracellular matrix (ECM) to regulate adhesions, propel their migration [@pone.0069850-Li1] and to sense the ECM stiffness by a process generally referred as mechanosensing [@pone.0069850-Engler1], [@pone.0069850-Discher1]. In our organism, cells are often embedded in three-dimensional (3D) ECMs, which they deform in all spatial directions by generating three-dimensional forces in order to migrate [@pone.0069850-Bloom1]. Even cells that form stable two-dimensional (2D) monolayers, such as vascular endothelial cells, are known to exert three-dimensional traction forces [@pone.0069850-Hur1] both in isolation and confluency [@pone.0069850-Hur2]. The ability of cells to apply three-dimensional forces on two-dimensional layers is also important for the extravasation of leukocytes during the immune response [@pone.0069850-Rabodzey1] and for cancer cell invasion [@pone.0069850-Poincloux1], [@pone.0069850-Aung1].\n\nThe past few years have witnessed the development of several 2D traction force microscopy (TFM) methods, which allow investigators to measure only the in-plane (tangential) components of the traction stresses generated by cells adhering to plane substrata [@pone.0069850-Dembo1]--[@pone.0069850-Trepat1]. More recently, 3D TFM methods have been introduced allowing for the determination of the out-of-plane (normal) component of the traction stresses [@pone.0069850-Hur1], [@pone.0069850-Maskarinec1]. However, these 3D TFM methods are based on numerical calculations performed on large volumetric grids, which can limit their"
+"Definition of MDSC\n==================\n\nAt steady-state, myelopoiesis is a structured process where progeny of common precursors acquire specific markers and functions of circulating leucocytes, and in doing so progressively lose the ability to self-renew. The turnover of mature leucocytes is substantial, with billions of cells generated and replaced daily. A variety of pathological conditions can perturb the steady supply of leucocytes resulting in emergency myelopoiesis[@b1], which serves to provide cells to eliminate potential threats, either abnormal cellular growth (cancer), infectious agents or tissue damage. If these conditions resolve quickly, the balance of myeloid cells is restored without negative consequences for the host. However, a number of conditions associated with various types of chronic inflammation, autoimmune diseases and cancer results in aberrant, sustained myelopoiesis characterized by the accumulation of immature myeloid cells that deviate from the standard path of differentiation. These cells are distinct from mature, terminally differentiated myeloid cells (macrophage, dendritic cells or neutrophils) and have an activation programme (pathologic activation), which is different from that of mature myeloid cells.\n\nEarly studies on inflammation in the mouse highlighted a shared, systemic expansion of myeloid cells bearing the markers CD11b (CR3A or integrin \u03b1M) and Gr-1 (anti-Gr-1 mAbs recognize epitopes common"
+"The transport of vesicular carriers in the secretory pathway is a multistep process that includes vesicle budding, tethering, docking, and fusion^[@R1]^. Vesicle tethering, the initial contact between an intracellular trafficking vesicle and its membrane target, requires the participation of both long coiled-coil tethers and multi-subunit hetero-oligomeric tethering complexes (MTCs)^[@R2]^. Tethering complexes, in concert with small Rab GTPases, Sec1/Munc18(SM) proteins, and SNAREs, regulate the docking of a vesicle to its acceptor compartment, and thereby determine the targeting specificity of vesicles. Such targeting is a critical determinant of protein sorting, and thus maintaining the compartmental identity within the secretory pathway.\n\nMTCs form a group of large evolutionary conserved peripheral protein complexes that function throughout the secretory pathway. Included within this superfamily of proteins is a family termed CATCHR (complexes associated with tethering containing helical rods) that consist of the Conserved Oligomeric Golgi (COG) complex, the Golgi-associated retrograde protein (GARP) complex, the Exocyst complex, and the Dsl1 complex^[@R3]^. Multiple modes of interaction between MTCs and other components of the vesicle docking/fusion machinery have recently been suggested^[@R4]--[@R7]^.\n\nThe COG complex consists of eight subunits named COG1--8^[@R8],\\ [@R9]^, grouped into two subcomplexes: COG1--4 (Lobe A) and COG5--8 (Lobe B)^[@R10],\\ [@R11]^. The COG complex functions in"
+"Introduction {#s1}\n============\n\nThe Internet has emerged as an important tool for modern clinical practice. It provides health professionals with access to current, best evidence and facilitates the translation of research to clinical care. According to a recent survey, nephrologists search for medical information to guide the treatment of patients at least once per month \\[[@SFS152C1]\\]. To access best evidence, physicians can no longer rely on browsing a few key journals as relevant literature is widely dispersed. In nephrology alone, relevant literature is published across over 400 journals \\[[@SFS152C2]\\].\n\nNumerous tools are available to healthcare professionals when searching for primary literature online. These include subscription-free databases such as PubMed, Google Scholar and Scirus (which are freely accessible via the Internet), and subscription-based bibliographic databases such as EMBASE, MEDLINE and ISI Web of Knowledge. Subscription-free resources enable global access to important clinical information. This is especially important in developing nations where physicians and institutions may lack the funds needed to maintain database and journal subscriptions.\n\nWhile nephrologists increasingly rely on bibliographic databases for clinical information, evaluations of database performance are limited \\[[@SFS152C3], [@SFS152C4]\\]. Evaluating the performance of a bibliographic database involves the consideration of several factors \\[[@SFS152C5]--[@SFS152C8]\\]. For example, an important"
+"This paper was published ASAP on July 9, 2014. Due to production error, it was published with an error in equation 1. The corrected version was reposted on July 22, 2014.\n\nIn 1992, Potts and co-workers^[@ref1]^ discovered in the cyanobacterium *Nostoc commune* a gene encoding a product resembling protozoan and mammalian myoglobins. It was remarkable that a protein commonly associated with dioxygen transport was found in cyanobacteria and intriguing that the gene was located within a nitrogen fixation operon. Subsequent investigations have provided evidence that *N. commune* \"cyanoglobin\" belongs to a distinct and well-represented lineage of the hemoglobin (Hb) superfamily,^[@ref2]^ which has been given the general name of truncated hemoglobins (TrHbs) in reference to their primary structures containing \u223c30 fewer amino acids than myoglobin (Mb). *N. commune* cyanoglobin is thought to be involved in dioxygen scavenging, presumably to protect the nitrogenase from oxidative damage.^[@ref3]^\n\nShortly after the discovery of cyanoglobin, two light-induced TrHb genes, *LI410* and *LI637*, were found in the unicellular photosynthetic eukaryotic alga *Chlamydomonas eugametos* (*moewusii*).^[@ref4]^ Crystallization and subsequent structure determination of the globin domain of the *LI637* gene product (hereafter CtrHb) provided the first glimpse of a TrHb fold.^[@ref5]^ The heme group is buried in the protein,"
+"Introduction\n============\n\nEstablishing readability or the readability grade level has been widely used in many countries. An appropriate level of readability is important in health and drugs texts, since understanding them may influence treatment decisions and potentially, patient outcomes. An inappropriate ease of readability has been globally recognized and in some developed countries the solutions have been suggested. The present study has aimed at contributing to the present knowledge and at exposing an established problem. Namely, English text studies related to the medications have often been published \\[[@ref1]-[@ref8]\\], however Slovene texts have just started to be analyzed.\n\nAlongside many pharmaceutical companies, one generic drug producer has been present on the Slovenian market for some time; another pharmaceutical producer of generic drugs was also active, but was taken over by a larger international producer. The cost of the majority of prescription drugs is covered by health insurance schemes, when treatments comply with necessary prescription procedures and the patients have been paying their premiums regularly. The Slovenian pharmaceutical market has become increasingly competitive. Drug registration procedures have been largely facilitated by common European Union procedures, and some new drugs registered according to national and other procedures. Areas of responsibility of the Agency"
+"Certain chemicals present in consumer products and food can disrupt the action of steroidal androgens in fetal life, with irreversible consequences for later life stages. In the male rat, exposure to such chemicals during development leads to incomplete masculinization and severe malformations of the reproductive organs ([@b8-ehp-117-1839]; [@b53-ehp-117-1839]; [@b55-ehp-117-1839]). Because of their relevance to humans, the effects seen in laboratory animals have led to considerable concerns. Substances of interest, so-called antiandrogens, include certain phthalates (widely used as plasticizers), a few pharmaceutical agents, and some fungicides. Phthalates have attracted significant recent interest, with several regulatory bodies currently engaged in risk assessments. As yet, these regulatory efforts have taken little account of realistic human exposures to several phthalates and other antiandrogens simultaneously ([@b2-ehp-117-1839]; [@b5-ehp-117-1839]; [@b36-ehp-117-1839]; [@b37-ehp-117-1839]; [@b45-ehp-117-1839]). With the aim of exploring the effects of combined exposure to antiandrogens during gestation, we conducted large developmental toxicity mixture experiments in the rat with the widely used plasticizer di(2-ethylhexyl) phthalate (DEHP), the fungicides vinclozolin and prochloraz (present in certain food items), and the pharmaceutical finasteride.\n\nWe chose to examine these antiandrogens because they can disrupt male sexual differentiation in different ways, by a variety of mechanisms. In fetal life, testosterone is a key driver"
+"Measuring viral load has now become a cornerstone of therapy for many chronic viral infections like Hepatitis B, Hepatitis C, HIV, etc. There are several challenges in measuring these viral loads, which are as follows:\n\nNonavailability of a universal standard/control.Differences due to nucleotide sequences selected from different areas of the virus and this is particularly relevant where specific dye chemistry is being applied.Biology of the infection where different levels of viral shedding into the circulation may cause differences in the circulating viral load.Presence of inhibitors of PCR amplifications in the sample. Moreover, similar techniques are also used for Nucleic Acid Amplification Testing to detect the presence of transfusion transmissible viruses with negative serology.\n\nHence, there is a need for universally acceptable tests to detect viral load predictably and there should be minimum variability of the detected viral load from one laboratory to another.\n\nThe paper by Naresh on in-house development of RQPCR technique for detection of Hepatitis B viral load should be evaluated from this perspective.\\[[@ref1]\\] The process described by Naresh seems to be robust and correlation with plasmid control is also very good. The authors have chosen three areas, i.e. surface antigen, core and X region of HBV genome"
+"The World Health Organization has developed a single international standard for the information that authors of clinical trials must disclose \\[[@B1]\\]. The informed consent form (original or subsequent versions if the trial protocol necessitates) is not among the listed items. More recent schemes to expand registration of clinical trials also do not include full disclosure of informed consent forms \\[[@B2],[@B3]\\]. We strongly feel that the exclusion of informed consent is a serious omission in our current attempt to make clinical trials more transparent; we give four specific reasons in support of this view:\n\n1\\. The patients and the public should know whether the study involves a medication that has already been shown to be effective in other similar studies. Informed consent forms are supposed to include this information to help patients make an informed decision about the possible benefit they may get from participating in the trial. Although all clinical trials should ideally be conducted with the goal of improving medical knowledge, other reasons for clinical trials, including simple promotion, are seen \\[[@B4]\\]. There is little scientific or societal gain in repeating clinical trials with medications that have already shown efficacy \\[[@B5]\\].\n\n2\\. There can be considerable variation in how"
+"Printable and flexible electronic materials have gained a tremendous amount of interest both in academia and in industry, due to their potential impact in many areas, including advanced manufacturing, healthcare, diagnostics, wearables, renewable energy, and defense, to name a few. As we were preparing this Special Issue, we had the following questions in mind: What is the future of printable and flexible electronics? How will it advance the sensor technology? What is the current state-of-the-art for wearable sensors? In this Special Issue, we focus on the latest advancements, current challenges, and new opportunities in the world of printable and flexible electronics. Both fundamentals and applications are covered in this issue. The fundamentals include novel materials, manufacturing techniques, and characterization, among others. In terms of applications, chemical and biological sensing, bioelectric signal measurements, strain and pressure sensing, and energy storage were discussed. The goal of this Special Issue is to stimulate the community by addressing the key issues on the topic in the hope that printable and flexible electronics will make a greater impact in our society.\n\nOut of the 12 articles published in this volume of the Special Issue, 11 are original research papers and one is a review article."
+"*The Journal of Cell Biology* instituted electronic submission of manuscripts in December, 2001. Our brief experience in handling the review process electronically has raised an important issue regarding the manipulation of digital images that I would like to bring to the attention of the members of the cell biology community, who are our authors and reviewers. Our concern is not that the manipulation of digital images is happening with greater frequency, but that there is the potential for it to be detected less frequently by our reviewers.\n\nWe are aware that most people who receive a manuscript for review electronically simply print out the file they receive and read the printed manuscript. Many image manipulations, however, are masked on the printout, and thus reviewers are approving data that they may have questioned if they received glossy figures. Often the manipulations are visible if the reader takes the time to look at the figures on the screen, instead of on the printout. I encourage reviewers to take this extra step when they have finished reviewing the printed manuscript.\n\nIn the face of this potential loss of quality control, we at the *JCB* have instituted an additional step in our production process"
+"Introduction {#s1}\n============\n\nIt has been argued that tackling the spread of heritable diseases in managed populations of animals is an obligation for animal breeding, both for farm and for companion animals [@pone.0012797-Flint1]. Among companion animals the extent of inherited disease in pedigree dog breeds has recently come under scrutiny [@pone.0012797-Higgins1], [@pone.0012797-Bateson1] and it has been reiterated that the appropriate use of genetic selection schemes could be used to tackle such diseases [@pone.0012797-Lohi1]. Thus, researchers have a responsibility to make the best use of the data available to provide the tools that will enable breeders to reduce the disease burden across pedigree dog breeds through effective and efficient genetic selection.\n\nHip dysplasia is an important and complex genetic disease in dogs, and is one of the most prevalent diseases among larger breeds [@pone.0012797-Lust1]. It has both genetic and environmental influences [@pone.0012797-Ohlerth1], [@pone.0012797-Wood1], [@pone.0012797-Silvestre1] with evidence of gene effects at multiple loci [@pone.0012797-Todhunter1] confirming complex underlying genetics. It is a developmental orthopaedic disorder characterised by the formation of a loose, ill-fitting coxofemoral (hip) joint [@pone.0012797-Brass1], and over time, the malformation leads to abnormal wearing of bone surfaces and the appearance of the osteoarthiritic signs of degenerative joint disease (DJD) [@pone.0012797-Maki1]. Since"
+"Introduction {#section1-1076029619836171}\n============\n\nPatients with hemophilia A display phenotypic heterogeneity: Patients with the same levels of factor VIII (FVIII) activity or inhibitor titers may present with different bleeding tendencies.^[@bibr1-1076029619836171]^ Blood coagulation is a complex physiological process, and the generation of thrombin is the outcome of coagulation cascade activation. The most widely used coagulation tests including the prothrombin time (PT) and the activated partial thromboplastin time (APTT) mainly assess the initiation phase of coagulation during which only 3% to 5% of thrombin is formed.^[@bibr2-1076029619836171]^ Thus, these in vitro tests as well as clot-based FVIII activity and FVIII inhibitor assays do not always reflect the in vivo hemostatic conditions. In contrast, global hemostatic assays measure total thrombin generation, and thus recent guidelines have proposed using global coagulation assays to assess the risk of bleeding or thrombosis.^[@bibr3-1076029619836171]^\n\nCurrently, there are 3 global assays that can measure or estimate thrombin generation potential, either from direct measurement or derivation from coagulation wave form analysis: thromboelastography (TEG), Innovance ETP (endogenous thrombin potential), and Thrombinoscope. The TEG can assess the efficiency of whole blood coagulation including the process of clot formation and fibrinolysis, reflecting the function of clotting factors, platelets, fibrinogen, and the fibrinolytic proteins. The kinetics"
+"Since its discovery in 1991, *Porcine circovirus type 2* (PCV2) has been one of the most present swine virus within the domestic population, reaching seroprevalence levels near to 100%[@b1][@b2]. Even though PCV2 is a small non-enveloped ssDNA virus with a circular 1766--1768\u2009bp long genome[@b3], the complexity of Porcine circovirus diseases (PCVD)[@b4] lies in every other trait, from the variety of subclinical and clinical syndromes[@b5], to the multifactorial nature of the disease onset[@b6], passing through the plethora of transmission routes which help the dissemination and the persistence of the pathogen[@b7]. Other fascinating aspects of this small virus are the remarkable genetic variability and peculiar evolutionary pathways that have showed to be particularly relevant also in relation to the changes in clinical manifestations occurring through time.\n\nAt least five Open Reading Frames (ORF) have been reported to be effectively transcribed, but the most studied and widely sequenced region is the ORF2, which encodes for the Cap protein[@b3][@b8][@b9][@b10]. This protein represents the only component of the viral capsid and has been proven to be the major target of the host immune response[@b11][@b12][@b13]. ORF2-based classification criteria[@b14][@b15] have been collectively adopted to define PCV2 genotypes because of its higher phylogenetic signal and lower tendency"
+"Memory based learning and rigorous pra\u00adctices have been the primary elements of ancient schools in India and the students could standardize things as per their subjects. In the West, the Greek physicians used to standardize the medicinal world. *Hippocrates* (460 BC) introduced and illustrated certain practices, which became the basis of modern medical science. The Hippocratic School of medicine revolutionized medicine in ancient Greece, establishing it as a discipline distinct from other fields that it had traditionally been associated with, thus establishing medicine as a profession. The old schools of medicine were notable for their strict professionalism, discipline and rigorous practice. This unmistakably maintained the sincerity of purpose of the physicians and their application of knowledge.\n\nIronically the present day Medicine is not characterized by the concepts of traditional schools of medicine and approaches. There has been an exponential increase in the knowledge regarding the basis of each and every disease thus impacting its influence on current medical education system and training. The disease or disorder subjugates various parameters which are further classified into numerous issues. The advancement of technology has brought up the level of clinical practice beyond prescriptive and drug based therapies. The insight of the present day"
+"Modern medicine and scientific research owe a special debt to the care and well-being of service personnel who endure, sometimes multiple, deployments in times of war and conflict. The intense nature of violent conflict, isolation and distance from their family and home, and exposure to harsh conditions and chemicals puts these populations at risk for both acute and chronic, often lifelong adverse patient-related physical and mental health outcomes.\n\nIn 2018 the Editors of Patient Related Outcome Measures launched a Thematic Series entitled Veterans and Military Patient-Related Health Outcomes, seeking to publish research studies in topics concerning veterans and military health. We invited studies that identify and measure clinically relevant outcomes cross-sectionally and longitudinally, as well as studies to identify the effectiveness of interventions to improve patient-related outcomes in veterans and military service personnel.\n\nIn this Thematic Series, Hahn et al reported the development and validation of a patient-reported outcome measurement system for caregivers of civilians or service members/veterans with traumatic brain injury, investigating the acceptability of a computer-based survey administration platform among caregivers. The study discerned important considerations for surveying outcomes among caregivers of United States service members.[@b1-prom-10-081] Also, in the domain of instrument development, Gutierrez et al discussed the"
+"Full text\n=========\n\nGene expression analysis by cDNA microarrays is a powerful tool for characterizing the variation in transcriptional programs in cells and tissues. We have analysed surgical specimens from 40 human breast tumors using cDNA microarrays representing 8000 human genes. From 20 of the tumors, pairs of biopsies were obtained both before and after a 16-week course of doxorubicin chemotherapy. Two of the tumors were paired with lymph node metastases. Expression patterns reflecting specific features of physiological variation and cellular composition of the tumors provided unique molecular portraits of each tumor. Different clusters of co-expressed genes, like the estrogen receptor, the *ERBB2* gene and basal cell specific genes, were used to further subclassify the tumors. The different subgroups, identified by unique expression patterns, were associated with clinical parameters such as overall survival. Also, the *TP53* mutation status in the tumors was associated with disease outcome within these subclasses. Although the sample size in any of the subgroups is too small to support any statistically robust tests, our preliminary results show the potential of gene expression-based subtyping of breast cancer in predicting clinical behaviour and therapy response."
+"Smart or stimuli-responsiveness[@b1] that modifies properties in response to external stimuli represents a growing cadre of materials that support various applications, including controlled-release agents[@b2][@b3], responsive coatings[@b4], and adaptive shape-memory materials[@b5]. In addition to the separation of molecules by size and charge for which traditional membranes are employed, responsive membranes such as human skin demonstrate a smart valve function controlled by external stimuli[@b6]. Recent advances in nanotechnology have been interested in designing smart materials that mimic the processes found in natural systems. In this point, synthetic membranes capable of responsive functions find broad ranges of applications.\n\nDifferent from homogeneous polymeric materials, nanocomposites composed of metal nanoparticles (NPs) dispersed in a polymer matrix exhibit novel properties[@b7]. Composed into a responsive composite material, the role of each component is cooperative leading to characteristic collective property. In this point, blends and chemically-linked particle-polymer systems are physically different in many aspects. Composite materials are widely reported to upgrade stiffness and strength of a polymeric materials without a significant loss in resilience or toughness. One example, adding mica to nylon produces a five-fold increase in the yield and tensile strength of the material[@b8][@b9]. Even though precise control of NP dispersion in the polymeric matrix has been"
+"Continuous mechanical ventilation (CMV) in acute respiratory insufficiency is associated with diaphragmatic inactivity, leading to atrophy and loss of diaphragmatic force. These detrimental changes in the diaphragm increase morbidity and mortality of intensive care patients. Unlike locomotory skeletal muscles, which develop atrophy after several days of inactivity[@b1], atrophy in the diaphragmatic muscle and the loss of its functionality begin within hours after the onset of CMV[@b2][@b3]. This rapid process of diaphragm dysfunction with CMV is commonly referred to as ventilator-induced diaphragmatic dysfunction (VIDD)[@b4][@b5]. The mechanisms responsible for VIDD are multifactorial, although the process of diaphragm dysfunction with disuse is fundamentally linked to production of reactive oxygen species (ROS)[@b6]. Another potential mechanism contributing to the onset of VIDD is an imbalance in diaphragmatic oxygen and nutritive supply-demand. Specifically, the time-dependent reduction in diaphragm blood flow after the onset of CMV[@b7], potentially causing ischemia, associated tissue hypoxia and a shift to anaerobic metabolism promoting muscular fatigue are suspected mechanisms[@b7][@b8]. Indeed, hypoxia-inducible factor 1-alpha (HIF1-A) mRNA was up-regulated with CMV in the diaphragm, although there were no elevations of other hypoxia sensitive markers (e.g., vascular endothelial growth factor)[@b9]. Therefore, whether diaphragm tissue hypoxia associated with prolonged inactivation is induced and may contribute to"
+"Introduction\n============\n\nInsomnia is a common disorder and, in the realm of psychiatric care, one of the most common residual symptoms in major depression after antidepressant treatment is offered \\[[@b1-212257]\\]. Insomnia is a commonly induced side-effect as well. Insomnia can be an acute predictor of who will ultimately attempt suicide \\[[@b2-212257]\\]. It continues to be a clinical target symptom of interest for clinicians who treat psychiatric conditions, medical conditions, pain conditions, or associated sleep disorders. There are clearly indicated hypnotic agents and many off-label medications that may be used to improve sleep duration or quality. This offers an opportunity for clinicians to engage in rational polypharmacy in order to treat insomnia alone or when part of a comorbid condition \\[[@b3-212257]\\]. The most widely used prescription hypnotic agents since the 1960s have utilized the same mechanism of action to induce sleep. Here, gamma-amino butyric acid (GABA) neuronal activity is enhanced by positive allosteric modulation (PAM). Classically, if GABA~A~ receptor PAM occurs in wakefulness brain centers, alertness falters and sleep prevails. Alternatively, if GABA~A~ receptor activity increases in sleep-promoting centers, then sleep prevails more directly \\[[@b4-212257]\\]. The classic benzodiazepine hypnotic agents work through both of these mechanisms, as do the barbiturates and"
+"All relevant data are within the paper.\n\nIntroduction {#sec001}\n============\n\nObservation of the trends in a range of fields indicates a variety of computer software applications. Computer software can be found embedded in many devices and equipment, such as hand phones, automobiles and aircraft. In addition, software is increasingly used to support critical business applications and industrial processes. Most of these fields depend on software for their basic functioning. Software failure can lead to critical events and fatal consequences in safety-critical applications as well as in business applications. In order to meet customer expectations and needs, the software must have high reliability. The increasing demands of software functionalities are leading to various issues including the scalability and degree of concurrency of the software system. Customer satisfaction is also a serious challenge; thus, software reliability engineering must live up to the needs of today's complex software systems and their specific challenges \\[[@pone.0163346.ref001]\\].\n\nThe reliability approach is formalized to explain the failure behaviour within a system. Software reliability is defined as the probability that the software system will perform a required function correctly (failure-free) in a stated environment for a specified period of time. Due to the heterogeneity of the execution environment"
+"Background\n==========\n\nThe Dabaoshan Mine, built in 1958, is located in the southeast of Shaoguan City, Guangdong Province, and is considered as a large-scale and integrative quarrying mine, which plays an important role as a base for both nonferrous metal materials and steel industry in southern China. The Dabaoshan Mine is a multi-metal sulphide mineral deposit. The superior part of orebody is of limonite with a reservoir of 20 million tons, and the inferior part of orebody is of copper-sulphide with a reservoir of 20 million tons. Since the 1970\\'s, the mineral separation has been incomplete in the Dabaoshan Mine, and most of the lean ore was discarded and became gradually weathered. During the operation, substantial waste water was discharged directly into the environment after leaching, ore dressing, and washing processes. Both discarded ore and waste water constitute the severe environmental pollutants to the surrounding and downstream areas.\n\nThe acid excretion water from the Dabaoshan Mine contains high content of heavy metals. Previous surveys \\[[@B1],[@B2]\\] showed that the PH of the excretion water was 2.15; and heavy metal content in the excretion water was very high. Concentrations of cadmium, zinc and lead in the irrigation water of the nearby crop"
+"One of the most remarkable developments in supramolecular chemistry in the last two decades is the evolution of halogen bonding[@b1][@b2] from being an intriguing structural feature to becoming a powerful tool in crystal engineering[@b3][@b4][@b5][@b6], which is also applicable to systems and processes as diverse as luminescent[@b7] and non-linear optical[@b8] materials, photo-patterning of surfaces[@b9], the assembly of fractal patterns from molecular building blocks[@b10], supramolecular gelation[@b11], organocatalysis[@b12], macromolecular alignment at macroscopic scale[@b13], anion recognition[@b14], transmembrane anion transport[@b15][@b16] and mimicking the activity of the deiodinase enzyme[@b17].\n\nOur current understanding attributes such interactions to the depletion of electron density in a region of space surrounding the nucleus of a halogen atom in a molecule (termed a sigma hole)[@b11], which consequently is attracted to lone-pairs and *\u03c0* clouds of electrons. This electrostatic factor is supplemented by polarization of the electron density---which in a strong case would be modelled by the mixing of electron donor and acceptor orbitals---and electron correlation manifested in the London dispersion force. Those stabilizing contributions are countered by the Pauli repulsion and the balance results in interaction energies of about 5--70\u2009kJ\u2009mol^\u22121^ and preference for a linear *R*-*X*^**...**^:*B* geometry (*X* is a halogen atom and *B* a Lewis base)[@b18][@b19][@b20]. The conditions"
+"INTRODUCTION\n============\n\nIt is a fascinating thought that the single cell zygote contains all the information required for the development of the adult organism. Understanding how this information is encoded and deciphered is a major uncompleted scientific challenge. A group of genes known as homeobox genes has emerged as important master regulators of development. These genes have been highly conserved throughout evolution. They are expressed during embryonic development in a highly co-ordinated manner and continue to be expressed in virtually all tissues and organs throughout adult life.\n\nHomeobox (*Hox)* genes were discovered following the observation of two striking mutations in the fruit fly, *Drosophila melanogaster*. In the *antennapedia* mutation the antennae are changed into legs, whereas in the bithorax mutation, the haltere (a balancing organ on the third thoracic segment) is transformed into part of a wing. These changes were described as homeotic transformations from the Greek word homeosis, signifying a change of a complete body structure into another. *Drosophila* geneticists devised the term 'homeotic selector gene' to encapsulate the concept that a master regulatory gene could control the development of each segment of the fly. Subsequently *Drosophila* was found to contain a cluster of genes consisting of the *bithorax*"
+"\"Diversity and Quality\". With that in mind, we worked for the 24^th^ International Conference of Indian Association of Palliative Care organized at Coimbatore, India from 10^th^ to 12^th^ February 2017. The conference was jointly organised by the G. Kuppuswamy Naidu Memorial Hospital and Coimbatore Cancer Foundation.\n\nThe theme of our conference was Adding Value to\n\nAwarenessLearningDeciding RightCare until the End.\n\nAs with the previous conferences, we focused to improve the credibility of information and to help advance the effectiveness, and equitability of scientific information disseminated.\n\nOur emphasis on giving members of the audience a range of topics from recent evidence, interactive hands on sessions, topics related to advocacy, team work, organization, and philosophy was well received.\n\nWe are glad we were given a good feedback from the multidisciplinary audience, which numbered close to 1000, which was probably one of the highest numbers participating in the history of this conference. The delegates represented 16 countries and from19 states and 4 Union Territories of India.\n\nWe received a significant number of abstracts from a whole lot of students, doctors, nurses, social workers, psychologists, and members of several palliative care organisations. We had a committee to review and select those for oral and"
+"Sir,\n\nWe read with great interest the case report titled, \"Inadvertent migration of guidewire into Murphy\\'s eye of endotracheal tube during percutaneous dilatational tracheostomy\" by Binita *et al*.\\[[@ref1]\\]\n\nWe wish to highlight procedural modification we are doing in our Intensive Care Unit to tackle such inadvertent complication.\n\nWe agree with the authors that migration of guidewire into the Murphy\\'s eye of endotracheal tube during percutaneous tracheostomy without bronchoscopic guidance is a rare complication, which we also encounter rarely but we follow a procedural improvisation by ensuring free movement of guidewire back and forth at each step, thus ensuring proper placement of guidewire.\n\nIn case of guidewire inside the Murphy\\'s eye, there will be kinking of guidewire after dilatation with metal/plastic dilator, thus the free back and forth movement of the guidewire will not be appreciated, or in other words, if the free movement of guidewire not felt, a possible diagnosis of guidewire kinking is made.\n\nIn our case series of 300 cases of percutaneous tracheostomy without bronchoscopic guidance, we had 18 cases where guidewire got kinked, hampering the free back and forth movement during the procedure.\\[[@ref2]\\] We removed the guidewire and again a fresh puncture of trachea done to complete"
+"INTRODUCTION {#s1}\n============\n\nBenthic foraminifera (eukaryotic single-celled organisms) have existed since the Paleozoic and colonize a variety of marine sediments, ranging from shallow water environments to the deep sea. Many species produce an inorganic shell (test), which is preserved in accumulating sediment layers after their death. Based on these attributes, benthic foraminifera serve as important tools for paleoenvironmental reconstructions, including estimations of organic matter fluxes in marine sediments and paleoproductivity studies (e.g. [@BIO030056C1]; [@BIO030056C29]). They mainly feed on microalgae or phytodetritus (e.g. [@BIO030056C7]; [@BIO030056C19]; [@BIO030056C39]) and their response to variations in phytodetritus fluxes can be observed on foraminiferal community compositions ([@BIO030056C27]) or metabolic activities ([@BIO030056C22]; [@BIO030056C41]). However, there is still a lack of studies quantifying foraminiferal carbon and nitrogen metabolism to improve the understanding of the connection between foraminiferal biomass and sediment organic matter fluxes.\n\nHigh organic matter fluxes are characteristic for estuarine environments, where planktonic primary production can reach a gross particulate production of up to 176\u2005g\u2005C\u00a0m^\u22122^\u00a0year^\u22121^ ([@BIO030056C67]). These fluxes show strong seasonal changes in quantity, characterized by high fluxes (500--2000\u2005g\u2005C\u00a0m^\u22122^\u00a0day^\u22121^) in summer months, typically ending with a high productivity peak in autumn, followed by a quick decrease towards winter months"
+"As a child I remember playing in a friend's somewhat dilapidated house and enjoying racing around an upstairs gallery and making out the curious shapes on the royal arms in plaster over the fireplace. Little did I know then that New Hall, Elland, had been the site of some of the earliest experiments to test Harvey's theory of the circulation, or that a hill visible from my junior school's playing field had witnessed important experiments on barometric pressure. Indeed, the name of Henry Power, doctor, scientist and one of the early members of the Royal Society, was unknown in the small town where he once lived and practised. Dr Hughes has done a great service in rescuing this important Restoration scientist from an obscurity that is more than local.\n\nThis engaging book clearly describes Power's scientific and medical work, emphasising his wide-ranging curiosity as well as his experimentalism. Indeed, given the author's own expertise, one would have liked to have had more quotations from Power's notebooks, as well as a more detailed comparison of his medical practice with that of other contemporaries. He developed a wide clientele, although several of the places cited by Dr Hughes on p. 69 are"
+"INTRODUCTION\n============\n\nThe present genomic era was made possible by the automated determination of nucleotide sequences and restriction digest fingerprints from electrophoretic gel images. Systems to perform these tasks were developed soon after the introduction of large-format film scanners in the 1980s ([@b1],[@b2]) and continue to facilitate what would otherwise be a rate-limiting step in sequence determination and assembly. Now a major challenge of genomics is the discovery of single-nucleotide differences, such as naturally occurring single-nucleotide polymorphisms (SNPs) and induced point mutations ([@b3]--[@b5]). Many methods to discover such differences are in use, among which are those that compare differences in physical characteristics of DNA fragments recognizable in images produced by gel electrophoresis and other technologies. However, recognition of subtle differences between otherwise identical patterns is potentially rate-limiting for these methods.\n\nA popular strategy for SNP and mutation discovery is to observe novel fragments produced by cleavage of a mismatch between annealed DNA strands ([@b6]). Mismatch cleavage of heteroduplexed DNA allows discovery of single-base differences in pooled samples ([@b7]). This is an especially valuable feature for discovery of rare SNPs and induced mutations, which are difficult and costly to detect by sequencing ([@b5]). Software specifically designed for mapping novel fragments found"
+"Bacteriophage research has seen many peaks and troughs over the past century ascending with phage therapy and application in the early 1900\\'s; a research peak which was largely overshadowed by the dawning of the antibiotic era, and which has now deservedly regained attention as an approach against the problematic rise in antibiotic-resistant pathogenic bacteria. Following this initial scientific highlight, the advent of molecular biology and biotechnology sparked a renewed interest in phages and their encoded enzymes and promoters, which are still employed as research tools today. Much of this research was conducted using phages of Gram-negative bacteria, particularly *Escherichia coli*, due to the reliability of the host and the ease of protein (over) production, in particular many enzymes, in a compatible host background. Consequently, coliphages such as T4 and lambda served as model phages in the development of molecular tools and the fundamental understanding of phage-host interactions. The advent of new generation sequencing technologies has in recent years provided a vast array of sequence data relating to Gram-positive phages and their hosts, which in turn has permitted the development of analogies between Gram-negative and Gram-positive phages. For example, sequence analysis of *Bacillus subtilis* and *Lactococcus lactis* phages SPP1 and Tuc2009,"
+"Introduction {#s1}\n============\n\nAvailable evidence suggests that food security for Aboriginal and Torres Strait Islander (ATSI) peoples in Australia has not yet been achieved. ATSI peoples living in remote, regional, and urban parts of Australia are vulnerable to food insecurity for a range of reasons that tend to include poverty, low income or welfare dependence, and a lack of access to affordable and healthy food. Food insecurity among ATSI peoples has a long history that began with the colonization of Australia and today is exacerbated by government policy interventions and economic influences.[@r1] The much higher rate of illness and disease that ATSI peoples experience compared to non-indigenous Australians is directly related to food insecurity and is a clear consequence of the barriers related to food availability, access, and use faced by ATSI peoples. There is an unacceptable food-related health gap between ATSI peoples and non-indigenous Australians, revealing an urgent need to improve food security for ATSI peoples throughout the country.\n\nThis paper examines food insecurity among ATSI peoples, as well as Australian government efforts, particularly since the early 2000s, to improve their situation. The paper first considers what constitutes a human rights-based approach to achieving food security. Second, it describes"
+"Sir,\n\nLaparoscopic (transperitoneal or retroperitoneoscopic) donor nephrectomy (DN) has become the gold standard for kidney retrieval from living donors. It requires dissection on the surface and around aorta at level of origin of renal artery to obtain good length of renal vessels during left DN. In the process, many lymphatic channels in the periaortic region are severed. Usually, they seal off on their own. Rarely, they continue to leak leading to chyloretroperitoneum/chylous ascites. We encountered one such patient who had chyloretroperitoneum following retroperitoneoscopic left DN.\n\nA 48-year-old healthy male underwent uneventful left retroperitoneoscopic DN. Post-operative period was smooth and he was discharged on 3^rd^ post-operative day (POD). He presented with left flank pain, swelling, fever, nausea and vomiting on 14^th^ POD. On examination, his vital signs were normal. A tender lump was present in left flank extending from hypochondrium to left iliac fossa. His hematological and biochemical profile was normal. Ultrasound abdomen showed fluid collection with scanty loculi in left flank. Central port site was opened under local anesthesia and a 30 French drain tube was placed into the retroperitoneum. Stat output was 1.6 l of milky white fluid. Gram staining and culture was of the fluid was non-contributory. Biochemistry"
+"Introduction {#mzx149s7}\n============\n\nThere has been a growing body of research that focus on recognizing and responding to clinically deteriorating patients in general ward settings in the past decade \\[[@mzx149C1]--[@mzx149C4]\\]. Much of this interest was prompted by studies that demonstrated patient deterioration not being recognized and responded to in a timely manner \\[[@mzx149C5]--[@mzx149C10]\\]. This lapse in patient care has led to an increase risk and incidences of serious adverse events such as unplanned admissions to intensive care units, in-hospital cardiopulmonary arrests, and unexpected deaths \\[[@mzx149C11], [@mzx149C12]\\]. Improving timely recognition and prompt interventions is therefore pivotal to the provision of safe and quality care to a deteriorating patient before his condition becomes life-threatening \\[[@mzx149C13]\\].\n\nInternational concerns over delays or failure to recognize and escalate care for clinically deteriorating ward patients have led to the widespread implementation of a hospital-wide patient safety initiative known as the rapid response system (RRS) in acute hospitals \\[[@mzx149C14], [@mzx149C15]\\]. The RRS is designed with afferent and efferent components, and mechanisms for quality control, audit and administration \\[[@mzx149C16]\\]. The afferent arm involves monitoring and identifying deteriorating patients using a set of activation criteria, commonly known as the Early Warning Scoring System (EWSS), which is based on abnormal"
+"Specifications TableSubjectSocial SciencesSpecific subject areaTransportation, Travel Behavior AnalysisType of dataTableHow data were acquiredComputer-Assisted Telephonic Interview (CATI) surveyData formatRaw\\\nAnalyzed\\\nFilteredParameters for data collectionThe survey addressed individuals older than 18, employee active status, living or residing in Cluj Metropolitan Area, and willing to share their current travel behavior and response to public transport improvement policy.Description of data collectionThe respondents were accessed by phone following Random Digit Dialing procedure in order to ensure demographic and spatial coverage for the sample. The respondents were asked to participate in a 15-min telephonic interview on matters of travel behavior.Data source locationCity/Town/Region: Cluj Metropolitan Area, Transylvania\\\nCountry: RomaniaData accessibilityData accompanies the current article.Related research articleCristian To\u015fa, Hitomi Sato, Takayuki Morikawa, Tomio Miwa\\\nCommuting behavior in emerging urban areas: Findings of a revealed-preferences and stated-intentions survey in Cluj-Napoca, Romania\\\nJournal of Transport Geography\\\nDOI [10.1016/j.jtrangeo.2018.02.011](http://10.1016/j.jtrangeo.2018.02.011){#intref0010}**Value of the Data**\u2022Data contains commuter level information on current and prospective travel behavior, socioeconomic characteristics, derived spatial features, and attitudinal data for transport services in emerging urban areas.\u2022Stakeholders with interest in transport policies can be provided with important insights on public response to non-coercive actions with regards to sustainable transportation in urban areas.\u2022The empirical study could serve as a reliable framework for"
+"1. Background {#sec122666}\n=============\n\nEnterococci are important nosocomial pathogens ([@A23349R1]). They cause various infections including urinary tract infections, sepsis, endocarditis, wound infections and bacteremia ([@A23349R2]). Amongst enterococci, *Enterococcus faecalis* is the most common species among clinical enterococcal infections. On the other hand, *E. faecium* causes 10 - 20 percent of infections yet in comparison to other enterococci species, they show higher antibiotic resistance ([@A23349R1], [@A23349R3]).\n\nEnterococci, not only carry intrinsic resistance against some antibiotic agents, they can also acquire resistance via mutation, transposable elements or conjugative plasmids ([@A23349R1]). In addition, the ability of enterococci to form biofilm has also been of growing concern in the recent years. The use of indwelling catheters can intensify biofilm production of enterococci, which would lead to increase in urinary infections in catheterized patients ([@A23349R4]). Antibiotic resistance and biofilm formation in bacteria have been under intensive investigation in urinary tract infections and endocarditis, during the recent years ([@A23349R1]), in particular the pili and its gene cluster (*ebp*). This attention, of course, is worthwhile because biofilms can be the source of 80% of chronic infections in humans and their presence can increase antibiotic concentration by up to 1,000 folds ([@A23349R5], [@A23349R6]).\n\n2. Objectives {#sec122667}\n=============\n\nIn"
+"Introduction {#s1}\n============\n\nBecause of the potential use of nano-sized particulate systems for pharmaceutical or medical purposes, the inhalation and pulmonary deposition of nanoparticles is a vigorously discussed topic among nanomedicine researchers. However, the potential adverse health effects from nanoparticles are also of interest to nanotoxicologists, and the risk assessment of such systems in any application is a topic of increasing concern to both regulatory agencies and the public. The ongoing controversial discussions on the use of nanotechnology further emphasize the demand to carefully elucidate the biological fate, particularly the clearance, of inhaled nanoparticles in the human body [@pone.0040775-Nel1]. In the lungs, clearance occurs either by the mucociliary escalator, by alveolar macrophages, or by translocation across the epithelial layer [@pone.0040775-Patton1], [@pone.0040775-Geiser1].\n\nFrom the perspective of both nanotoxicology and nanomedicine, it appears essential to understand the bio-nano interactions of inhaled nanomaterials [@pone.0040775-Schleh1], [@pone.0040775-Sung1]. Non-cellular elements of the so-called air-blood barrier may play a key role here because this is the first biological matter that contacts nanoparticles after inhalation and deposition in the lungs. In the peripheral deep lungs, the so-called alveolar lining fluid, an ultra-thin layer that consists of an aqueous hypophase and a surface-active lipid-protein mixture, known as pulmonary surfactant,"
+"1. Introduction {#s0005}\n===============\n\nThe contractile properties of cardiac muscle influence the filling behaviour of the heart, determining the maximal diastolic volume, thereby providing a set point for systolic performance via the Frank-Starling mechanism [@bb0005]. Contractile function is ultimately dictated by the properties of the muscle\\'s constituent sarcomeres, repeated units of uniform thin and thick filaments, the relaxed length of which is thought, in vertebrates, to be governed by the giant molecular spring titin [@bb0010], [@bb0015]. Sarcomere assembly is a highly orchestrated process, involving multiple protein components, which dynamically adapts throughout perinatal heart development to accommodate physiological hypertrophic cardiac growth. During this period, various myocardial proteins, including myosin heavy chain (MyHC) [@bb0020], troponins [@bb0025], tropomyosin [@bb0030] and titin [@bb0035], undergo an isoform switch from foetal to adult type in order to adjust ventricular filling. Given the association of these genes with human cardiomyopathies [@bb0040], [@bb0045], [@bb0050], [@bb0055], [@bb0060], novel genetic animal models are required to provide an understanding of the developmental sarcomere transitions that are underpinned by splicing [@bb0065].\n\nSarcomere assembly initiates with actin polymerization, prior to myosin incorporation [@bb0070]. Titin acts as a template to ensure the regular interdigitation and centring of thick and thin filaments; it undergoes significant"
+"There are many critical care books that encompass knowledge, skills and expertise in critical care nursing. As a nurse who is very hands-on and spends most of her time in the clinical area, I value a textbook that combines clinical practice and knowledge.\n\nThis textbook is ideal for nurses who want to understand practical issues that may be experienced while caring for the critically ill at the bedside.\n\nThe authors obviously have great knowledge and experience in this arena, and have ensured that they have updated topics from the first edition such as sepsis and neurointensive care.\n\nAll chapters have sections on trouble shooting, such as resolving outflow problems in peritoneal dialysis and problems associated with electrocardiogram monitoring. These are the sorts of clinical problem that inexperienced nurses have concerns about and want to be able to remedy systematically at the bed space.\n\nThis book will also appeal to experienced critical care nurses, especially as a reminder if they have not made use of certain skills or experienced certain illnesses for a long time. It will also appeal to pre-registration and post-registration courses in intensive care nursing, especially as it has a \\'test yourself\\' section at the end of each"
+"Rolling adhesion is a common process by which cells attach themselves to surfaces under shear flow, such as in the circulatory system. Leukocytes in the blood utilize this mechanism to locate inflammation sites throughout the body. During an inflammation response, endothelial cells lining the blood vessels surrounding an infection site express adhesion proteins called selectins that are specific to leukocyte surface receptors. As the first step of the leukocyte adhesion cascade, leukocytes captured via selectin-specific interactions passively roll on the blood vessel wall under blood flow toward the inflammation site in a process known as rolling adhesion[@b1][@b2][@b3]. Malfunction of any adhesion molecules involved in this process leads to severe immune disorders such as the leukocyte adhesion deficiencies (LAD)[@b4]. Rolling adhesion behavior is also exhibited by circulating tumor cells (CTCs) which is believed to enhance cancer metastasis[@b5][@b6][@b7][@b8]. Therefore, quantitative understanding of rolling adhesion is necessary to enable practical applications such as cancer screening and treatment[@b9][@b10][@b11].\n\nAt the molecular level, this adhesion is mediated by catch-bond-like interactions[@b12][@b13] between P-[@b14] and E-selectins[@b15] expressed on endothelial cells lining blood vessels and P-selectin glycoprotein ligand-1 (PSGL-1) found at microvilli tips of leukocytes[@b16]. Despite our understanding of the individual components, how the molecular details of adhesion"
+"Introduction {#Sec1}\n============\n\nStudies of mate choice traditionally focus on females because these are usually the sex that invests the most into reproduction and, hence, should be more selective in regard to their mating partners (Andersson [@CR4]; Trivers [@CR84]). Variability in the quality of available females and the costs of mating may, however, favor the evolution of mate choice in males as well, even in species with no sex-role reversal (Edward and Chapman [@CR26]; Kokko and Monaghan [@CR50]). In particular, male mate choice is particularly likely to evolve when multiple females are available at the same time and when the rate of encounters with females is high (Kokko and Monaghan [@CR50]), such as in many group-living primates.\n\nSeveral primate species have evolved a certain degree of male mate choice to limit the costs of reproducing and allocate limited sperm resources toward the most valuable females (Kappeler [@CR48]; Keddy-Hector [@CR49]; Setchell and Kappeler [@CR75]). Male--male competition for access to mates, including monopolization of females, is often costly for male primates because it may increase the risk of injury (Drews [@CR24]) and affect a male's feeding time, energy balance, or physiological stress levels (Alberts *et al*. [@CR1]; Bergman *et al*. [@CR12]; Georgiev"
+"Introduction\n============\n\nOver the past century, polycythemia vera (PV) has undergone substantive changes in its concept and diagnostic criteria. The disease was first described in 1882^[@bib1]^ by Louis Henri Vaquez (1860--1936) and further elaborated by William Osler (1849--1919) in 1903.^[@bib2]^ William Dameshek (1900--1969) included PV as one of the 'myeloproliferative disorders\\' in 1951.^[@bib3]^ In 1976, the clonal nature of PV was deciphered,^[@bib4]^ but it took another 20 years before William Vainchenker (*b*. 1947) discovered its signature mutation (*JAK2*V617F),^[@bib5]^ which is, however, neither specific to PV nor believed to constitute the disease-initiating event.^[@bib6]^\n\nFormal clinical research in PV started in 1967 with Louis Wasserman (1912--1999) establishing the Polycythemia Vera Study Group.^[@bib7]^ The Polycythemia Vera Study Group conducted a number of clinical trials in PV including its seminal contribution of drug leukemogenicity associated with chlorambucil and P32.^[@bib7]^ The Polycythemia Vera Study Group is also credited for the first consensus diagnostic criteria in PV,^[@bib7]^ which have since undergone substantial revisions by the World Health Organization (WHO) subcommittee for classification of myeloid malignancies. The most recent WHO document on PV underscores the diagnostic value of *JAK2* mutations and bone marrow morphology.^[@bib8]^\n\nThis study is distinguished from previous studies in PV in its strict use"
+"Dr. Aharon Oren, the Editor and one of the List Editors of the Journal IJSEM, has informed us of a few minor errors in the protologues present in this publication which would prevent valid publication of the proposed names. The nomenclatural types we proposed for the new orders *Brachyspirales* ord. nov., *Brevinematales* ord. nov. and *Leptospirales* ord. nov. and the emended description we proposed for the order *Spirochaetales* (Buchanan, [@B2]) (Approved Lists 1980) were not in accordance with Rule 21a of the Bacteriological code and the etymology of the names of the family *Borreliaceae* fam. nov. and the orders *Brachyspirales* ord. nov., *Brevinematales* ord. nov. and *Leptospirales* ord. nov. were not in accordance with Rule 9 and Recommendation 6 of the Bacteriological code (Lapage et al., [@B6]). Hence, we are resubmitting revised protologues of the emendations and newly proposed taxa, correcting the minor errors present in the original submission.\n\nEmended description of the order *Spirochaetales* Buchanan, [@B2] (approved lists 1980)\n=======================================================================================\n\nThe order contains two families, *Spirochaetaceae* and *Borreliaceae*. Organisms are helical or coccoid, 0.1--75 \u03bcm in diameter and 3.5--250 \u03bcm in length. Cells do not have hooked ends. Cells may possess flagella. Periplasmic flagella overlap in the central region"
+"Colorectal cancer (CRC) is the most common gastrointestinal cancer and its aetiology involves an interaction of genetic and epigenetic alterations with environmental factors such as diet components that contribute to cancer development. A correct balance between kinase and phosphatase activities is essential in maintaining cell homeostasis ([@bib9]). The presence of alterations affecting kinase activities has been shown to be recurrent in many cancers, and therapies based on kinase inhibitors have been developed in the previous years. Although the role of phosphatases remains underexplored in comparison, it is true that phosphatases like protein phosphatase 2A (PP2A) have progressively been considered as potential tumour suppressors.\n\nProtein phosphatase 2A is a major serine/threonine phosphatase that consists of a heterotrimer that includes a catalytic, a scaffold, and a regulatory subunit involved in the specificity and localisation of the holoenzyme. Owing to the multiple existing isoforms and splicing variants for each PP2A subunit, especially in the case of the regulatory subunit, PP2A can form a wide variety of heterotrimeric complexes with distinct substrate specificities and they therefore have different biological functions ([@bib1]; [@bib30]; [@bib7]). Of importance, PP2A plays a pivotal role in regulating many signalling pathways ([@bib16]; [@bib10]; [@bib11]; [@bib17]) and its inactivation has been"
+"Who would imagine that networking can start even before the birth of an organization? In our case the conception of our (baby) organization had taken place some time before the incident I am going to narrate. The pregnancy was proceeding in a healthy manner. Then sometime in 1991 two persons met while waiting in a queue for coffee during a break in an international conference in Mumbai. One of them was the Medical Director of a hospice in the UK and the other was a person from the Bangalore corporate sector, a dreamer who till then had nothing to do with palliative care. Dr. Jeremy Johnson, had just begun to take an interest in palliative care in India and Kishore Rao, a corporate executive, had begun dreaming of setting up a hospice in Bangalore after his retirement. The occasion was the fifth anniversary of Shanti Avedna Sadan and the participants came from India and many other countries. Shanti Avedna, set up in 1986 was, to my mind, the first formal palliative care centre in the country and the meeting between Dr. Jeremy Johnson and Kishore Rao was quite fortuitous. The meeting was the beginning of a network which has grown"
+"Introduction {#S0001}\n============\n\nPharmacy is the health profession that is committed to ensuring safe and effective use of medication and it links the health sciences with the basic sciences.[@CIT0001] Pharmacy is among the respected professions worldwide, and it has experienced tremendous developments over the years.[@CIT0002]\n\nNowadays pharmacists' scope of practice widened from previous dispensing and suppling of medications to a variety of health services straddling prevention, addressing patient needs and expectations. All transition of focus is related to change of health care system, aging populations, health care workforce supply issues, emerging chronic diseases and changing expectations have re-engineered pharmacy in many developed nations.[@CIT0003],[@CIT0004]\n\nFor advancing pharmacy knowledge in a specific field or area of interest, postgraduate education (PGE) opportunities are the major options for pharmacy students and graduates. Often PGE is needed as a prerequisite for certain employment opportunities as well as to diversify pharmacists' skills and knowledge within the health care environment.[@CIT0005] Postgraduate education in Ethiopia is popular and it enhances job prospects. Also, there is Higher Education Relevance and Quality Agency (HERQA) which ensures whether higher education curriculum supports the countries' development needs. Postgraduate Master's programs under the school of pharmacy in Ethiopia include Clinical Pharmacy, Pharmacology, Pharmacognosy,"
+"Introduction {#s1}\n============\n\nThe emission of volatile organic compounds by plants as a response to herbivore attack is a widespread phenomenon. Such herbivore-induced volatile emissions have commonly been interpreted as a means of indirect defence of the plant, since predators and parasitoids can use these odorous cues to locate their herbivorous prey and hosts, respectively [@pone.0047589-Dicke1], [@pone.0047589-Turlings1]. Most studies on the function of herbivore-induced plant volatiles (HIPVs) are laboratory based and only a few have demonstrated a HIPV-mediated increase in carnivore attack rates on herbivores under field conditions [@pone.0047589-Kessler1]--[@pone.0047589-Thaler1]. The limited evidence that plants actually benefit from attracting natural enemies of herbivores continues to raise scepticism as to the indirect defence function of inducible volatiles, especially in the case of attracting parasitoids [@pone.0047589-Faeth1]--[@pone.0047589-Kessler2].\n\nThe tritrophic study system comprising maize, caterpillars and associated parasitoids represents one of the first examples demonstrating the importance of HIPVs in host location by parasitic wasps [@pone.0047589-Turlings2], but so far the phenomenon has not been studied thoroughly under field conditions for the said group of organisms. Somewhat equivocal circumstantial evidence for the action of HIPVs in the field stems from a study carried out in Switzerland: more entomophagous insects - parasitic Hymenoptera, Anthocoridae and Syrphidae -"
+"**Core tip:** This review focuses on the role of MUTYH, linked to MUTYH associated polyposis syndrome, on human neoplastic and non-neoplastic diseases, different to polyposis and colorectal cancer, considering its involvement in disorders based on oxidative stress damage. *MUTYH* pathogenic variants are independent predictors of poor prognosis in sporadic gastric, salivary gland secretory, pancreatic ductal, lung and cervical cancers, whereas some variants are involved in degenerative disorders, including neurological and ocular diseases. This provides novel insights for identifying the molecular basis of *MUTYH* pathogenesis in the light of recent advances, to better understand its potential in disease prevention and identify new therapeutic targets.\n\nINTRODUCTION\n============\n\nBiallelic germline *MUTYH* (MutY homolog *Escherichia coli*, homolog of *MYH*, *hMYH*) gene variants were historically identified in a fraction of *Adenomatous Polyposis Coli* (*APC)* mutation-negative cases with a phenotype overlapping with attenuated familial adenomatous polyposis (AFAP) or classical familial adenomatous polyposis (FAP) (MIM\\# 604933)\\[[@B1],[@B2]\\]. In humans, MUTYH protein is considered a cell protective factor able to counteract oxidative damage. It is a DNA glycosylase involved in the restoration of post-replicative mispairs in double-stranded DNA, where MUTYH recognizes and specifically removes adenine or 2-hydroxyadenines misincorporated in 7,8-dihydro-8-oxoguanine (8-oxoG) pairs with adenine or cytosine inducing G:C to"
+"Introduction\n============\n\nEnsuring access to primary care by encouraging young doctors is increasingly being perceived as a governmental responsibility within the context of providing services to the public. This responsibility is also being passed by the legislature to the universities in the form of pertinent recommendations \\[[@R1]\\]. Evidence speaks for influencing the choice of medical specialty through making changes in medical education; the structure and method of teaching medicine (including the time point, duration and intensity of contact with primary care) are important for the later selection of a specialty in ambulant medical care \\[[@R2]\\]. With the revision of the licensing regulations (\u00c4rztliche Approbationsordnung) of July 24, 2012, medical students in the clinical study phase now must demonstrate the completion of a four-week clerkship in a primary care medical practice (FHV) when registering for the second part of the state medical exam after June 10, 2015. This clerkship can take place in the medical practices of general practitioners, internists without a specialty, or pediatricians.\n\nAccording to the expectations of the health administration, this required clerkship is supposed to encourage young physicians at the beginning of their careers and strengthen the field of general practice. Besides the influence of a particular"
+"Introduction {#sec1}\n============\n\nVertebral destruction can result from different pathologies. The causes could be infectious, metabolic, or neoplastic conditions.[@bib1] From the neoplastic conditions, 95% of the cases are metastatic tumors.[@bib1] Other than metastasis, differential diagnosis for isolated spine-destroying neoplastic conditions include chordoma, giant-cell tumor, aneurysmatic cyst, osteoid osteoma, osteoblastoma, plasmacytoma, osteosarcoma, Ewing\\'s sarcoma, and neuroblastic tumors.[@bib1] Tumors originating from neural tissue in the spinal canal may rarely cause bony scalloping.[@bib2] There are also few case reports of schwannomas with associated vertebral body destruction.[@bib3], [@bib4] Otherwise, it is very rare for tumors originating from the spinal canal neural tissues to cause significant bony changes.\n\nSpinal cord astrocytomas (SCAs) are rare intramedullary lesions.[@bib5] Although in the pediatric population they represent the single most common histologic type of intramedullary lesion, in adults they are less common than ependymomas.[@bib5] Most SCAs are low-grade lesions, but approximately 25% of cases are high-grade, World Health Organization grade (WHO) III and IV.[@bib5] In adults, the lesions rarely present in patients older than the age of 60 years.[@bib6] According to a retrospective review of a 20-year experience with these lesions at Duke University, the mean age at presentation was 22 years with a male preponderance of 70%.[@bib7]\n\nClinical"
+"Introduction {#s1}\n============\n\nScience is disproportionately produced at research centers within a few select regions [@pbio.1001740-Bornmann1],[@pbio.1001740-National1]. This distribution contributes to \"brain drain\"---the cultural and geographical separation of researchers from their communities of origin [@pbio.1001740-Franzoni1]. In places lacking research centers, brain drain precludes achieving a critical mass of scientific expertise and the development of science, technology, engineering, and mathematics (STEM). Displaced scientists gradually become disconnected from their home communities and colleagues, presenting a challenge to maintaining research collaborations that could benefit their communities of origin. Insidiously, dispersion also presents socio-cognitive challenges to scientists who see themselves as underrepresented in the larger culture of science [@pbio.1001740-Payton1]--[@pbio.1001740-Chang1].\n\nSocial networks hold enormous promise for \"connecting\" dispersed groups and providing new opportunities for fellowship and mentorship among underrepresented communities in science. Faced personally with these obstacles, in 2006, we created Ciencia Puerto Rico (CienciaPR; [www.cienciapr.org](http://www.cienciapr.org)), an online network that connects scientists with geographic, academic, and/or cultural ties to Puerto Rico. CienciaPR was built to counteract the negative effects of scientific brain drain by: (1) promoting scholarly interaction among self-identified members of an otherwise dispersed community; (2) providing visibility to diverse scientific role models; and (3) supporting research and science education through initiatives that culturally resonate"
+"Introduction {#section5-1745506520918335}\n============\n\nGood health and psychological wellbeing are attracting growing attention as desirable and closely related constructs that encompass more than simply the absence of illness and disease.^[@bibr1-1745506520918335]^ Physical, mental, social and behavioural aspects of these constructs together with the burden of any illness, injury, pain or disability are important considerations in the study of health and psychological wellbeing. Factors with the potential to affect directly or indirectly on the health and psychological wellbeing of mature-aged (middle age and older) women are important to identify, not least because these women represent an expanding proportion of the general Australian population^[@bibr2-1745506520918335]^ but also because with advancing age, health and psychological wellbeing become increasingly prominent and interdependent.^[@bibr1-1745506520918335]^\n\nThe physical changes that affect a woman's body as a result of ageing have the potential to affect health and psychological wellbeing and should be considered more than inevitable changes. For many women, breasts contribute to their personal sense of attractiveness^[@bibr3-1745506520918335]^ and feminity^[@bibr4-1745506520918335]^ throughout their lifetime. The physiological changes that occur in breasts with ageing are well described^[@bibr5-1745506520918335][@bibr6-1745506520918335][@bibr7-1745506520918335]--[@bibr8-1745506520918335]^ and are typically reported by women as an increase in breast size and ptosis.^[@bibr4-1745506520918335]^ Menopause is also a transitional period that influences a range of breast characteristics.^[@bibr7-1745506520918335]^"
+"Introduction {#section1-0748730419876781}\n============\n\nThe temporal organization of most societies is complex and requires the arrangement of many different aspects, from school/work and transport schedules to the opening times of shops and recreational facilities. This complexity is aggravated by the conflict that often arises between biological (internal) time and social (external) time. A mismatch between internal and external time leads to chronic sleep deprivation and a condition called social jetlag ([@bibr35-0748730419876781]). Minimizing social jetlag is important for health ([@bibr29-0748730419876781]; [@bibr34-0748730419876781]). In addition, populations show a wide distribution of so-called early and late chronotypes, namely, individuals who sleep at different times ([@bibr27-0748730419876781]). To accommodate sleep and other individual needs, flexible working hours have been proposed as a possible solution ([@bibr4-0748730419876781]).\n\nSo far, the vast majority of chronobiology research has focused on circadian (daily) time, but biological timing spans over different time scales, from tidal (12.4 h) to annual (365.25 days) rhythms. Describing the influence that these other biological cycles have on human behavior and physiology may be relevant for the temporal organization of society as well. For instance, school and working hours could be adjusted according to seasonal changes in biological timing.\n\nSeasonal changes derive from the Earth's moving around the Sun."
+"1 Introduction\n==============\n\nWhen the human genome was released as a first draft ([@btz031-B8]), researchers started to manage these kinds of large, fragmented and rapidly evolving complex datasets by creating genome browsing and database systems such as EMBL-EBI Ensembl ([@btz031-B1]). The availability of a reference genome allows definition of a coordinate system, in which genomic data, such as collaboratively defined gene models, are described unambiguously by chromosomal positions. Ensembl publishes several data releases per year, rendering it a valuable resource for consistent and tightly integrated data. These data are used in high-throughput genomic data analyses, which are frequently carried out in the R statistical programing language using tools provided by Bioconductor ([@btz031-B7]).\n\nHere we present *ensembldb*, a Bioconductor package enabling the creation and usage of comprehensive, locally stored Ensembl-based offline annotation databases. In addition to gene model annotations we include protein annotations in the pre-built databases, offer a fast and powerful filter mechanism and provide functions for the mapping of arbitrary positions between the genome, exome, transcriptome and proteome.\n\n2 Implementation and available data\n===================================\n\nEnsembl is one of the main annotation resources for genomic data with a web service for online data access and APIs enabling programmatic data access."
+"Introduction {#s0005}\n============\n\nCyclic oculomotor nerve paresis is a rare condition which is characterized by episodic contraction and relaxation of the muscles supplied by third cranial nerve. Rampoldi first described this condition in 1884 where he reported two cases and termed it as an oculo-palpebral imbalance.[@b0005] The characteristic findings are an alternating paretic phase wherein the eyelid becomes ptotic, eyeball rotates downward and outward, pupil is dilated and a spastic phase when ptotic eyelid elevates, eyeball returns to midline and pupil gets constricted. Various medical and surgical treatment modalities have been described to control the cyclic phases. Baclofen which is a central muscle relaxant was tried and was found to be ineffective.[@b0010] Levator transposition procedure was effective in abolishing the eyelid movements in 3 patients.[@b0015] We report a case of cyclic oculomotor paresis and spasms (COPS) where tarsofrontal silicone sling was performed for correction of ptosis and was effective in reducing the cyclic eyelid movements and provided good cosmetic outcome.\n\nCase report {#s0010}\n===========\n\nA 26-year-old male presented with complaints of abnormal movement of the right upper eyelid since childhood. The abnormal movements developed following an episode of fever at 1.5\u00a0years of age. His antenatal and birth history were"
+"Introduction {#s1}\n============\n\nImproper early clearance and missed unstable cervical spine injuries result in life-long disability and lifetime costs of over US\\$2\u2009million.[@R1] Not only can these injuries be missed due to more acute physiological insults at the time of presentation, such as hemorrhage and airway compromise, but cervical spine injuries can also manifest in a delayed fashion where spine instability leads to a secondary injury days later. To further complicate the diagnosis and management of these injuries, early identification of cervical spine injuries is dependent on patient's cooperation. The estimated prevalence of cervical spine injury in alert trauma patients is 2.7%, but the risk is 7.7% in obtunded patients.[@R2]\n\nTrauma patients frequently present with depressed mental status, and the increased risk of cervical spine injury in this subgroup leads to prolonged collar immobilization. Prolonged collar immobilization exposes patients to multiple in-hospital risks. The risk of collar-related pressure ulcers increases by 66% for every additional day of use.[@R3] Additional complications of delayed collar clearance include: difficult intubation, difficult central line insertion, increased intracranial pressure (ICP) and secondary brain injury due to internal jugular compression and additional positioning and aspiration pneumonia with subsequent delayed weaning from ventilators.[@R4] Historically, a commonly suggested"
+"Learning pointsThe possibility of a phaeochromocytoma should be considered in patients with takotsubo cardiomyopathy, particularly if occurring in connection with potentially triggering physical factors such as severely fluctuating blood glucose.The diagnosis of phaeochromocytoma may be easy to miss but important to keep in mind if abnormal reactions to a provocative procedure as oral glucose tolerance test.Multidisciplinary management and expanded testing are important in patients with takotsubo and atypical presentation.\n\nIntroduction\n============\n\nPhaeochromocytomas are catecholamine-producing tumours of the chromaffin cells of the adrenal medulla (80--85%) or extra-adrenal tissues, i.e. paraganglioma (15--20%).[@ytz177-B1] The prevalence in the western population has been estimated to 1:4500--1700 and the annual incidence 3--8 cases/million, with 10% of phaeochromocytomas being malignant, and 10--20% familial.[@ytz177-B2] Patients with phaeochromocytomas typically present with symptoms associated with excess levels of catecholamines: hypertension (98%) and the triad of headache, sweating, and palpitations (50--60%).[@ytz177-B1] Phaeochromocytomas are associated with impaired glucose tolerance or even overt diabetes in 20--40% of cases. Post-operative hypoglycaemia is a well-recognized feature of phaeochromocytoma, whereas hypoglycaemia as an initial symptom seems to be very rare.[@ytz177-B3]\n\nMore severe presentations of phaeochromocytomas, such as non-cardiogenic pulmonary oedema, acute renal failure, acute myocardial infarction, myocarditis, or other forms of acute cardiomyopathy, with or without"
+"Spinal cord injury (SCI) is a devastating condition that not only results in a loss of motor functions but also severe autonomic dysfunctions (Krassioukov and Claydon, 2006). Autonomic dysreflexia (AD) is a life threatening episode of transient hypertension that occurs up to 30x/day (11x/day on average) in those with cervical or high thoracic SCI (Hubli et al., 2015). Most common triggers of AD are from stimuli such as a full bowel and/or bladder, or sexual arousal (Teasell et al., 2000). Penile vibrostimulation (PVS) is a clinical procedure for sperm retrieval used for the purpose of family planning or fertility assessment that unfortunately iatrogenically induces episodes of AD (Elliott, 2006). Recently, we published a clinical trial highlighting that prazosin may be a viable option for treating AD secondary to PVS (Phillips et al., 2014).\n\nCurrently, the most commonly used medication to mitigate the severity of AD episodes during PVS is nifedipine (Adalat), an immediate-release calcium channel blocker (Krassioukov et al., 2009). However, individuals with SCI experience persistently low resting blood pressure (BP) as well as orthostatic hypotension (Krassioukov and Claydon, 2006). While nifedipine is effective at significantly reducing the severity of BP increases secondary to AD, it unfortunately has the tendency"
+"In the current pandemic crisis, remember to 'Follow WOMEN' and 'Avoid touching MEN'. Follow 'WOMEN', i.e. Wash your hands frequently with soap and water; Obey social distancing; Mask is a must if you leave your house; Eat a healthy diet rich in vegetables and fruits; N -- No going out if you are not feeling well. Avoid touching 'MEN' i.e. Mouth, Eyes, and Nose .... because the COVID 19 virus can enter your body via any of these gateways. This is the advice from the Departments of Health worldwide. Of the three entry points, the least considered, has been the eyes.\n\nMany people wear face masks, but far fewer consider the need for eye protection. Although the eye is probably a less important gateway for the virus, in the last few days, evidence has emerged of the likelihood of transmission via the conjunctival epithelium \\[[@bib0005]\\]. So, the question arises \"What does this mean for optometrists and ophthalmologists and their patients?\"\n\nWearing glasses or a visor may reduce risk of contamination, but it does not protect against COVID 19 infections \\[[@bib0010]\\]. This is a similar situation to wearing a regular surgical or other face covering in that there is an imperfect"
+"Dear Editor,\n\nInfection control still represents one of the most important issue in clinical practice, particularly in critically-ill patients. Indeed, it has to be considered as a mandatory approach in clinical practice for all healthcare workers, nonetheless it is one of the most difficult to learn and to apply. A good and significant methodology to acquire a state of mind focused on infection control during clinical practice should start early during the training of healthcare workers and should be carefully managed, likely using all possible and available learning tools. It should also involve patients and their relatives, aiming to minimize possible infection spread. Previously case studies from popular culture have been proposed as teaching tool for medical student, but possibly also for all those individuals having relation with healthcare facilities. More recently Star Wars series has been used as learning tool to focus on pathophysiology of the lung according to one of the most important character of Star Wars series, Darth Vader. Indeed Star Wars and related imaginary world holds some other important learning suggestions to emphasize another important feature of the tragic story of this popular character, or else the infection control after severe skin burn in one of"
+"Atrial fibrillation (AF) classifications that are used to recommend treatment decisions are based on AF episode duration [@bib1]; however, a number of observations suggest that within classification categories, AF is a structurally and electrically diverse arrhythmia. First, ablation shows variable success between apparently similar patients when controlling for comorbidities and left atrial (LA) dimensions. Second, some patients require multiple ablation procedures to achieve freedom from AF despite durable pulmonary vein isolation, whereas others require only a single procedure. Finally, the natural history of AF varies, with differing rates of progression to persistent AF seen. In line with these observations, reduced conduction velocity and shortened refractoriness have been associated with increasing severity, duration or recurrence of AF in some [@bib2], but not all [@bib3], [@bib4], studies.\n\nRecently, structural [@bib5] and voltage-defined [@bib6] targets for intervention beyond pulmonary vein isolation have been proposed. Although low voltage is correlated with the presence of magnetic resonance imaging indices of atrial fibrosis [@bib7], preservation of normal bipolar voltage does not imply absence of fibrosis [@bib8]. Therefore, bipolar voltage measured only during sinus rhythm or fixed coupling interval pacing may fail to detect atrial structural change. Furthermore, whether LA conduction abnormalities or morphological electrogram changes occur"
+"###### Strengths and limitations of this study\n\n-   The large and representative sample (n=2229) of lower secondary school students who responded to the science achievement test improves the external validity of our findings.\n\n-   Estimating students' proficiencies and task difficulties using Rasch modelling, we could compare students' proficiency in science with the difficulty of identifying and appraising a health claim in a fictitious brief news report.\n\n-   All achievement test items were piloted twice to ensure a valid and reliable measure of scientific literacy, and the use of a digitalised assessment tool reduced sources of errors.\n\n-   We did a secondary analysis of test data collected in 2013, thus a shift in proficiency in subsequent student cohorts may have occurred.\n\n-   Using raters to code responses to the open-constructed 'news report' item, there is a potential of misclassifying responses owing to rater subjectivity.\n\nBackground {#s1}\n==========\n\nNews media is a leading source of health and scientific information for the public,[@R1] including adolescents and young people, who frequently encounter and share news and information through digital media.[@R3] According to Eurostat, more than two-thirds of young people access online news media regularly.[@R4] More than half also deliberately search for health information online,"
+"Introduction\n============\n\nNetball is one of the most popular women's sports, and is played by more than 20 million people across more than 80 countries ([@B56]). Since 1963 a netball World Championship tournament has been played every 4 years. In 1990 netball first featured in the Commonwealth Games as a demonstration sport, and has since been played competitively for medals since 1998 ([@B56]). Despite substantial international popularity, netball remained an amateur sport for several decades. However, netball now has 61 countries recognized by the International Netball Federation, which includes several professional netball leagues. This recently obtained professional status of netball will no doubt generate new pressures and demands common within professional sport, one of which will be the increased demand for successful on-court match performance. To optimize match performance, it is necessary to assess performance variables in order to provide practical feedback to players and coaches, which will guide coaches decision making and subsequently the coaching process ([@B5]).\n\nPerformance analysis (PA) in sport involves analysing and evaluating the technical, tactical, physical, and cognitive aspects of performance in training and competition to better understand the components of successful performance ([@B34]; [@B5]). There is a substantial body of PA research associated with"
+"Background\n==========\n\nInclusion of conserved regions of the HIV genome into vaccine candidates may help to overcome problems of global sequence diversity and could provide beneficial effects by inducing T cell responses for which CTL escape is likely associated with fitness costs.\n\nMethods\n=======\n\nWe rationally designed an immunogen sequence consisting of \\'\\'conserved elements\\'\\' (CE) that includes 7 segments of the Gag p24 protein. Responses to CE and to the rest of p24 and the entire viral proteome were assessed in HIV controllers (n = 15) and HIV non-controllers (n = 10) using a comprehensive 18 mer overlapping peptide set spanning the entire viral proteome and an 11 mer overlapping (by 10 residues) peptide set spanning Gag p24 and covering all CE and the most frequent occurring mutations in this region.\n\nResults\n=======\n\nControllers and non-controllers mounted comparable number of responses to either entire p24 or CE only (8 vs. 7 for p24 and 3 in both groups for CE). Despite these frequent reactivities in non-controllers, the contribution of CE responses to total p24 magnitude was significantly lower in non-controllers (p = 0.043). In addition, controllers showed a significantly higher recognition of variants, both to the CE (median variant reactivity"
+"Water polo is an Olympic sport with high demands on the shoulder joint as the players swim in rapid sprints suddenly changing direction, have physical contact with other players, and repetitively throw a 400- to 450-g ball. This activity generates considerable stress in the glenohumeral joint by 2 main factors, both requiring significant muscular strength. The first component is throwing, which is executed with a maximum angular velocity of 1137 deg/s and a ball velocity of up to 19.7 m/s.^[@bibr17-2325967114531213]^ The second component is swimming, performed with a constant and lower angle velocity but greater numbers of repetitions than throwing.\n\nAlthough shoulder injury and overuse patterns vary by sport and position, there are common movements for all overhead athletes. Concerning throwing, many of the injury patterns and biomechanical motions in water polo players are similar to other throwing athletes. To our knowledge, no studies have been published in which the shoulders of water polo players were assessed by magnetic resonance imaging (MRI) and compared with a control group.\n\nThe shoulder problems of professional swimmers are typically caused by freestyle and butterfly strokes, resulting in a microinstability with a cranial shift of the humeral head, leading to subacromial impingement and bursitis,"
+"The oil palm is a monocot of the family Arecaceae and of the tribe Cocoineae belonging to the genus *Elaeis*. The genus contains three species: *Elaeis guineensis* Jacquin originating from Africa, *Elaeis oleifera* (HBK) Cort\u00e8s originating from South America, and *Elaeis madagascariensis* Beccari found in Madagascar. The most widespread species, *E. guineensis*, is grown for its fleshy fruits, from which mesocarp palm oil is extracted, and its kernel, from which palm kernel oil is extracted. *E. oleifera* is richer in unsaturated fatty acids. It displays some very worthwhile characteristics for genetic improvement, notably slow vertical growth, the quality of its oil, and resistance to several fungal diseases.\n\nIn oil palm breeding programs, *E. guineensis* and *E. oleifera* palms selected in several geographic origins are inbred or crossed to make breeding populations of restricted origin, intra- or inter-specific hybrids, and backcrosses ([@iev066-B17]). Backcrosses involve crosses between a parent of purely *E. guineensis* origin and a parent arising from a hybridization between the two species of interest (*E. guineensis*\u2009\u00d7\u2009*E. oleifera*). They are used to introgress traits of interest from *E. oleifera* (Eo) into the genome of *E. guineensis* (Eg) ([@iev066-B29]). In our study, we focused on BC1 backcrosses ((Eo\u2009\u00d7"
+"Introduction {#s1}\n============\n\n*\"...it appears that the true history of the colonization of the land, now Bermuda, is lost forever in oblivion\"* [@pone.0011375-Taylor1]\n\nStudies of island biodiversity have focused largely on adaptive radiations associated with neoendemism (i.e., \"cradles\" of diversity) [@pone.0011375-Schluter1]--[@pone.0011375-Losos1]. There are myriad factors that promote spectacular biodiversity on islands, but the factors that contribute to neoendemism ultimately derive from the fact that the islands formed *de novo* with no connection to a larger landmass and thus have abundant \"empty\" ecological niche space. However, the isolation that defines islands can also preserve genetic diversity of relict lineages, a pattern known as paleoendemism [@pone.0011375-Gillespie1], [@pone.0011375-Stebbins1]. The most prominent example of this phenomenon among vertebrates is the tuatara (*Sphenodon*) that represents a clade of reptiles once widespread, but now restricted to two remaining species found only on the offshore islands of New Zealand. Moreover, given numerous threats such as climate change, introduced species, and habitat destruction, insular fauna are subject to increased risk of extinction [@pone.0011375-Jamieson1]. This vulnerability is of particular concern for paleoendemics, as these taxa represent a disproportionately high amount of phylogenetic diversity [@pone.0011375-Faith1]--[@pone.0011375-Isaac1].\n\nThe islands of Bermuda (32.33\u00b0N, 64.75\u00b0W) are an isolated, 54 km^2^ archipelago (referred to as"
+"> This is a *PLOS Computational Biology* Methods article.\n\nIntroduction {#s2}\n============\n\nDetermining the evolutionary relatedness of two protein sequences is most successfully performed by amino acid sequence comparison [@pcbi.1003247-Soeding1]--[@pcbi.1003247-Altschul2]. However, it is well known that structure can be preserved even when sequence has diverged past the point of amino acid similarity recognition [@pcbi.1003247-Kinch1], suggesting that sequences can bestow local, subglobal, and global properties to a protein that can be preserved in the absence of strict conservation of the side chain atoms. In other words, similar properties could exist horizontally in a sequence even when recognizable vertical conservation is lost [@pcbi.1003247-Schlessinger1]. Even if such similarities are due to analogy rather than homology [@pcbi.1003247-Krishna1], approaches are needed that can augment sequence based analysis by matching patterns that may be independent of amino acid conservation at each position.\n\nComparison of three-dimensional atomic structures [@pcbi.1003247-Sadreyev1]--[@pcbi.1003247-Holm1] is one example of such pattern matching. However, protein function and evolution arise from a manifold of physical, chemical, and biological mechanisms, only partly accounted for by side chain identity or structural similarity [@pcbi.1003247-Tokuriki1]--[@pcbi.1003247-Liberles1]. It may be the case that proteins can also be meaningfully characterized by other attributes, such as the energetic contributions to stability [@pcbi.1003247-Gu1] or"
+"INTRODUCTION\n============\n\nHigh-throughput sequencing (HTS) technology is designed to measure the composition of large and diverse pools of genetic material. The associated data lend itself well to exploratory studies addressing universal issues, such as genetic variation within populations ([@gkt094-B1],[@gkt094-B2]) or somatic mutation landscapes ([@gkt094-B3]). Despite the important insights gained from such holistic approaches, a significant portion of biology research consists of in-depth analysis of individual genes or pathways. It is therefore relevant to devise effective methods to exploit existing HTS data in these small-scale and in-depth projects without necessitating use of overly specialized computer platforms.\n\nIn practice, the raw input to an HTS workflow---regardless of whether it is obtained from an in-house sequencer, service provider or public data repository ([@gkt094-B4])---typically consists of set of reads in FASTA or FASTQ format. Many workflows begin by mapping the reads onto a reference genome using a fast aligner \\[e.g. Bowtie ([@gkt094-B5]), GSNAP ([@gkt094-B6]), SOAP ([@gkt094-B7]), SNAP ([@gkt094-B8]), mr(s)Fast ([@gkt094-B9]), RazerS ([@gkt094-B10],[@gkt094-B11]) and others\\] and later perform project-specific computations, such as variant detection on the aligned data \\[SAMtools ([@gkt094-B12]), GATK ([@gkt094-B13]) and others\\]. Other workflows, for example for detection of fusion genes \\[deFuse ([@gkt094-B14]) and others\\], begin their work directly on the raw reads."
+"Slipped capital femoral epiphysis (SCFE) results in a more or less pronounced deformity of the hip joint. Severe slips presumably pose a higher risk of early osteoarthritis (OA) (Hagglund et\u00a0al. [@C12], Loder et\u00a0al. [@C19], Rahme et\u00a0al. [@C23])\n\nThe goal when treating SCFE is to prevent further slip by stabilizing the epiphysis. This can be done with a smooth pin with a hook device or a short threaded screw to allow further growth and remodeling, or with a threaded screw with compression to close the physis (Hansson [@C13], Aronsson et\u00a0al. [@C1]). The long-term goal is to achieve congruent hip joints that function painlessly at a high level without subsequent OA.\n\nFor severe deformities, secondary surgical treatment has become more common (Azegami et\u00a0al. [@C2]). Open surgery with dislocation of the hip, or arthroscopic surgery, can be performed to remove any bony prominences that cause impingement. Additional surgical options aim to re-orient the femoral head to avoid impingement and provide better congruity of the hip joint. Some of these procedures are extensive and entail high complication risks (Azegami et\u00a0al. [@C2]).\n\nSensitive diagnostic tools are needed to identify early cartilage degeneration after SCFE, both in the natural course"
+"Background\n==========\n\nHIV genomic sequence variability has complicated efforts to generate an effective globally relevant vaccine. Our strategy for HIV-1 vaccine design is to select epitopes that can induce broad and dominant HLA-restricted immune responses targeted to the regions of the viral genome conserved in sequence, three-dimensional configuration, and across time which may represent regions that are constrained due to functional or structural limitations. These \"Achilles' Heel\" epitopes would be ideal candidates for inclusion in an epitope-based HIV vaccine.\n\nMethods\n=======\n\nHighly conserved T-cell epitopes were selected using the EpiMatrix suite of immunoinformatic tools. This analysis was first performed in 2002 on 10,803 HIV-1 sequences available at that time and again in 2009 on an expanded 43,822 sequences. Selected epitopes were validated for binding and immunogenicity with PBMCs from HIV-infected donors in Providence, RI and Bamako, Mali.\n\nResults\n=======\n\n38 highly conserved HLA-A2 candidate epitopes were selected. Analysis done in 2009 revealed surprising stability of 25 of the epitopes selected in 2002 and identified an additional 13 highly conserved HLA-A2 candidates. Thirty-five (92%) of the 38 selected epitopes stimulated IFNg response in PBMC from at least one subject. Twenty-one of 25 peptides selected in 2002 were validated in assays performed"
+"Maryland has become the first state to ban arsenical feed additives used in chicken production.[@r1] Signed 22 May 2012 by state governor Martin O'Malley, the ban applies mainly to a drug called roxarsone (sold as 3-Nitro^\u00ae^) and takes effect 1 January 2013.\n\nProduced by Pfizer subsidiary Alpharma LLC and used for nearly 60 years to prevent and treat infections caused by parasites called coccidians, roxarsone also helps chickens grow faster with less feed. It's not known how roxarsone kills coccidians, according to John Barta, a professor of parasitology at the University of Guelph, Canada.\n\nAt the time roxarsone was approved, scientists believed its organic arsenic base would be excreted unchanged. Then emerging research showed that birds can metabolize organic arsenic to the more toxic inorganic form.[@r2] Furthermore, whereas fresh poultry waste does contain predominately organic arsenic, in the soil it degrades to inorganic arsenic, which has been found to run off into receiving waters and accumulate in stream sediments.[@r3] In studies of these environmental media in the Delmarva Peninsula, spreading the waste of roxarsone-fed poultry on soil was associated with inorganic arsenic concentrations that occasionally exceeded federal and state re-med-iation standards; how-ever, deep ground-water, the major source of drinking water"
+"Data are available upon request\n\nIntroduction {#sec001}\n============\n\nIn recent years, there has been a rapid expansion of antineoplastic drugs. The availability of more therapeutic options represents a challenge to oncologists, who must select the best treatment for any individual. In the majority of instances, oncologists must rely on best evidence to make that selection. Using this approach, only a fraction of patients responds to any chemotherapy regimen, and this fraction diminishes with successive lines of chemotherapy due to emergence of resistance. While predictive markers may refine treatment selection, there are no predictive biomarkers for most agents. Moreover, predictive biomarkers identify individuals who do not respond, but do not guarantee benefit.\n\nAn alternative approach is to develop an improved means to assess response to systemic therapy, soon [after]{.ul} drug has been administered. Such an adaptive approach would enable the oncologist to change therapies in a timely manner, before disease progression, and before major toxicities and high costs are incurred. Currently, treatment efficacy is monitored radiographically by computed tomography (CT) scan or magnetic resonance imaging (MRI). For solid tumors, treatment effect typically appears as a reduction in tumor size \\[[@pone.0213942.ref001]\\] or tumor attenuation \\[[@pone.0213942.ref002]\\]. Radiographically evident response may not appear until"
+"Surgeons have applied the principles of tissue engineering for years; they transplant and shift bone and other tissues within a patient to promote regenerative potential. The advent of technology for fabricating structures (eg, matrices, TCP bone fillers, etc.) with geometric fidelity, compositional consistency, and tissue-specific identity offers further promise that regenerative potential of tissue and whole organ systems can be achieved. While attaining scar tissue might be sufficient for soft tissue applications such as skin or in muscle or tendon, achieving an outcome in most orthopedic indications that is not mechanically solid and weight-supporting would be insufficient.\n\nImplicit in the strategy of repairing bone is a need to gain restitution of space, achieve mechanical integrity, and regenerate functional continuity. When the biology or anatomy are insufficient to attain a full repair, therapeutic use of graft material has been used to omit compliance features such as strain tolerance, reduced stiffness, and attenuated strength, and instead promote primary or membranous-type bone formation within the physical approximation of a graft material. In the broadest sense, 3 basic components are required of a graft: osteoprogenitor cells, osteoinductive factors, and an osteoconductive matrix or scaffold.\n\nA more critical assessment would discriminate cell lineage and capacity"
+"Application of resuscitation science to improve patient care and outcomes requires effective strategies for education and implementation. Systematic reviews suggest that there are significant opportunities to improve education, enhance individual and team performance, and avoid delays in implementation of guidelines into practice. It is within this context that the International Liaison Consensus on Resuscitation (ILCOR) Education, Implementation, and Teams (EIT) Task Force was established and addressed 32 worksheet topics. Reviewers selected topics from the *2005 International Consensus on Cardiopulmonary Resuscitation* (*CPR*) and *Emergency Cardiovascular Care* (*ECC*) *Science With Treatment Recommendations* [@bib0005] and new topics identified by an expert group.\n\nOne challenge for the EIT Task Force was extrapolating outcomes from simulation studies to actual patient outcomes. During the evidence evaluation, if the PICO (*P*opulation, *I*ntervention, *C*omparator, *O*utcome) question outcomes were limited to training outcomes such as improved performance on a manikin or simulator, studies were classified to a level of evidence (LOE) according to study design (e.g., a randomised controlled trial \\[RCT\\] on a manikin would be LOE 1). Manikin or simulator studies were labeled as LOE 5 irrespective of the study design if the PICO question also included patient outcomes.\n\nThe following is a summary of key 2010 recommendations"
+"Introduction {#s1}\n============\n\nBiological fluids like synovial fluid, vitreous humor, cerebrospinal fluid, blood, lymph, and mucus are biopolymer solutions of water, protein macromolecules, and cells [@pone.0065014-Tuchin1], [@pone.0065014-Assunta1]. They serve as shock-absorbers, allergen and bacteria trappers, nutrient and oxygen distributers, and lubricants in different organ systems [@pone.0065014-Assunta1]--[@pone.0065014-SharifKashani1]. To fulfill these roles, bio-fluids maintain distinct viscoelastic behavior, exhibiting both solid and fluid-like features under different loading conditions and size scales [@pone.0065014-Lai1]--[@pone.0065014-Nickerson1]. Disease progression in multiple organ systems is frequently accompanied by altered viscoelastic properties of bio-fluids. For instance, in rheumatoid arthritis and osteoarthritis, the reduction of glycosaminoglycan hyaluronate and lubricin contents alters the viscoelastic properties of synovial fluid, compromising its shock-absorbing capability, in turn damaging cartilage under loading condition [@pone.0065014-Jay1]. The abundance of evidence on the reduced viscosity of synovial fluid in the course of osteoarthritis has led to development of Viscosupplementation, a treatment approach in which diseased synovial fluid is replaced with an elastoviscous hyaluronan solution [@pone.0065014-Divine1]. In the case of another bio-fluid, vitreous humor, altered viscoelastic properties are believed to be associated with age and numerous ocular pathologies such as retina tear and detachment [@pone.0065014-SharifKashani1], [@pone.0065014-Lee1]. The significant evidence on the role of bio-fluid viscoelasticity in disease initiation and progression,"
+"Background {#Sec1}\n==========\n\nProviding large numbers of undergraduate students in scientific disciplines with engaging, authentic laboratory experiences is important to promote inquiry-based, conceptual learning \\[[@CR1]\\], but challenging in terms of resourcing \\[[@CR2]\\]. Constraints in a real lab (wet-lab) setting include limited and out-dated laboratory equipment, unavailable materials and difficulties in demonstrating techniques due to large class sizes resulting in student crowding \\[[@CR3]\\]. These resourcing issues have implications for cost, health and safety as well as efficacy of teaching and learning. Such issues have affected the Muscle Diseases practical class within Musculoskeletal Diseases, an undergraduate Pathology course for 3rd year Science students at UNSW Australia. Student enrolments in the Musculoskeletal Diseases course have risen markedly over the past 5 years. This has made it logistically very difficult to teach technical and diagnostic laboratory elements and the use of protein analysis apparatus (Western Blotting) in that practical class. Such technical skills are linked to conceptual frameworks that underpin the diagnosis of muscular dystrophy. Furthermore, the use of Western Blotting apparatus in a real lab setting is time-consuming and cumbersome and tends to detract from the diagnostic aspect of the practical class \\[[@CR4]\\].\n\nMoreover, the focus of the labs is on acquiring technical"
+"Epilepsy is a chronic neurological disease and patients with epilepsy have an increased risk for cognitive, behavioral, and psychosocial disorders that can adversely impact the quality of life. Various factors like common underlying predisposition, mechanisms underlying epileptogenesis, direct effects of seizures, and adverse effects of anti-seizures drugs or other non-pharmacological therapies may play a causal role in such epilepsy associated comorbidities. New and validated screening approaches as well as novel therapeutic approaches are warranted, that may help with the early detection and treatment of comorbid conditions. Experimental models of epilepsies can play a critical role for improving our understanding of not only of the fundamental mechanism of epileptogenesis but also to generate new insights regarding the relationship between epilepsy and related comorbidities.\n\nThis Research Topic compiles 12 articles, including 3 reviews, 1 mini-review, and 8 original research contributions from leading scientists in the field. The collection of papers on this topic offers an up-to-date overview of current knowledge and approaches for studying epilepsy and related comorbidities. The articles highlight the pivotal role of numerous experimental and clinical studies that have elucidated novel mechanistic insights about the pathophysiology of these conditions. Translational perspective of research in this domain as well as"
+"Background\n==========\n\nPhase III clinical trials in areas including acute stroke and traumatic brain injury commonly use ordinal functional outcome scales as their primary outcome measure. Conventionally these scales are analysed by dichotomising the ordinal scale into a binary scale:- 'dead or dependent' versus 'independent'. This can potentially discard much relevant information, reducing both the clinical relevance of the results and the statistical efficiency of the analysis.\n\nMethods\n=======\n\nMethodological work in stroke (by the OAST Group) and in traumatic brain injury (by the IMPACT Investigators) has demonstrated that using more appropriate approaches to the analysis of ordinal outcome scales, such as proportional odds regression or the 'sliding dichotomy', can potentially lead to substantial efficiency gains relative to the conventional dichotomous analysis. However, to date relatively few trials have prospectively adopted ordinal techniques for their primary analysis. We report here how in SCAST \\[[@B1]\\], a major Phase III trial of blood pressure reduction in acute stroke, ordinal methods were adopted for the primary analysis of the modified Rankin Scale (mRS), an ordinal functional outcome scale.\n\nResults\n=======\n\nSince ordinal methodology was evolving in parallel with the conduct of the trial, the Statistical Analysis Plan was not finalised until close to"
+"INTRODUCTION\n============\n\nMuch within the profession of massage therapy is done according to tradition. From an epistemological viewpoint, tradition is a way of knowing or, by extension, being, that is based upon both tenacity and authority and not always in best practices^([@b1-ijtmb-4-4-33])^. As the profession of massage therapy moves in the direction of evidence-based medicine, or evidence-informed practice^([@b2-ijtmb-4-4-33])^, the opportunity to re-evaluate massage therapy education presents itself.\n\nThe traditional approach to massage therapy education has been for massage therapy students to learn specific 'recipes' by which to treat patients. In practice, no patient is exactly the same as the one for whom the recipe was created. Jones and Rivett^([@b3-ijtmb-4-4-33])^ recognize that education for manual therapists, including massage therapists (MTs), must support the development of clinical reasoning skills so MTs can create and adapt care to environments, scenarios, and patient presentations. The main purpose of health care practitioners' education, therefore, can be seen as turning unskilled novices into confident, skilled professionals^([@b4-ijtmb-4-4-33])^.\n\nHiggs and Jones^([@b5-ijtmb-4-4-33])^ define clinical reasoning as \"a process incorporating the elements of cognition, knowledge, and metacognition\". Essentially, it is clinical reasoning that enables a health care professional to be autonomous. These authors suggest that clinical reasoning also creates responsibility,"
+"The Setting {#sec1-1}\n===========\n\nThe coastal city of Chennai is the largest city in South India with a population of nearly 5 million the it is densely populated and industrialized. While lakes and marshlands formed an important part of the Chennai landscape in the past, these have been depleted by rampant and unregulated construction activity and the number of wetlands in the city has decreased from 150 to only 27 currently.\\[[@ref1]\\] The Northeast (NE) monsoon (from October to December) is the major source of precipitation for the city and provides drinking water for the rest of the year. Monsoons are unpredictable and can develop into cyclones, which regularly affect large parts of the Eastern coastline of the Indian subcontinent including Bangladesh and Myanmar.\n\nChennai has had private tertiary care facilities much earlier than other Indian cities and is known as the health care capital of India. These hospitals cater to patients from both within and outside India. Global Hospital is a tertiary care hospital in the South of Chennai. The area surrounding the hospital was predominantly a marshland. This has gradually been encroached in the last 10--15 years. The hospital campus is spread over 24 acres of land and all"
+"1.. Introduction {#s1}\n================\n\nThe presence of active volcanoes on the Antarctic continent and several islands in the Southern Ocean was recorded by early polar explorers, such as Sir James Clark Ross who observed an eruption of Mount Erebus in 1841 \\[[@RSOS191501C1]\\]. These clearly visible volcanoes have been the subject of geological and biological research for a long time (e.g. \\[[@RSOS191501C2],[@RSOS191501C3]\\]). The presence of volcanic and measurable tectonic activity, such as eruptions, steam fields, fumaroles and earthquakes on the Antarctic Peninsula, Marie Byrd Land, Victoria Land, the islands of the South Shetlands and South Sandwich Arc and their surrounding seas (e.g. \\[[@RSOS191501C2],[@RSOS191501C4]\\]), has implied the presence of sub-ice and submarine volcanism and hydrothermal activity \\[[@RSOS191501C5]--[@RSOS191501C8]\\].\n\nIn the Antarctic and Southern Ocean marine environment, shallow-water hydrothermal fumaroles occur in the caldera of Deception Island and are characterized by depleted marine life with low species richness and faunal abundance compared to other Antarctic shallows (e.g. \\[[@RSOS191501C9]--[@RSOS191501C11]\\]). Hot vents and cold seeps have been discovered in the Bransfield Strait in 990--1500 m depth \\[[@RSOS191501C12]--[@RSOS191501C17]\\], in the Larsen B ice shelf area, eastern Antarctic Peninsula, in 215--850 m water depth \\[[@RSOS191501C18]--[@RSOS191501C20]\\], and on the shelf of South Georgia in 250--350 m water depth \\[[@RSOS191501C21],[@RSOS191501C22]\\],"
+"Introduction {#Sec1}\n============\n\nA skeletal muscle fibre (also known as a myofibre) is typically 10 to 80\u00a0\u00b5m in diameter and can be up to 25\u00a0cm in length. Myofibres of this size cannot be supported by a single myonucleus (Hall and Ralston [@CR5]; Edgerton and Roy [@CR2]; Ralston and Hall [@CR8]). Hundreds of nuclei are then needed to support and coordinate the large and lengthy myofibres (Hall and Ralston [@CR5]; Edgerton and Roy [@CR2]; Ralston and Hall [@CR8]; Levy et al. [@CR6]). Along with osteoclasts and cytotrophoblasts, skeletal muscle fibres are one of only three truly multinucleated cell types in the body. Surrounding each nucleus is a theoretical territory of cytoplasm for which gene expression is controlled---the myonuclear domain (MND) (Hall and Ralston [@CR5]; Edgerton and Roy [@CR2]; Ralston and Hall [@CR8]; Levy et al. [@CR6]). Nuclei help the generation of proteins for their respective MNDs to meet the changing demands of the cells. Theoretically, if MNDs are too large, portions of the fibre may not receive enough mRNA or proteins necessary for function, leading to dysfunction (Qaisar et al. [@CR7]; Levy et al. [@CR6]). Undersized MNDs may lead to overlapping regions that cause excessive stress on each myonuclei,"
+"INTRODUCTION {#s1}\n============\n\nAn appreciation of what the conspecifics are doing is fundamentally important for the organization of behaviour. This is so from the subtleties of peer pressure in humans, via coordinated hunting in wolves, penguins, or sharks, the intricate interactions in social bees, wasps and termites or the swarming of locusts, to the rituals of courtship in their respective form throughout the animal kingdom. Understanding these processes, however, faces a dilemma: a study case is needed that is both simple enough to be experimentally tractable, and complex enough to remain interesting. We wondered whether one compromise case can be larval *Drosophila*, because these animals have a brain with only about 10.000 neurons, which can be manipulated one at a time. Despite this numerical simplicity of their brains, the behaviour of *Drosophila* larvae is not hard-wired ([@b8]; [@b4]; [@b21]): for example, presenting an odour with a food reward establishes associative memory that is specific for the kind and the intensity of the trained odour. However, it is unclear to which degree in this type of assay a given individual target larva is affected by what a surrounding group of larvae is doing. We ventured into an analysis of this question"
+"Over the past decade, Web\u00a02.0 applications, defined as internet-based tools that allow users to generate and manage content, have demonstrated the potential to revolutionize the search of up-to-date health information by users and the respective dissemination by health professionals \\[[@CR1]\\]. Considered the 'social Web', this updated web-based platform facilitates personable interactions between individuals, whether sharing educational or entertainment information (e.\u2009g. YouTube, Instagram, blogs, podcasts) or networking (e.\u2009g. Facebook, Twitter, Google Plus) \\[[@CR2]\\]. Traditional health promotion tools, such as television or radio broadcasts, newspapers or pamphlet distribution, used in mass media campaigns have demonstrated positive influences on health behaviours \\[[@CR3]\\]. By incorporating these technological advances of the 'social Web' into traditional health promotion tools, health teams can develop local or national primary, secondary or tertiary prevention campaigns that improve dissemination of health information to available users. This potential benefit of the use of social media technology in campaigns has been demonstrated in a\u00a0review of case studies \\[[@CR4]\\].\n\n'Social mobilizers', on the other hand, are key to implementing local or national health initiatives in the field and building rapport with community members \\[[@CR5]\\]. Although no standard definition of community mobilization exists \\[[@CR6]\\], this notion refers to facilitating change"
+"Introduction {#s1}\n============\n\nDirected cell migration is fundamental to diverse physiological processes, including developmental morphogenesis, cancer metastasis, and the immune response. To directionally migrate, cells must sense signals from the extracellular environment and transduce the signals to downstream effectors that polarize the cytoskeleton and regionally regulate its organization and dynamics [@pone.0041413-Horwitz1]. It is well established that the actin and microtubule (MT) cytoskeletal systems are critical to directed cell movement. The actin cytoskeleton is the primary force generator for cell migration: Rapid polymerization of F-actin drives lamellipodia/lamella protrusions in the cell leading edge, and contraction of acto-myosin bundles in the cell body causes retraction of the trailing cell rear [@pone.0041413-Pollard1].\n\nThe MT cytoskeleton is required for rapid, directed migration of tissue cells [@pone.0041413-Rodriguez1], however its role in cell motility is less clear than that of actin. MTs are thought to provide critical cell polarization cues that dictate spatial regulation of protrusive and contractile actin-based processes [@pone.0041413-Rodriguez1]. Indeed, the MT cytoskeleton displays a characteristic polarized organization and dynamics in migrating cells. MTs growing from the MT-organizing center (MTOC) and Golgi apparatus orient towards the leading edge lamella/lamellipodia region [@pone.0041413-Rodriguez1], [@pone.0041413-Miller1]. In addition, MT dynamic instability is polarized in migrating cells. MTs in"
+"Cell death can take many shapes. Programmed 'apoptotic\\' and uncontrolled 'necrotic\\' cell death mark the extremes of the spectrum of possibilities.^[@bib1]^ Whereas the induction of apoptosis follows distinct signaling steps and cleanly removes a cell from its tissue, necrosis represents the cell\\'s wholesale disintegration and is in general harmful to the organism. Massive cellular insults lead to necrosis. It appears, however, that cells have some choice in the mode of their demise depending on the severity of the insult. Hypoxic cores in solid tumors^[@bib2]^ or perfusion-impaired brain tissue in stroke,^[@bib3]^ for instance are typically necrotic, but possess an apoptotic shell.\n\nThe same can be seen for lysosomal damage.^[@bib4],\\ [@bib5],\\ [@bib6]^ Lysosomes can rupture during ischemic or traumatic cell injury,^[@bib7]^ giving rise to both apoptotic and necrotic outcomes.\n\nLysosomes are cellular organelles with a proteolytic function and possess an impressive set of protease enzymes^[@bib8]^ dedicated to the degradation of both intracellular material, such as damaged or old organelles, and extracellular components such as matrix proteins. The release of the lysosomal proteases into the cytosol sentences the cell to death by autodigestion.\n\nIn a recent *Cell Death Discovery* article,^[@bib9]^ we looked at the fate of the major regulators of apoptosis, the bcl-2"
+"Introduction\n============\n\nThe structure of a typical root is organized from the outermost to the innermost rings as: epidermis, cortex, endodermis, pericycle and the stele tissues. The root epidermis, endodermis and pericyle are each formed of a single layer of cells, whereas the cortex comprises one to several cellular layers. In *Arabidopsis thaliana,* roots contain a single-layer cortex and tomato (*Solanum lycoperisicum*) roots have three layers.^[@bib1]^ Each of the root tissue layers is comprised of a unique cell population, demonstrating different degrees of morphological, as well as functional specialization.^[@bib2]^\n\nDue to the spatial distribution of the layers, suboptimal soil conditions impart varying degrees of effects on root cells. These cellular layers also play different roles in affecting the root architectural system and functions therein. For instance, when plants are subjected to Al toxicity, distortion of the dynamics of microtubes occurred in epidermal and outer cortical cells, but not in the tissues located more centripetally in the roots.^[@bib3]^ A more recent freeze--thaw experiment showed that Al-treated roots had more damage in the epidermal and outer cortex cells due to binding of Al to the cell wall and Al-induced oxidative cellular damage.^[@bib4]^ Similar phenomena of positional effects of root cellular layers are"
+"Introduction {#Sec1}\n============\n\nAccurate scaling of drug plasma clearance (CLp) from adults to children is important for the definition of first in child doses and hence robust study design involving younger children. To date, physiologically based pharmacokinetic (PBPK) models represent the most mechanistic method to scale CLp across the paediatric age range. PBPK models quantify the interactions between drug-specific and system-specific parameters and predict paediatric CLp by accounting for developmental changes in the system-specific parameters and how they impact drugs with specific properties. Application of these models is considered best practice in pharmaceutical industry, but obtaining PBPK ontogeny functions for a given drug is time-consuming and complex due to the requirement of a wide range of drug-specific and system-specific information. Moreover, all information may not always be available for each drug or each population. This leads to a need for simplified scaling functions which are more convenient for defining paediatric CLp in pharmacometrics. As multiple system-specific parameters may change in the paediatric population and as the impact of each of these changes on paediatric CLp may be different for each given drug with different characteristics, the challenge in developing simplified scaling functions is to aggregate all relevant information in functions"
+"INTRODUCTION\n============\n\nIn the recent decades, video games (VGs) industry has expanded to the point of becoming one of the largest multimedia economic activities in the world. Thanks to their great availability and accessibility, VGs have become immediately and extremely popular among children, adolescents and adults. They appeared for the first time in the 1962 at M.I.T., when Steve Russell created *Spacewar!*, the very first VG of the history, with essential graphics and luminous dots moving on the display^[@r1]^. Then, mainly thanks to technological evolution, games ever more immersive and rich in details have been developed, contributing to the creation of new genres and types of VGs.\n\nSuch a great success of videogaming industry, together with the fact that it became one of the most popular recreational activities practiced by children and adolescents, fostered a strong public debate about the possible effects of VGs exposure on human well-being. Recent studies showed that in western industrialized countries many children and adolescents play VGs for a very long time during the day^[@r2],[@r3]^. Several recent investigation have shown that children and adolescents live media-saturated lives: a percentage ranging from 83 to 97% has a home console for VG with which interact for several"
+"The moderate ingestion of caffeine has a psychostimulant effect on the body. The molecular mechanism has been shown to involve caffeine binding as an antagonist[@b1] to cell surface adenosine receptors and/or blocking the binding site of cyclic AMP (cAMP) phosphodiesterase (PDE) and thereby decreasing its activity[@b2]. Further, excessive levels of caffeine, or caffeine overdose, can result in various systemic symptoms known as caffeine intoxication. At the cellular level, a high dose of caffeine results in various responses, including cell death, delays in the cell cycle, the impairment of DNA repair and recombination, and perturbed intracellular calcium homeostasis[@b3]. In the case of cell death, caffeine has been shown to exert its fatal effect by evoking an apoptosis cascade that involves PI3K/Akt/mTOR signalling[@b4][@b5]. However, all of the potential mechanisms by which a caffeine overdose results in cell death remain to be clarified.\n\n*Dictyostelium discoideum*, which is known as the cellular slime mould, is a social amoeba that feeds on bacteria and grows by division until the bacteria are consumed. Upon starvation, the amoebae start to develop and form a fruiting body consisting of a mass of dormant spore cells suspended on dead stalk cells. This eukaryote has been utilized as a model"
+"Introduction\n============\n\nImplant rehabilitation necessitates an adequate conformation to the residual alveolar crest, including bone height and width; this condition is often neglected, especially in the case of edentulism, either age-related or subsequent to facial trauma.\n\nVertical and horizontal resorption makes it difficult to place implants. In the presence of severe bone atrophy, it is possible to restore a correct bone conformation with different techniques such as vascularized and non-vascularized bone grafts, guided bone regeneration, and tissue engineering.[@B1]\n\nIn oral surgery, crucial attention is paid to graft techniques. Autologous bone, having osteoconductive, osteoinductive, and osteogenic properties (known as the \\\"regenerative triad\\\"), is unanimously considered to be the gold standard in peri-implant bone reconstruction surgery.[@B2]\n\nAutologous bone can be collected from intra- or extra-oral sites. For intra-oral sites, the symphysis menti, mandibular ramus, and maxillary tuberosity would be available, and for extra-oral sites, the iliac crest, tibial plateau, rib, and calvaria would be available. The intra-oral sites offer numerous advantages compared to the extra-oral ones, such as easier surgical access, shorter surgical time, absence of cutaneous scarring, and reduced morbidity, but they allow obtaining only limited bone amounts. The selection of the donor site mainly depends on the dimensions of the"
+"See original paper on 335\n\nThe accuracy of blood pressure measurement in managing hypertension cannot be overemphasized. Studies report that there are several issues with office blood pressure measurements. First, they are highly variable, and second, they do not accurately reflect blood pressure in real life \\[[@b1-kjfm-40-5E]\\]. Blood pressure outside the clinic can be measured by monitoring home blood pressure (home blood pressure monitoring, HBPM) or ambulatory blood pressure (ambulatory blood pressure monitoring). HBMP markedly contributes towards hypertension management, as it helps diagnose white coat hypertension and improves cardiovascular disease risk prediction.\n\nIn addition, many studies have reported on the other benefits of HBPM, including its effect on blood pressure control and drug compliance of hypertensive patients.\n\nIn the present issue, Muhammad et al. \\[[@b2-kjfm-40-5E]\\] investigated whether HBPM can improve office blood pressure control and treatment compliance among hypertensive patients. Eighty-eight subjects with hypertension were randomly assigned into an HBPM or usual care group. The authors compared the office blood pressure and medication adherence score at randomization and at the end of the follow-up period (2 months) between the groups, and found no significant differences across all variables.\n\nIn the light of these results, can we conclude that there are"
+"The advent of laser-based coherent THz emission and THz detection schemes more than 25 years ago[@b1][@b2] has revolutionized linear spectroscopy and imaging[@b3] in the THz frequency range and helped to improve our fundamental understanding of matter tremendously. THz pulses have since been utilized as gentle sensitive probes of fundamental low-frequency excitations in solids, liquids or gases[@b4][@b5][@b6][@b7]. Key of the success of this technology is the possibility to generate and detect these THz pulses coherently, thereby providing an excellent dynamic range and circumventing detection of the large intrinsic thermal background in the THz regime.\n\nMore recently, the generation of THz pulses with much higher field amplitudes has become possible, which permitted a conceptually new approach for investigating low energy degrees of freedom in matter[@b8][@b9]. In this approach, the high THz-fields are utilized for the driving (rather than probing) of these modes to much higher amplitudes so that e.g. the induced coherent dynamics of a particular low energy degree of freedom can be visualized directly in the time domain. Thereby fascinating examples of so called coherent THz control could be demonstrated (e.g. coherent THz control of spins[@b10]). One particular class of experiments aims to utilize the much higher THz field to drive"
+"Introduction\n============\n\nTwenty year ago, [@B19] recommended cultural managers to give performing arts a marketing orientation, where target audiences' needs and preferences are central to all decision making. It appears that putting music fans at the epicenter of marketing strategies has become especially relevant in this digital day and age. In that sense, the evolution of music consumption models paired with recent technological advances now offers audiences new ways to participate in live music never thought of before, including *virtually* attending gigs. Therefore, knowledge about music fans' reasons and motivations to attend live concerts will extend our understanding of music audiences, a key aspect of arts marketing ([@B26]; [@B8]).\n\nContextually, understanding concert-goers' motivations to participate in live performances is increasingly important since attendance represents an essential and growing share of revenues for the music industry and performers alike ([@B14]). For example, the Spanish music industry's incomes plummeted because of digital piracy, the economic crisis, and a cultural sales tax of nearly twice the European average. Still, revenues from live music concerts grew a steady 10% over the last years to reach \u20ac194.5M in 2015 ([@B1]).\n\nToday's ubiquitous access to digital content and social networks has modified consumers' relation to music"
+"Introduction {#s1}\n============\n\nHuman-centered bipedal robots, such as exoskeletons, powered prostheses and humanoids are demonstrating increasing levels of functionality, reliability, and safety, and are now breaching the barrier of surviving in a rapidly evolving market. In this crucial process, the lack of accepted standards to evaluate the different facets of robotic performance is hampering the efficient introduction of these new technologies into the different application domains, each of them characterized by the needs, requirements, and regulations of diverse users. A systematic benchmarking methodology to assess robotic systems on a quantitative and reproducible basis is eagerly awaited, as demonstrated by the numerous workshops and discussions on this topic in the most relevant international forums of the last 5--10 years. Benchmarks allow comparing systems to each other and against accepted references, and are therefore useful not only to end-users in search for the most suitable solution, but also to developers aiming to identify and solve the critical shortcomings of their machines. Solid benchmarks usually arise from research results, and are eventually converted into international standards after an iterative process that can last years. It can be argued that the more effort is done by the research community in identifying effective benchmarking methods,"
+"Introduction {#s1}\n============\n\nBees navigate in a range of several kilometers around their hive and communicate about locations using the waggle dance to transmit information about the flight vector towards a feeding place or a nest site [@pone.0091364-vonFrisch1], [@pone.0091364-Seeley1]. Navigation and communication require multiple cognitive faculties. Among these are, for example, recognition of the sun compass, visual distance estimation, learning of multisensory cues inside and outside the hive and translating as well as reading the codes of the waggle dance, all processes that require integration of different navigational information. Several forms of memory have been found to guide navigation (recent reviews: [@pone.0091364-Gruter1], [@pone.0091364-Menzel1], [@pone.0091364-Menzel2], [@pone.0091364-Galizia1]). In particular, route flights between hive and feeder lead to a memory of the flight vector that are bound to the sun compass and can be communicated in the waggle dance. A more flexible memory about spatial relations of landmarks is formed during the exploratory orientations flights of bees leaving the hive for the first time. This latter form of memory allows bees to steer to learned locations e.g. the hive, a different feeding site, and a dance communicated site along novel short cutting routes. It has been concluded that that these multiple spatial representations"
+"Introduction {#s1}\n============\n\nThe detailed knowledge of plant anatomical characters and their variation among closely related taxa is key to understanding their evolution and function [@pone.0088199-Carlquist1]. Variation in anatomical structure is a result of several forces such as: the adaptation of species to the prevailing conditions in their habitats [@pone.0088199-NiklasK1], phenotypic plasticity as an ability of individuals with an identical genotype to develop differently - based on specific conditions during their ontogeny [@pone.0088199-Sultan1], [@pone.0088199-Pigliucci1], and evolutionary constraints (phylogenetic inertia) in which taxa that share part of their evolutionary history possess similar 'blue-prints' [@pone.0088199-Peat1]--[@pone.0088199-milauerov1]. One of the critical features of comparative studies on plant trait variations in relation to ecological adaptations is therefore the extent of phylogenetic relatedness among taxa [@pone.0088199-Dubuisson1], which makes them partly dependent in any statistical inference. In other words, part of the explanatory power uncovered by relating the anatomical traits to ecological preferences might be alternatively explained by phylogenetic inertia affecting both the similarity of anatomical traits among closely related taxa and the similarity of ecological niches that such taxa occupy [@pone.0088199-Harvey1].\n\nUnderstanding the evolution of plant structures requires separation of evolutionary inertia from a true adaptation to the environment. This is commonly done by comparing analyses"
+"1. Introduction {#sec137548}\n===============\n\nOrofacial pain is a challenge for dentists, maxillofacial surgeons and otolaryngologists around the world. The spread of pain and similarity of characteristic signs of different pain sources have made the diagnosis of the origin of pain difficult. The temporomandibular joint disorders (TMDs) are common causes of pain in the maxillofacial region. Understanding the common signs and symptoms of this disorder is important ([@A24395R1]). The importance lies in mimicking the symptoms of TMD and other conditions. Pain due to styloid process (SP) fracture is similar to that of TMD ([@A24395R2]). The styloid process of temporal bone is a cylindrical projection on the inferior aspect of petrous bone. The stylo-hyoid ligament (SL) is a fibrous cord, which is attached from the lesser cornu of the hyoid bone to the end of the styloid process. The combination of these three anatomical structures is known as the stylo-hyoid chain (SC). The proximity of SC to important anatomical structures like the contents of the carotid sheet reveals the importance of SP and SL ([@A24395R3]).\n\nElongation of SP or ossification of SL is a characteristic sign of Eagle's syndrome and leads to pain of the neck or sore throat ([@A24395R4]). Although the"
+"Introduction {#s1}\n============\n\nFor millennia, mankind has employed the principle of consecutively selecting random mutations to breed desired phenotypes into crops, livestock, pets and microbes, relying on a trial-and-error approach. This was transformed when modern molecular biology enabled systematic genetic manipulation and redesign of novel strains and genetically modified organisms. Initially the focus was removing cross-species boundaries, rearranging natural genetic building blocks and introducing minor modifications into DNA sequences. Until recently almost all genetic templates originated from natural sources, limiting the range of possibilities.\n\nThe present dawn of synthetic biology opens up entirely new horizons in genetic engineering. It promises combining technical engineering approaches with biological sciences and informatics to predict, simulate, and construct novel pathways, genomes and organisms faster and more precisely. With the growing availability of low-cost *de novo* gene synthesis, synthetic biology not only allows unrestricted and flexible design of non-natural DNA sequences, but also adapting coding sequences to the genetic requirements of the chosen target organism. *In silico* design of an optimal coding sequence for a given protein using a distinct arrangement of alternative codons is known as \"gene optimization\". Without altering the amino acid sequence, it is possible to enhance autologous and heterologous gene expression,"
+"Introduction {#S0001}\n============\n\nWith the increase in Internet accessibility, social media use has increasingly become part of daily life in numerous populations worldwide. Facebook (FB) is currently the most popular social networking site (SNS),[@CIT0001] with nearly one-fifth of the world's population being its daily active users.[@CIT0002] In Taiwan, the use of social media is common, with FB predominating among the various online social networks.[@CIT0003] Among Taiwanese Internet users, 85% visited FB more than three times per week.[@CIT0003]\n\nSNSs may cause users to encounter potentially harmful events. In a national online survey, 15% of the youths reported experiencing sexual solicitation on the Internet during the previous year; moreover, approximately 33% reported experiencing harassment, among which 9% stated that their negative experiences occurred on SNSs.[@CIT0004] Negative events occurring on SNSs, such as negative interaction quality, experience of negative social events, and cyberbullying, were associated with the risk of depression, low self-esteem, and low life-satisfaction.[@CIT0005]--[@CIT0007] Rosenthal specifically studied negative FB experiences, defined as either bullying or meanness, unwanted contact, or misunderstanding, and found that these experiences were associated with depression.[@CIT0007] Despite FB being\u00a0the most popular SNS, current knowledge on the prevalence and effect of negative FB experiences remains limited. Herein, we selected"
+"Isolated posterior cruciate ligament (PCL) ruptures are less common knee injuries compared with anterior cruciate ligament (ACL) ruptures. Isolated PCL injuries account for approximately 17% of all knee ligament injuries.^[@bibr11-2325967115599539]^ In a newly published article examining the epidemiology of all knee injuries among US high school athletes, the prevalence of ACL injuries was 25.4% and that of PCL injuries was 2.4%.^[@bibr21-2325967115599539]^ Although isolated PCL injuries are not uncommon in contact sports, such as American football, rugby, and soccer, few studies have reported the treatment and follow-up of isolated PCL injuries. Thus, it is difficult to provide evidence-based advice to patients concerning their treatment options. The majority of isolated PCL injuries are benign when it comes to regaining preinjury activity level.^[@bibr19-2325967115599539]^ However, the injury can be disabling for the affected patient, and it commonly results in a long recovery period. In some cases, the athlete may never compete again at the same level.^[@bibr18-2325967115599539],[@bibr19-2325967115599539]^ Usually, a nonoperative approach is first tried; for the majority of patients, this treatment approach results in a return to the preinjury activity level.^[@bibr16-2325967115599539],[@bibr19-2325967115599539]^ Limited research is available to provide universal guidelines for the nonoperative treatment approach, but active rehabilitation, including a PCL brace, and focusing on regaining"
+"Introduction {#s1}\n============\n\nPerinatally-infected adolescents living with HIV/AIDS are a group that presents novel challenges associated with long-term survival with chronic HIV/AIDS [@pone.0087322-Mofenson1], including social and cultural factors linked to development and sexual maturation [@pone.0087322-Remien1]. There is thus a pressing need for tailored, sensitive approaches to providing psychosocial care for HIV-positive adolescents [@pone.0087322-Mavhu1], [@pone.0087322-Ferguson1].\n\nDue to the scale up of antiretroviral therapy over the last decade, survival of perinatally-infected children has improved dramatically, enabling them to live into adolescence and beyond [@pone.0087322-Brady1]. As they do so, the issue of informing adolescents about their HIV status arises, a process termed \"status disclosure\" [@pone.0087322-Wiener1]--[@pone.0087322-WHO1]. Although status disclosure can also refer to the act of a person living with HIV/AIDS sharing his or her status with others (also known as \"public\" or \"social\" disclosure) [@pone.0087322-Wiener2]--[@pone.0087322-Yoshioka1], in this paper we solely address the issue of telling adolescents about their status and making this status understood. In the literature on pediatric HIV disclosure, a distinction is often made between \"full\" and \"partial\" disclosure [@pone.0087322-Wiener1], [@pone.0087322-WHO1], [@pone.0087322-DeBaets1]. In this study, we define full disclosure as having been achieved not only when an adolescent has received all the information about his or her HIV-status but also when"
+"Introduction\n============\n\nEnvironmental pollution and worker health protection play nowadays a key role in electronic manufacturing, driving cutting-edge technologies towards an ongoing reduction of toxic and contaminating substances in their production lines. The development of a 'green' nanofabrication process is not only beneficial from an environmental point of view, but also reduces the costs associated with the disposal of hazardous chemicals and creates a friendly working environment. Furthermore, avoiding organic solvents and corrosive reagents enables the direct patterning of a wide range of biomaterials that were incompatible with previous processes.\n\nIn light of this, the greatest challenge for emerging nanofabrication technologies will be the integration of ecofriendly fabrication approaches with the cost effective and high throughput procedures required in large scale industrial production. To this end, next-generation lithographic methods should rely on inexpensive, biodegradable and easily accessible materials.[@cit1]--[@cit3]\n\nFollowing the recent developments in the semiconductor and flexible electronics industries, among the emerging high-resolution patterning techniques, nanoimprint lithography (NIL) can be considered the most promising approach for mass production of innovative optic and electronic devices. Features as small as 10 nm can be produced using NIL,[@cit4] and when compared to electron beam lithography (EBL) and other high-end photolithographic methods, NIL is"
+"1. Introduction {#sec1}\n===============\n\nBicycle-sharing systems (BSSs) are usually used in two different ways: as an isolated service or as an intermodal service providing the missing link between existing points of other transport and desired destinations. Such systems are recognized to have environmental, traffic, and health benefits because they are emission-free, can augment public transport, and provide an incentive for athletic activity. In addition, they offer convenience for people who can use the service without the costs and responsibilities associated with owning a bicycle. DeMaio et al. indicated that there were three generations of BSSs, with the earliest dating back to the 1960s in Netherlands \\[[@B1]\\]. The \"Witte Fietsen\" (White Bikes) program was introduced on July 28, 1965, in Amsterdam, marking the initiation of the first-generation system. These white bikes were shared informally and not tracked, leading to numerous bike-thieves. In 1991, a coin-deposit system was introduced in Denmark, marking the initiation of the second-generation system. The third-generation system, which uses information technology to track bicycles and users, first emerged in the late 1990s in Europe and then extended to many cities all over the world. By the end of 2016, approximately 1,175 cities or districts in 63 countries have"
+"The ability to reliably assess local predation threats allows prey to balance the often conflicting demands of reducing predation risks while still maintaining sufficient time and energy to engage in other fitness related activities such as foraging ([@zoz050-B37]; [@zoz050-B26]). Chemosensory cues provide valuable sources of public information regarding the identity and intensity of local predation threats ([@zoz050-B34]), allowing for context appropriate behavioral trade-offs. For example, wood mice *Apodemus sylvaticus* reduce foraging behavior when in the presence of predatory chemical cues ([@zoz050-B45]). Likewise, desert isopods *Hemilepistus reaumuri* use the presence vs. absence of the odor of scorpion *Scorpio palmatus* to make fine-scale risk assessments ([@zoz050-B51]).\n\nWithin aquatic systems, prey are widely known to assess predation risk directly from chemosensory information originating from the predator ([@zoz050-B34]) or through cues released by conspecific and/or heterospecific prey-guild members ([@zoz050-B48]; [@zoz050-B26]). Perhaps most studied among aquatic prey are the damage-released chemical alarm cues, which are released via mechanical damage, as would occur during a predator attack ([@zoz050-B16]; [@zoz050-B6]; [@zoz050-B26]). Given the mechanism of release, these cues are reliable indicators of local predation risks ([@zoz050-B18]; [@zoz050-B17]) and can elicit strong species-typical antipredator responses in nearby conspecifics and heterospecific prey-guild members ([@zoz050-B26], [@zoz050-B17]).\n\nIn addition to the"
+"Introduction {#s1}\n============\n\nUnder normal volemia conditions, increased natremia or plasma osmolality involves compensatory responses such as water intake, sodium appetite inhibition, plasma release of oxytocin (OT) and vasopressin (AVP), and consequently renal sodium excretion and water retention [@pone.0074689-Vivas1]. The central circuit involved in the control of these behavioral and physiological responses induced by hypernatremia has been studied, analyzing the expression of brain immediate early genes [@pone.0074689-Morgan1]--[@pone.0074689-Rinaman1]. Enhanced *c-fos* expression as shown by increased Fos immunoreactivity was identified within the magnocellular groups of OT and AVP hypothalamic paraventricular and supraoptic nuclei (PVN and SON), and matching the observed increase of both peptides in plasma [@pone.0074689-Rinaman1], [@pone.0074689-Verbalis1]. The increased natremia and osmolality is centrally detected by the circumventricular organs of the lamina terminalis (CVOs of LT), which have osmo- and sodium-sensitive cells and have shown increased Fos immunoreactivity (Fos-ir) after different paradigms of body salt loading [@pone.0074689-Rinaman1]--[@pone.0074689-Oldfield1]. At brainstem level, this stimulus involved the activity of the lateral parabrachial nucleus (LPBN), locus coeruleus (LC), ventrolateral medulla (VL), nucleus of the solitary tract (NTS) and area postrema (AP). Together, all these areas work in coordination to mediate the autonomic, endocrine and behavioral responses inherent in osmoregulation [@pone.0074689-Rinaman1], [@pone.0074689-Olson1], [@pone.0074689-Hochstenbach1].\n\nOur previous results"
+"INTRODUCTION\n============\n\nAlthough the abundance of messenger RNAs (mRNAs) in the cell is the net result of mRNA synthesis and degradation, expression profiling experiments usually take a snapshot of the mRNA levels in the cell and do not capture the dynamics of mRNA synthesis and breakdown. This lack of information on the dynamic component of the regulation of mRNA levels limits biological investigations in general and proper modeling of transcriptional networks in systems biology approaches in particular. When mRNA synthesis is shut down completely, the effect may be immediate for very short-lived mRNAs but only manifest after hours or days for mRNAs with long half lives. The current study fills in part of this gap and surveys mRNA degradation rates during muscle differentiation on a genome-wide scale. With the availability of these data, the genetic network orchestrating muscle differentiation can be revised and improved.\n\nFrom the results of previous genome-wide analyses of mRNA degradation rates, we know that there are large differences between the stabilities of individual mRNAs, and that mRNA stability is strongly related to the molecular function of the encoded protein ([@B1; @B2; @B3; @B4; @B5; @B6; @B7; @B8]). However, the mechanisms underlying differential stability of transcripts remain"
+"Madam,\n\nI read with interest the review entitled \"WHO safe surgery checklist: Barriers to universal acceptance.\"\\[[@ref1]\\] The World Alliance for Patient Safety initiated work on the challenge of surgical safety in January 2007. The World Alliance published World Health Organization Surgical Safety Checklist (WHO SSC) and Implementation Manual in June, 2008.\\[[@ref2]\\] It is amusing to note that 10 years after its introduction in clinical practice, the issue needs to be reviewed because it is still not universally followed.\n\nThe authors have reviewed the published articles citing barriers in the implementation of WHO SSC. The authors have focused their manuscript on contemporary publications. It is indeed most disturbing to note that a major reform introduced by the world\\'s apex healthcare regulator, to ensure safe surgery, has still not been accepted by a large part of the medical world and we are still seeking to review why this prime initiative has still not been adopted.\n\nUnfortunately, large teaching institutes have failed to join the WHO SSC bandwagon due to a detached and apathetic attitude toward patient safety, despite the fact that surgical errors are more common in teaching hospitals. The hierarchical system in the teaching hospitals and disconnect between the patient and"
+"Introduction {#section1-0969733019871685}\n============\n\nThis article seeks to explore the context of pain management at the end of life for people who use substances. These reflections are based on a wider unique project funded by (National Lottery Community Fund) examining end-of-life care for people who use substances.^[@bibr1-0969733019871685]^ This theoretical exploration stems from data generated from five strands of the project which included a rapid evidence assessment (REA),^[@bibr2-0969733019871685]^ interviews with individuals with palliative care needs who use substances.^[@bibr3-0969733019871685]^ Interviews were also conducted to explore family, carer and friends' experiences of people using substances at the end of life,^[@bibr4-0969733019871685]^ to examine practitioners' perspectives^[@bibr5-0969733019871685]^ and to gain key informant insights into the issues pertinent to this population.^[@bibr6-0969733019871685]^ We examine the dominant narrative genres that frame the stories related to pain management and substance use and how this delineates and defines the ethical landscape. We argue that the narrative positioning of 'recovery' remains unhelpful within the context of end-of-life care with implications both for health and social care professionals and people who use substances. We contextualise these data through a narrative approach^[@bibr7-0969733019871685][@bibr8-0969733019871685][@bibr9-0969733019871685][@bibr10-0969733019871685]--[@bibr11-0969733019871685]^ highlighting how constructions such as 'recovery' narratives can unhelpfully define the frames of reference for appropriate responses to people using substances at the"
+"Sir,\n\nThank you for reading our article with interest.[@ref1] We appreciate your efforts in bringing out certain details[@ref2] which probably would help the readers to understand the article in a more scientific way. However, we would clarify the points which have been raised by you.\n\nIn a randomized control trial, prior power analysis is not mandatory to start with. At the start of study, usually it is kept at minimum 80% to calculate the size of samples. But if the sample size seems to be inadequate, power analysis can be done at the end. When this study was planned, more and more patients were opting for hamstring graft rather than bone patellar tendon bonegraft (BTB), so we were not very sure as to how long and what sample size it would take to complete this study. Hence an initial sample size calculation was not performed. Patients who underwent primary anterior cruciate ligament (ACL) reconstruction using BTB were considered in the group. Those who underwent ACL reconstruction by quadrupled hamstring graft were excluded which is understood. The numbers of males and females in the study have been mentioned. Randomization was done approximately for 20 months and not for 4 years. After"
+"In this issue of *Virulence*, the authors of the article entitled \"Virulence genes and cytokine profile in systemic murine *Campylobacter coli* infection\" utilized a mouse model in order to explore the pathogenic mechanisms and cytokine responses involved in *Campylobacter coli* (*C. coli*) systemic infections.[@cit0001] The clinical isolate *C. coli* 26536 was first analyzed for the presence of known virulence genes by polymerase chain reaction, and then these genes were sequenced before and after *C. coli* 26536 infection of Balb/c mice to ensure that these genes were stable. *C. coli* 26536 were found to persist in the liver and the spleen of the Balb/c mice for at least 8\u00a0days, with greater persistence in the liver. The observed cytokine profiles in the plasma and liver of infected mice were clearly different, demonstrating differences between the systemic and local inflammatory responses. This study is the first to focus on clarifying some of the mechanisms involved in the pathogenesis of systemic. *C. coli* infections that can occur in immunocompromised individuals.\n\n*Campylobacter* continues to cause the greatest number of confirmed foodborne bacterial infections in developed countries, and the incidence of infections caused by *Campylobacter* has increased from 2008 to 2012.[@cit0002] *Campylobacter* are gram negative,"
+"The task of the Scientific Chairperson is a package deal with multiple challenges which call for meeting constitutional obligation, aspirations of the delegates, and expectations of pharmaceuticals. The other challenges include identifying topics and faculty, outsmarting the exhibitors, overcoming the innate desire of the registered delegate to spend as little time in the halls where scientific sessions are in progress and seek relaxation elsewhere.\n\nI will deal with one challenge after another.\n\nCONSTITUTION {#sec1-1}\n============\n\nThis book frequently changes color and contents, more frequently than an amoeba changes shape. In addition, its organization leaves much to be desired since different dictates are in different places and not easy to unravel. It is more like a game of a treasure hunt. Over and above, the Chairman\\'s head will be on the block if he/she overlooks any event mentioned somewhere. The Constitution mandates certain events and activities at specified time and it is a smart move to first provide slots for events. If by oversight a plenary event is not provided in the mandated slot, then to accommodate one such session 5 others have to be rescheduled.\n\nSCIENTIFIC TOPICS {#sec1-2}\n=================\n\nThere is nothing homogenous about the aspirations of our delegates. While"
+"Background\n==========\n\nWith the advent of high dimensional genomic data, researchers are able to study changes in the expression of several hundreds and thousands of variables such as genes or CpG's under various experimental conditions (or phenotypes) in a given cell culture, tissue or an organism etc. Although identification of differentially expressed individual variables across experimental conditions is of general interest, in recent years there is considerable interest in analyzing sets of variables that belong to some pre-specified biological categories such as signaling pathways and biological functions. Numerous statistical and computational methods have therefore been developed for such analyses. Although the methods described in this paper are broadly applicable to any high dimensional data where the sets and subsets are pre-defined, for simplicity of exposition, we shall describe the methodology in the context of gene expression data. The available gene set analysis (GSA) methods can be broadly classified into two categories. Loosely speaking, the first category of methods, often referred to as competitive gene set methods, tries to answer questions such as \"Given the collection of differentially expressed genes identified by a statistical/bioinformatics methodology, how enriched is a pre-specified set?\" For example, suppose *S*~1~ and *S*~2~ are two pre-specified sets"
+"INTRODUCTION\n============\n\nThere are a variety of odors in our environment. If the molecule of \u03b2-phenylethyl alcohol reaches at the olfactory epithelium of your nose, you recognize it as a fragrance of rose. On the other hand, the amyl acetate molecule is perceived as the odor of bananas.\n\nThe olfactory system can well be understood by being compared with the color vision system. Light is defined as electromagnetic radiation visible to the human eye and has wavelengths between 380 and 780 nm. Light of a single wavelength has a characteristic color among spectral colors. As Isaac Newton pointed out that \"The rays are not coloured\" in the 17th century, color is a subjective experience and is not a physical property of light. For example, if red light and green light enter the eye simultaneously, the resulting color perceived in the brain is pure yellow, which is indistinguishable from single-wavelength yellow light, though the physical properties of these lights are totally different. Moreover, a mixture of red and blue lights produces magenta, an extra-spectral color.\n\nAll colors perceived by humans are represented by an appropriate mixture of three primary colors, red, green, and blue. The physiological basis of the presence of"
+"Small RNAs are famous for their gene-silencing ability. But new results from Tomoko Kuwabara, Fred H. Gage (Salk Institute, La Jolla, CA), and colleagues show that some tiny RNA species turn genes on, not off.\n\nFigure*NRSE* dsRNA (red) makes NRSF/REST (green) an activator in differentiating neurons.Gage/Elsevier\n\nThis new class of RNAs is needed to make neurons. \"Small double-stranded RNAs exist in reasonably high concentrations in cells that have just committed to neuronal lineages,\" says Gage. These RNAs are homologous to a promoter sequence called *NRSE/RE-1*, which is found in a wide range of genes that are expressed only in neurons. In other cell types, these genes are known to be shut off by the NRSF/REST repressor.\n\nThe group shows that this repressor becomes an activator when *NRSE* dsRNAs are around. As a result, neuronal genes are turned on, and multipotent adult neural stem cells become neurons.\n\nThe NRSF/REST protein binds strongly to the dsRNA, and the two probably sit on promoters as a complex. When both are present, histone acetylases and chromatin-remodeling proteins replace the deacetylases and methyl-DNA binding proteins that are found at neuronal gene promoters when only NRSF is expressed.\n\nThe dsRNAs are found in regions of the"
+"Introduction\n============\n\nInterest in safety and clinical outcomes of inpatients has been growing in Japan, because the 100,000 Lives Campaign was introduced under the Japanese Patient Safety Act in 2008. In this act, an introduction of the Rapid Response System (RRS) was one of the mainstreams to inpatients\\' care. However, many Japanese healthcare providers cannot understand how to achieve the introduction of the RRS, because there are few who have knowledge of the system. Therefore, we developed a new introductory training course for the RRS. The educational effectiveness was analyzed through the surveillance questionnaires after the course.\n\nMethods\n=======\n\nThe educational program includes a lecture series concerning the outline and management methods, introduction of facilities that have already deployed, small group discussions, and teaching methods-of-training for the medical emergency team using a simulator. Evaluation was made in the five-point scale by 82 participants (58 physicians, 16 nurses and eight other professions) throughout seven courses. The questionnaires are: A. understanding of RRS, B. knowledge acquisition about patient safety, C. expectation for decreasing the cardiopulmonary arrest by RRS, and D. expectation for decreasing the psychological burden by RRS.\n\nResults\n=======\n\nSeventy-three participants (89.0%) answered the questionnaires. The numbers of participants who scored"
+"Q: Last month you paid tribute to your colleague Dr\u00a0Sheikh Humarr Khan from Sierra Leone, who ran the only medical unit in the world devoted exclusively to the care of patients with viral haemorrhagic fever and who died of Ebola virus disease in July. Why are so many health workers dying, even those wearing the recommended protective clothing?\n\nA: There is a lot of focus on personal protective equipment -- the suits, gowns and masks seen on so many photographs of the outbreak. But this is only one of many important aspects of safe patient care. In many places the demand for patient care has outstripped the available human resources. For example, a couple of months ago a WHO physician, David Brett-Major, and I made rounds at the Kenema treatment centre in Sierra Leone, where the nurses were on strike. The two of us were the only health-care workers on that ward of 60 patients with Ebola virus disease. Even if you wear the recommended gear, much more is needed, such as supervision and sanitation officers to decontaminate the area regularly. Asking a health-care worker to safely care for patients without support personnel is like asking a pilot to"
+"Despite the progress in techniques for cancer prevention, detection, and treatment, as well as for increasing the public awareness in recent years, this disease is projected to become the leading cause of death worldwide. Advancements in omics, analytical procedures, and high throughput screening in the last five years have led to the realization that human diseases and especially cancer are more complex than were originally conceived. Cancer is not a static entity that can be easily monitored and manipulated. It is characterized by a dynamic and time-dependent network of constantly altered molecular and cellular interactions between players in different pathways. This network is not invariable and rigid but is constantly reshaped and altered conforming to the pliable signaling processes/responses implicated. Its complexity is apparent by the fact that the disease state is not a disruption of a single node or specific nodes in the network organism but is organism-patient dependent, thus requiring personalized perspective approaches.\n\nNumerous challenges hamper effective cancer treatment and development of effective drugs such as ineffective therapeutic drug concentration reaching the tumor site, life-threatening side-effects caused by nonspecific tissue distribution of anticancer agents, and acquired resistance of the cancer cell upon chemotherapy that triggers cross-resistance to a"
+"Proteases were originally started out as simple destructive enzymes in order to digest proteins and to provide amino acids to ancient organisms, but many proteases evolved in later times are specialized to change activity, localization, and binding properties of proteins and thereby affect many cellular functions. More than four hundred thousand proteases in all organisms can be classified into 9 categories and numerous subfamilies[@b1][@b2]. Among these proteases, ADAMTS family as a subclass of ADAM (a disintegrin and metalloproteases) family constitutes a group of zinc-dependent secreted proteases widely expanded during metazoan evolution, including 6 members in flies, 5 members in nematodes, and 19 members in mammals[@b3].\n\nThese ADAMTSs are involved in many biological actions by processing mostly ECM and some non-ECM substrates. For example, ADAMTS-1 cleaves versican and aggrecan, and plays a key role in the ovulation process[@b4][@b5]. ADAMTS-2, 3, and 14 cleave procollagen I\u2009[@b6][@b7][@b8], and mutations in ADAMTS-2 cause Ehlers-Danlos syndrome, a connective tissue disorder[@b7][@b9]. ADAMTS-7 and 12 are significantly upregulated in arthritic patients[@b10]. Besides ECM proteins, ADAMTS-13 cleaves von Willebrand factor (vWF) in blood, and mutations in ADAMTS-13 result in thrombotic thrombocytopenic purpura (TTP)[@b11]. In addition, ADAMTSs either enhance or inhibit cancer development. The level of ADAMTS-7 is"
+"Introduction {#s1}\n============\n\nAtherogenesis is the initiating step of atherosclerosis, and can be considered the key-point for a better understanding of the entire process, as several factors and mechanisms are also related to plaque progression in the clinical scenario (Weber and Noels, [@B19]).\n\nPlaque initiation steps take place in the following environments: Systemic blood environment (proatherogenic or atheroprotective) constituted of inflammatory and lipid factorsEndothelial blood-vessel interface, which expresses adhesion molecules for monocyte intra-lesional transferSub-endothelial intimal space, where proteoglycans retain LDLIntimal and intima-media interface, scenario for vascular smooth cell (VSMC) phenotype switch and activation toward migratory and proliferative conditions (Libby et al., [@B8])\n\nTraditional views of atherosclerosis, basically seen as a lipid-based disorder, have been modified by the recognition of the multifactorial etiology of this disease (Lamon and Hajjar, [@B4]), involving the interplay of genetic, phenotypic and environmental factors that have to be integrated into a unified scheme. According to this theory, the most likely sequence of events occurring in the initial phase of atherosclerosis comprises vascular dysfunction and/or injury, monocyte recruitment and foam cell formation, lipid deposition, vascular smooth muscle cell proliferation and synthesis of extracellular matrix (Libby, [@B7]). The interaction of all these factors confers to the resulting atherosclerotic"
+"Introduction {#s1}\n============\n\nThe ability to navigate is a challenging, high-order cognitive problem. Even in the simplest setting, such as in travel to a landmark in plain sight over open terrain (e.g., towards a church spire), navigating involves determining the required direction of travel and estimating how far to proceed. In reality, however, navigation is rarely this straightforward. Everyday experience typically requires navigation in multiple distinct contexts, varying in time course, familiarity and environmental complexity. For example, walking to work typically involves following a learned route to a known location, whereas walking to a new location for the first time involves mapping out an entirely new route to the goal. In addition to differences in the nature of the navigation required, differences in the properties of the surrounding environment and distance to be covered also exert a defining influence on the combination of cognitive processes involved in navigation (e.g., crossing a toy strewn nursery vs. driving to the airport). Despite the variety and complexity of cognitive processes involved, four decades of electrophysiological and neuroimaging research has successfully identified a number of distinct brain regions that are critical for specific operational aspects of navigation.\n\nA wealth of evidence indicates that hippocampal"
+"Introduction\n============\n\nHealth care products which are manufactured from noble raw materials such as metals, silicone, fabrics, and rubbers are used countless times among patients in health care services. These products need to be decontaminated with each use, as a way to avoid the risk of cross-contamination by microorganisms.\n\nChoosing a decontamination method depends on the specific risk from a product to cause infections. The current adopted theoretical framework is, generally speaking, the same that was proposed in 1958, when minimum safety procedures were determined to be adopted according to the various risk degrees; that is, sterilization for critical materials - the ones which get in contact with sterile human tissues; the high-level disinfection; and, if possible, sterilization for semicritical materials - the ones which get in touch with nonintact skin or mucous membranes; and cleaning that is followed by intermediate or low-level disinfection as a standard procedure for non-critical materials - the ones which contact intact skin or which do not get in contact with patients [@B1]. At the time, the authors have not emphasized the previous need of cleaning as an essential procedure for processing materials to be disinfected or sterilized, which is nowadays adopted as a strong"
+"1. Introduction {#sec0005}\n===============\n\nResuscitation during the latter part of the 19th century and early 20th century might include the use of brandy or other forms of alcohol. The literature of the Heroic Age of Antarctic exploration (1897--1922) contains many references to \"medicinal\" (or similar descriptions of) brandy. For example Wilson said of Scott\\'s first expedition; \"No alcohol was taken on sledge journeys, except for a small can of brandy for emergencies\"[@bib0005] and Ekel\u00f6f, doctor to the Swedish Antarctic Expedition (1901--1904), describing the use of spirits, said: \"For the second year there were only very few bottles left, which were reserved for festive occasions or for medical use\".[@bib0010] Spirits other than brandy could be used: on the Belgian expedition, Amundsen \"gave Tollefsen a glass of cherry liqueur on the doctor\\'s advice\" for \"exhaustion, mixed with madness\"[@bib0015] but other spirits were thought less useful. Thus Bernacchi on the Southern Cross expedition (1898--1900), in complaining that the expedition leader had consumed all the brandy, wrote in his diary: \"Unless the doctor has a bottle or so, we have not a drop of brandy at Cape Adair for medicinal purposes. On this occasion we were obliged to use whiskey. It is really scandalous.\"[@bib0020]"
+"Malaria is an infectious disease that profoundly affects many developing countries. With hundreds of million cases and one million deaths each year, malaria poses a tremendous health and economic burden to the affected regions.[@bib1] There is still no effective antimalarial vaccine available and we still heavily depend on low molecular weight entities to treat the affected population. Quinine, chloroquine, mefloquine and artemisinin derivatives have play an important role in the treatment of malaria. However, widespread drug resistance has made many of these compounds less effective. Artemisinin is the only anti-malarial for which there are yet no reported cases of clinical resistance. However, parasite tolerance to artemisinin has been observed recently[@bib2] and it seems likely that resistance will emerge soon. Therefore, it is important to discover new chemotherapies that are effective against the multi-drug resistant parasite strains.[@bib3] In this Letter, we discuss an effort[@bib4] to find and optimize novel antimalarial entities using a cell-based screening strategy.\n\nCurrently there is a need for novel chemical scaffolds with different mechanisms of action, since most of the current approved antimalarial drugs belong to the aminoquinoline family. In order to find new chemical scaffolds, we initiated a compound screen using our in-house kinase inhibitor collection"
+"Problem {#sec0001}\n=======\n\nThe COVID-19 pandemic has created difficulties with execution of traditional didactic curricula. Programs have restricted in-person gatherings and increased use of work-from-home models. Essential staff involved in execution of didactics have also been subject to furlough. The pandemic has directly affected facilitator health and time for preparing and delivering didactics; this impact has been highly variable across regions and institutions.\n\nDespite these challenges, it is imperative that programs continue to deliver quality didactic education. The Accreditation Council for Graduate Medical Education (ACGME) has issued statements indicating that \"programs should continue to provide education to residents/fellows, when feasible, utilizing remote conferencing technology, web-based resources, and other innovative tools.[@bib0001]\" Program directors need innovative approaches to ensure that didactics are held regularly, are high quality, and engaging to learners at a time of significant stress.\n\n\"Megaflip\" is a novel form of open-access national didactics. These sessions are multicenter educational experiences using materials from The Organization of Neonatal-Perinatal Medicine Training Program Directors National Neonatology Curriculum, a standardized, peer-reviewed curriculum utilizing flipped classrooms.[@bib0002] In the National Neonatology Curriculum flipped classrooms model, learners are assigned prework, consisting of short videos and reading materials in preparation for the \"classroom\" session. The classroom session focuses"
+"In this chapter we describe the distribution of several known shift-prone patterns and stimulatory signals and how they relate to the concept of singular genomic elements. We also discuss how their characteristic distribution can be utilized for identification of novel recoded genes and describe studies where such strategies have been employed.\n\nSingular Genomic Elements {#Sec1}\n=========================\n\nA characteristic property of all biological systems is diversity and specialization of their component parts that play distinctive functional roles. The tendency for specialization and uniqueness is profound on the genomic level, as the existence of identical multiple copies of the same gene (unless they relate to mobile elements) is rare. Functional specialization of gene products demands similarly specific regulation of their biosynthesis and processing. Such specificity can be achieved through a combinatorial effect of several regulatory mechanisms acting on different levels of gene expression -- from initiation of transcription to posttranslational modifications, where similar regulatory sequences occur in groups of functionally related genes. Specificity is gained through differential combination of these sequences which could be idiosyncratic for a particular gene. However, it is attractive to imagine a simpler scheme where a unique regulatory element would be responsible for the regulation of a specific"
+"INTRODUCTION {#s1}\n============\n\nBalance refers to the adjustment of position in active movements and the maintenance of an appropriate position in response to external stimuli. The maintenance of balance requires normal pressure and an appropriate integration process at the higher center with continuity of the center of gravity within the support plane. The improvement and maintenance of balance is very important, because a decrease in balance increases the frequency of falls and aggravates the physical impairments of patients[@r1]^)^. Aging brings about anatomical and physiological changes, and such physiological conditions as a loss of perception, dysfunction of the musculoskeletal system, and instability of posure positions, which are connected to balance problems and can lead to serious injuries. In particular, visual acuity, pallesthesia, proprioceptive sense, relative degradation of the lower extremity muscle strength, and delayed response time can all affect balance and cause accidental falls.\n\nTreatment methods for enhancing balance recovery and position adjustment include trunk stabilization exercises, fixed bicycle riding exercises, visual feedback training, and Swiss ball workouts. In recent years, studies have been actively conducted on exercise methods based on motor learning theories for voluntary problem solving with visual, auditory, and biofeedback methods in continuous exercise tasks and conditions. Furthermore,"
+"Vertebrate organ development is a complex process that begins in the early embryo and continues until the functional capacity of the organ meets adult requirements. Organ growth and maturation occupy a significant period of life and involve major anatomic changes, yet relatively little is known about the cellular dynamics that underlie these changes.\n\nNew technologies can illuminate cellular mechanisms that drive organ morphogenesis. Recently, Livet and colleagues introduced a system that allowed labeling designations of \\~90 colors to murine neurons^[@R1]^. With this technology, termed 'Brainbow', they could visualize adjacent neurons and their connections in the brain with high resolution. The ability to assign many colors to different cells in a population can also be applied to understand cell proliferation and lineage decisions.\n\nThe heart is a set of chambers comprised predominantly of the contractile units, cardiomyocytes. Genetic fate-mapping has been performed to determine how separate lineages contribute to developing cardiac structures in mice and zebrafish^[@R2]--[@R6]^. Additionally, single-marker clonal analysis has traced the activity of individual cells during embryonic heart patterning^[@R7]--[@R10]^. These studies have enhanced our understanding of cardiogenic mechanisms in early embryos. Nevertheless, a large gap remains in comprehending how the size, shape, and structure of an adult heart are"
+"Introduction {#s1}\n============\n\nIn today\\'s clinical practice, routine monitoring of general anaesthesia is based mainly on cardiovascular parameters and motor responses. If surgical stimulation provokes neither movement, nor an increase in heart rate or blood pressure, it is assumed that the anaesthesia is sufficient. However, during neuromuscular blockade, in the presence of beta-blockers, or in patients who only tolerate 'light levels' of anaesthesia, these clinical parameters may fail to reliably monitor the depth of anaesthesia. Despite the stability of these parameters, patients may become conscious during surgery, potentially leading to explicit memory of words spoken in the operating room, discomfort, or pain. In addition, if the central processing of stimuli is not sufficiently blocked, implicit memories may be acquired via auditory or other sensory input under general anaesthesia. Possible consequences of intraoperative awareness include nightmares, or even symptoms of a posttraumatic stress disorder [@pone.0008876-Schneider1].\n\nAs recently suggested by us [@pone.0008876-Marsch1], [@pone.0008876-Becker1] and others [@pone.0008876-Li1], RQA of EEG recordings appears to be a highly promising tool for monitoring the depth of anaesthesia. One of the basic requirements for monitoring the hypnotic level of anaesthesia is the ability to separate consciousness from unconsciousness. The present analysis was performed to assess the ability"
+"Introduction {#S1}\n============\n\nThe dexterity of the digits of the hand is one of the hallmarks of human motor control and a central factor in the evolution of our species. The highly individuated movement enables complex and dynamic interaction with the environment, such as for manipulating tools and objects. Motion ([@B1]) and force ([@B2]) independence are especially great in the index finger and thumb, the two most functionally important digits.\n\nYet, coordination between these digits is critical for proper execution of a number of important tasks. During object manipulation through pinch, for example, the thumb and index fingertip forces must create equal and oppositely directed forces to prevent slip of the object. Alteration in the force created by one digit, such as might arise due to perturbations or changing conditions such as sweat, requires immediate compensation by the other digit.\n\nThe finger and thumb have multiple degrees-of-freedom (DOF) available which can be exploited to match the other digit's movement; this redundancy, however, contributes substantially to variability in movement ([@B3]). By introducing coupling between these DOF, variability in motor output can be reduced ([@B4]), thereby improving performance of the digits in a coordinated task. Accordingly, research has shown evidence for neural"
+"Transition elements, such as copper, iron, or zinc, are essential nutrients for plants. They participate in every biological process. However, intracellular metal levels must be maintained within a narrow physiological concentration. Too little, and not enough cofactors are available to the cell; too much, and Fenton-type reactions and mismetallation events will disrupt many cellular processes. As a result, plants have developed complex systems to control metal uptake and to deliver them to all tissues and cells. In this Research Topic, we have collected some of the most recent work furthering our understanding of Metallic Micronutrient Homeostasis in Plants.\n\nPlant dependence on metals contrasts to the common low bioavailability of these nutrients in many soil types. Growing evidence indicates that plants have optimized the use of metals facilitating their relocation from one cellular compartment to another, depending on their need in different physiological processes. In this Topic, [Zhang and Kr\u00e4mer](https://doi.org/10.3389/fpls.2018.01641) have reanalyzed available bioinformatic data to show that there is a diurnal regulation of the translation of proteins involved in Fe-S metabolism in *Arabidopsis thaliana*, including that of frataxin, a protein involved in iron transfer in Fe-S protein biogenesis, and also in copper control in mitochondria and chloroplasts, as reviewed in"
+"Background\n==========\n\nRandom-sequence peptide library screening approaches represent an increasingly popular and powerful tool for identifying binding partners for antibodies and other proteins as well as carbohydrates, pharmaceuticals, and other small molecules. Peptide library methods generally fall into two categories: molecular display approaches such as phage display, and immobilized arrays such as SPOT. Display approaches can typically accommodate much larger libraries, but information is typically obtained only on the clones that survive several rounds of panning, resulting in a population that is heavily biased in favor of clones whose sequences facilitate growth \\[[@B1]\\]. In contrast, array based approaches may be used to screen smaller libraries with higher throughput than display approaches and semi-quantitative binding information is obtained on all of the peptides in the library. New technologies both on the display side and the array approach promise to overcome these limitations \\[[@B2]-[@B4]\\]. The decreasing cost of both sequencing and peptide synthesis as well as applications such as profiling the humoral immune response \\[[@B5]\\] promise to increase interest in connecting random-sequence peptide mimotopes to protein sequences occurring in nature. Therefore, an increase in the demand for appropriate algorithms and software to facilitate the data analysis would also be expected.\n\nWhile the"
+"The development of three-dimensional culture scaffolds represents a revolutionary step forward for in vitro culture systems. Various synthetic and naturally occurring substrates have been developed that support 3D growth of cells. In most fields, including mammary gland biology and tumorigenesis, the two most common substrates used are the basement membrane rich extracellur matrix (ECM) isolated from Engelbreth-Holm-Swarm (EHS) mouse sarcomas (e.g. Matrigel) and collagen extracted from rat-tails. The processes of 3D culture in these two substrates has remained unchanged for nearly half a century: cells are either mixed with unpolymerized matrix to disperse them randomly throughout the substrate upon polymerization or overlaid randomly on top of a preformed hydrogel. While effective in generating organoid/tumoroid structures, the random nature of these processes has many drawbacks that limit the reproducibility and tunability of the experimental design. Furthermore, random cellular distributions limit the utility of these substrates for studying interactions within the cellular microenvironment, which have been shown to be critical for the control of stem and cancer cell function \\[[@R1]\\].\n\nTo overcome these issues, computer numerically controlled (CNC) devices can be adapted to precisely control cellular deposition within hydrogels. An example of these devices can be found in the three-axis control of"
+"Understanding how nervous systems integrate sensory information to generate behavioral outputs is key to our efforts to analyze how nervous systems function. This is a daunting challenge, given the immense complexity of most nervous systems. Even within the nervous systems of insects like *Drosophila*, there is a daunting complexity, with over 100,000 neurons and 100s of cell types that can make analysis very difficult. Despite this challenge it is possible to build an understanding of how a system works if it can be broken into simple modules that can be placed into a functional hierarchy. The power of this type of approach is evident in the vertebrate spinal cord, where the complex sensory motor circuitry that controls locomotion is generated from distinct pools of progenitor cells. These progenitors form discrete and identifiable populations of interneurons, each with defined roles in the locomotor circuits (Grillner and Jessell, [2009](#cne23988-bib-0012){ref-type=\"ref\"}). Furthermore, this functional organization has a deep evolutionary significance, with progenitor domains and transcription factors that define different interneuron classes being conserved between fish and mammals (Lupo et al., [2006](#cne23988-bib-0022){ref-type=\"ref\"}) despite their very different modes of locomotion.\n\nThese organizational principles are similar to the insect ventral nervous system (VNS), which, like the spinal"
+"To the editor:\n\nWe have seen a 52-year-old man with AML-FAB M2a subtype, who had no history of viral hepatitis. He had history of mild indirect hyperbilirubinemia with normal transaminase levels after he took paracetamols in the past two years, and the same phenomenon occurred to his siblings, children and nephews. He received three cycles of chemotherapy containing daunorubicin, idarubicin, pirarubicin, cytarabine, and obtained CR in the first cycle. His bilirubin level was normal before chemotherapy; however, mild non-hemolytic indirect hyperbilirubinemia happened to him during each cycle of chemotherapy (Figure [1](#F1){ref-type=\"fig\"}). Neither autoimmune antibodies, nor serology of viral hepatitis were positive. CT scan revealed that liver parenchyma, gallbladder and bile duct were all normal. The histopathology of a liver biopsy showed mild chronic hepatitis and hepatocellular cholestasis. The expression of UGT1A1 gene was found to decrease by 20%. The diagnosis of Gilbert\\'s syndrome was confirmed.\n\n![**Bilirubin level during chemotherapy and allogeneic hematopoietic stem cell transplantation**. Chronological dates of the treatment courses were indicated. (A). the first cycle of chemotherapy of DA regimen \\[Daunorubicin 60 mg/d from day 1 to 3, Cytarabine (Ara-C) 200 mg/d from day 1 to 7\\]. (B). the second cycle of chemotherapy of IA (Idarubicin 10 mg/d"
+"Introduction {#s1}\n============\n\nThe RNA world is \"almost a logical necessity\", for example by the fact that aminoacyl-tRNA synthetases are not among the most ancient proteins [@pcbi.1003936-Aravind1]. Despite eminent attempts [@pcbi.1003936-Wochner1], [@pcbi.1003936-Attwater1] we still lack a generalized RNA replicase that would be able to unzip and copy general, long RNA templates, similar to the contemporary activity of, say, the Q*\u03b2* replicase [@pcbi.1003936-Blumenthal1], made of protein. A way out could be the assembly, out of replicable shorter pieces, of a replicase and an associated ligase [@pcbi.1003936-Ellington1], encouraged by the recent finding of a collectively autocatalytic ligase-based RNA network [@pcbi.1003936-Vaidya1]. Twenty years ago the possibility of an early evolution of a division of labor between gene () and enzymatic () RNA strands was raised: \"The fate of both the plus () and minus () strands is important for the following discussion. If both strands are to be replicated, both of them must be recognized by the replicase: the 3\u2032 and 5\u2032 ends of the same strand must therefore be complementary (it is assumed that replication goes in the 5\u2032\u21923\u2032 direction as today). Interestingly, violation of such a complete symmetry opens up the possibility for a very early origin of \"transcription\" in the"
+"Introduction\n============\n\nAndrologic and male infertility procedures represent a distinct class of urologic surgeries. In contrast to other urologic procedures, which may involve intra-abdominal organs and thus require general anesthesia, andrologic and male infertility procedures are performed in the penis and scrotum, where pain can be fully controlled with local anesthesia. Office-based surgical procedures under local anesthesia offer several potential advantages over those performed with general or monitored anesthesia, including absence of post-op extended recovery, elimination of risk of pulmonary or cardiac complications, ability to communicate with the patient, avoidance of side effects from general anesthetic medications, and improved convenience for patients and surgeons.\n\nDespite these known benefits, relatively little has been published on the topic of office-based andrologic and male infertility procedures ([@r1]). Authors have previously described performing several andrologic and male infertility procedures under local anesthesia including hydrocelectomy, malleable penile prosthesis, microepididymal and testicular sperm aspiration (MESA)/TESE, orchiectomy, spermatocelectomy, and varicocelectomy ([@r1]-[@r15]). However, many of these reports include the use of IV sedation, monitored anesthesia care, or are limited to 3^rd^ world countries, with relatively few described in contemporary practices. Additionally, to our knowledge, no studies have reported on the complex procedure of vasoepididymostomy (VE) under local anesthesia"
+"Introduction\n============\n\nIn patients requiring hemodialysis, the upper limb is the preferred choice for access creation. Unfortunately, due to lack of an optimal health care system in Pakistan, most of the patients for hemodialysis access present late. These patients have central catheters in place. Their forearm veins have already been exhausted due to multiple venipunctures or previously failed hemodialysis accesses. They develop central venous stenosis quite earlier. The lower limb is the next option for creating a dialysis access in patients who have bilateral upper arms central stenosis.\n\nLower leg prosthetic grafts are reported with a higher incidence of graft and wound infection. Patency is lower because of the early formation of neointimal hyperplasia at the graft-venous anastomosis. They are also associated with higher risk of steal syndrome. One option in the lower extremity is creation of arteriovenous (AV) access using the great saphenous vein. This has not shown good results, likely related to its thick wall and multiple valves acting as a nidus for neointimal hyperplasia. Reports on saphenous vein superficialization demonstrated poor results.^[@R1])^\n\nThe femoral vein (FV) is good conduit for creating an AV access. It has proved useful in a variety of settings favoring a large venous"
+"Introduction {#Sec1}\n============\n\nViral respiratory infections constitute an important\u00a0health concern worldwide. Many respiratory viruses cocirculate in the population, and coinfections are commonly reported. However, the type(s) of interaction between distinct viruses, the mechanism and consequences of these multiple infections on disease severity have not been clearly established yet.\n\nAdaptive immunity is not expected to impact coinfections by distantly related viruses while competition for cellular processes (such as nucleotide and lipid biosynthesis, carbon metabolism, protein synthesis...), and/or innate immunity may play a role. Numerous epidemiological studies have described either positive or negative associations between given respiratory viruses based on statistical analyses, with some pairs of viruses being frequently co-detected in patients and others very rarely^[@CR1]--[@CR8]^. In line with these observations, experimental coinfections have also put forth different types of viral interactions, from unidirectional of mutualistic inhibition of growth due to competition for cellular resources^[@CR9]^ to synergism^[@CR10]^. The role of innate immunity in viral interference has also been illustrated both in old studies^[@CR11],[@CR12]^ and in recent mathematical simulations^[@CR13]^. However, the actual impact of the antiviral action of interferons (IFNs) and in particular of type III IFN in respiratory virus-specific interference has not been studied in depth in a relevant model.\n\nThe"
+"Problem\n=======\n\nThis quality improvement project was undertaken at St Thomas\\' Hospital Birth Centre (HBC) by four fourth year medical students, under the supervision of an obstetric consultant and two junior doctors. St Thomas\\' is a tertiary teaching hospital in London, UK and is the base for maternity services for the Guy\\'s and St Thomas\\' (GSTT) NHS Foundation Trust. With 22 beds on HBC, an average of 40 patients are admitted each day. The department has 90 staff members in total with 15 present on each shift. St Thomas\\' HBC patient population encompasses South-East London and annually sees approximately 6000 births.\n\nAs part of GSTT protocol, venous thromboembolism (VTE) risk assessment of women on HBC is completed on two separate computer systems. One is BadgerNet, Clevermed version 2.9.1.0, a maternity electronic record where antenatal, postnatal, and delivery details are recorded. The second system is the electronic patient record (EPR), iSOFT version 1.6. The CQUIN target is for 95% of patients to have a VTE assessment completed within 24 hours of admission. Previously women who delivered during their admission had their VTE assessment completed on BadgerNet, while those who were admitted but did not deliver were assessed on EPR. To simplify"
+"Abbreviation used in this paper: AMP-PNP, adenylyl-imidodiphosphate.\n\nIt\\'s no secret to electrophysiologists that single-molecule methods have driven some of the most impressive advances in our understanding of how biomolecules function. In fact, the power of single-molecule techniques had become abundantly clear by the mid 1980s, when a review of patch-clamp results noted \"It is now routine to observe the behavior of one protein molecule with a time resolution approaching 10 \u03bcs. Amazing!\" ([@bib4]). Further technological developments have made single-molecule methods available to a growing range of biophysical subfields, including the study of motor proteins, or mechanoenzymes ([@bib7]). As the techniques have become more robust and reliable, many of the key biochemical tools that have long been exploited in ensemble-averaged experiments, such as use of small-molecule inhibitors, are finding their way into single-molecule motility assays. A new report by Subramaniam and Gelles (on p. 445 of this issue) signals this growing trend by describing novel behaviors of single kinesin proteins in the presence of adenylyl-imidodiphosphate (AMP-PNP), a nonhydrolyzable analogue of ATP known to inhibit kinesin\\'s catalytic activity. Surprisingly, the authors found that kinesin motors could still move when one of its twin heads was hobbled by the analogue.\n\nSince the discovery"
+"Introduction {#s1}\n============\n\nCilia are microtubule-based projections from the cell body (general references <http://www.ifcbiol.org/Primaryciliumweb/index.html>). Cilia grow from the mature mother centriole of the mother-daughter pair of centrioles in the cell\\'s centrosome [@pone.0027058-Rieder1]. Solitary or sensory cilia are present in most cells of the body and their functions are only now beginning to be defined. Their existence has been known from morphological studies since the sixties [@pone.0027058-Satir1]; however, because very little has been known about their functions, not much attention has been paid to this particular organelle until recently.\n\nSeveral observations have illustrated the importance of the solitary cilium: 1) Smell, taste, and vision occurs via modified cilia: olfactory or gustatory sensory cilia and outer segments of rod cell, respectively (see e.g. Figure 15-43 of [@pone.0027058-Alberts1]. 2) Some receptors are specifically located on neurocilia [@pone.0027058-Handel1]. 3) mutations that occur in proteins resulting in mislocation of normal ciliary proteins or malfunction of solitary cilia itself in the renal epithelium produces a polycystic kidney disease phenotype, which is characterized by the transformation of an absorptive epithelium into a secretory one with formation of cysts [@pone.0027058-Calvet1], [@pone.0027058-Lin1], [@pone.0027058-Luo1], [@pone.0027058-Nauli1]. 5) Defects in solitary cilia present during development result in inversion of the normal left-right"
+"Sir,\n\nMr. Welliver and Dr. Jones did a nice job expounding on our discussion of residual neuromuscular blockade and appropriate monitoring of patients who have received neuromuscular blocking agents. A good teaching point is that patient variability is the norm and not the extreme. The majority of patients, barring any significant health issues changing the overall metabolism or function of neuromuscular blocking agents, will fall within a bell shaped curve when it comes to recovery from neuromuscular blockade. However, patients lying at the far ends of that curve will not be uncommon in your practice when enough patients are seen. That is why quantitative clinical indicators of recovery should be followed in all cases. Furthermore, frank discussions need to occur between us and our surgical colleagues when further neuromuscular blockade is requested. It makes sense that the surgeons want the surgical field to be optimized in all cases, but overall patient safety which includes recovery from neuromuscular blockade and the avoidance of inappropriate extubation needs to be considered as well. All have to be on board with the benefits and potential complications when re-administration of neuromuscular blocking agents occurs especially near the end of the surgical case. It should be"
+"Introduction\n============\n\nThe chemistry of multimetallic transition metal complexes has received considerable interest in recent decades for its potential in catalytic applications and small molecule activation.^[@cit2],[@cit3]^ The proximity of contrasting d-block metal centres can promote reactivity beyond the scope of homometallic compounds. An understanding of the interaction between the metal centres is key to enabling predictions of their reactivity and thus the development of multimetallic systems suitable for catalytic applications.\n\nWhile many successes have resulted from a focus on the d-block metals, the manipulation of interactions between f-element cations and transition metal centres is an area that remains poorly understood. Heterobimetallic bonds with f-block elements are extremely rare, and homometallic bonds as yet unseen, in sharp contrast to much of d-block chemistry.^[@cit1]^ The few reports of compounds that feature bonds between d- and f-block elements have begun to help to improve our understanding of the nature of metal--metal bonding. Furthermore, the 5f orbitals have sufficient spatial extension that renders the d--f intermetallic bond a possibility, and thus the isolation of actinide-transition metal complexes a particularly interesting target.\n\nComplexes with bonds between uranium and transition metals are rare and limited to iron,^[@cit4]--[@cit6]^ ruthenium,^[@cit4],[@cit7]^ cobalt,^[@cit8]--[@cit10]^ rhenium,^[@cit11]--[@cit13]^ group 10 metals,^[@cit14]^ and silver.^[@cit15]^ The"
+"Each year, nearly 500,000 Americans suffer from acute thermal burn injuries requiring medical treatment, resulting in approximately 40,000 hospitalizations and 3400 deaths.^[@CIT0001]^ Burn treatment is dictated by the depth and extent of the injury, with deeper and more extensive injuries requiring early excision and timely treatment with autologous split-thickness skin grafts (STSG) to achieve definitive closure and optimize clinical outcomes. Although the use of STSG is considered standard treatment, grafting is associated with significant pain, pruritus, infection, dyschromia, dyspigmentation, delayed healing, and hypertrophic scarring.^[@CIT0004],[@CIT0005]^ Furthermore, in large TBSA injuries, donor site availability is a limitation for rapid wound closure using traditional skin grafting techniques.\n\nThe clinical benefits of earlier intervention for burn wounds are well recognized and include increased survival, reduced hospital length of stay, decreased hypertrophic scarring, decreased pain duration, and reduced infection-related complications.^[@CIT0006]^ The realization that a treatment in which minimal split-thickness donor skin could be used to achieve definitive closure for burn wounds in a clinically advantageous time frame led to the investigation of strategies to harness the healing potential of the patient's own skin.\n\nThe ReCell^\u00ae^ Autologous Skin Cell Harvesting Device (ReCell, Avita Medical, Valencia, CA, USA) was designed for point-of-care processing of a small split-thickness"
+"Introduction {#s1}\n============\n\nLikely effects of climate change are rising temperatures in some food production areas, water shortages and rising grain prices due to increased demand for human food and biofuel feedstuffs [@pone.0006676-Stern1]--[@pone.0006676-Searchinger1]. As a result, future dairy farming systems may become increasingly reliant on pasture instead of grain to feed cows. In this scenario, the selection of dairy cows that can produce at high levels with lower levels of feeding is important. As cattle reproduce slowly, we need to develop methods to select suitable cattle before the change in production systems occurs. Fortunately the range of production environments in which dairying is already carried out in Australia is wide, from fully pasture based systems to fully feedlot based systems, and from tropical climate to temperate climate [@pone.0006676-Hayes1]. This gives us a chance to discover loci or genetic markers that can be used to select cattle that are suitable for future farming systems.\n\nGenetic variation in the sensitivity of milk production of dairy cows to environment has been reported. For example, as heat stress is increased, dairy sires change ranking in their estimated breeding values (EBVs) for milk yield [@pone.0006676-Hayes1]--[@pone.0006676-Ravagnolo1]. Some re-ranking of dairy sires based on the level of"
+"Background {#Sec1}\n==========\n\nSkeletal malocclusion affects oral health and is highly associated with dental trauma and masticatory difficulties as secondary effects of parafunction and teeth crowding \\[[@CR1]\\]. Orthognathic surgery (OGS) is used to resolve imbalances involved in the craniofacial structure and skeletal malocclusion, thereby improving the oral and facial function and aesthetics of the patient. The efforts of both orthodontists and surgeons can dramatically improve the quality of life of patients experiencing functional and aesthetic discomfort. However, jaw misplacement by a surgeon during OGS is difficult for an orthodontist to revise after the operation. During traditional bimaxillary OGS, the maxilla is first moved, and the mandible is relocated relative to the maxilla. Therefore, it is most important to move the maxilla to a planned position during OGS. Efforts to achieve such outcomes include freehand relocation \\[[@CR2]\\] and the use of an internal reference point, which are currently applied by several surgeons. However, external reference points are the most accurate method to use during LeFort I osteotomy \\[[@CR3]\\]. In recent years, the progress in OGS has mainly resulted from the use of a virtual surgery plan (VSP) to accurately reposition the bone segments \\[[@CR4]\\]. There are problems associated with conventional OGS"
+"In a recent paper, Sorrentino et\u00a0al., reported that a homeopathic preparation of an extract from *Arnica montana* L, known as *Arnica* 1000\u00a0K, significantly reduced the amount of post-operative blood and seroma (improving bleeding) in female subjects who underwent an unilateral total mastectomy.[@bib1] This double blind randomized controlled trial versus placebo was performed throughout two years-long period, from 2012 to 2014, and about 53 patients (26 cases and 27 controls) with an age range 20--75 years and hospitalized for unilateral total mastectomy, were enrolled.[@bib1] In their study, the authors stated that patients underwent also a standardized protocol of treatment for surgical procedures including an antithrombotic prophylaxis with 4000 UI heparin 12\u00a0h before surgery.[@bib1] Patients who followed a randomization blinded protocol received a 30% v/v ethanol preparation of *Arnica* 1000\u00a0K (five drops sublingual) or a placebo (i.e. simply 30% v/v ethanol) from 1 day before surgery to the fourth day following surgery, which was performed by the same surgical team.[@bib1] Those patients treated with *Arnica* 1000\u00a0K and collected in the group who excluded subjects who violated the protocol (PP group), showed less blood leakage and seroma (serum from surgical drainages) release from post-operatory drainages, reporting a better"
+"This year marks the 50th anniversary of the founding of the American Society for Cell Biology (ASCB). We decided that a fitting way to honor this occasion would be to look forward to the next 50 years of cell biology. To take on this daunting task, we invited a group of cell biology thought leaders to write essays on their perspectives on the future of cell biology for this special issue of *MBoC*. We gave the authors wide latitude to write about topics that they found interesting and important for the future of cell biology but suggested that they contemplate such questions as: Where is cell biology headed in the next 50 years?What are the big unanswered questions and challenges for cell biology?How can young scientists best prepare themselves to meet these challenges?\n\n![Douglas R. Kellogg, Features Editor](zmk0221096780002){#FU1}\n\n![David G. Drubin, Editor-in-Chief](zmk0221096780001){#FU2}\n\nCell biology is a melting pot for diverse disciplines and experimental philosophies, so we aimed for a diverse group of authors to provide a wide range of perspectives on the future of cell biology, although we knew it would not be possible to be comprehensive.\n\nThe extraordinary achievements in cell biology over the last 50 years are good"
+"Introduction {#s1}\n============\n\nTraditionally in mental health, there has been a strong emphasis on defining recovery in terms of symptom resolution. However, there is increasing recognition that defining remission solely on the basis of clinical symptoms is inadequate. Frequently, these 'remitted' patients with diagnoses of major depression [@pone.0058176-Zimmerman1], bipolar disorder [@pone.0058176-Fagiolini1] or psychosis [@pone.0058176-Oorschot1] remain functionally impaired. Zimmerman et al. [@pone.0058176-Zimmerman1] demonstrated that half of patients with major depression who were classified as remitted based on rating scale criteria did not consider themselves to be *in remission*. Critically, these individuals were significantly more impaired in their work performance and social relationships. It is likely that subsyndromal symptoms, particularly depression [@pone.0058176-Fagiolini1] and negative symptoms [@pone.0058176-Bowie1], contribute to these 'residual' functional deficits across the major psychiatric disorders. Of significance, cognitive vulnerabilities may *additionally* contribute to persisting disability given evidence that neuropsychological dysfunction predicts later socio-occupational functioning, over and above symptom levels, as observed in depression [@pone.0058176-Withall1], bipolar disorder [@pone.0058176-Martino1], and schizophrenia [@pone.0058176-Green1].\n\nWhile in chronic cohorts psychotic disorders are associated with more pronounced neuropsychological and psychosocial disability than affective disorders [@pone.0058176-Simonsen1], neuropsychological performance appears to predict functional outcome irrespective of diagnosis [@pone.0058176-Simonsen1]. Accordingly, neuropsychological deficits have been proposed as endophenotypes that cut"
+"How the flamboyant ornamental traits used to attract mates in various species evolve is a question that has been debated since Darwin\\'s time (Cronin [@b1]). There are many theoretical models suggesting how preferences and ornaments coevolve (reviewed by Mead and Arnold [@b2]; Kuijper et al. [@b3]). However, there is an overlooked difficulty with these models. They either lack an explicit directionality for the exaggerated trait, or predict that secondary sexual ornaments should be just as likely to evolve to be smaller (hereafter referred to as \"reduced\" traits) as to be larger (hereafter referred to as \"exaggerated\" traits) than the natural selection optimum.\n\nIn his original setting out of the runaway process, Fisher referred to sexual preferences being for a \"plumage character\" (Fisher [@b4]). His verbal framework was based upon an initial majority of females with a particular preference. This arbitrary initial preference eventually causes a runaway, but there is no reason why it should be toward exaggerated rather than reduced traits (Dawkins [@b5], p. 215). This symmetry between exaggeration and reduction is seen in the classic mathematical models of the Fisher\\'s process (Lande [@b6]). Under this framework, upon which many other models are based (see Mead and Arnold [@b2]; Kuijper"
+"Morphogens that spread from a point or line source are useful for patterning and for defining the outer bounds of a tissue. How to convert such a gradient into uniform cellular growth is, however, far from obvious. Can a pro-growth morphogen avoid encouraging excessive growth near its source and inadequate growth further away?Dragana Rogulja and Kenneth Irvine (Rutgers, Piscataway, NJ) now provide one possible solution for cells that will become fly wings. The cells, they find, make their division decision in response to a gradient rather than absolute concentrations of the Decapentaplegic (DPP) morphogen.\n\nFigureDPP pathway changes in one area (green) affects division (red) in other areas.IRVINE/ELSEVIER\n\nThe Rutgers group expressed or repressed the DPP pathway in small clones. In both cases they saw new cell division both within the clone and in neighboring areas. This nonautonomous growth had not been evident in previous experiments, probably because the earlier experiments used expression systems with a long lag time. The new experiments used drug-inducible expression to get tighter temporal control.\n\nThe researchers believe that cells measure the difference between their own DPP expression level and that of their neighbor, and go through cell division only if there is a difference. This"
+"Introduction {#Sec1}\n============\n\nHeat wave early warning systems alert the public and health officials to impending hot weather and activate interventions to protect the public from the negative health impacts from extreme heat. Beginning in 2012, public health units (PHUs) across Ontario worked with various partners to develop a province-wide Heat Warning and Information System (HWIS). This was a unique collaboration that brought together all orders of government with different mandates, needs, and degrees of activity and experience around heat warning systems. All partners involved came together voluntarily and agreed on a common purpose and process. Unlike other activities spurred by heat emergencies, the development of a HWIS for Ontario was undertaken proactively and driven by public health units. This case study outlines the process for establishing the harmonized system in Ontario, including the impetus for action, the role of key partners, and the launch of the new system. Several key lessons are described that could help other jurisdictions looking to implement their own harmonized systems.\n\nContext {#Sec2}\n=======\n\nHeat events can have a major impact on health. In the summer of 2003, Europe experienced unseasonably hot weather which resulted in approximately 70,000 deaths (Robine et al. [@CR11]). Canada is"
+"Introduction {#s1}\n============\n\nGlucose repression ensures that yeast cells use preferred carbon sources until available supplies are exhausted. Much of the regulation of glucose-repressed genes occurs at the level of transcription [@pone.0003213-Carlson1], [@pone.0003213-Gancedo1], and in yeast, Adr1 has a pivotal role in expressing these genes [@pone.0003213-Schuller1], [@pone.0003213-Young1]. Control of Adr1 occurs at several levels: through transcription of its gene [@pone.0003213-Dombek1]; post-translational modification of the protein [@pone.0003213-Sloan1]; and access to, or ability to stably bind promoters [@pone.0003213-Young2], [@pone.0003213-Tachibana1]. The latter two mechanisms appear to be the most critical, because in glucose-repressed cells, raising Adr1 protein levels to be comparable to those in derepressed cells does not activate transcription of *ADH2* or other Adr1-regulated genes [@pone.0003213-Sloan1], [@pone.0003213-Voronkova1]. Adr1 does not bind its cognate promoters in these conditions, so even at elevated protein levels, post-translational and promoter-binding regulation keep its activity in check [@pone.0003213-Sloan1], [@pone.0003213-Young2].\n\nSeveral lines of evidence suggest regulation of Adr1 binding and activity by post-translational modification. Derepression of the Adr1-regulated gene *ADH2* can occur in the absence of protein synthesis [@pone.0003213-Sloan1]. Snf1, a central kinase in transcription of glucose-regulated genes, is required for Adr1 promoter-binding [@pone.0003213-Young2]. Snf1 is the yeast homolog of the AMP-activated protein kinase, and activation of Snf1"
+"The conclusion of [@b10-ehp0115-a00126] that \"Exposure to *Pfiesteria* Species in Estuarine Waters Is Not a Risk Factor for Illness\" is unsupported because *a*) a description of *Pfiesteria*-related fish kills in the Chesapeake estuaries during 1999--2002 was omitted; *b*) quantitative data on *Pfiesteria* were not collected; *c*) data on visual contrast sensitivity (VCS) were collected but not reported; *d*) a comprehensive list of other results was not presented; and *e*) data were lost due to a 30% attrition rate. These data are needed to justify or negate the conclusion.\n\nSince the first reports of environmental *Pfiesteria*-related illness ([@b12-ehp0115-a00126]) and successful treatment ([@b13-ehp0115-a00126]), all reports were associated with concurrent *Pfiesteria*-related fish kills ([@b4-ehp0115-a00126]). Numerous kills were reported in the Chesapeake and North Carolina estuaries through 1998 in association with *Pfiesteria*-like zoospore concentrations of 600--35,000 cells/mL water ([@b1-ehp0115-a00126]). [@b2-ehp0115-a00126] previously reported relationships between impairment and increased time spent in Chesapeake estuaries. Although the degree of recovery could not be determined because premorbid data were unavailable, most of the untreated participants improved within 3--6 months. However, in 1999--2002 neither Maryland nor North Carolina reported *Pfiesteria* concentrations reaching 600 cells/mL and associated fish kills ([@b9-ehp0115-a00126]; [@b11-ehp0115-a00126]). [@b10-ehp0115-a00126] used a polymerase chain reaction (PCR) method to"
+"Large accumulations of algae, or harmful algal blooms (HABs), can release toxins and contribute to oxygen-depleted \"dead zones\" in waters, causing human health problems and disrupting food webs.[@r1] Costs associated with closed fisheries and beaches caused by marine HABs total at least \\$82 million annually[@r2]; freshwater HABs can complicate water treatment and decrease recreational revenue, accounting for millions more in costs.[@r3] Now consortia of researchers across the country are developing forecasts to help local public health officials better monitor and respond to HABs.\n\nAnthropogenic nutrient enrichment and a warming climate are contributing to increased frequencies, intensities, and distributions of freshwater cyanobacteria HABs worldwide.[@r1]^,^[@r4]^,^[@r5] When cyanobacteria covered much of Lake Erie's western basin in July 2011, levels of the cyanotoxin microcystin-LR reached 1,000 \u00b5g/L in near-record[@r6] water temperatures averaging just above 77\u00b0F.[@r7] An Ohio Department of Health representative reports nine probable cases of algal-caused illnesses in Ohio in 2011 (unpublished data); however, many cases of illness attributable to HABs, especially milder cases, are probably never reported.\n\nAlthough reports of marine HABs---which include blooms of the dinoflagellates *Karenia brevis* and *Alexandrium* spp. and the diatoms *Pseudo-nitzschia* spp.---appear to be increasing,[@r1] researchers lack the long-term data sets needed to prove incidences really are"
+"Antimicrobial drug--sensitive bacteria become resistant to antimicrobial drugs through a variety of mechanisms, such as chromosomal mutations that up-regulate the expression of antibiotic-resistance genes, DNA uptake through transformation, or the process of conjugation. The ability of plasmids to evolve independently of their hosts has allowed numerous resistance genes from diverse species of bacteria to assemble within single plasmids and spread into a wide variety of organisms ([@R1]). The mobilization of a chromosomal resistance gene to a plasmid is an important event because the mobilized gene is now capable of spreading widely throughout diverse species of bacteria and because the fitness advantage that a plasmid confers generally increases as it acquires more resistance genes ([@R1]).\n\nThe class A \u03b2-lactamases have been the most frequently encountered plasmidic resistance genes. Class A \u03b2-lactamases from the TEM group have occurred at a particularly high frequency; in many surveillance studies, they have been identified as the resistance determinants most frequently encountered ([@R2]--[@R9]). The first *bla*~TEM~ allele, *bla*~TEM-1~, is a plasmidic allele that was first isolated in 1963 ([@R10],[@R11]). Currently, \u2248160 different plasmidic alleles encode unique TEM \u03b2-lactamase enzymes ([www.lahey.org/Studies](http://www.lahey.org/Studies)), and all are descended from a single plasmidic ancestor, *bla*~TEM-1~ ([@R12]).\n\nThe SHVs are another group"
+"Introduction {#s1}\n============\n\nAlkaloids play key roles in plant ecology by targeting the central and peripheral nervous systems of invertebrate and vertebrate animals, affecting their behavior, eliciting toxicoses, and reducing herbivory [@pgen.1003323-Wink1]. Alkaloids are very common in plants as well as certain plant-associated fungi, particularly those in the family Clavicipitaceae. Plant parasites such as *Claviceps* species often produce high levels of ergot alkaloids or indole-diterpenes, probably to defend their resting and overwintering structures (commonly called ergots) [@pgen.1003323-Paoutov1], [@pgen.1003323-Uhlig1]. A closely related group of fungi, the epichloae (*Epichlo\u00eb* and *Neotyphodium* species) live as systemic symbionts of grasses, and produce a wide array of alkaloids that combat various herbivorous animals, a key determinant of mutualism in many grass-endophyte symbioses [@pgen.1003323-Schardl1], [@pgen.1003323-Iannone1].\n\nFungi of family Clavicipitaceae are generally biotrophs that grow in invertebrates, fungi, or plants. The major clade of plant-associated Clavicipitaceae [@pgen.1003323-Spatafora1] includes mutualistic symbionts as well as plant pathogens, many of which produce alkaloids with diverse neurotropic effects on vertebrate and invertebrate animals with important implications for human health, agriculture and food security [@pgen.1003323-Schardl2], [@pgen.1003323-Clay1]. Most species of plant-associated Clavicipitaceae grow in or on grasses, but the group also includes systemic parasites of sedges or other plants, and heritable symbionts of"
+"Introduction\n============\n\nBlood pressure levels tend to aggregate in families due in part to shared genetic predispositions. In fact, about 40% of the variability in blood pressure is explained by genetic factors and the risk of developing it after age 50 doubles for each first-degree relative with a history of hypertension[@B01]. Blood pressure is regulated by multiple mechanisms involving several non-allelic genes with small additive effects. Although the specific mechanism altered cannot be identified in about 90% of cases, the individual genetic variants (alleles) or combinations of alleles (haplotypes) involved in the regulation of blood pressure are genetic factors with more likelihood of increasing the risk of developing hypertension.\n\nGenetic variants or polymorphisms associated with the regulation of urinary excretion of sodium and vasomotor regulation are potential risk factors for the development of hypertension. Among the former are the polymorphisms 448g\\>T or R65L or rs2960306, 679C\\>T or A142V or rs1024323 and 1711C\\>T or A486V or rs1801058 of the gene GRK4 that encodes the kinase 4 of receptors coupled to the G protein, specifically D1 and D2 dopamine receptors, which mediate the natriuretic effect of catecholamine in the proximal convoluted tubule of the nefron[@B02]. Among the latter are the highlighted polymorphisms"
+"Introduction {#cox042s1}\n============\n\nIn response to harsh conditions, many species appear to be more frequent under canopies of adult plants of other species which provide a less stressful micro-environment ([@cox042C15]). This association has been called 'nurse plant syndrome' ([@cox042C27]) or 'nurse--prot\u00e9g\u00e9' interaction ([@cox042C11]). Cactaceae is a plant family in which many species grow primarily under nurse plants ([@cox042C16]). Relationships can vary between cactus species and environments and perhaps multiple causes could be involved in facilitation by nurse plants ([@cox042C38]; [@cox042C26]). Thus, shade can be beneficial by reducing overheating, excessive transpiration and photoinhibition that plants growing in open areas may experience ([@cox042C16]; [@cox042C28]). However, shade may also represent a cost for the cacti in terms of photosynthetically active radiation because it could induce stress by limiting photosynthesis and arrest plant development ([@cox042C23]). Some cactus species, however, occur equally under nurse plants and in open spaces ([@cox042C22]), for which the mechanisms avoiding photoinhibition are unknown.\n\nPhotoinhibition is defined as any downregulation of the photosynthetic apparatus in response to excess light when more sugar is produced in leaves than can be utilized by the rest of the plant and/or more light energy is harvested than can be utilized by the chloroplasts for the"
+"Introduction {#section1-2058-5241.5.190032}\n============\n\nFrozen shoulder, despite being a common and debilitating complaint, is a subject of considerable uncertainty both within scientific literature and clinical practice. Even its name is a topic of serious contention in the medical profession; across papers published over the past 70 years, alternative names put forward or utilized in leading journals have included 'adhesive capsulitis',^[@bibr1-2058-5241.5.190032]^ 'fibrotic capsulitis',^[@bibr2-2058-5241.5.190032]^ 'primary idiopathic stiff shoulder',^[@bibr3-2058-5241.5.190032]^ and 'contracture of the shoulder'.^[@bibr4-2058-5241.5.190032]^ These terms have all been applied to the painful, debilitating contraction of the shoulder^[@bibr5-2058-5241.5.190032]^ which has been the subject of many attempts at definition. Most of these attempts do not deviate far from that given by Codman in 1934,^[@bibr6-2058-5241.5.190032]^ usefully provided in updated terminology by Bunker in 2009:\n\n1.  'This is a condition which comes on slowly with pain over the deltoid insertion, inability to sleep, painful incomplete elevation and external rotation, the restriction of movement being both active and passive, with a normal radiograph, the pain being very trying and yet all patients are able to continue their daily habits and routines.'^[@bibr4-2058-5241.5.190032]^\n\nThere have been very few notable improvements on Codman's definition. For example, the American Shoulder and Elbow Surgeons (ASES) in their 2011 consensus paper provided the following"
+"Non-specific presenting symptoms and the rarity of childhood cancer can result in diagnostic delays ([@bib5]). As described by [@bib17], these can result from prolongation of the patient/parent appraisal interval (time from symptom onset to first medical presentation, that is, 'parent- or patient-associated delays\\') or the diagnostic interval (time from first presentation to the time of histopathological diagnosis or first diagnosis-specific healthcare, that is, 'healthcare-associated delays\\'). Numerous risk factors for delays have been investigated for both paediatric and adult cancers, with cancer type and stage, parental education, age, nature of presenting symptoms and understanding of symptom significance implicated ([@bib5]; Quaife *et al*, 2014).\n\nPoorer outcomes are often attributed to long diagnostic times and many paediatric medical malpractice suits revolve around alleged delays ([@bib18]). However, although rapid diagnoses improve survival in many adult cancers ([@bib1]) and in retinoblastoma ([@bib6]; [@bib14]), the prognostic implications of diagnostic delays on other paediatric cancers remain unclear ([@bib2]; [@bib9]; [@bib18]).\n\nThe implications of delay on aspects other than survival have not been widely studied. Few articles address the psychological challenges associated with childhood cancer diagnosis ([@bib7]; [@bib4]; [@bib8]). These studies suggest that significant delays may have profound emotional impacts; however, they do not explore interviewees\\' perceived implications"
+"INTRODUCTION {#sec1-1}\n============\n\nThis article narrates a few of my experiences and their effects on my understanding, selected for their novelty. Some of NIMHANS alumni may remember having heard bits and pieces of these experiences. The experiences profoundly influenced my clinical conduct by: (i) affecting the manner of my 'professional' cognition, (ii) prompting me to develop few constructs or concepts for bringing about some semblance of holism to my understanding, (iii) contributing to gradual emergence of a few ideas as principles of therapy that I try to adapt in my therapeutic work. I suspect that most fellow professionals would have encountered similar experiences and arrived at similar or different conclusions. After all, variability is a characteristic of natural phenomena in every dimension of its manifestation. If we can pool such experiences, some principles may eventually emerge, common to most professionals. Consequently, I hope that the following narrative will prompt the reader to reflect on them. I expect that, in the long run, investigative-psychiatry will accord equal importance to subjective experiences and their possible validity, leading to enrichment of psychotherapeutic literature.\n\n'SCIENTIFIC PRECISION,' OR PROBABILITIES AND 'SPECTRUMS'? {#sec1-2}\n=========================================================\n\nI followed-up same patients for over 3\u00bd years while working at Napsbury"
+"Background\n==========\n\nIt is widely understood that in evaluating the ethical aspects of medical and psychological research, ethics committees typically apply a common set of secular principles to all project proposals.\\[[@B1]\\] The four clusters of principles are respect for autonomy, nonmaleficence, beneficence and justice. Autonomy (derived from the Greek *autos* \\'self\\' and *nomos* \\'rule\\') relates to the freedom of people to make intentional decisions independent from controlling influences. Nonmaleficence is the obligation to do no harm, whereas beneficence relates to helping others and promoting good. Justice is the impartial, equitable and appropriate treatment of all -- the fair distribution of benefits, risks and costs.\n\nThese principles are not necessarily complimentary and may be conflicting or at times even mutually exclusive. This may require balancing of one principle against another. There is a *prima facie* obligation to fulfil a principle unless a stronger obligation overrides this on a particular occasion. The safety of, and benefit to, the individual is usually considered to take precedence. For example, should an individual participant be at any risk of harm then the potential good to society or future individuals with relevant needs must heavily outweigh the potential risk.\\[[@B2]\\]\n\nA primary function of an ethics committee"
+"Pr\u00e8s de 30 % des infections respiratoires d'origine virale sont caus\u00e9es par des virus non encore identifi\u00e9s. Cependant, le d\u00e9veloppement d'approches mol\u00e9culaires a permis de s'affranchir d'une contrainte de la virologie traditionnelle, l'isolement de virus en culture. Ces nouvelles techniques ont permis d'identifier les g\u00e9nomes de nouveaux virus directement sur pr\u00e9l\u00e8vements chez les malades, sans n\u00e9cessit\u00e9 de les cultiver en laboratoire.\n\nSix virus respiratoires importants ont \u00e9t\u00e9 identifi\u00e9s depuis 2001 : les m\u00e9tapneumovirus humains, le coronavirus du SRAS, le coronavirus NL63, le coronavirus HKU1, les bocavirus humains et, d\u00e9but 2007, un nouveau membre de la famille des *Polyomaviridae*, le virus KI. Cette famille comprend aujourd'hui 4 virus capables d'infecter l'homme : BK et JC, probablement pr\u00e9sents \u00e0 l'\u00e9tat latent chez 75 et pr\u00e8s de 100 % des adultes respectivement, KI, dont on sait encore peu de choses, et SV40, un virus de singe dont la transmission \u00e0 l'homme fait actuellement d\u00e9bat.\n\n![](fx1.gif)\n\nL'\u00e9quipe de David Wang vient de caract\u00e9riser un nouveau polyomavirus : le virus WU, \u00e0 partir d'une aspiration naso-pharyng\u00e9e chez un enfant de 3 ans pr\u00e9sentant des signes de pneumonie. Le g\u00e9nome viral, clon\u00e9 fragment par fragment \u00e0 partir de l'\u00e9chantillon, a \u00e9t\u00e9 enti\u00e8rement reconstitu\u00e9 et s\u00e9quenc\u00e9. D'apr\u00e8s"
+"*Motor sensation* is defined as sensation induced by body movements, including cutaneous and proprioceptive sensations induced by voluntary and involuntary movements. Motor sensation provides feedback that enables perception of the body's position and accurate movements during motor learning (Brindle, Mizelle, Lebiedowska, Miller, & Stanhope, [@CR5]; Khoshnoodi, Motiei-Langroudi, Omrani, Ghaderi-Pakdell, & Abbassian, [@CR24]). Thus, a lack of motor sensation causes inaccurate movements. For example, if tactile sensation of the tongue is diminished by treatment with lidocaine or capsaicin, the accuracy with which the subject can control a prosthetic device with the tongue is reduced (S. A. Boudreau, Hennings, Svensson, Sessle, & Arendt-Nielsen, [@CR3]). Motor sensation is also used in cognitive learning. Cutaneous and proprioceptive sensations induced by finger and arm movements can facilitate recognition of an object's shape through touch (Heller, [@CR16]; Heller & Myers, [@CR17]; Yoshioka, Craig, Beck, & Hsiao, [@CR34]). Thus, motor sensation is involved in various learning processes.\n\nInduction and emphasis of motor sensation may facilitate learning. For example, in rehabilitation, walking speed and distance improve through forced movement (Colombo, Joerg, Schreier, & Dietz, [@CR9]; Fleerkotte et al., [@CR11]; Hesse, Uhlenbrock, Werner, & Bardeleben, [@CR18]; Hidler et al., [@CR19]; Hornby et al., [@CR20]). In addition, emphasis of motor"
+"FDA Status: Not Applicable\n\n**Summary:** dGEMRIC is able to detect the earliest cartilage damage in asymptomatic patients with FAI, the results of this study confirm that cam morphology is associated with progressive localised cartilage damage within the superior lateral acetabulum and that dGEMRIC scanning is able to predict radiographic progression of osteoarthritis secondary to cam morphology.\n\n**Background:** The diagnosis of early osteoarthritis is essential to enable the development of new therapies. Delayed Gadolinium Enhanced MRI of Cartilage (dGEMRIC) can detect cartilage damage in asymptomatic hips with cam morphology but without radiographic evidence of degenerative change. Furthermore, the degree of glycosaminoglycan depletion correlates with the magnitude of the cam deformity. It may eventually be possible to select asymptomatic individuals with cam morphology for intervention to prevent future osteoarthritis, yet at present there remains only limited evidence that baseline dGEMRIC values predict disease progression.\n\n**Objective:** To explore whether dGEMRIC values correlate with the size and position of cam morphology and determine whether baseline dGEMRIC predicts radiographic osteoarthritis progression at five-year follow-up.\n\n**Design:** Prospective study of individuals with a family history of osteoarthritis who underwent clinical evaluation, radiographic, and dGEMRIC assessment at baseline and five year follow-up. Cam morphology was defined as an"
+"It seems that history repeats itself. Yet again, in the 21^st^ Century, chloroquine (CQ) and hydroxychloroquine (HQ) are involved in deciding the outcome of battles that will change the course of history. But in today\\'s battle against COVID\u201019, the question is whether chloroquine is a weapon of good or bad. Use of the extract of the bark of the *Cinchona officinalis* to fight fever has been taking place for centuries (originally in Peru) being introduced in Europe in 1663 by the Spanish Conquistadors. Quinine was also instrumental in protecting invaders in their bid for conquest; most notably the English in India and the Dutch in the Indonesian islands. In the American secession war, the Peruvian bark extract was, at that time, exported by sea. The northern coalition that dominated the sea during the war blocked the supply to the South. It has been estimated that for every three soldiers killed in battle another five were killed by malaria. Clearly this medicinal product played a major part in the outcome of this American war. Today, again history repeats, and yet again this drug is likely to play a major part in determining the politics of the USA.\n\nIn the 19^th^ century,"
+"1. Introduction {#s0005}\n===============\n\nCrude petroleum is an unrefined petroleum hydrocarbon mixture which has from simple to complex structures such as resins, asphaltenes and others. Chemically, it is composed of hydrogen, carbon, sulphur, nitrogen, oxygen and metals [@b0005]. Polar compounds contained in crude petroleum contain heteroatoms of oxygen, nitrogen or sulphur and are ascertained by so many names, including heterocyclics, resins and NSO~3~ [@b0010]. Heterocyclic compounds of crude petroleum may be composed of metals in salts of carboxylic acids form or distinctively as porphyrin chelates or organo-metal complexes [@b0010], [@b0015]. When it is refined, its contents entail different fractions which are majorly used as fuels. The nearly unavoidable importance of these fractions is what makes them in constant and daily contact with human such as petrol, diesel and lubricating oils for powering automobiles, kerosene for cooking, and heavy gas oils for tarring roads [@b0005]. Over the years, the increased trend in the domestic and industrial utilization of crude petroleum and its products has necessitated its concomitant exposure of humans and other animals to its high level risk [@b0020]. In certain cases, these products such as kerosene, diesel, and gasoline find itself into the food chain and gradually build up its"
+"Introduction {#Sec1}\n============\n\nTerahertz (THz) frequency technology has stimulated a major surge in interdisciplinary research over the last decade, inspiring both fundamental insights and new applications in microscopic^[@CR1]^ and macroscopic systems^[@CR2]^, as well as highlighting potential new research avenues in the fields of biomedical imaging, astronomy, security, and high-resolution sensing, for example. The quantum cascade laser (QCL)^[@CR3]^ has been central to this, and has elevated THz photonics to a new level of performance, and possibility. The groundbreaking QCL design, which exploits intersubband transitions between electronic wave functions engineered on a nanometer scale, enables the optical dispersion, carrier transport and gain spectrum to be tailored, allowing a wealth of unique physical properties and operational characteristics to be achieved.\n\nThe development of modern nanofabrication technologies, combined with new laser resonator concepts, have recently enabled the control and confinement of electron and photon paths in optoelectronic devices with an unprecedented degree of control. For example, microcavities^[@CR4]^, photonic crystals^[@CR5],[@CR6]^, and both pseudo-random^[@CR7],[@CR8]^ and random^[@CR9]^ photonic structures, can manipulate and confine light in small volumes, and at targeted frequencies. This has further expanded the functionality of the THz QCL, allowing operation at a single emission frequency^[@CR7]^ or over a broad (0.5\u2009THz) frequency bandwidth, or"
+"Introduction\n============\n\nGlial cells mediate the crosstalk between neurons and vascular cells, and in particular communication within the retinal neurovascular unit [@B1]. Retinal neurodegeneration is accompanied by glial activation and vasoregression, which is characterized by pericyte loss and subsequent acellular capillary formation [@B2]-[@B4], as demonstrated in a model of ciliopathy-associated retinal degeneration [@B5], [@B6]. Ciliopathy is a group of human genetic disorders such as Bardet-Biedl syndrome, polycystic kidney diasease (PKD) and retinitis pigmentosa, caused by the abnormal formation or function of cellular cilia. Ciliopathies often share common features such as retinal degeneration, brain anomalies, cognitive impairment, renal and liver dysfunction. Approximately 10-30 % of patients that suffer from ciliopathies, e.g. Senior Loken syndrome, show signs of retinal degeneration (retinitis pigmentosa). Also, mutations in nephrocystin 1-6 [@B7] and rhodopsin cause autosomal dominant retinitis pigmentosa [@B8]. The PKD rat is a model of induced ciliopathy arising from a transgene that overexpresses a truncated human polycystin-2 gene in the kidney, large and small intestine, pancreas and photoreceptors in the retina [@B6], [@B9]. In this model, vasoregression starts between 4 and 8 weeks after birth, and is accompanied by microglia activation. M\u00fcller glia undergo reactive gliosis and multiple cellular changes, including the redistribution of"
+"Introduction {#S1}\n============\n\nCutting edge, innovative science and technology creates a need for industry-specific training for scientists. Translation of discoveries into healthcare solutions is rife with pervasive, global challenges and an increased need for PhD level researchers and positions. However, most PhDs have little knowledge of industry trends, strategy and structure. Many PhD graduates and post-doctoral researchers are facing a difficult career path ahead, as faculty positions are in short supply as is the funding that is necessary to remain on the tenure track \\[[@R1]\\]. Hence, many PhDs find themselves in the precarious position of preparing for alternative paths, primarily working within the life sciences industry. In addition, industry jobs are competitive, especially as cutbacks in research and development (R&D) budgets limit the number of open positions. To be successful competing for the limited available jobs, we believe that scientists would benefit from training focused on translating their knowledge of academic R&D into a knowledge base more suitable to the industry setting.\n\nThe Clinical and Translational Science Awards (CTSA) initiative of the National Institutes of Health (NIH) National Center for Advancing Translational Science (NCATS) endorses educational and training programs that cultivate leaders in the biomedical research workforce \\[[@R2],[@R3]\\]. Our institution's"
+"**To the Editor**: We report findings from a household-based study on the protective effects of vaccination against pandemic (H1N1) 2009 among Japanese children. In Japan, prioritized vaccination started in October 2009, focusing on health care workers, pregnant women, persons with underlying diseases, and children 1--9 years of age. Only nonadjuvant split vaccines (inactivated) produced by 4 manufacturers (Denka Seiken, Tokyo, Japan; Kaketsuken, Kumamoto-shi, Japan; Kitasato, Tokyo, Japan; and Biken, Suita-shi, Japan) were used by the end of January 2010 ([@R1]). Because the protective effects of vaccination at the individual level are best measured by household data ([@R2]), we conducted a retrospective household survey involving 1,614 nonrandomly sampled households (i.e., based on area sampling of households across Japan, according to the regional population size, with a total of 6,356 household members), in which the earliest cases were diagnosed from October 2009 to mid-February 2010. Our study aimed to assess vaccine-induced reductions in susceptibility and infectiousness among children by using the household secondary attack rate.\n\nInfluenza cases were defined as confirmed cases (i.e., diagnosed by real-time PCR) or influenza-like illness (ILI) cases (i.e., in febrile patients \\[[\\>]{.ul}37.5\u00b0C\\] with cough and/or sore throat). The cases had to meet the following inclusion criteria for"
+"Introduction {#s1}\n============\n\nEvolutionarily conserved hair follicle cycling is thought to provide mechanisms for controlling the length of hair in specific body sites, and to allow the periodic shedding of fur in response to seasonal changes in mammals [@pgen.1000573-Stenn1]. The periodicity of the hair growth cycle ranges from approximately three-weeks in synchronized hair follicles of mouse dorsal skin to several years in hair follicles of human scalp where the follicles undergo an extended period of hair growth [@pgen.1000573-Paus1]. In mice, hair follicle morphogenesis is completed around postnatal day (P) 14, at which time the follicle enters a phase called catagen. During catagen, extensive apoptosis in the lower two-thirds of the follicle results in its dramatic regression, leaving intact the stem cell-containing bulge region. The hair follicle then goes through a relative quiescent phase referred to as telogen. Following telogen, the stem cells become activated, likely in response to inductive signals from the dermal papilla, and the follicle enters the growth phase characterized by active keratinocyte proliferation and differentiation known as anagen. During the first two natural hair growth cycles in mice, the follicles of the dorsal skin are synchronized in progressing through the cycle, allowing the study of the mechanisms"
+"Figure 1\u03b1-globin genes (green) can stay near (left) or stray away (right) from their home territories (red).On page 177, Brown et al. follow the nuclear positioning of the globin genes during erythroid differentiation and find that they are often close to each other during active transcription. However, such associations do not appear to be a requirement for transcriptional regulation, but rather a consequence of it.\n\nThe \u03b1- and \u03b2-globin genes are highly transcribed for a brief time during the maturation of red blood cells, with each gene producing about the same amount of mRNA. But the chromosomal contexts for the genes are very different. The human \u03b1-globin genes lie in a gene-dense subtelomeric region that is constitutively in an open chromatin conformation. The \u03b2-globin genes are in an AT-rich region that is open only during erythroblast development.\n\nAt the point of maximal transcription, the \u03b1-globin genes were frequently decondensed and distinct from their chromosomal territories. By contrast, the \u03b2-globin genes remained close to their native chromosome arms, as did the mouse \u03b1-globin genes, which lie in a less gene-rich region than their human counterparts.\n\nMoreover, the human \u03b1-globin alleles associated near one another in approximately half of the transcribing cells"
+"**Learning Point for this Article:**\n\nThe treatment of traumatic bone loss is difficult and under certain circumstances, in a disadvantaged environment, it may be necessary to reintegrate a bone fragment expelled on the ground with very satisfactory results.\"\n\nIntroduction {#sec1-1}\n============\n\nThe reconstruction of diaphyseal bone segments remains a major challenge in the conservation of limbs regardless of the etiology of bone defect. This problem is still poorly solved by classical techniques, and amputation of the limb is still relevant. The most common methods are vascularized bone transfer (fibula), the segmental transfer method according to Ilizarov, and the sequential method of the induced membrane according to Masquelet. Bone autograft is not recommended when the loss of substance exceeds 4---cm. Beyond 6 cm, autologous bone grafts undergo a phenomenon of resorption even in a well vascularized muscular environment \\[[@ref1], [@ref2]\\]. We report a 10 cm traumatic bone loss of the right distal femur which we treated by trimming, reintegration, and stabilization by an external fixator.\n\nCase Report {#sec1-2}\n===========\n\nMrs. M.S., aged 35, was in the back of a motorcycle driven by her husband when they were hit by a motor vehicle. She dropped on the tar with the open trauma"
+"The logistic regression model is the workhorse of epidemiological data analysis[@b1]. The model helps to clarify the relationship between multiple exposures and a binary outcome. Researchers can easily adjust for confounding factors and assess interactions by entering appropriate covariates into a logistic regression model. An (exponentiated) regression coefficient of a main-effect term in the model is an adjusted odds ratio, and a test of the regression coefficient of a cross-product term is a test for multiplicative interaction. Logistic regression analysis is readily implemented using existing statistical software, and this has contributed to it becoming a routine procedure for epidemiologists.\n\nLogistic regression is a generalized linear model with a 'logit' link function[@b2]. (A link function specifies how the exposure variables are related to the mean response.) Statistics textbooks often describe two other link functions for a binary outcome, the 'probit' and the 'complementary log-log' links, though these two link functions are less often used in epidemiology.\n\nIn this paper, we focus on a causal model which has recently received much attention from the epidemiologic community, namely, the sufficient-component cause model (causal-pie model)[@b1][@b3][@b4][@b5][@b6][@b7][@b8][@b9][@b10][@b11]. The model is mechanism-based, aiming at elucidating the possible mechanisms through which multiple exposures interact in causing an outcome."
+"Introduction {#Sec1}\n============\n\nImagine sitting on a train that has just stopped at a station. You gaze out of the window and see the carriages of another train at the adjacent track. After a while, you feel that your train is leaving the station, only to realize moments later that it is the other train moving while yours is still standing. In this case, you incorrectly attributed your visual sensation to a plausible external cause. However, the likelihood of your interpretation was high, given that the window view changes are similar, irrespective of which of the two trains move. Misinterpretations of the causes of sensory experiences do not happen very frequently in everyday life, because the world around us changes in somewhat predictable ways and ambiguous situations such as in the example above are rare. Our knowledge and prior experience help us to perceive and understand what happens around us so that we can act and respond appropriately and adaptively. The idea that prior experience shapes perception can be traced back to the seminal work on human perception by von Helmholtz^[@CR1]^. More recently, it became the cornerstone of predictive coding models of perception and cognition^[@CR2]--[@CR4]^. Predictive coding models assume cortical"
+"Very few institutions and organizations have been spared from fundamental coronavirus 2019 (COVID-19) impact. This most certainly includes professional medical societies. Although some change has been wrought directly by the pandemic itself, much has been secondary to a dramatic acceleration of trends that were underway already.\n\nToday's American Academy of Ophthalmology (AAO) first met in 1896 as the Western Ophthalmic and Oto-Laryngologic Society to serve \"the interests of men who combined all three specialties in their practices.\"[@bib1] (At that time, otology and laryngology were considered separate practices.) In 1903, it was renamed the American Academy of Ophthalmology and Oto-Laryngology. The following year, the first woman was elected to membership and \"men\" became \"men and women.\" Its interests were interpreted broadly. As early as 1903, the American Academy of Ophthalmology and Oto-Laryngology contacted public health authorities across the country regarding streetcars, noise pollution, and the latter's effects on hearing.[@bib2]\n\nThe member value proposition for major medical specialty societies such as the AAO diversified over ensuing generations. Although the primary value has always been education (as reflected in regular member surveys), advocacy and federal and state government relations have emerged a solid second in the value pantheon. Others include practice management resources,"
+"Summary of Chapters {#Sec1}\n===================\n\nThroughout the book chapters, researchers have highlighted the recent advancement in microfluidic areas, particularly those involving microdroplets.\n\nSimon and Lee focused on microfluidics droplet manipulations and applications, including droplet fusion, droplet fission, mixing in droplets, and droplet sorting. By combining these operations, they have shown promising applications in executing chemical reactions and biological assays at the microscale.\n\nDay and Karimiani discussed dropletisation of bio-reactions.\n\nZhang and Liu elaborated the physics involved in multiphase flows and microdroplets dynamics. They emphasized the important dimensionless parameters relating to droplet dynamics with droplet generation process as an example.\n\nBarber and Emerson discussed the fundamental droplet handling operations and the recent advances in electrowetting microdroplet technologies. They also provided an overview of droplet-based electrowetting technologies in biological and chemical applications.\n\nDroplet-based microfluidics as a biomimetic principle in diagnostic and biomolecular information handling were highlighted by K\u00f6hler addressing potential of applying segmented fluid technique to answer to the challenges of information extraction from cellular and biomolecular systems.\n\nUsing the flow rates, applied pressures, and flow rate ratios in a closed feedback system, the active control of droplet size during formation process in microfluidics was achieved by Nguyen and Tan.\n\nVelev, Petsev,"
+"INTRODUCCI\u00d3N {#sec1-1}\n============\n\nLos adenomas hipofisarios son de los tumores m\u00e1s frecuentes del sistema nervioso central, siendo la p\u00e9rdida visual el s\u00edntoma m\u00e1s com\u00fan, alcanzado una incidencia de hasta el 70%.\\[[@ref1][@ref16]\\] La indicaci\u00f3n e importancia de la descompresi\u00f3n de la v\u00eda \u00f3ptica mediante la ex\u00e9resis quir\u00fargica de estas lesiones radica en evitar la progresi\u00f3n de los da\u00f1os estructurales de la v\u00eda visual y permitir la restituci\u00f3n de los da\u00f1os funcionales, siendo el grado de recuperaci\u00f3n postoperatorio dif\u00edcil de determinar y variable entre los pacientes.\\[[@ref14]\\] La evaluaci\u00f3n oftalmol\u00f3gica preoperatoria resulta, por lo tanto, relevante siendo la campimetr\u00eda computarizada el estudio de elecci\u00f3n para la determinaci\u00f3n de la funci\u00f3n visual. Sin embargo, esta resulta una medici\u00f3n subjetiva que requiere la colaboraci\u00f3n, atenci\u00f3n y compresi\u00f3n por parte del paciente para que arroje resultados v\u00e1lidos. A partir de la introducci\u00f3n de nuevas tecnolog\u00edas en los \u00faltimos a\u00f1os, se han incrementado los esfuerzos para mejorar la evaluaci\u00f3n de los pacientes y poder determinar aquellos que tendr\u00e1n m\u00e1s posibilidades de recuperaci\u00f3n o incluso normalizaci\u00f3n del d\u00e9ficit visual. Los potenciales evocados visuales multifocales y la tomograf\u00eda de coherencia \u00f3ptica (TCO) de la capa de fibras nerviosas de la retina surgen como herramientas diagn\u00f3sticas que proveen informaci\u00f3n valiosa"
+"![Jaouad Hammou](jceh_30_98_039_f01){#F1}\n\n![Gardachew Tiruneh](jceh_30_98_039_f02){#F2}\n\n![Abebaw Kebede](jceh_30_98_039_f03){#F3}\n\n**Children can be effective behaviour-change ambassadors and schools can act as key sites for health interventions to combat trachoma, especially when awareness forms part of the curriculum. These examples from Morocco and Ethiopia illustrate the important role that schools can play in efforts to end trachoma.**\n\n![Young girls practising good hygiene in the South Gondar zone. ETHIOPIA](jceh_30_98_039_f04){#F4}\n\nChildren are particularly vulnerable to ocular *C. trachomatis* infection, which causes trachoma. The bacteria can spread easily to siblings and playmates via flies, towels and dirty hands. Good hygiene and facial cleanliness form part of the World Health Organization (WHO) SAFE strategy: Surgery to correct trichiasis, Antibiotics to reduce active infection, and Facial cleanliness and Environmental improvements to reduce transmission. School-based trachoma interventions provide an opportunity to raise children\\'s awareness of the importance of hygiene. Typically, these interventions involve students learning about the causes and consequences of trachoma and the behaviours they can adopt to avoid contracting the disease. They then, in turn, disseminate these messages further amongst their families and community members.\n\nMorocco was one of the first countries to implement the comprehensive SAFE strategy at scale. Progress was rapid, thanks in large part to strong"
+"Public health interviews (i.e., partner services), during which persons with diagnosed human immunodeficiency virus (HIV) infection name their sexual or needle-sharing partners (named partners), are used to identify HIV transmission networks to guide and prioritize HIV prevention activities. HIV sequence data, generated from provider-ordered drug resistance testing, can be used to understand characteristics of molecular clusters, a group of sequences for which each sequence is highly similar (linked) to all other sequences, and assess whether named partners are plausible HIV transmission partners. Although molecular data in higher HIV-morbidity states have been analyzed ([@R1]--[@R3]), few analyses exist for lower morbidity states ([@R4]), such as Wisconsin, which reported 4.6 HIV diagnoses per 100,000 persons aged \u226513 years in 2016 ([@R5]). The Wisconsin Division of Public Health (DPH) analyzed HIV sequence data generated from provider-ordered drug resistance testing and collected through routine HIV surveillance to identify molecular clusters and describe demographic and transmission risk characteristics among pairs of persons whose sequences were highly genetically similar (i.e., molecular linkages). In addition, overlap between partner linkages identified during public health interviews and molecular linkages was assessed. Overall, characteristics of molecular clusters in Wisconsin mirrored those from states with more HIV diagnoses, particularly in that most"
+"Introduction {#s1}\n============\n\nGenetic variability in natural plant populations holds the potential to deal with multiple biotic and abiotic stresses. The potential to select a superior line increases with genetic diversity, the discovery of which becomes an important tool in plant breeding. On depletion of genetic variability, plants are unable to cope with unfavourable environmental conditions or pathogens and pests. Diversity studies also facilitate the conservation and management aims of a particular plant species. For the effective use of genetic diversity in plant breeding, knowledge of its extent and distribution plays a crucial role. Considering its significance, a large number of studies have been performed to estimate genetic diversity employing various methodologies in multiple plant species. Assessment of genetic variability employing molecular markers has proved to be a keystone to understanding the genomic constitution, categorizing the genes responsible for important traits, the classification and conservation of genetic variation in plant germplasm and developing selective proliferation approaches for plant propagation.\n\nWheat production in developing countries moved from defective to surplus ([@PLV083C50]) during the Green Revolution ([@PLV083C26]). Being a good source of carbohydrate, protein, sugar, fat, fibre and minerals, it provides half of the energy requirements of the human population ([@PLV083C60]; [@PLV083C58];"
+"The increase in identification of putative biomarkers and opportunities to develop tailored treatments are due to emergence of *omics* technologies. Application of pharmacogenetic knowledge with the help of quick and cheap companion diagnostics in the primary care setting is expected to deliver improved treatment and reduced heathcare costs. Warfarin and aspirin are the two most widely prescribed drugs for preventing cardiovascular diseases. Long term aspirin use has also been shown to reduce risk, recurrence and mortality from colorectal cancer. However, they both have narrow therapeutic windows and several genetic polymorphisms have been noted to influence their dose and efficacy. We therefore have launched two collaborative projects: first, to study the genetics of warfarin safety in the Gujarati Indian population and second, to identify further polymorphisms that modulates aspirin's colorectal cancer chemopreventive efficacy. Understanding the impact of polymorphisms on dose and efficacy for these drugs would lead to development of a combined panel of markers that would predict accurate therapeutic dose with minimal risk for adverse reactions. These markers will be deployed at the point of care settings using a novel handheld genotyping device which will use disposable microfluidic cassettes and silicon nanowires currently developed by QuantuMDx. Results, future work, opportunities"
+"The highly diversified *Trypanosoma cruzi* protozoan of the Order Kinetoplastida and family Trypanosomatidae is important in the medical and veterinary fields ([@B7]). American Trypanosomiasis, widely known as Chagas disease, is caused by *T. cruzi* infection and affects mammals. This disease is enzootic from the 42nd parallel north in Northern California down to the 42nd parallel south in the Chubut province of Southern Argentina, where the hematophagous triatomines (Reduviid: Triatominae) bugs agents transmit *T. cruzi* to hundreds of species belonging to eight classes of mammals. Amerindians readily acquired *T. cruzi* from insect vectors that fed on domesticated mammals, and the infections were then passed on to European and African settlers and their descendants ([@B27]). In the past century, these infections have become hyper-endemic to Latin America and are now present on five continents ([@B23], [@B1], [@B20]. Acute *T. cruzi* infections are often either asymptomatic or oligosymptomatic and self-limited, but chronically infected people may develop Chagas disease, which is now a leading cause of heart failure in the Western hemisphere. Chagas disease is a clinical condition observed in approximately 30% of people infected with *T. cruzi*; in most cases, the disease attacks the heart (94.5%), but it can also cause megacolon and"
+"Historically, a cautious approach to refeeding has been taken due to lack of evidence about refeeding syndrome. The aim of this study was to evaluate outcomes following the introduction of a more aggressive feeding protocol in a paediatric eating disorder program. This included commencing at a higher energy intake, more rapid energy increases and macronutrient manipulation of meal plans while maintaining a food based approach.\n\nA restrospective audit of 38 Austin Hospital patients admitted for medical stabilisation of their eating disorder, using rapid refeeding protocols, were compared to previous refeeeding protocols. Thirty-seven patients (97%) were commenced on 8.2 megajoules (MJ) or more and increased to 11 MJ within one week. Previously, 23 patients (60%) had commenced on 6.8 MJ or less. With more intensive feeding 30 patients (79%) gained more than the target of 1 to 1.5 kilograms per week (compared to 35% previously). Evidence of refeeding syndrome was identified and treated in only two patients (5%). Only one patient required a lower energy intake (6.5MJ) with reduced contribution to energy from carbohydrates (40%) due to high risk of refeeding syndrome.\n\nThese findings suggest more rapid refeeding can be achieved safely with a food based approach in this patient group."
+"1.. Introduction {#s1}\n================\n\nLarger birds and quadrupeds tend to support their weight during locomotion with more upright, relatively stiffer limbs \\[[@RSBL20130414C1],[@RSBL20130414C2]\\]. This has been attributed to the structural challenges imposed by scaling: geometrically similar forms of consistent material properties scale body weight in proportion to the cube of length, but strength scales in proportion to cross-sectional area---a square of length. More upright postures result in ground reaction forces passing closer to the joint centres, thereby reducing the externally applied moments and the mechanical loading on the supporting tissues. However, the geometric benefits of upright limbs would also apply to small animals, allowing them even lighter limbs for a given safety factor, or an improved safety factor for geometrically similar bones and muscles. To date, there has been no mechanical or energetic account for smaller animals benefitting from more crouched postures; some benefits relating to stability, manoeuvrability or control are generally suggested \\[[@RSBL20130414C1]--[@RSBL20130414C3]\\].\n\nTheoretically, minimal-work walking and running require biologically unachievable, infinite, 'impulsive' forces \\[[@RSBL20130414C4],[@RSBL20130414C5]\\]. Consider running: an exceedingly stiff, upright leg operating at a very low duty factor *\u03b2* (proportion of the stride period with the foot in contact with the ground) allows nearly vertical (albeit very high) forces,"
+"***Background.***\u2003Healthcare associated infections negatively impact patient outcomes and increase healthcare costs. Interventions have focused on specific risk factors, the presence or absence of indwelling urinary catheter for example, and interventions that could be applied across broadly have been limited. Following the publication of the experience with Chlorhexidine bathing on central line infections and MDRO acquisition in critically ill and bone marrow populations, we sought to examine the impact of this intervention on CLA-BSI, CA-UTI, and MDRO acquisition when applied to patients in both critical and acute care.\n\n***Methods.***\u2003This qausi-experimental study examined the impact of CHG-bathing to all patients (1) in an adult critical care unit or (2) on an acute care floor if the patient had a central line, indwelling urinary catheter, or colonized with CRE. At the request of the stem cell attending, allogeneic bone marrow transplant patients were excluded. The rate of device related infections where compared pre and post intervention.\n\n***Results.***\u2003For CAUTI, The average monthly rate per 1,000 IUC days fell from 4.3 prior to HG bathing to 2.8 post implementation (p-value \\<0.001). For CLA-BSI, the average rate for the whole hospital declined from 3.2/1,000 central line days to 0.88/1,000 central line days (p-value"
+"The Royal College of Psychiatrists has reduced its annual subscription rates to \u00a330 for members working in countries classed as B and C or D according to the World Bank criteria if their monthly income in 2008 is below \u00a31000. Further details are available from the College Membership Office.\n\nThe College's Faculty of the Psychiatry of Old Age has a bursary for psychiatrists practising in low-income countries in the field of mental health in older people, to attend the annual residential meeting in Barcelona on 5--6 March 2009. Further information is available from <kkottasz@rcpsych.ac.uk>.\n\nIn July 2008 the College launched a new grade of membership, Specialist Associateship, open to registered specialists who qualified abroad but who currently work in the UK. Further information is available from <latkinson@rcpsych.ac.uk>.\n\nThe Bangladesh Association for Child and Adolescent Mental Health (BACAMH) was launched in May 2008. Its mission is to promote the mental health of children, adolescents and their families through training, research, prevention and collaboration. See the Association's website, <http://www.bacamh.99homepages.com>."
+"Introduction {#s1}\n============\n\nFlowering is an important process essential for sexual reproduction, seed development and fruit production. Although flowering is composed of a series of typically irreversible sequential events, reversion from floral to vegetative growth is frequently observed in nature. Reversions can be divided into two categories: inflorescence reversion, in which vegetative growth is resumed after or intercalated within inflorescence development, and flower reversion, in which vegetative growth is resumed in an individual flower [@pgen.1000818-Tooke1],[@pgen.1000818-Battey1]. Reversion, which can serve a function in the life history strategy (perenniality) or reproductive habit (pseudovivipary), is essential for the life cycle of some plant species [@pgen.1000818-Tooke1],[@pgen.1000818-Battey1].\n\nVivipary in flowering plants is defined as the precocious and continuous growth of the offspring while still attached to the parent plant [@pgen.1000818-Elmqvist1],[@pgen.1000818-Goebel1]. Vivipary can be divided into two distinct types: true vivipary and pseudovivipary [@pgen.1000818-Elmqvist1]. True vivipary is a sexual reproduction process in which seeds germinate before they detach from maternal plant. On the other hand, pseudovivipary is a specific asexual reproductive strategy in which bulbils or plantlets replace sexual reproductive structures [@pgen.1000818-Elmqvist1],[@pgen.1000818-Coelho1]. Pseudovivipary has been widely recorded in monocots, in particular grasses that grow in extreme environments [@pgen.1000818-Tooke1], [@pgen.1000818-Elmqvist1], [@pgen.1000818-Coelho1]--[@pgen.1000818-Moore1]. Characteristics of the environments which favour"
+"Introduction {#s1}\n============\n\nSeveral non-human animal species are capable of using tools [@pone.0052074-Beck1], [@pone.0052074-Shumaker1]. However, capuchin monkeys, apes, and corvids are the species that have produced the most impressive examples [@pone.0052074-McGrew1], [@pone.0052074-Hunt1]. Among those are cases of sequential tool use in which a tool is used to obtain another tool, which subsequently will serve to obtain an out-of-reach goal (e.g., food). Nonetheless, instances of sequential tool use among non-human animals are rather scarce. Bird & Emery [@pone.0052074-Bird1] have argued that the difficulty in sequential tool use stems from three problems: First, the subject must recognize that one tool can be used on another or on nonfood items. Second, the subject must resist the immediate motivation to use the tool to attempt to access the food directly, and third, the individual must be capable of hierarchically organized behavior.\n\nIn the laboratory, one of the most common tasks to test sequential tool use consists of presenting subjects with a reward that is out of reach, a readily available tool that is not long enough to reach for the reward but long enough to reach for another tool, which can be used to reach for the reward. Subjects have to use the tools"
+"The topic of recent advances in information technology has attracted a wide range of articles on technology theory, applications from many aspects, and design methods of information technology. Reviewing the papers in this topic, it is clear that all fields such as computer science, cloud computing, wireless sensor network, prediction, image annotation, and storage have been involved. And the publications about recent advances in information technology tackled significant recent developments in the fields mentioned above, both of a foundational and applicable character.\n\nAlso, we can easily find that most contributors regard \"information technology\" as synonymous with tools such as the computer, mobile, and tablet and such issues as instructional design, mobile learning, social networking, and open sources. Through the topic\\'s development, research designs are appropriate for studying the potential of information technology applications under controlled situations.\n\nThis special issue includes a collection of 100 papers selected from 466 submissions to 36 countries or districts. All submitted papers followed the same standard (peer-reviewed by at least three independent reviewers) as applied to regular submissions.\n\nThe paper entitled \"*A self-adaptive parameter optimization algorithm in a real-time parallel image processing system*\" by G. Li et al. proposed an adaptive load capacity balance strategy"
+"Introduction\n============\n\nSince the first demonstrations of Huang *et al* in 1991,[@b1] the optical coherence tomography (OCT) technology has changed our understanding and consequently our practice of ophthalmology.[@b2] Recently, a significant part of published OCT studies concerned the management of idiopathic epiretinal membrane (iERM) and vitreomacular interface (VMI) diseases. The high sensitivity of OCT[@b3] as well as its very detailed three dimensional imaging when compared with stereoscopic ophthalmoscopy or photography[@b4] [@b5] allows clinicians to use this unique, non-invasive technique to fully visualise the dynamics of the epiretinal traction and the subtle structures in and around the VMI.[@b6] [@b7] As a result, the applications of the modern versions of the OCT have been extended beyond the diagnostic decision-making stage to more sophisticated purposes. Many studies have clearly confirmed the pivotal role of the OCT in all three main steps in the epiretinal membrane (ERM) management: (1) preoperatively: giving a comprehensive view of the pathophysiology of the ERM[@b3] and additionally to provide a fine structural assessment of the retinal layers and the VMI;[@b8] [@b9] (2) intraoperatively: guidance of the surgeon, based on preoperative OCT images, in the membrane peeling process;[@b10] [@b11] and (3) postoperatively: predicting the course of macula recovery after membrane"
+"Background\n==========\n\nA recent study showed that lumbar epidural steroid injections increased osteoporotic spine fracture risk.\n\nAim\n===\n\nWe further evaluated associations between steroid injections and osteoporotic fracture risk by analyzing the Medicare database and including large joint and transforaminal steroid injections; as well as osteoporotic hip and wrist fractures. A systemic effect would increase risk in all fracture locations regardless of injection site. A local effect would result in a disproportionate increased risk of spine fractures when steroids were injected into the spine.\n\nDesign\n======\n\nEpidemiological study using national administrative data.\n\nMethods\n=======\n\nPatients who had a steroid injection into the epidural space (ESI), transforaminal space (TSI) or large joint (LJSI) were identified. Patients younger than 65 and those diagnosed with a prior osteoporotic fracture were excluded. Patients were followed continuously until fracture, withdrawal from Medicare or death. Kaplan-Meier survival and Cox regression analysis were performed to determine adjusted fracture risk (Adjusted Hazard Ratio (HR)) for each type of injection, accounting for patient characteristics such as age, sex, Charlson Comorbidity Index (CCMI), Cushing's syndrome or long term steroid use.\n\nResults\n=======\n\nOsteoporotic spine fracture risk after ESI, TSI or LJSI was influenced by age, race, sex and CCMI. The"
+"Background\n==========\n\nThe International Cowden Consortium (ICC) created operational diagnostic criteria that specify gastrointestinal (GI) hamartomas as a minor criterion. Previous review of reported case studies found that 35-85% of Cowden syndrome (CS) patients had GI hamartomas. Our goal is to describe the GI phenotype of our PTEN mutation positive (+) series.\n\nMethods\n=======\n\nBlood was collected for PTEN mutation analysis and medical records were requested to document diagnoses. Patients who are PTEN+ with \u22655 GI polyps, \u22651 of which is hyperplastic (hyp) or hamartomatous (ham, n=4) or who met relaxed ICC criteria (n=118) were analyzed. Upper and lower GI endoscopy and pathology reports were reviewed and findings are reported descriptively. Fisher\\'s 2-tailed exact test and unpaired T-tests were utilized for comparison of PTEN+ patients with and without polyps.\n\nResults\n=======\n\nOut of 122 PTEN+ patients, 64 underwent \u22651 endoscopy, and 60(50%) had polyps or colorectal cancer (CRC). Average age at first colonoscopy and upper endoscopy was 37yrs (range: 2-73) and 40 (2-73) respectively. Number of polyps ranged from 1-innumerable. Polyps were found in the colorectum, ileum, duodenum, stomach, and esophagus. Pathology includes serrated adenomas; ham, hyp, adenomatous (ade), and inflammatory polyps; lymphoid aggregates; neuromas; lipomas; and ganglioneuromas. 16 patients"
+"Thyroid cancer is the most common endocrine malignancy. Around 5% of the general population have palpable thyroid nodules and this number increases to 50% with the use of ultrasonography[@b1]. Although most nodules are benign, there were estimated \\~300,000 newly diagnosed thyroid cancer cases worldwide in 2012, 2.1% of all newly diagnosed cancers[@b2]. Most thyroid carcinomas arise from the thyroid follicular cells and the vast majority can be grouped into two histological types: follicular (10--15% of cases) and papillary (80--85% of cases) thyroid carcinoma or FTC and PTC, respectively, commonly referred to as differentiated thyroid carcinomas (DTC)[@b3].\n\nThe World Health Organisation defines PTC as 'a malignant epithelial tumour showing evidence of follicular cell differentiation and characterised by distinctive nuclear features'[@b4]. Accordingly, although the papillary architecture is a distinctive trait of classic PTC (two-thirds of cases), the formation of papillae is not a requirement for PTC diagnosis. On the other hand, the definition of FTC is based on malignancy and lack of the diagnostic nuclear features associated with PTC. About 50% of PTC cases present cervical lymph node metastasis (LNM) and distant spread is present in up to 20% of FTC. Both histotypes present good overall prognosis but survival rates drop in"
+"The demands on clinical care systems, disruptions to educational institutions, economic chaos, and societal upheaval that the COVID-19 pandemic has brought on are unprecedented in our collective memories. To call this an existential crisis for academic medical centers (AMCs) may be hyperbole, but at a minimum it has wrought a defining moment. The rapidity and breadth of creative innovations developed in response to the crisis and implemented across AMCs and their missions are also unprecedented. When the pandemic has subsided, the world will have changed. What will the legacy of the 2020 COVID-19 pandemic be for medical educators and U.S. AMCs?\n\nFor years, commentators have noted that education and clinical care are 2 areas relatively unaffected by the disruptive changes that have transformed other sectors, ranging from banking to retail to manufacturing. Not because the need for transformational (not simply incremental) change was not identified, not because there were no innovative options available, not because leaders ignored the need,^[@R1]^ but because a host of barriers, ranging from payment to regulatory to the natural human inclination to resist change, all impeded the implementation of many innovations.\n\nIronically, now a biologic agent, the COVID-19 virus, seems to be the catalyst for disruption"
+"Introduction {#s1}\n============\n\nThe Rosetta software suite, an object-oriented protein structure prediction tool [@pone.0021931-LeaverFay1], can effectively perform protein structure prediction and design [@pone.0021931-Das1] [@pone.0021931-Kaufmann1]. Common tasks such as design, docking, and folding produce text files containing the Cartesian coordinates of each atom of the protein. Molecular visualization tools are used later to interpret the output [@pone.0021931-ODonoghue1]. Thus, visualization is typically separated from Rosetta. Output structures could be viewed after a simulation, but not during a calculation or protocol. Real-time structural visualization would facilitate development of new methods and make Rosetta more accessible to new users.\n\nRosetta protocols are useful to a broad range of scientists, but many protocols are complex. Scientists who are not trained in computation can become frustrated with Rosetta\\'s steep learning curve. Two new interfaces to Rosetta were built to bridge this gap. PyRosetta [@pone.0021931-Chaudhury1] is a Python-based interface to Rosetta objects and protocols enabling users to easily develop custom algorithms and to explore Rosetta through the Python interpreter. RosettaScripts [@pone.0021931-Fleishman1] provides an XML-scriptable interface to Rosetta allowing users to design custom algorithms. PyRosetta and RosettaScripts have successfully lowered the barrier to learn Rosetta by providing an interactive and scriptable layer. To further improve access to Rosetta,"
+"Introduction\n============\n\nFreshwater fish are listed among the most threatened organisms at the European level (Freyhof and Brooks [@b16]). Beside habitat destruction, water pollution and overharvest, the deliberate or accidental release of non-native fish is a major driver for the decline or loss of native species (Maitland [@b28]; Didham et\u00a0al. [@b11]; Freyhof and Brooks [@b16]). Stocking and translocation of non-native taxa can have a series of detrimental effects, with competition for habitat and trophic niches, predation, and disease transfer being often reported (Vitule et\u00a0al. [@b55]). Furthermore, the introduction of exotic taxa can lead to hybridization and varying degrees of genetic introgression, when closely related lineages are introduced and reproductive barriers are absent or incomplete (Allendorf et\u00a0al. [@b2]).\n\nStocking-induced secondary contact is particularly pronounced in salmonid species. This is given by their elevated socioeconomic importance and the general practice to \"enhance\" declining populations with hatchery fish. In many cases, stocking practices ignored the original genetic architecture of the concerning species, thus bringing into contact isolated populations or even highly divergent phylogenetic lineages (Su\u0161nik et\u00a0al. [@b51]). Theoretically, stocking might provoke different genetic consequences: no admixture, when life-history traits impede hybridization (Gandolfi et\u00a0al. [@b19]), partial admixture, when strong"
+"Introduction\n============\n\nAnesthetic goal during the conduct of neurosurgery is to maintain a balance between optimal cerebral hemodynamics and oxygenation. An ideal anesthetic should provide a slack brain and excellent analgesia and facilitate a rapid recovery. Dexmedetomidine is a superselective \u03b1-2 agonist that can reduce the consumption of anesthetics and provide optimum analgesia through its opioid-sparing property. [@JR_1] It facilitates an ideal anesthetic background for neurosurgery as it does not interfere with intraoperative neuromonitoring and has an opioid-sparing effect, with the added advantage of preserving the respiratory drive in the immediate postoperative period. [@JR_2] Neurosurgeries differ from routine general surgeries in terms of the longer duration and differing anesthesia concerns. [@JR_2]\n\nThe effect of dexmedetomidine in neurosurgeries has been evaluated in the past. However, these studies did not use the depth of anesthesia monitoring such as bispectral index scale (BIS) as an end point to titrate anesthetic drugs and therefore were inconclusive. [@JR_3] [@JR_4] Moreover, these studies had varying outcomes ranging from a delayed recovery to the recovery time remaining unaffected. [@JR_1] [@JR_2] [@JR_3] [@JR_4] The need for an early neurologic assessment in the postoperative period is of paramount importance in neuroanesthesia practice. Hence, a prompt recovery in the immediate"
+"Introduction {#s1}\n============\n\nIn constitutional states such as Switzerland, the use of coercion against persons requires explicit legal legitimation (see below); moreover, within this legal framework, ethical justification is regarded to be mandatory. Medicine and healthcare workers are, therefore, obliged to consistently justify any limitation of their patient's personal freedom within reason, specifically to prevent harm to the patient or others. Some of the questions regarding the use of coercion are, e.g.: How to appropriately manage an inpatient violating the house rules and refusing long-term medication? Is involuntary hospitalization of an incompetent patient with aggressive and self-harming behavior justified? Examples such as these illustrate that the lack of insight and cooperation as well as aggressive patient behavior are central issues that indicate not only a psychiatric context. Critically ill patients in somatic care may also trigger discussion on coercive measures. Coercion may concern treatment, diagnostic measures, patient location, accommodation, and social environment. It may also affect the therapeutic alliance between patient and therapist and, thus, cause problems for the involved healthcare professional ([@B1]--[@B3]). Quantitative data on coercive measures applied in patient care are \"hard to compare, since coercive measures are rarely systematically recorded, nor calculated and analyzed or expressed in"
+"Prostate cancer is the third leading cause of cancer death in American men. The rationale behind the therapeutic approaches that manage this disease for decades is mainly based on the fundamental works by Charles Huggins, the Nobel Laureate in medicine, revealing the androgen-dependent nature of prostate cancer. Thus, hormone therapy was implemented in the clinical setting and androgen-deprivation therapy (ADT) has been one key regimen for patients with recurrence after localized treatments, such as prostatectomy. However, resistance to ADT eventually occurs and leads to castration-resistant prostate cancer (CRPC). Studies of this progression found that cancer cells can utilize multiple mechanisms to overcome the castrated level of testosterone, including altered expression/mutations in the androgen receptor (AR) or intratumoural biosynthesis of its agonist (i.e. dihydrotestosterone) via perturbed steroid metabolism \\[[@R1]\\].\n\nSince CRPC in part still relies on functions of the AR, novel therapeutics inhibiting either steroid metabolic enzymes or the AR have improved the survival rates in CRPC patients. However, none of those are curative, and resistance eventually develops \\[[@R2]\\], consistent with the repeated cycles of treatment-dormancy-relapse in managing prostate cancer \\[[@R3]\\]. To make the situation worse, recurrent prostate cancer becomes even more malignant and capable of spreading out to other areas"
+"CASE REPORT {#s1}\n===========\n\nA 25-year-old woman had approximately 1 year of intermittent low-grade fevers (antipyretic unresponsive), with fatigue, malaise, proximal muscular aches, sweats, poor appetite, and 20 pounds weight loss. Her history was significant for birth by cesarean section at 38 weeks for fetal distress, unspecified upper airway surgery in infancy, intermittent fevers that spontaneously resolved in early childhood, mild childhood asthma, frequent otitis media requiring tympanostomy tubes into adulthood, environmental allergies with sinus congestion, eczema, and hives, and frequent viral upper respiratory infections and pharyngitis. In addition, she had self-limited \"chronic lymphocytic thyroiditis,\" irritable bowel syndrome, and pneumonia as a young adult, but she had no diabetes mellitus or known immunodeficiency. Her ethnicity was Arab and European for her paternal and maternal lineages, respectively, and her family history included a paternal aunt and uncle with unclear fevers in childhood that spontaneously resolved.\n\nPhysical examination, routine blood tests (including complete blood count \\[CBC\\]), and chest x-ray were unrevealing. A detailed body temperature log (digital oral readings 8:00 [am]{.smallcaps}, noon, and 8:00 [pm]{.smallcaps}) displayed exaggerated diurnal temperature variation, with relatively normal morning temperatures and intermittent evening elevations (Figure [1](#OFW127F1){ref-type=\"fig\"}A). Figure 1.Pattern of fevers. (A) Ten days of representative body temperatures"
+"There are many well-crafted vignettes in this book, some excellent big pictures and perhaps also a massive, wide screen production struggling to be set free. For some years I used cases described by Richard Cabot in his *Differential diagnosis* (Philadelphia, 1911) as the basis for student essays. These records are succinct models of clinical investigation in which Cabot employs all the laboratory and bedside tools newly available to the early twentieth-century physician to diagnose and treat his patients. I asked students to compare them with the recorded histories of consultations made by an eighteenth-century doctor, usually the Cumberland physician William Brownrigg.[1](#fn1){ref-type=\"fn\"} Cabot\\'s cases are perfect for teaching most things an undergraduate might be expected to know about the history of relatively recent clinical medicine. They are hospital-based and scarcely anything can be learned of the patient\\'s way of life save his or her occupation. Physical examination, pathological anatomy, surgical referral, the microscope and the X-ray all appear. The contrast with the case notes made by an eighteenth-century doctor is quite marked. Cabot, to all appearances, was a modern and a principal one at that. The \"sick man\" has disappeared from his histories in so far as Cabot never puts in"
+"GITR/TNFRSF18 is a member of the TNF-receptor superfamily preferentially expressed on regulatory T cells (Tregs) and activated T effector cells. Antibody agonists to GITR claim two distinct mechanisms to overcome the repressive tumor microenvironment and drive anti-tumor efficacy *in vivo*: receptor agonism (forward signaling) on T effector cells and Fc\u03b3R-mediated Treg depletion. We sought to better understand the contribution of these two mechanisms using pharmacodynamic readouts relating target coverage, Treg depletion and efficacy using isotypic variants of a surrogate antibody against mouse GITR, DTA-1.\n\nFirst, target coverage was determined in spleen, tumor and draining lymph node following treatment with a single dose of mouse IgG2a DTA-1. In this study, efficacy correlated with doses that covered \\>90% GITR-expressing intratumoral leukocytes and depleted \\>90% intratumoral Tregs at 24 hours post-dose. Though displaying equivalent agonistic activity *in vitro* and achieving a similar level of target coverage, the mouse IgG1 N297A variant of DTA-1 neither depleted Tregs nor displayed anti-tumor activity *in vivo*, in confirmation of recent literature. To further explore the influence of Fc engagement, additional DTA-1 isotypic variants were generated and tested *in vivo*. In this study, we confirmed that preferential engagement of Fc\u03b3 receptors was necessary for optimal activity, as the"
+"Background\n==========\n\nSelection for general immune response in poultry has been proposed as a sustainable alternative to selection for resistance against specific diseases, because progress with the selection for resistance approach might be hindered by interactions between host and pathogen which would lead to continuous adaptability on both sides. In addition, it would not be feasible to select for disease resistance against the tremendous number of different pathogens that an animal could face in his entire life cycle. Several general immune traits were experimentally selected for in chicken lines \\[[@B1]\\] revealing that the different immune response mechanisms may have different genetic components \\[[@B2]\\].\n\nThis study was based on three lines of White Leghorn Chickens that have been selected for 12 generations for one of three different immune response traits, high antibody response (ND3), cell mediated activity (PHA) and phagocytic activity (CC). Line ND3-L was selected on ND3, line PHA-L was selected for PHA, and line CC-L for CC, but all lines were measured for all three traits. The fourth line was a contemporary random bred Control maintained throughout the selection experiment. The results of the selection have been described by Pinard van der Laan \\[[@B2]\\]. Briefly, 200 chicks per line"
+"Introduction\n============\n\nIn aortic stenosis (AS), patient symptoms and outcome are determined by the severity of the valve stenosis, but also by the myocardial response to the generated afterload---a process that appears crucial, but is incompletely understood.[@ehx353-B1] Our scientific exploration of this uses two main approaches. Clinically, the myocardium is measured by assessing structure and function using imaging \\[echocardiography, cardiovascular magnetic resonance (CMR)\\].[@ehx353-B2] Pathophysiologically, the myocardium is assessed histologically on tissue samples. It is believed that a complex interplay of cellular changes (including hypertrophy and cell death by apoptosis or autophagy), microvascular ischaemia, and alterations of the extracellular matrix occurs with final common pathways leading to myocardial fibrosis (MF). Most of the evidence for this has been from a few small biopsy or autopsy studies. Whereas autopsy descriptions of MF can provide a global view, in *in vivo* studies, sampling is limited by biopsy size, and fibrosis is typically described only by the quantity of collagen deposition \\[collagen volume fraction (CVF)\\]. However, histological analysis of heart tissue also allows differentiation of fibrosis subtypes based on location and morphological characteristics of collagen deposits (focal microscopic scars, diffuse interstitial and perivascular strands; see [Supplementary material online, *Figure S1*](#sup1){ref-type=\"supplementary-material\"}), with the functional impact"
+"Wilkinson JM, Lee MRF, Rivero MJ, Chamberlain AT. Some challenges and opportunities for grazing dairy cows on temperate pastures. Grass Forage Sci. 2020;75:1--17. 10.1111/gfs.12458\n\nHighlightsGrazing plays a central role in the nutrition of dairy cows in many regions of the world.Challenges to efficient management of grazed pastures include variable herbage supply and low herbage intake, which limit milk output per head.Opportunities for improved efficiency include more accurate diet formulation, breeding superior plant cultivars to improve ruminal efficiency and enhance product nutritional quality, application of robotics, sensors and artificial intelligence to improve grazing management and pasture utilization, and wider consumer recognition of the perceived enhanced value of milk from grazed cows.\n\n1. INTRODUCTION {#gfs12458-sec-0002}\n===============\n\nHerds of dairy cattle grazed on grasslands are ubiquitous worldwide, and their daily management ranges from semi\u2010nomadic to closely controlled intensive grazing (FAO, [2009](#gfs12458-bib-0047){ref-type=\"ref\"}). The emphasis in many regions is on production per head, especially where grazing plays a central role in the sustenance of the family and local community or where nutritional status of the individual animal is a key aesthetic attribute (Coote, [1992](#gfs12458-bib-0023){ref-type=\"ref\"}). On the other hand, in pasture\u2010based production systems in temperate regions, the capital cost of land is a relevant component of"
+"Introduction {#section1-0047287513478505}\n============\n\nThe tourism sustainability debate has drawn increased attention to the environmental factors of destinations. However, the role and importance of environmental resources had been embedded in tourism research long before this environmental debate began ([@bibr33-0047287513478505]; [@bibr43-0047287513478505]). Many tourism researchers have studied environmental resources' tourism potential and how they trigger tourism demand and bring value to a destination. Initially, the researchers' interests in the issue was merely academic; however, given the increasing environmental awareness in society and the fact that tourism may cause the deterioration of environmental resources and force mass tourism destinations into economic decline, researchers have become interested in this issue for policy relevance reasons. For destinations, environmental issues are now more important than ever before and are now an integral part of their sustainable development strategies. The \"new tourists,\" defined by [@bibr46-0047287513478505] more than a decade ago, are ecologically aware; they demand more environmental resource--based experiences and are becoming sensitive to the actual environmental quality of destinations, which increasingly influences their price--quality ratio judgments. For example, research on the Balearic Islands ([@bibr1-0047287513478505]) has shown that tourists have become increasingly demanding in regard to the natural surroundings and their quality. Indeed, in the late twentieth century,"
+"Diabet. Med. 36: 644--652 (2019)30761592\n\nWhat\\'s new?Participants in clinical trials of automated insulin delivery systems report perceived benefits and burdens of these systems. It is not yet known if these perceptions predict their likelihood of uptake and continued use.Currently, there are no available validated and reliable measures assessing the psychosocial aspects of automated insulin delivery systems.This study adds to the current science by providing an essential ingredient in the ongoing assessment of automated insulin delivery systems. Specifically, it offers information regarding the initial psychometric properties of the INSPIRE measures, a developmentally sensitive suite of measures for youth, adults, parents and partners.The measures assess the positive expectancies of users. The measures can support clinical practice by providing important insights into the onboarding and support needs of persons transitioning to these novel systems.\n\nIntroduction {#dme13930-sec-0007}\n============\n\nAutomated insulin delivery systems are associated with improved glycaemic outcomes, including reduced HbA~1c~, increased time spent within glucose targets and reduced hypoglycaemia [1](#dme13930-bib-0001){ref-type=\"ref\"}, [2](#dme13930-bib-0002){ref-type=\"ref\"}. Multiple clinical trials assessing the feasibility and safety of different systems are underway, and the duration of the studies has increased [3](#dme13930-bib-0003){ref-type=\"ref\"}, [4](#dme13930-bib-0004){ref-type=\"ref\"}, with some following participant outcomes for as long as 6 months in free\u2010living, home settings [5](#dme13930-bib-0005){ref-type=\"ref\"}. These systems differ"
+"Introduction {#s1}\n============\n\nIndividuals with spinal cord injury (SCI) often require rehabilitation strategies and assistive technologies to facilitate their daily tasks. Functional electrical stimulation (FES) enables these individuals with neuromuscular disability to execute functional activities such as walking, cycling, and standing up, as well as improving their blood flow and sensory awareness (Petrofsky, [@B27]). FES activates the nerves using small electrical currents, thereby recruiting muscles to produce non-physiologically evoked contractions and retrain atrophied muscles, thereby partially or fully regaining lost functions (Hamid and Hayek, [@B13]). Electrical stimulation can be applied through the skin surface or via intramuscular electrodes to evoke contractions of the non-innervated muscles (Ferrarin and Pedotti, [@B9]). The intensity and temporal characteristics of the stimulation must be regulated to prevent rapid-onset muscle fatigue that leads to failure to perform the desired movement.\n\nWhen an able-bodied individual performs exercise, over time the muscles becomes fatigued due to repetitive muscle activity, and thus are not be able to reach a set level of maximum voluntary contraction (MVC) force to maintain the current task (Barry and Enoka, [@B2]). The definition of muscle fatigue in an engineering context is when the muscle\\'s physiological performance change before being finally unable to produce any"
+"Applications of high-content screening (HCS) ^[@R1]--[@R7]^ are circumscribed by several practical aspects, including low sample throughput and absence of sorting capability. Moreover high-resolution 2-D images consume limited detector bandwidth, introduce a data acquisition delay that is a barrier for real-time decisions needed for sorting, and introduce noise via inaccuracies in image segmentation. Imaging flow cytometers based on wide-field CCD imagers ^[@R8]^ have similar throughput limitations to microscopes. To address these restrictions we have developed a multi-channel parallel microfluidic cytometer (PMC) that is based on analog detection combined with parallel microfluidics. By taking approximately 1/1000 the amount of data per cell compared to a CCD image, we are able to drastically reduce the data-buffering and storage requirements and can simplify the classification algorithm to a fraction of a microsecond. Furthermore, parallel microfluidics overcome the sample-changeover bottleneck of a single-channel flow cytometer (FCM). Therefore the new architecture circumvents many of the throughput limitations of both HCS and FCM, but combines many of the best features of each technology.\n\nWhile multi-color 1-D imaging reduces the data load of HCS, the corollary disadvantage is a sparser image and a greater number of potentially ambiguous images. The question is how well can a sparse 1-D"
+"Introduction {#s1}\n============\n\nMalaria is responsible for an estimated 250 million episodes of clinical disease and 600,00 to 1.2 million deaths each year [@ppat.1003303-WorldHealthOrganisation1], [@ppat.1003303-Murray1]. Notwithstanding recent reductions in the burden of malaria in some endemic areas, sustained control, elimination or eradication of the disease will require a highly efficacious vaccine that prevents malaria transmission as well as reducing the burden of disease. As a benchmark in malaria vaccination, multiple immunisations of \u03b3-radiation-attenuated *Plasmodium* sporozoites (\u03b3-Spz) can protect both mice and humans against sporozoite challenge [@ppat.1003303-Nussenzweig1], [@ppat.1003303-Clyde1]. The elicited protection targets the development of liver stages and completely prevents blood stage infection, resulting in sterile immunity. This experimental vaccine approach has now been replicated using other whole sporozoite immunisation strategies that include infection under drug cover and genetically arrested parasites [@ppat.1003303-Mueller1]--[@ppat.1003303-Friesen1]. Naturally acquired pre-erythrocytic immunity is likely multifactorial [@ppat.1003303-Offeddu1], involving both antibodies and T cells. However, CD8^+^ T cells are the prime mediators of protection after \u03b3-Spz vaccination in mice [@ppat.1003303-Schofield1], [@ppat.1003303-Weiss1], and interferon (IFN)-\u03b3 is a signature of effector function [@ppat.1003303-Ferreira1].\n\nHow CD8^+^ T cells are primed, modulated, and maintained following immunisation, and how these cells execute protective functions, are key considerations for vaccine design and can only be"
+"Introduction {#Sec1}\n============\n\nAlternative metrics (altmetrics) is a new fast-moving area in scientometrics (Galloway et al. [@CR16]). Initially, altmetrics---a collection of many web-based indicators---have been proposed as a supplement to traditional bibliometric indicators. They measure attention related to research papers on internet platforms. The core of altmetrics is gathered from social media platforms, but mentions in mainstream media or in policy documents also belong to the umbrella term altmetrics (National Information Standards Organization [@CR29]; Work et al. [@CR45]). According to Haustein ([@CR22]), sources of altmetrics can be grouped into (i) social networks, (ii) social bookmarks and online reference management, (iii) social data (e.g., data sets, software, presentations), (iv) blogs, (v) microblogs, (vi) wikis, and (vii) recommendations, ratings, and reviews.\n\nRecently, some indicators based on altmetrics have been proposed which are normalized with respect to the scientific field and publication year. These indicators were developed because studies have shown that altmetrics are---similar to bibliometric data---field- and time-dependent (see, e.g., Bornmann [@CR4]). Some fields are more relevant to the general public or a broader audience than other fields (Haustein et al. [@CR23]). The Mean Normalized Reader Score (MNRS) was introduced by Haunschild and Bornmann ([@CR19]) for normalization of data from social bookmarks"
+"I am delighted to have this opportunity to mark Professor Lord Walton's outstanding personal contribution to Muscular Dystrophy UK or, as the charity was known when founded in 1959, the Muscular Dystrophy Group of Great Britain and Northern Ireland.\n\nIt is remarkable that John Walton has maintained such loyal and committed support for the charity over so many years. It is difficult if not impossible to think of anyone else who has made a similar, lifelong contribution in giving support and showing complete dedication to a single cause in this way.\n\nIn his autobiography, 'The Spice of Life', John recounts how he started work as a young doctor with Professor Fred Nattrass at Newcastle. Through their clinical practice, they developed a shared interest in understanding the underlying causes of muscular dystrophy and related neuromuscular conditions and, further, the need for research and greatly improved clinical care. They established the Muscular Dystrophy Group initially as an interest group within the unfortunately named Central Council for the Care of Cripples in the mid-1950s before the Group broke away from the Central Council in 1959 and was established as a charity in its own right.\n\nThe charity's founding members were John and Professor"
+"1. Introduction {#sec0005}\n===============\n\nA large proportion of research targeting neurophysiology relies on *in vivo* animal experiments, utilizing a plethora of techniques such as electrophysiology, circuit tracing, and optogenetic and pharmacological manipulations. While conducting these experiments in a live organism is inevitable to study neuronal processes, preparatory steps can be conducted in alternative models. Broadly, two types of instances can be distinguished, i.e. (1) the training of entrance level scientists and (2) establishing a new *in vivo* experiment. Conducting stereotactic craniotomies, virus injections and implantations requires not only fine motoric skills but also knowledge of how to use the equipment (e.g. an intuition of the degrees of freedom of stereotactic arms) and how to handle delicate probes (e.g. electrophysiological electrodes). With our model, all of those procedures can be trained without an animal. Further, for setting up a new neurophysiological *in vivo* experiment, functionality and noise levels of the setup need to be tested, which includes both individual tools such as electrodes, fibers and recording devices, as well as aspects of the behavioral setup or arena used for recordings. Even if individual tools or procedures have been applied successfully in the lab, unanticipated complications can arise from a newly assembled"
+"Vaccines: Preventing Disease Protecting Health does not provide the type of vaccine-specific information as Plotkin and Orenstein\\'s Vaccines ([@R1]), nor does it provide the details on the immune system of Bloom and Lambert\\'s The Vaccine Book ([@R2]). The book does not cover every important vaccine issue, such as ethical issues in vaccine trials and the conduct of clinical trials; most critically, it lacks an index. But these limitations are minor compared to what the book provides.\n\nThis relatively small book provides state-of-the-art information by those who are directly involved with vaccine and immunization programs. The book evolved from a meeting held November 25--27, 2002, in Washington, D.C., at which many of the world\\'s top vaccine scientists reported on their research. As the book jacket states, the roster of authors reads like a Who\\'s Who in vaccine research and public health immunization programs. This publication comes from the Pan American Health Organization (PAHO), the World Health Organization (WHO) Regional Office, which has been at the forefront of almost every major vaccine initiative for the past 30 years, including the eradication of polio, elimination of measles, and strategies to control rubella and neonatal tetanus. These programs have served as models emulated by"
+"Problem\n=======\n\nObtaining microbiology specimens from infants and children can be a challenging task. Not only is it distressing for the patient and parents, but the process involves a lot of time, and preparation, from the clinical team. In young infants, sedation is sometimes used to perform lumbar puncture in difficult cases. A delay in receiving microbiology results can impact clinical management, leading to empirical antibiotic treatment of infection and unnecessary, distressing repeat investigation. All microbiology specimens are sent to an off-site laboratory for analysis. With multiple steps in the transport process involving clinicians, porters, and laboratory staff, the pathway is complex with multiple potential causes for the delay in obtaining results. All stakeholders involved were keen to investigate and improve this vital service.\n\nBackground\n==========\n\nThe project was carried out in the Paediatric Department at a Central London teaching hospital. The Paediatric Department comprises four children\\'s wards with over forty beds, the Paediatric Intensive Care Unit and the Paediatric Accident and Emergency. A departmental audit highlighted a delay in this transport process with some samples taking in excess of eight hours to reach the laboratory and others reported as 'missing'. The audit did not highlight where delays were taking"
+"Introduction {#s1}\n============\n\nThe accurate processing and integration of multiple external signals is a common feature of biological networks in normal health and complex disease. As illustrated by the examples of oxygen handling [@pgen.1000129-Suzuki1], energy control [@pgen.1000129-Spiegelman1], and ion homeostasis [@pgen.1000129-Hentze1], such accuracy frequently involves the precise coordination of multiple cellular pathways, and mechanisms for regulating and balancing opposing activities. In cancer networks, many similar requirements for pathway balance are likewise found as successful tumorigenesis requires the robust integration of both pro- and anti-oncogenic pathways controlling cellular proliferation, apoptosis, motility, adhesion and senescence [@pgen.1000129-Choi1],[@pgen.1000129-Nilsson1]. The importance of balancing opposing activities in cancer is illustrated by genes such as *HEF1* (*NEDD9*), a metastasis-related gene [@pgen.1000129-ONeillG1] and *HMMR*, a gene involved in centrosome formation (Pujana et al. 2007). Either repression or overexpression of *HEF1* can cause mitotic defects [@pgen.1000129-Pugacheva1],[@pgen.1000129-Dadke1], indicating that its activity in tumors requires tight regulation. Similarly, subtle alterations of *HMMR* expression in normal mammary tissues may promote breast tumorigenesis, underscoring the need to keep the *HMMR* gene tightly regulated [@pgen.1000129-Pujana1]. Such findings support the notion that balancing the activity of positive and negative effectors is likely to be a central requirement of many cancers.\n\nAt the systems-level, pathway balance"
+"Knowledge of plant and environmental factors determining photosynthesis by submerged plants is essential for understanding aquatic plant ecophysiology and ecosystem productivity, as well as submergence tolerance of terrestrial plants. Following the pioneering studies by Arens ([@B3]) and Steemann Nielsen ([@B103]) on the use of dissolved inorganic carbon (DIC) for photosynthesis of aquatic plants, numerous studies on the regulatory role of light and DIC for underwater photosynthesis of aquatic plants have been conducted. Particularly, the use of DIC by aquatic plants has fascinated researchers and been reviewed several times (e.g., Madsen and Sand-Jensen, [@B44]; Maberly and Madsen, [@B39]; Raven and Hurd, [@B73]) because this process is important for growth and survival and the uptake mechanisms are very different from those of terrestrial, amphibious, and floating leaved plants exposed to atmospheric air (definitions of these life forms and examples of species are in Sculthorpe ([@B93])). Since the physical conditions differ markedly between water and air, we have often been approached by researchers asking for practical advice, unavailable in the literature, before engaging in work with underwater photosynthesis. Thus, this review serves to offer the background and a practical guide for measurements of carbon fixation by plants when under water.\n\nMoreover, a growing"
+"Respiratory tract infections (RTIs) and asthma are major components of acute and chronic morbidity in childhood, and they place a considerable burden on children, their families, and society ([@kwy053C1], [@kwy053C2]). Asthma has multiple causes, including genetic predisposition, environmental exposures, and interactions between these factors and a child's developmental stage ([@kwy053C3]). Although a strong association between microbial (including viral) infections and asthma in children from infancy to school age has been shown in studies ([@kwy053C4], [@kwy053C5]), the direction of causation is unclear and may be bidirectional ([@kwy053C3]). Several pathways from microbial infections to atopic conditions have been proposed: Microbial infections can have protective effects (the hygiene hypothesis) ([@kwy053C6], [@kwy053C7]) or be provocative ([@kwy053C8]--[@kwy053C12]) of subsequent asthma. A reverse causation mechanism has also been proposed in which atopic conditions increase the susceptibility to infections ([@kwy053C3], [@kwy053C13]--[@kwy053C15]). The association between infections and childhood asthma also may not be causal; rather it may be due to shared genetic components that induce susceptibility to both ([@kwy053C16]).\n\nResearch on asthma is hampered by the complexity of asthma presentation; asthma is particularly difficult to assess in children younger than age 6 years ([@kwy053C17]). The interpretation of results from observational studies is not straightforward because, at an early"
+"Sirs\n\nVisual allesthesia is a condition in which visual images are transposed from one half of the visual field to the other. The most common cause is an acute right parietal stroke, but allesthesia can result from other lesions and mechanisms. We describe the unusual case of a man with continuous transposition of his right visual field into his left due to epilepsia partialis continua.\n\nA 57-year-old, right-handed man with a remote gunshot wound to the right parietal lobe presented with the complaint of seeing everything on his right-side moved to his left-side. He initially developed paroxysmal episodes that began with an awareness that visual objects were transposed from his right visual field to his left. The transposed objects were less distinct than the original, appeared further away, and involved background as well as foreground. The patient turned his eyes and his head to the left in order to capture the original left-sided images. The transposition persisted a few minutes after removal of the original visual stimulus and despite closing either or both eyes. About a minute into the transpositions, he experienced other sensory phenomena including a repetitive \"clicking or crackling\" sound on the left side and a numbness of"
+"\"Neither microbial genes nor microbial names cause any harm to the body, but microbial product may do. The presence of very active microbial biological compounds in the gut may have physiological and pathophysiological consequences for the host. Tore Midtvedt (2008)\"\n\nAccording to modern scientific doctrine, the human being is a 'superorganism', the consortium of numerous *Eukarya, Bacteria, Archaea*, and *Viruses*. Various host indigenous microorganisms should be considered as essential complex extracorporal physiological systems that play a fundamental role in human health and disease. Host microbiota and other functional and metabolic systems, connected with host eukaryotic cells, are working together profitably for the whole organism and for its separated components in the concrete environment conditions. Unfortunately various unfavorable biotic or abiotic factors and stress agents (diet, age, sex, pharmaceutical, even surgical interventions, etc.) can produce microecological disorders resulting in tissue, organ and regulatory systems disturbances that can lead to an increase of a disease development risk ([@CIT0001]--[@CIT0005]). It means the modulation of microbe/microbe and microbe/host interactions is an extremely important, fundamental, and applied problem in modern biology and medicine. To date, to maintain and restore the gut microbial community, three therapeutic approaches have dominated: probiotics, prebiotics, and synbiotics ([@CIT0004], [@CIT0006]--[@CIT0010]). As"
+"###### Summary box\n\n-   Establishment of a trauma registry is the first step to understanding the regional epidemiology of injury and establishing an effective trauma system.\n\n-   Road traffic crashes result in 30%--86% of all trauma admissions in low-income and middle-income countries.\n\n-   Almost half of all motor vehicle collision victims were the main providers for their family.\n\n-   Data from the Sri Lankan Trauma Registry demonstrated that only 52% of patients arrived at the hospital within 2\u2009hours after injury, with very few of these patients receiving any prehospital care.\n\n-   Work overload of medical officers led to a significant amount of missing data, and the slow tablet speed and poor internet connectivity within the wards led to a 30\u2009min data entry time for a single patient.\n\n-   From the data obtained in this study, plans have been developed to conduct trauma first aid workshops and training programmes for school children and sports clubs, as well as public and media awareness programmes, of the importance of injury prevention in Sri Lanka.\n\nIntroduction {#s1}\n============\n\nEvery year more than 50\u2009million people sustain road traffic injuries requiring medical care[@R1] and 1.25\u2009million die from their injuries.[@R2] Those who survive"
+"Introduction {#s1}\n============\n\nAn integrated strategy of surgery, antibiotics, facial cleanliness, and environmental improvement -- the SAFE strategy in short -- is recommended to eliminate blinding trachoma in endemic countries by the year 2020 [@pntd.0002223-World1]. The F and E components aim to reduce the transmission of *Chlamydia trachomatis* via flies, fingers, and fomites within the community [@pntd.0002223-Emerson1]. Face washing is promoted specifically to keep faces free of infectious ocular and nasal discharge, and make them less attractive to eye-seeking flies. The construction and use of latrines are promoted as a form of fly control to reduce fly-to-eye contact [@pntd.0002223-Emerson1], [@pntd.0002223-Emerson2]. Improved accessibility to clean water is also promoted, but whether or not water is used for hygiene is more important than absolute access to clean water in trachoma prevention. Where water is not readily accessible, household use of a limited supply of water may not be prioritized for bathing [@pntd.0002223-Bailey1]--[@pntd.0002223-West1]. These aims of the F and E components go beyond trachoma control and align with other major initiatives, such as the WASH program of UNICEF and Millennium Development Goal (MDG) 7c which, by 2015, aim to provide access to clean water and sanitation to all children and to reduce by"
+"INTRODUCTION\n============\n\nChild\\'s cognitive development relies mainly on the development of speech and language.\n\nSpeech is the process whereby groups of sounds or words are produced by the physical mechanism during the act of communication.^[@B1]^ Language is used to convey meaning with the help of symbols (words) representing objects or events that are organized into patterns (sentences).^[@B2]^ Language is governed by a set of semantic (meaning) and syntactic (grammatical) rules.\n\nThe conditions that are involved in speech and language problems are unusual voice quality, lack of fluency, articulation disorders, grammatical errors (syntax), vocabulary (semantics), etc.^[@B3]^ These problems may or may not appear together. Every effort should be taken to recognize the speech disorders as they may turn into permanent communicative disorder if left untreated.\n\nAccording to American Speech-Language-Hearing Association (ASHA), expressive language and vocabulary problems can be minimized by early speech and language intervention.^[@B4]^\n\nProper communication plays a significant role in gaining cooperation and providing effective treatment of children.^[@B5]^ Pedodontists have significant role in developing dentition as well as the overall development of the child by treating young children with effective communication establishment, because they are more aware of how the oral structures affect the speech. For instance, speech is"
+"Background\n==========\n\nModern dance developed from expressionist dance, which rejected the rules of ballet. It originated in Germany in the 1920s and was defined by rules of a specific technique evolved in the USA in the years 1930--1950, employing elements of African and Native American folklore. Modern dance employs all the techniques of ballet; however, a modern dancer is not obliged to uncritically follow the classical rules of execution of these techniques.\n\nClassical style strongly emphasizes esthetics, precision, and height. In modern dance, the distance and motion through space is of utmost importance.\n\nCohan writes that the most important elements of a modern dancer's work are: \"ground work\", \"work with the center of gravity\", and \"motion in space\" \\[[@b1-medscimonit-20-1082]\\]. He mentions that the most important thing in a well performed movement is self-awareness, and that modern dance consists of \"centering, gravitation, balance, posture, gestures, rhythm, motion in space, and breathing\".\n\nAlthough ballet is a form of art, it has much in common with professional sports. Modern style choreographers often propose very dangerous dancing movements from the point of view of biomechanics of the locomotor system. These dangerous situations created by \"movement designers\" are often the result of absence of basic"
+"Investigators from Pavia, Rho, Brescia and Milan, Italy, studied 22 patients diagnosed with GLUT1 deficiency syndrome (GLUT1DS) to document clinical or genetic differences between patients with familial *SLC2A1* gene mutations (n=11) and those with sporadic mutations (n=11). Direct gene sequencing in sporadic cases revealed 7 missense, 3 nonsense, and 1 splice site mutation. In the group with familial inheritance, all patients presented with missense mutations. Important differences were observed regarding clinical features. Overall, patients with sporadic mutations had a more severe phenotype than those with familial inheritance. They had more severe intellectual disability, earlier epilepsy onset and greater tendency to be refractory to AEDs treatment and more disabling movement disorders. In the familial group, relatives carrying *SLC2A1* mutations presented with heterogeneous clinical features of variable severity. Furthermore, two patients with genetically confirmed GLUT1DS had siblings with a similar type of epilepsy but without *SLC2A1* gene mutations.\n\nThe milder phenotype observed in the familial group, and the reported phenotypic variability among family relatives, confirms the heterogeneity of the clinical expression of *SLC2A1* mutations. This raises the question of the incidence of GLUT1DS, using a ketogenic diet in less symptomatic patients, and genetic counseling concerns. Authors also suggest that symptomatic patients negative"
+"Dear Colleagues,\n\nWe have always been working hard to keep the Brazilian Journal of Cardiovascular Surgery (BJCVS) active and up-to-date, despite the uncertainties that pervade the political, economic, social and scientific activities in our country.\n\nThose who did not imagine the evil influence that would be exerted by the instability that has taken place in the public or private Universities, were wrong. The negative impact on teaching and research, caused by a lack of resources, was enormous.\n\nMuch more serious was the impact on hospitals, medical clinics, primary healthcare centers, Intensive Care Units (ICUs), as well as on health equipment, dependent on federal, state, municipal or private funding, due to the widespread undercapitalization of governments and the population, seriously damaging the patient care, and the data generation, essential to the research.\n\nThe question that won\\'t go away is: What does the BJCVS have to do with all this background?\n\nUnfortunately, we have a lot to do with it, because the manuscripts that come to us are basically from \\\"Stricto or Lato Sensu\\\" postgraduate programs, related to patient care, and to a lesser extent regarding the basic research.\n\nIn the Editorial Issue 31-1 of the BJCVS, I pointed out that we"
+"1. INTRODUCTION {#sec1-1}\n===============\n\nChickenpox is highly contagious, usually mild childhood disease caused by varicella-zoster. Rash usually begins with several red spots (macula) which are soon filled with liquid creating small vesicles. Vesicles appear in groups, first on body and afterwards are spread on extremities, face and scalp in two to four day. Varicella is contagious disease characterized by itching (pruritus) and skin rash (vesicles filled with liquid) which is later converted to crusts. In prodromal period, usually day before rash appears patient may have mild fever and exhaustion (1). More severe secondary infection can indicate hospital treatment. Chickenpox is spread by airborne infections or direct contact with liquid form vesicle. Person having this disease can infect others during period of 2 days before rash develop and up to 6 days after first vesicles appears, or even until vesicles are turned into crusts. Incubation period range from 10-21 days. Most of children are infected with virus until 10 years of age. Patients after disease usually acquire lifelong immunity. Diagnosis is confirmed based on specific clinical course and positive epidemiological data (2, 3) . Therapy is supportive with antipyretics and analgesics, topical and antimicrobial in case of infection (4). Newborns are"
+"Introduction {#s1}\n============\n\nThe cupin superfamily of proteins possesses remarkable functional diversity with representatives found in Archaea, Eubacteria, and Eukaryota [@pone.0074477-Dunwell1], [@pone.0074477-Dunwell2], [@pone.0074477-Dunwell3], [@pone.0074477-Dunwell4], [@pone.0074477-Dunwell5]. The identification of the cupin superfamily was originally based on the recognition that the wheat protein germin shared a nine amino acid sequence with another protein, spherulin, produced by the slime mold *Physarum polycephalun* during starvation [@pone.0074477-Dunwell3]. This sequence similarity was also observed in a number of seed storage proteins called germin-like proteins (GLPs). Knowledge of the three dimensional structures of these proteins led to the collective name \"cupin\" on the basis of their \u03b2-barrel shape (\"cupa\" means \"small barrel\" in Latin) [@pone.0074477-Dunwell4]. Characteristic features of proteins with this fold include high thermal stability and resistance to proteases. These features are consistent with their high degree of subunit contacts, hydrophobic interactions, and short loops. The cupin domain was originally described as two conserved motifs, each composed of two \u03b2-strands [@pone.0074477-Dunwell2], [@pone.0074477-Dunwell5]. Motif 1 was designated as G(X)~5~HXH(X)~3,4~E(X)~6~G and Motif 2 as G(X)~5~PXG(X)~2~H(X)~3~N. The two motifs are separated by an intermotif region which ranges from 15 to 50 amino acids long. With more sequences analyzed, it became clear that the primary sequence of the two motifs"
+"The Moore's law juggernaut may finally be slowing down because of severe short channel effects experienced by active transistors, and also due to formidable interconnect bottlenecks arising from the current copper-trace based technology. Electrical interconnect performance has degraded significantly in terms of both speed and power dissipation in large part due to the fact that aggressive downscaling in feature sizes negative impacts both the resistances and inductances of metal wires. Si optical interconnects have become an increasingly attractive alternative since they promise to provide greater bandwidth, lower power consumption, decreased latency, higher resistance to electromagnetic interference, and reduced signal crosstalk[@b1]. However, optical interconnects can only hope to replace electrical interconnects when these have both better performance and can be cost-effectively manufactured in high volumes.\n\nThe major challenge for the adoption of silicon optical interconnects lies in achieving seamless, monolithic integration of photonics and electronics within standard CMOS processing technology. Among the various material choices for Si photonics, Ge is particularly attractive thanks to its pseudo-direct bandgap structure and compatibility with Si integrated-circuit technology[@b2]. The effectiveness and functionality of many important key components for Si/Ge photonics, including photodetectors[@b3], modulators[@b4], and light sources[@b5], have already been demonstrated. Given their micrometer-scales in thickness"
+"Method details {#sec0005}\n==============\n\nIn this paper we describe a generic way of considering incomplete but gradually expandable sociological data in agent-based modeling. In extension to Axelrod's model of cultural dissemination [@bib0005], we developed a generic procedure for feeding the model with data that can be completely or partially contrived at first, and can be easily updated later on when additional information becomes available. Our aim was to conceive the model in a way that allows for informative utilization even without exact data. We applied the method in simulating the bottom-up diffusion of photovoltaic citizen power plants in Austria [@bib0010], [@bib0015]. The focus was on complementing individual traits of respondents from an empirical survey with missing information on peer effects. In order to allow for utmost flexible consideration of impact strength and decision uncertainties, a generic function for varying relevant parameters is proposed. Background information regarding the application of the method described in this specific case, and a brief description of the original Axelrod model are provided in the section 'Additional information' towards the end of the paper.[1](#fn0005){ref-type=\"fn\"}\n\nPreprocessing of data {#sec0010}\n---------------------\n\nIn the social sciences, data is often gathered in the form of a questionnaire where respondents are"
+"Autophagy represents a self-repair mechanism in which the defective or damaged cellular components, including the cytoplasmic organelles are entrapped in a double lipid bilayer termed phagophore.[@ref1] The phagophore and the material entrapped together are referred to as autophagosome. Once combined with a lysosome, it is referred to as an autolysosome, marking the initiation of enzymatic degradation of the sequestered content.[@ref2],[@ref3] By-products of autophagy including amino acids and sugars are recycled back into the cytosol.[@ref1] Failure in autophagy leads to cell death either through apoptosis or necrosis. Common pathologies including infections, degenerative disorders, heart disease have been linked to an overall failure in the cells autophagic system.[@ref4],[@ref5] Suzuki and Ohsumi utilized yeast genetics to decode more than 30 autophagy-related genes.[@ref6] Studies have shown that autophagy is not a non-specific mechanism, but that it follows an organelle specific disposal process targeting substrates, including peroxisomes, ribosomes, mitochondria, invading bacteria and protein aggregates.[@ref7]-[@ref10] Though the molecular mechanism of autophagy is not fully elucidated, studies including that of Bj\u00f8rk\u00f8y *et al*. have shown that ubiquitination plays a major role in aggregate targeting.[@ref11] Several studies have also shown that specific proteins tag the cytoplasmic organelle inducing autophagic degradation.[@ref1] Though the cytoprotective role of autophagy serves to"
+"Introduction {#s1}\n============\n\nAccumulating neuroanatomical, neuroimaging, neuropsychological, and behavioral evidence has informed our present understanding of emotional speech processing. It has become evident that emotional speech processing is a highly complex endeavor mediated by a differentiated network of fronto-temporal, fronto-parietal cortices, the amygdala, and the basal ganglia (BG). Specifically, it has been proposed that emotional speech processing can be divided into several sub-processes after the first encounter with an emotionally marked stimulus (identification of emotional significance, detailed emotional perception of stimulus, conceptual evaluation; see e.g. [@pone.0017694-Schirmer1], [@pone.0017694-Wildgruber1]). However, while there is growing evidence on the brain structures involved in emotional speech processing, the temporal dynamics of specific sub-processes and their impact on specific brain structures are less clear. For example, imaging studies using PET, fMRI, or TMS do not allow to clearly specify the time-course of activation patterns. However, event-related brain potential (ERP) lesion studies offer the possibility to explore which brain areas are linked to specific processing steps due to their fine grained temporal resolution. Thus, the present study applied ERPs to investigate sub-processes of emotional speech processing in patients with BG lesions in comparison to healthy controls. This patient group was of interest for two reasons: 1) the"
+"Scientific progress and related technology move apace, as do the volume and range of information available in the medical and basic scientific literature. Information technology provides access to but not necessarily critical evaluation of a large proportion of such information resources. Sifting the most relevant and highest quality papers from this potential wealth of knowledge generates a significant challenge. Whereas the current publication volume renders comprehensive reading impossible, the selective assessment of high impact journal publications remains the mainstay of academic communication and is essential for maintenance of a vibrant intellectual process for most clinical investigators and scientists.\n\nThis month, *Arthritis Research & Therapy*provides a new approach to highlighting key recent observations through the provision of a literature \\'viewpoint\\'. Recognizing that the mainstream \\'arthritis\\' literature is readily accessible and extensively addressed in the journal in the format of review, commentary and original paper, this section rather will provide a short overview of one or several closely related papers published very recently. The focus of this section will be to address scientific areas removed from the immediate arthritis literature, with the intention of drawing insight and expertise from advances in other fields.\n\nSelected papers will be drawn primarily from Faculty of"
+"INTRODUCTION\n============\n\nExperimentally determined biomacromolecular three-dimensional (3D) structures typically are deposited in the Worldwide Protein Data Bank (wwPDB) ([@gkr1134-B1]) as a requirement by most journals including *NAR*. As of September 2011, there were over 76\u2009000 entries in the PDB (*cf.* [Table 1](#gkr1134-T1){ref-type=\"table\"}) of which \u223c9000 entries had been solved by NMR. The BioMagResBank (BMRB) ([@gkr1134-B4]) serves as a global repository of experimental NMR data, such as restraints, assigned chemical shifts and dynamic order parameters. Together, these repositories present a valuable resource for numerous research areas in the life sciences. Table 1.PDB entriesSetEntriesPDB76\u2009003\u2003\u2003\u2003\u2003Solution NMR9042NRG-CING8915\u2003\u2003\u2003\u2003Proteins7967\u2003\u2003\u2003\u2003Dimers413\u2003\u2003\u2003\u2003Complexes1235\u2003\u2003\u2003\u2003Ligands384Deposition\u2003\u2003\u2003\u2003Before 19909\u2003\u2003\u2003\u20031990-20001920\u2003\u2003\u2003\u2003After 20007113[^1]\n\nA series of experiments have shown that many NMR structures can be improved if they are recalculated from the original experimental data using present-day software and refinement protocols ([@gkr1134-B5]) including the STAP database published in this 'Database' issue of *Nucleic Acids Research*. These efforts have revealed that the deposited experimental data were highly heterogeneous in format, completeness and quality. Recently, we performed a large-scale optimization of X-ray derived PDB entries ([@gkr1134-B8]), which showed that nearly three quarters of these could be improved in terms of fit with the experimental data and geometric quality ([@gkr1134-B9]). The"
+"Introduction {#s1}\n============\n\nWhile externally imposed perturbations initially degrade skilled reaching movements, humans learn to control their movements predictively rather than through successive corrections [@pone.0004214-Shadmehr1]--[@pone.0004214-Tong1]. Computational models have suggested that endpoint variability and deviations from rectilinearity might be minimized concurrently based on a common performance error [@pone.0004214-Jordan1], [@pone.0004214-Todorov1]. Indeed, the characteristic bell-shaped velocity profiles and rectilinear trajectories of horizontal reaching movements [@pone.0004214-Morasso1]--[@pone.0004214-Flash1] were simulated robustly and with varied dynamic loads, through minimization of endpoint variability alone [@pone.0004214-Harris1]. Recent models propose an alternative view suggesting that to maximize performance, trajectories may be \"reoptimized\" and have a curved shape [@pone.0004214-Izawa1]. Indeed, various types of curved trajectories were reported; for example, when subjects reached along a curved path that conformed to the stiffness of a virtual disk [@pone.0004214-Chib1], or when visual feedback was displayed in joint rather than in Cartesian coordinates [@pone.0004214-Flanagan1], or when adapting to visuomotor rotations when visual feedback was limited to the endpoint [@pone.0004214-Scheidt1]. Scheidt and Ghez (2007) suggested that their results were accounted for by a computational model in which intended trajectories and final hand position are driven by separate controllers.\n\nIntrigued by these studies, we reasoned that while the spatio-temporal criteria for success constitute explicit demands of the"
+"HER2-positive breast carcinomas have been shown to display an early peak of relapses in the first 4 years after surgery, especially in the node-positive subgroup. To explain this observation, growth factors released at the time of surgery were investigated. The level of growth factors of the EGF family, detected in postsurgical sera from breast carcinoma patients, was found to correlate with surgical invasiveness. Indeed, following radical mastectomy, higher levels of serum EGF-like factors were found than after conservative surgery. This implicates that the growth of tumors overexpressing HER2, activated by these growth factors, should be stimulated after invasive surgery. Two retrospective analyses of the HER2 status of primary tumors included in a randomized clinical trial addressing the issue of conservative versus invasive surgery and of radiotherapy were performed by immunohistochemistry using the standardized herceptest. Survival analysis according to surgery indicated no differences in HER2-negative cases but indicated a poorer survival for HER2-positive node-positive patients who had mastectomy in comparison with those who had conservative surgery. Furthermore, local relapses in patients who had conservative surgery without radiotherapy were found to be anticipated in the HER2-positive subset. This is a \\'proof of principle\\' that surgery by inducing growth factor release may be"
+"Introduction\n============\n\nRecent investigations have revealed that the state of post-ischemic brain recirculation is of major importance in recovery from sudden death, and we developed an isolated global ischemic brain model that excludes the confounding variables of bypass, donor blood, and whole body damage to investigate the strategy of controlled reperfusion. This study examines primary damage of cerebral function and tissue with uncontrolled brain reperfusion following 30 minutes of brain ischemia, and tests whether controlled brain reperfusion can attenuate the damage.\n\nMethods\n=======\n\nSixteen pigs underwent 30 minutes of global brain ischemia by clamping major neck vessels via a small suprasternal incision. Seven pigs then received uncontrolled reperfusion with normal blood, while the other nine pigs received controlled reperfusion by infusing a modified (leukodepleted, hypocalcemic, hyperosmolar, alkalotic, normoglycemic, antioxidant enriched) warm blood solution into both carotid arteries for 20 minutes. Six pigs underwent Sham operation. Brain oxygen uptake and venous conjugated dienes (CD) were measured during reperfusion. The neurologic deficit score (NDS) (0 = normal, 500 = brain death) was determined at 24 hours after ischemia, and brain water contents and cerebral infarction by 2,3,5-triphenyl tetrazolium chloride staining were assessed post mortem.\n\nResults\n=======\n\nSham pigs were neurologically normal at"
+"The 26S proteasome is an adenosine triphosphate (ATP)-dependent multisubunit protease complex that degrades polyubiqutinated proteins in a regulated manner. This 2.5-MDa compartmentalized protease contains \u223c33 distinctive subunits in two major subcomplexes, the 20S core particle and 19S regulatory particle (RP/PA700). The 26S\\'s central regulatory hub is its hexameric ATPase complex (Rpt1-6), located at the 19S base. The ATPase ring\\'s N terminus (containing a coiled-coil domain) is intimately integrated with subunits involved in scaffolding, ubiquitin chain binding and processing. Its C-terminal side associates with the 20S proteasome via its C-terminal HbYX motif, which induces 20S gate opening to promote substrate entry. This architecture places the ATPase ring in a position where it can accept protein substrates on its N-terminal side, then, in an ATP-dependent manner, translocate them through its central pore and into the 20S for their degradation[@b1][@b2][@b3][@b4]. Archaea also have a proteasomal ATPase complex homologous to Rpt1-6 called PAN, which binds and similarly regulates the archaeal 20S proteasome.\n\nRecent 26S cryo-electron microscopy (EM) analyses revealed that large conformational changes occur in the 19S when the ATPases bind ATP\u03b3S or substrates[@b5][@b6][@b7]. These similar ATP-bound and substrate-bound conformations are thought to be degradation competent. ATP (but not adenosine diphosphate (ADP)) binding to"
+"Introduction\n============\n\nThe need to couple functional measurements (nearly exclusively electrical measurements for channels) with other physical methods informing about membrane dynamics or structure (with respect to both lipid matrix and protein or peptide effectors) is a long-standing issue in Biophysics. It requires ingenious experimental set-ups that often compromise between the high sensitivity and rapid kinetics allowed by electrophysiological recordings (at the single-channel level, 1-10 molecules can be functionally monitored in a membrane area of, say, 1 mm^2^ on a millisecond timescale) and the usually low signal to noise ratio associated with optical or spectroscopic methods. Refer to the review by MacDonald and Wraight ([@B1]). Nevertheless, beginning with the classical papers on natural excitable membranes of the sixties, eg. ([@B2]), successful and meaningful studies have been reported ever since, perhaps with fewer such attempts reported recently despite technological improvements. Some of these technologies are still in development, for example, near-field optical microscopy and fluorescence correlation spectroscopy, among others.\n\nIn spite of the fact that planar lipid bilayers are still the best-suited artificial membrane system for the study of reconstituted ion channels and receptors, data dealing with their physical characterisation, especially as regards dynamics are scant. The dynamics of molecules in"
+"Are public schools in the United States engines of mobility or agents of inequality? Can schools in low-income communities provide a pathway out of poverty, or are the constraints of poverty too great for schools to overcome? Such questions are at the heart of debates about the role of education in social mobility in the United States. Despite decades of research, however, we still lack clear answers.\n\nIn this article, I provide new evidence to inform these debates. It suggests that the lack of a clear answer to the question is explained in part by the substantial variation in the role of schooling in shaping educational opportunity across places. Early childhood conditions are more important in some places, educational opportunities during the elementary and middle school years more important in others.\n\nThe article also provides a demonstration of how administrative test score data can be used to construct high-resolution place- and age-based measures of educational outcomes, despite a number of major limitations of available administrative data. In particular, the standardized tests used in schools vary across place, grade, and year; the resulting scores are typically coarsened into a small number of ordinal categories whose definitions also vary across place, grade,"
+"Introduction {#s1}\n============\n\nRegulated proteolysis is an indispensible mechanism for cell physiology. By controlling protein degradation, protein levels can be modulated without generating toxic waste products. Proteases are classified according to their reactive site residues into clans and families. The clan of cysteine proteases includes the Calpain family. Calpains are non-denaturing proteases that respond to local changes in calcium. Amongst their many functions, Calpains are involved cytoskeleton remodeling [@pone.0011940-Lebart1].\n\nCalpain 3 (CAPN3) is a muscle specific Calpain family member. When mutated it causes Limb-Girdle Muscular Dystrophy (LGMD) 2A (OMIM\\#253600, the most common form of LGMD in many populations). [@pone.0011940-Ono1] It is currently not known how CAPN3 functions and how its dysfunction causes disease. CAPN3 shares \u223c50% identity with Calpain 1 and 2 (MIM\\*114220 and \\*114230, respectively)[@pone.0011940-Kinbara1] on amino acid level, but is unique in that it contains three specific insertion sequences (NS, IS1 and IS2) which have to be autolytically removed for CAPN3 to become proteolitically active. Like Calpains 1 and 2 CAPN3 has a calcium-sensing domain, which operates with nanomolar sensitivity and influences protease activation and activity [@pone.0011940-Murphy1]. In muscle tissue most, but not all, of the CAPN3 protein can be found in an inactive form bound to the"
+"Introduction {#s1}\n============\n\nThe cellular machinery of many biological functions is based on dynamic, reversible molecular interactions, and therefore characterization of the stoichiometry, specificity and cooperativity of protein-protein and protein-nucleic acid interactions is of key importance in cell biology. Such interactions include self-associations, two-component heterogeneous associations, as well as multi-protein assemblies. Sedimentation velocity (SV) analytical ultracentrifugation (AUC) has been applied to such studies in numerous biological systems, and provides exquisitely rich information on the properties of individual molecules, their complexes and their interactions [@pone.0083439-Zhao1]--[@pone.0083439-Arisaka1]. A classic biophysical method which has seen substantial instrumental, theoretical, and computational improvements in recent years [@pone.0083439-Schuck1], SV has unique virtues for deciphering the binding properties of proteins in free solution, due to the strongly size-dependent movement of macromolecules in the centrifugal field, leading to hydrodynamic separation and characteristic patterns of co-migration that can be observed with high resolution. Two widely used conventional optical detection systems, an absorbance spectrophotometer and a Rayleigh interferometer, generally provide sufficient sensitivity for the label-free detection of macromolecules in the high nM to mM range. In favorable cases, concentrations as low as \u223c10 nM (for a 50 kDa protein) can be reached with far UV absorbance [@pone.0083439-Zhao2], but the concomitant low"
+"Introduction {#sec1-1}\n============\n\nThe majority of Oman is geographically a desert and 25% of children account for total population residing in suburban, rural areas and most walk with open foot wear for daily activities. Thus they are exposed to wide range of injuries from simple puncture wounds to complete penetration caused by date thorns and wooden splinters. The significant numbers of injuries are minor and cause short-term discomfort. However most of the patients rarely seek medical attention.\n\nMost of deep seated infections of structures of foot reported in literature are commonly due to prick injuries related to thorns, nails. However, no case of isolated osteomyelitis of navicular bone caused by neglected foreign body has been reported in literature. Most of isolated cases are primary acute or subacute osteomyelitis. Late presentation can be possible in Middle East countries due to negligence of patients. Pain and inability to bear weight are the main concerns of the affected patient, as the mobility is impaired\n\nCase Report {#sec1-2}\n===========\n\nWe present a previously healthy 10 year old boy, presented with history of on and off pain in the left foot for 3 months duration. He was treated with analgesics and observation. Later, patient presented"
+"Introduction\n============\n\nThe rapid evolution of the Covid-19 pandemic has fundamentally challenged our health care delivery system, as the need for social distancing to curb disease spread is critical to public and health-care provider safety.[@r1]\n\nIn most health care organizations, a majority of ambulatory clinic appointments have been in-person visits, with person-to-person connection and physical examination as central elements of the diagnostic and therapeutic relationship.\n\nTelephone and video visits are convenient for patients because they don't require taking time off work, finding childcare/eldercare, or driving to a clinic appointment.[@r2] Health care systems can use telemedicine to increase overall access, scale provider services by allowing care to happen from many locations, prevent exposure, and direct patients to appropriate levels of care.[@r3] With technological advances, video visits have become much more convenient for patients and providers. However, until just recently academic medical centers (AMCs) have been slow to adopt video visits. There has been no clear consensus on the quality of clinical care delivered via such visits and patients have not demanded them.[@r4]\n\nIn March 2020, the number of SARS-CoV-2 infected patients began to escalate, making it crucial to find methods to provide high-quality medical care without exposing the clinic staff or"
+"Introduction {#pmbaa4cb7s1}\n============\n\nRadionuclide imaging with Metaiodobenzylguanidine (mIBG) has a fundamental role in the diagnosis, staging and evaluation of treatment response in childhood neuroblastoma and adult neuroendocrine tumours (NETs) (Gelfand [@pmbaa4cb7bib009], Shapiro *et al* [@pmbaa4cb7bib025], Brisse *et al* [@pmbaa4cb7bib005]). Scintigraphy is routinely undertaken using ^123^I-mIBG in preference to ^131^I-mIBG, because better quality images can be obtained from 159\u2009keV ^123^I gamma photons and twenty times more ^123^I activity can be administered for diagnostic scans (Shapiro *et al* [@pmbaa4cb7bib024], Matthay *et al* [@pmbaa4cb7bib018]). Iodine-123 is also advocated for treatment planning prior to ^131^I mIBG therapy (Monsieurs *et al* [@pmbaa4cb7bib021]), despite the fact that the images obtained have been shown to be less sensitive in detecting lesions than post-therapy ^131^I-mIBG scans (Yang *et al* [@pmbaa4cb7bib029]). In response an alternative positron emission tomography tracer, ^124^I, has been used in attempts to improve diagnostic image quality and quantitative accuracy for dosimetry (Huang *et al* [@pmbaa4cb7bib014], Koopmans *et al* [@pmbaa4cb7bib016]). As ^124^I-mIBG is not widely available and its clinical efficacy remains unproven, ^123^I-mIBG remains the standard.\n\nAlthough ^123^I predominantly emits gamma photons at 159\u2009keV (83% abundance), photons above 500\u2009keV (2.3% abundance) are also emitted. These high energy photons penetrate the septa of low-energy"
+"Introduction {#s1}\n============\n\nThe concept of species, linked intrinsically to the process of speciation, has been the source of long-standing debate of an intensity matched by few others in biology. Lineages within a species that are presumably under various stages of speciation have been an integral part of this discussion. From a taxonomic perspective, the intraspecific category representing diverging lineages within a species is often the subspecies [@pone.0041058-Mulcahy1]. Patten and Unitt [@pone.0041058-Patten1] define subspecies as \"a collection of populations occupying a distinct breeding range and diagnosably distinct from other such populations\", a definition generally accepted in practice. Subspecies have traditionally been circumscribed based on discontinuities in the geographical distribution of phenotypic traits [@pone.0041058-Mayr1], which has sometimes resulted in highly subjective delimitations. It is common practice in taxonomic revisions for several closely related taxa to be lumped together as subspecies, or subspecies to be elevated to the level of species. It follows that various taxa currently considered subspecies might represent *bona fide* species. Indeed, it has been suggested that trinomial names in collections should be maintained since some subspecies may represent true species [@pone.0041058-Frost1]. Apart from their relevance in taxonomy, they are commonly used as tools in biodiversity assessment and to"
+"Introduction {#Sec1}\n============\n\nWith the aim of producing better decisions and fostering legitimacy (Bobbio [@CR8]), participation tries to raise acceptance and integrate different values into the decision-making process. According to Fiorino ([@CR48]), there are at least three different rationales for undertaking public participation: substantive, normative and instrumental. The substantive argument states that considering lay assessment of risks often leads to better decisions than merely relying on experts' judgement. The normative rationale is based on the notion that the public is best qualified to decide on matters that lie in their own interest. Finally, the instrumental argument reasons that decisions that are taken in consent with laypeople are more likely to be legitimate and accepted. Other authors (i.e. Arnstein [@CR6]; Rowe and Frewer [@CR42]; EIPP [@CR15]) discern different levels of inclusion in public engagement practices: from information through consultation to participation. In extreme forms, participation enables citizens to take decisions themselves. From a science and technology studies perspective, Lengwiler ([@CR29]) argues that in most cases participatory approaches are aimed at taking decisions on the science policy level and not at actual research practices. The methods used and their intentions are highly diverse and the decision-makers' motivations for bringing about participatory exercises"
+"Methylmercury (MeHg) easily crosses the blood--brain barrier and accumulates in the central nervous system, where it is demethylated to inorganic mercury. Chronic perinatal exposure to environmentally relevant levels of MeHg is associated with the occurrence later in childhood of neurobehavioral problems such as impaired attention and fine motor function. Animal studies confirm this association, but epidemiologic evidence is mixed despite extensive study. Moreover, MeHg toxicity and the period of time before effects appear are not completely understood, as few studies have been conducted beyond the first months or years of life in either animals or humans. Researchers now demonstrate in a mouse model that effects from early exposure to methylmercury can occur years after early-life mercury levels in the brain have declined **\\[*EHP* 116:746--751; Yoshida et al.\\]**.\n\nIn the current study, investigators used two strains of mice---the wild-type C57BL strain and the genetically manipulated metallothionein (MT)-null strain. The latter was used to examine potential genetic susceptibility to the toxic effects of MeHg exposure, as MT-null mice do not produce metallothionein-I and II proteins that can bind metals and protect against their toxic effects. Mice were exposed through diet to low levels of MeHg (5 \u03bcg/g diet) from the first day"
+"Introduction {#section1-2374373518788851}\n============\n\nDespite all the efforts of both governmental and nongovernmental organizations to improve oral health, oral disease burden is still high globally, especially in developing countries. Among the major barriers that have been consistently echoed by several authors as militating against the desired improvement in oral health is individual attitude and oral health behavior ([@bibr1-2374373518788851],[@bibr2-2374373518788851]).\n\nHealth attitude has been defined as \"opinions, feelings, and associated beliefs toward individual health,\" while health behavior refers to \"behavior patterns, actions, and habits that relate to health maintenance, restoration, and improvement\" ([@bibr3-2374373518788851]). Health behaviors can be broadly classified into health-enhancing or health-impairing behaviors. It has been established that behavior and behavioral modification can be used to influence health outcomes.\n\nBaxter ([@bibr4-2374373518788851]) examined the relationship between health behaviors and health outcomes and demonstrated its role in morbidity and mortality. Connor and Norman stated that significant mortality is caused by behavior of individual, but such behaviors are modifiable and this change can influence health outcomes ([@bibr5-2374373518788851]). They reported that health-improving behaviors are associated with low morbidity and high subsequent long-term survival ([@bibr5-2374373518788851]).\n\nPatients utilizing dental services can be grouped into nonattenders, problem-oriented attenders, and regular attenders ([@bibr6-2374373518788851]). Regular dental visit has been shown to"
+"Introduction {#s1}\n============\n\nA minority of HIV-1-infected patients, defined as elite controllers (ECs), demonstrate that effective control of viral replication and disease progression is possible in the absence of treatment [@ppat.1002170-Deeks1]. Deciphering the mechanisms of natural infection control in these patients is a critical step for designing successful vaccines and is considered a priority in the field [@ppat.1002170-Baker1]. Research on human ECs, however, is restricted to studies of the chronic infection, samples collected at random time points, and limited access to tissues, all precluding identification of early events responsible for virus control. These shortcomings have likely prevented a clear understanding of the immune mechanisms driving infection towards elite-controlled status. An animal model in which complete control of viral replication can be achieved in all cases has strong potential to effectively complement EC research in humans.\n\nPathogenic HIV and SIV infections of humans and RMs are characterized by progression to AIDS in a variable time frame [@ppat.1002170-Hirsch1] and are associated with: (i) massive, continuous viral replication [@ppat.1002170-Ho1], [@ppat.1002170-Wei1], with VL set-points being predictive for the time of progression to AIDS [@ppat.1002170-Mellors1]; (ii) continuous depletion of CD4^+^ T cells in peripheral blood [@ppat.1002170-Grossman1] which is more pronounced at mucosal sites [@ppat.1002170-Brenchley1], [@ppat.1002170-Mehandru1],"
+"Primary and secondary hydroxamic acids \\[R\u2032CON(R)OH, R\u00a0=\u00a0H or alkyl\\] constitute a class of metal ion chelating agents with great therapeutic potential.[@b0005; @h0015] A large number of naturally occurring hydroxamate-based siderophores (Fe^3+^ carriers) have been isolated and much effort has been devoted to the synthesis of bioactive hydroxamic acids.[@h0010; @b0010; @h0035; @h0040] Due to their metal ion binding ability, hydroxamic acids often behave as inhibitors of metalloenzymes (e.g., Fe^3+^-containing lipoxygenase, Zn^2+^-containing MMPs and HDACs and Ni^2+^-containing urease), which are implicated in the pathophysiology of human diseases.[@h0005; @h0015; @b0015]\n\nThe structures of hydroxamic acid analogues have been studied extensively using NMR and molecular modelling techniques.[@b0020; @b0025] For particular hydroxamic acid structures, the existence of different possible conformations in solution has been found to depend on the sample concentration, the temperature and the solvent.[@b0030] More specifically, the hydroxamate group may adopt *E* and *Z* conformations which are separated by a high energy barrier.[@b0035] Furthermore, tautomerism between the amide and the imide forms is possible, but the imide forms are found to be absent in solution.[@b0035] Various researchers have concluded that the *Z* conformation of the amide structure prevails since it becomes stabilized via hydrogen bond formation, either intramolecularly or intermolecularly to"
+"Cotyledons are essential for the early growth of seedlings until they become autotrophic[@b1]. During the first season, the roots of seedlings must reach soil containing sufficient moisture and nutrients to support growth, whereas the plumule must reach light to begin photosynthesis[@b2]. Additionally, reserved nutrients such as carbohydrates, organic nitrogen, phosphorus compounds, and inorganic ions are transported from the cotyledons into the developing seedling[@b3][@b4][@b5]. To investigate the role of cotyledons in early seedling development, we used species of the shrub genus, *Hakea*, as the model plant of our study.\n\n*Hakea* (Proteaceae) is endemic to Australia. This genus is known for its wide range of seed sizes (2--500\u2009mg) among the 150 extant species, 100 of which occur in south-western Australia, a region characterised by nutrient-impoverished soils and hot, dry summers[@b6]. Hakeas possess phanerocotylous epigeal seedlings (i.e., the cotyledons emerge from the seed coat, protrude above ground, spread laterally and are photosynthetically active) that is the most common type of seedling in the flora of south-western Australia[@b1]. Milberg & Lamont[@b1] noted that early removal of cotyledons caused death of *Hakea* species and suggested that the cotyledons must have an important nutritional function in the early establishment of their seedlings. *Hakea* seedlings are"
+"The third installment of the Aswan Heart Centre Science and Practice Series was held in El Gouna, Egypt, on February 1--3, 2013, at the beautiful satellite campus of the Technische Universit\u00e4t Berlin. This 3-day symposium ([Figure 1](#fig1){ref-type=\"fig\"}) focused on the unstable coronary plaque and acute coronary syndromes, bringing together leading international experts who bridged the spectrum of epidemiology, molecular mechanisms, clinical trials, and clinical practice. The program was designed to allow maximal interaction between the audience and the national and international faculty, and the topics were chosen to stimulate interaction between clinicians and basic scientists with the purpose of offering the very best to our patients. The venue had advanced audiovisual technology, allowing for recording of all of the presentations, which are now available online at the Aswan Heart Centre website (See <http://aswanheartcentre.com/2013-04-11-00-47-42/2013>), and the setting was stunning and relaxing ([Figure 2](#fig2){ref-type=\"fig\"}).\n\nThe first session of the symposium consisted of elegant discussions dedicated to the global epidemiology of coronary artery disease and acute coronary syndromes. Stuart Spencer, executive editor of *The Lancet*, discussed the Global Burden of Disease project that was highlighted in his journal in December 2012 and summarized earlier this year in his excellent review in Global Cardiology"
+"The issue of publication ethics is attracting ever increasing scrutiny. Of particular attention are duplicate publication, plagiarism, fabrication of data, inappropriate authorship, and conflict of interest (COI). The issue of COI is an increasingly serious issue for medical journals globally. Important documents concerning COI definition and disclosure include the COI Disclosure Form by the International Committee of Medical Journal Editors (ICMJE) ([@B1]) and flowcharts by the Committee on Publication Ethics (COPE) dealing with the omission of essential COI notes in research publications ([@B2]), which provide advice for publishers and editors. An additional source on COI is available from the International Society for Medical Publication Professionals (ISMPP) ([@B3]) which developed the Good Publication Practice guidelines, promoting collaboration between academics, medical writers, and pharmaceutical agents to promote the integrity and transparency in medical publications.\n\nDespite all the efforts to raise the awareness of different types of COI and the significance of the disclosure, recent studies reveal that more concerted efforts are required to educate reviewers, journal editors, and publishers on issues of COI ([@B4][@B6]).\n\nCOI arises when author, reviewer or editor have connections to a particular source/organization, causing a bias in their judgment of the journal manuscript, even if the ultimate decision"
+"In responding to trauma or to any life altering situation, such as a life-threatening medical diagnosis, people inevitably journey a profound intrapersonal change process (K\u00fcbler-Ross, [@CIT0024]; Mayan, Morse, & Eldershaw, [@CIT0035]). Depending on the magnitude of the trauma experienced, it is accepted that people transition through various phases in adjusting to the new or changed life situation (Parker & Lewis, [@CIT0043]). Cancer is documented as a traumatic and life-changing event (Smith, Klassen, Coa, & Hannum, [@CIT0055]) and has developed into a chronic disease (De Jong, Tamminga, De Boer, & Frings-Dresen, [@CIT0009]; Hoffman, Lent, & Raque-Bogdan, [@CIT0019]), a reality to which cancer survivors have to adapt.\n\nThe body of research, exploring the return to work (RTW) experience of cancer survivors, focusses predominantly on the health and well-being challenges they experience (e.g., Knott et al., [@CIT0022]; Main, Nowels, Caventer, Etschmaier, & Steiner, [@CIT0032]), and on the interventions needed to support them when re-entering the work context (e.g., Dewa et al., [@CIT0011]; Fong, Murphy, Westbrook, & Markle, [@CIT0015]; Messner & Vera, [@CIT0037]; Stergiou-Kita et al., [@CIT0059]). In these studies, RTW is regarded as a period consequent to successful cancer treatment, characterized by various physical and psycho-social challenges; however, research does seem to imply"
+"Visual kinetic analyses extract kinetic information from the naked-eye comparison of original or modified progress reaction profiles. These analyses are becoming a popular tool in chemistry and related disciplines, even replacing traditional kinetic analyses focused on the measurement of initial rates. This increasing popularity is due to the combination of recent advances in both reaction monitoring technology and the development of new kinetic analyses. This minireview is focused on the most recent analyses developed in the last fifteen years. Also, it highlights the main differences between the most traditional kinetic analyses and answers the most frequently asked questions by new users of visual kinetic analyses.\n\nIn the past, visual analyses of the slope and interception of linearized plots (Lineweaver--Burk,[@cit1] Eadie--Hofstee[@cit2],[@cit3] and Hanes--Woolf[@cit4] plots) have been used to quickly identify different types of inhibition and concentration dependences of substrates. However, the simplest comparison of two reaction curves is to visually discern whether they are identical, that is if they overlay. These visual analyses transform the axes to achieve the overlay of the progress reaction profiles. The transformations required to achieve this overlay provide information about the relationship between the different progress reaction profiles.\n\nThe strategy of overlaying reaction profiles was first"
+"Background {#Sec1}\n==========\n\nHepatic arterial injury is an uncommon complication of percutaneous biliary drainage interventions (Saad et al. [@CR7]). When symptoms of hemorrhage into the biliary tree such as pain, hemobilia, peri catheter hemorrhage and upper gastrointestinal bleeding persist despite conservative management, other interventions are indicated. These include upsizing of the biliary drainage catheter and arteriography/embolization. The angiographic manifestations of hepatic arterial injury include arteriobiliary or arterioportal fistula, pseudoaneurysm, extravasation and focal arterial caliber irregularity at the site of indwelling catheter. These findings may be obscured by the indwelling catheter and the contrast in the biliary ducts.\n\nSometimes antegrade angiography is not possible due to challenging anatomy and other techniques are required to control bleeding. We describe a case of intractable hemobilia from biliary drainage where altered anatomy by tumors precluded antegrade endovascular treatment. Cannulation of the injured artery via the biliary access site made distal and proximal embolization possible. Interventionalists should be aware of this option of managing biliary hemorrhage. Literature is reviewed.\n\nCase presentation {#Sec2}\n=================\n\nA 49-year-old male with metastatic colon adenocarcinoma presented with several days of fever, nausea, vomiting, jaundice and hyperbilirubinemia. His past medical history includes right hemicolectomy, right adrenalectomy, partial right hepatectomy and hepatic"
+"Background\n==========\n\nThe genomic variability of HIV viruses has impeded the development of globally relevant HIV vaccines with ability to induce strong and broad cellular and humoral immune responses. Many strategies, such as codon/RNA optimization, addition of highly efficient leader sequences, use of consensus or mosaic antigens, and electroporation (EP) have all been applied to enhance the breadth and magnitude of immune responses induced by DNA vaccines.\n\nMethods\n=======\n\nHighly optimized clade B and C consensus envelope DNA vaccines (pEY2E1-B and pEY3E1-C) were developed. Their immunogenicity was compared to the immune responses induced by an optimized mosaic gp160 envelope vaccine (pMosEnv) or optimized primary clade B and C envelope vaccines (pPK61-14 and p96ZM651gp140-CD5). The immunogenicity of these constructs was studied in different murine models. All vaccines were delivered using electroporation. Antibody responses were determined by ELISA and cellular responses by IFN-\u03b3 ELISPOT.\n\nResults\n=======\n\nAntibody analysis supported that the consensus immunogens induced stronger clade-specific antibody response than the primary immunogens, while the mosaic antigen was a poor inducer of antibody responses. Compared to the primary vaccine constructs, both consensus and mosaic constructs were more potent at driving diverse cellular immune responses. The strongest cross-reactive immune responses against various consensus peptides"
+"There is growing evidence about the interrelationship between martial arts training and aggressiveness, though the findings are not consistent with each other. The inconsistency is in part due to cross-sectional design of studies and presence of lots of psychological and environmental factors which are difficult to be controlled in such studies. Anger was defined by Spielberger as \"an emotional state that consists of feelings that vary in intensity from mild irritation or annoyance to fury and rage\" ([@CIT0001]). According to frustration-aggression hypothesis of Berkowitz, any negative affect including anger or fear can lead to frustration, which eventually may be expressed as aggression or avoidance behaviors respectively ([@CIT0002]).\n\nProvocation was reported as the best predicting factor for aggression, followed by anger rumination, gender and type of sport ([@CIT0003]). Anger which arises from frustration or provocation can eventually be expressed as aggression. Hostile or reactive aggression is a more prevalent consequence of anger compared with instrumental aggression which does not require anger to be expressed ([@CIT0003], [@CIT0004]).\n\nWe previously examined whether there was any relationship between the sports training and the adolescents' anger. The results showed that the anger rate was not different between judoka and non-athletes in girls, meanwhile both of"
+"Introduction {#Sec1}\n============\n\nMountainous ecosystems are highly sensitive to any disturbances in natural balance, what makes them especially interesting for observations of chemical and radiochemical contamination. The area of the Babia G\u00f3ra National Park (BPN), being located along the main ridge of the Flysch Carpathian Mountains, is just the proper place in this respect. The terrain belongs to the young folded mountains, built mainly of flysch and some other lithology. The area is characterized by highly variable and unique natural resources. The highest summit of the Babia G\u00f3ra Mountain's massif (west part of the Beskid \u017bywiecki chain of mountains) is Diablak reaching 1,725\u00a0m\u00a0asl. To protect this unique area the BPN and the UNESCO World's Biosphere Reserve were established. The area of the BPN, like other regions of Poland, was exposed to substantial contamination with radionuclides due to the Chernobyl accident in 1986 and nuclear weapon tests since the fifties of the twentieth century \\[[@CR1]--[@CR6]\\]. Researches on radionuclides distribution in the environment are important not only because these are perfect markers of the environment pollution but also because radioactive isotopes are not immobilized in soil but are constantly interchanged between inorganic matter and living organisms \\[[@CR7]\\].\n\nThe aim of"
+"Background\n==========\n\nCellulolytic enzymes (glucohidrolases - EC 3.2.1.-) are biocatalizators highly specific. They act in synergy to hydrolyze \u03b2-1,4 bonds between monosaccharide units of D-glucose in the cellulose chain releasing its constituents. Cellulases are categorized according to the place they act in the cellulosic fiber. Endoglucanases start hydrolysis, exoglucanases act in the reduced terminal produced by endoglucanases followed by \u03b2-glycosidase which act in the product of exoglucanases catalysis releasing glucose monomers.\n\nFungi are considered the best cellulolytic enzyme producers due to its natural cellulases that complete saccharification of lignocellulose. Species of *Penicillium*have been reported as excellent producers of cellulolytic enzymes when compared to commercial species and strains \\[[@B1]\\]. Aiming to contribute to biocatalytic processes and obtention of new sources for cellulolytic enzyme, this work has as objective the production of endoglucanases and exoglucanases from *Penicillium citrinum*isolated from an agro industrial residue in Amazon.\n\nMethods\n=======\n\nSample was isolated from sugar-cane bagasse in agro industry of Amazonas, by the municipality of Presidente Figueiredo-AM-Brasil, 110 km from Manaus. Molecular identification was made by ITS-18S gene amplification, followed sequence analysis of using software Bioedit Sequence Alignment Editor^\u00ae^and BLAST from NCBI (BLASTn). For the production of cellulolytic enzymes fungi was cultivated during 192h in"
+"Introduction {#s1}\n============\n\nMetacommunities are defined by dispersal connecting local communities of potentially interacting species [@pone.0019525-Holyoak1], [@pone.0019525-Leibold1]. Consequently, diversity and abundance of species in a spatially-structured region is determined by both local and regional processes. Dispersal into a patch may increase local population sizes by mass or rescue effects, or augment diversity through immigration of new species [@pone.0019525-Holyoak1]. From the perspective of the community of origin, however, dispersal also causes a loss of individuals [@pone.0019525-Gundersen1], [@pone.0019525-Holt1], [@pone.0019525-Amarasekare1]. There are few empirical studies of the effect of such loss on local populations and communities because of the difficulties in manipulating dispersal and observing whole communities.\n\nIn many natural systems, the onset of emigration from a patch is triggered by characteristics of the donor population as well as by local environmental conditions in that patch [@pone.0019525-Niitepld1], [@pone.0019525-Clobert1], [@pone.0019525-Travis1], [@pone.0019525-Altermatt1]. Among environmental factors, disturbance is thought to strongly affect dispersal [@pone.0019525-Bates1], [@pone.0019525-Bloch1], [@pone.0019525-Nakamaru1], [@pone.0019525-Southwood1], [@pone.0019525-Altermatt2] and metacommunity theory offers an ideal concept to study disturbances in a spatial context [@pone.0019525-Holyoak1], [@pone.0019525-Brown1]. Many disturbances are highly stochastic, and create both temporal and spatial variability in usable habitat patches [@pone.0019525-Sousa1], and may even increase fragmentation and reduce connectivity [@pone.0019525-Niemel1]. Disturbances such as floods or fires"
+"A high clearance of low-molecular substances such as urea and creatinine is generally considered advantageous in dialysis. The discovery in the 1990s of increased morbidity \\[[@GFS385C1]\\] and mortality \\[[@GFS385C2], [@GFS385C3]\\] in peritoneal dialysis (PD) patients with fast low-molecular (e.g. glucose, creatinine and urea) peritoneal transport (FLMT, also called 'high transport') was thus counterintuitive. Several explanations are possible:FLMT leads to increased glucose absorption, reducing the transperitoneal osmotic gradient necessary for ultrafiltration. Patients thus become overhydrated, leading to hypertension, left ventricular hypertrophy and inflammation. In patients in whom FLMT results in negative ultrafiltration, clearance will be paradoxically reduced, causing underdialysis.FLMT is associated with fast high-molecular (e.g. albumin, protein) transport (FHMT) \\[[@GFS385C4]--[@GFS385C9]\\], as assessed by albumin and/or protein clearance \\[[@GFS385C5], [@GFS385C10]\\] or by measuring the large pore transcapillary clearance (JvL) using the PD capacity (PDC) algorithm \\[[@GFS385C4], [@GFS385C7]\\] (*vide infra*). Patients will thus lose protein leading to malnutrition, immunoparesis, increased plasma viscosity, oxidative stress and an atherogenic lipid profile.The capillary wall is the main barrier to peritoneal transport. FLMT is therefore a marker of already existing vascular inflammation and/or pathological endothelial function, which will lead to accelerated arteriosclerosis and death, independent of dialysis treatment.Increased glucose absorption causes anorexia and malnutrition.A decade later, the"
+"Introduction {#s1}\n============\n\nProtein-protein interactions are essential in virtually every process within cells. The rate of protein complex formation is governed by diffusion and geometric constraints, followed by a structural reorganization to form a stable complex [@pone.0032804-Spaar1], [@pone.0032804-Janin1]. For certain proteins, a transient complex, the \"encounter complex\", accelerates the formation of the protein complex [@pone.0032804-Fawzi1]. The encounter complex is primarily formed from charge-charge interactions between proteins and operates by reducing the conformational search space [@pone.0032804-Ahmad1]. The existence of the encounter complex has been verified by several kinetic experiments [@pone.0032804-Schreiber1] and visualized using NMR paramagnetic relaxation enhancement, which is used for relatively weak and fast-exchanging protein-protein complexes [@pone.0032804-Tang1]. Protein complexes that are bound by non-covalent interactions are in dynamic equilibrium (i.e., they continuously switch between free and bound states) [@pone.0032804-Schreiber1], [@pone.0032804-Saitoh1]. If a peptide ligand has multiple binding sites that are located close to one another, an encounter complex would increase the speed in such a way that a protein shuttles between each binding site in the peptide ligand [@pone.0032804-Saitoh1].\n\nProtein-binding modules mediate protein interactions [@pone.0032804-Zarrinpar1]. The Src homology 3 (SH3) domain is one of the most abundant protein-binding modules and is shown in [Figure 1a](#pone-0032804-g001){ref-type=\"fig\"}. More than 11,000 different SH3"
+"Introduction {#Sec1}\n============\n\nThis paper focuses on the process by which persons recover those parts of the self and life that have been compromised by participation in mental health treatment systems and the stigmatizing culture in which treatment is embedded.[@CR1] In the development of a psychiatric disability, individuals experience a series of losses, including loss of hope, personal power, uniqueness, motivation, identity, self-respect, self-acceptance, relationships, and the opportunity to learn skills for making effective choices.[@CR2] While some losses are best addressed by individuals or with individual interventions---such as awakening hope, exploring identity, enhancing connections with others, reducing harm, and learning the skills of making effective choices---others are better addressed by seeking to increase the recovery-orientation of treatment program culture. The culture, and the interpersonal interactions that comprise it, become a primary intervention facilitating individuals' recovery from serious mental illnesses.\n\nDuring the era when state mental hospitals and therapeutic communities predominated, research often focused on ward culture,[@CR3] and this anthropological approach was extended to the early PACT program in Madison.[@CR4] In a National Association of State Mental Health Program Directors study investigating what helps and what hinders recovery, Onkin and colleagues extend this cultural approach by focusing on the role of"
+"As professional antigen presenting cells, Dendritic cells (DCs), undergo a well-defined activation process that render them competent to activate adaptive immune responses and also to control tolerance. As a result, DCs are considered key regulators of the immune system. DC activation via pathogen recognition or by tissue injury occurs by virtue of expression of pattern recognition receptors, which has been extensively documented in previous years. However, there is a growing body of evidence demonstrating that DC activation and function can be also finely adjusted by perturbations in cellular mechanisms that are normally associated with homeostasis, and that include processes such as cell polarity, changes in the secretory demand, endoplasmic reticulum (ER) stress, epigenetics, autophagy, and metabolism among others. Moreover, evidence is now emerging that environmental cues such as nutrient availability, antibody complexes, and sodium levels are also important regulators of DC biology. In this Research Topic, we have brought together a collection of 10 primary research and review papers from experts in their respective fields to home in novel and emerging regulators of DC function that go beyond canonical pattern recognition.\n\nSeveral cellular \"household\" processes that normally function to maintain intracellular homeostasis can also serve as regulators of DC function"
+"1.. Introduction\n================\n\nMicromachining has made possible the production of precision inertial sensors at a price that allows their usage in cost-sensitive consumer applications. Conventional rotating wheel as well as precision fiber-optic and ring laser gyroscopes all are too expensive and too large for use in most emerging applications. Micromachining can shrink the sensor size by orders of magnitude, reduce the fabrication cost significantly, and allow the electronics to be integrated on the same silicon chip \\[[@b1-sensors-09-02389]\\].\n\nPractically all MEMS gyroscopes use the Coriolis Effect; a proof mass is driven into oscillation (the drive mode) and in the presence of a rotational motion the proof mass starts to oscillate in the sense mode if sense and drive mode directions and the rotational axis are mutually perpendicular. During the development of micromachined gyroscopes, various actuation mechanisms have been explored to oscillate the vibrating structure in the primary drive mode; the most common ones include electrostatic, piezoelectric and electromagnetic means \\[[@b2-sensors-09-02389]--[@b5-sensors-09-02389]\\]. Electrostatic actuation using a comb drive design is the currently prevailing approach \\[[@b2-sensors-09-02389]--[@b3-sensors-09-02389]\\] as they require a low voltage and can excite high frequency resonant modes. However, the resulting deflection amplitude is relatively small. To detect the Coriolis-induced vibrations in the"
+"The GTPase Rab35 regulates the release of small vesicles called exosomes from the surface of glial cells, say Hsu et al.\n\nExosomes are formed in the lumen of specialized endosomes called multivesicular bodies (MVBs), which fuse with the plasma membrane to secrete the vesicles extracellularly. The process was first described as a way for differentiating reticulocytes to quickly discard their unwanted cellular contents. In other cell types, exosomes have signaling functions or mediate the transfer of mRNAs between cells. Oligodendrocytes secrete a lot of exosomes, but their role in the central nervous system isn\\'t clear---partly because molecules controlling the vesicles\\' release haven\\'t been identified.\n\nBecause Rabs and their accessory proteins regulate membrane trafficking, Hsu et al. investigated their function in exosome secretion by screening all 38 Rab GTPase-activating proteins (GAPs). Five GAPs inhibited exosome release from oligodendrocytes, including three closely related proteins that all switched Rab35 to the inactive, GDP-bound state. Knocking down Rab35 or expressing a dominant-negative version of the GTPase also blocked exosome secretion. Rab35 prepared MVBs for exocytosis by docking them to the plasma membrane.\n\nBoth Rab35 and MVBs were found in the myelin compartment of oligodendrocytes, which enwraps and insulates nerve cell axons. This suggests that"
+"Background\n==========\n\nOrthodontic treatment is extremely popular in modern society. Bonding of attachments to enamel is based on acid etching, resulting in microporosity that allows micro-retention of resin infiltrating into the enamel.\n\nAfter active orthodontic treatment, brackets are mechanically debonded and residual adhesive must be mechanically removed, since resin remnants accumulate dental plaque and might discolor \\[[@b1-medscimonit-20-1991]\\].\n\nCurrently, no technique allows removal of the composite remnants without any damage of the enamel surface. The underlying reasons are acid etching resulting in resin infiltration into the enamel \\[[@b2-medscimonit-20-1991]\\], and hardness of the enamel (about 5 in the Mohs scale) lower than that of the abrasive materials used (quartz, aluminium, carbon steel, zirconium oxide 7, and tungsten carbide 8).\n\nEfforts are made to minimize the loss of the enamel external layer, because it is hardest and richest in fluoride. Moreover, the enamel surface should be left as smooth as possible after debonding, since deep scratching is not polished through the years by tooth brushing \\[[@b3-medscimonit-20-1991]\\].\n\nThe aim of this systematic review was to review papers on the available methods of orthodontic adhesive removal after debonding metal brackets from human teeth in terms of iatrogenic enamel damage in order to find clear evidence"
+"Introduction {#cow056s1}\n============\n\nBiological invasions are recognized as an important biotic component of global change ([@cow056C89]; [@cow056C88]; [@cow056C66]). Invasive species alter the composition, structure and functioning of ecosystems, resulting in loss of biodiversity and displacement of native species ([@cow056C101]; [@cow056C91]). An emergent concern is that other components of global change, such as climate warming, might enhance the capacity of alien species to invade new areas ([@cow056C28]; [@cow056C98]; [@cow056C44]; [@cow056C86]; [@cow056C107]; [@cow056C90]). [@cow056C59] proposed that both components 'constitute a deadly-duo threatening species abundance, distributions and biotic interactions'.\n\nAt present, however, the organismal attributes that make invading species ecologically successful, in comparison to a native, remain as a poorly answered question ([@cow056C87]; [@cow056C97]; [@cow056C24]). The successful establishment and spread of invasive species in a recipient environment would be facilitated by the ability of an invasive species to maintain high physiological performance over a wide range of environmental conditions (i.e. generalist behaviour; [@cow056C71]; [@cow056C97]; [@cow056C2]; [@cow056C56]). Nevertheless, among native species a higher performance is typically constrained to a narrow range of conditions (i.e. specialist). As temperature has profound effects on organismal functions, this biotic environmental factor is gaining attention as a major driver of invasion success.\n\nIn this context, [@cow056C54] proposed, tested and"
+"INTRODUCTION\n============\n\nIt is not uncommon for families to bring multiple children for evaluation in the pediatric emergency department (PED) at a single visit. From our personal experience in an urban PED, these children often require less emergency department (ED) resources than patients presenting individually. Such non-acute visits can pose an obstacle to throughput and optimal use of the ED. A recent study by Kannikeswaran, et al[@b1-wjem-14-525] investigated the epidemiology of such visits to an inner city ED and concluded that these patients have lower triage acuity and low hospital admission rates when compared with the general patient population of individual pediatric ED patients. To our knowledge, no other studies have been published on families presenting to the ED with multiple children as patients.\n\nDefining which patients require ED care is a challenge. Studies looking at the use of EDs by \"non-urgent\" patients typically define these patients by triage acuity, need for procedural intervention, physician time, or by physician judgment of the need for evaluation or care within 24 hours.[@b2-wjem-14-525]--[@b5-wjem-14-525] The American College of Emergency Physicians (ACEP) defines an emergency as \"any medical condition of recent onset and severity, including but not limited to severe pain, that would lead a"
+"The Islamic Republic of Pakistan celebrated its Golden Jubilee in 1997, 50 years after the partitioning of United India from the British Raj. For Pakistan ([fig 1](#fig1){ref-type=\"fig\"}), this was also a time to evaluate the health and population status of its people. In Pakistan, during the 1940s, population growth rates begin to accelerate as health improvements lengthened life expectancy and birth rates remained high. In 1947, at the time of independence, Pakistan\\'s population was 31 million. By 1995 it had escalated to 140 million[@b1]\n\n![Map of Pakistan](umj7603-122-f1){#fig1}\n\nFamily planning programmes were started in the 1950s and 1960s by private and government institutions. Donors such as World Bank and the UN along with the government of Pakistan funded the programmes for family planning (FP). For years these institutions focused only on women as it was thought that FP was the preserve of women, therefore the audience was 100% female.\n\nIn 1947, the fertility rate was 7.5 per women and the population growth rate 4.5% per year. In the 1990s these were reduced to 5.1 and 2.9, respectively, but this reduction is negligible. Presently, 41% of the total population in Pakistan is under the age of 15 years. A large number of"
+"INTRODUCTION {#sec0001}\n============\n\nThe COVID-19 pandemic has created a new, unfamiliar, and unusual condition, both globally and locally. The \"stay at-home\" restrictions, together with the enforced physical distancing policy, have led to a critical disruption of personal and community life, of industry and economy, and especially of the world of culture and art. Most countries have adopted a policy of prohibiting group gathering. This has led to global cancelation of numerous performances, music festivals, concerts, musical tours, and even stopped studio recordings and rehearsals for an unknown period. After approximately 2 months, several countries have gradually started to examine \\\"back to normal\\\" strategies. Nonetheless, it is expected that the singing and music industry would return to performing live in front of audiences long after other industries return to normal activity due to the specific nature of the music industry, which gathers large crowds in close proximity, making physical distancing practically impossible.\n\nIn addition to the general policies advocated by local and global authorities, it was also reported that the public are less likely to attend future musical and singing events, even when they are allowed.[@bib0001] Moreover, people are more inclined to return to visiting museums, zoos, and sport events than"
+"Through an open letter in this journal, Katie Piper -- author, TV presenter and acid attack survivor, calls for action on corrosive substances.^[@bibr1-2059513117723769]^\n\nAnecdotally among my burns surgeon colleagues in the UK, there has been an increase in assaults with corrosive substances restricted to specific geographic pockets of the country. This is clearly a cause for concern, although it should be noted that of the estimated quarter of a million burn injuries per year in the UK, such injuries probably account for approximately 0.1% of all burns.\n\nA previous article in *Scars, Burns & Healing* has provided the best snapshot of evidence we currently have in the UK of the pattern of such injuries.^[@bibr2-2059513117723769]^ This study highlighted our lack of understanding and challenged previously accepted stereotypes regarding such injuries. For instance, twice as many men were assaulted in this way as were women. Furthermore, the figures for the cultural and ethnic backgrounds of the victims were:\"'Victims came from various cultural backgrounds such as Caucasian (16), African (3), Oriental (1) and South Asian Subcontinent (1).'^[@bibr2-2059513117723769]^\"\n\nHence, corrosive assaults in the UK appear to be a phenomenon that may be on the rise in certain geographic areas but not others, and appears"
+"At the beginning of the 1980s, researchers knew that actin filaments were present in all cell types and were important for force generation and cell movement. But relatively little was known about how actin monomers assembled into filaments. In fact, researchers didn't even possess information as fundamental as the rate constants of monomer association and dissociation. In 1981, however, Tom Pollard and Mark Mooseker successfully measured these rates using electron microscopy, a method not usually associated with a process as dynamic as actin polymerization ([@bib1]).\n\nAn electron micrograph shows long filaments grown at the barbed end of an actin bundle, in contrast to the shorter filaments assembled at the pointed end.Previous studies had used light-scattering spectroscopy to measure the elongation of actin filament populations in vitro. But in 1975, Tom Pollard and colleagues demonstrated that the two ends of actin filaments grew at different rates; the \"barbed\" end elongated rapidly while the \"pointed\" end grew slowly ([@bib2]). \"That meant it would be difficult to learn anything if you only had a cuvette full of actin filaments. You'd actually have to look at them directly to see what was going on at the two ends,\" explains Pollard, who now works at"
+"Introduction {#S1}\n============\n\nIn contrast to general English, clinical notes have significant differences in structure and content. For instance, clinical text often contains units of thought that fit the technical definition of sentences that are not terminated by the standard sentence boundary symbols or any symbols in many cases. Structures such as labels, section headers, text arranged in tables, and lists are examples of clinical text that do not follow general English rules for sentence termination. Furthermore, clinical text contains a disproportionately high number of acronyms, abbreviations, and ordinal numbers frequently decorated with punctuation symbols and containing variable capitalization. Segmentation errors caused by these ambiguities are magnified in downstream processing.\n\nPrevious research has shown that transfer learning in deep networks can improve generalization to tasks of related problems with small data sets \\[[@R1]\\]. Ensemble methods that engage in meta-learning through weighted voting models such as boosting, bagging, and stacking also reduce the generalization error over standard models \\[[@R2]\\]. We utilize transfer learning both in the use of word embeddings, and in our method for domain adaptation of models trained on one corpus to a different, but related corpus of clinical text.\n\nSentence boundary disambiguation (SBD), also known as sentence segmentation"
+"With your kind patronage and full support, *Journal of Traditional and Complementary Medicine* (JTCM) is one-year-old now. We already have five issues with 50 excellent articles in the past year. The number of visitors to the journal website is more than 130,000 since October 10, 2011 indicating the quality of the published papers. JTCM continues to grow and is getting stronger.\n\nJTCM strives to promote exchange of recent novel research findings in traditional and complementary medicine worldwide, and provide a convenient platform for sharing knowledge of traditional medicine. Towards this, JTCM is going to cooperate with Wolters Kluwer Health -- Medknow from 2013. In this collaboration, JTCM will be promoted to international academic community via more active and efficient strategies, and will provide novel, innovative, original, and important knowledge of traditional medicine. The papers published thus will be read and cited by a larger audience. JTCM is already indexed in Google Scholar, and the application for Medline is under processing. Hopefully, we could obtain good result very soon.\n\nWe sincerely hope that you continue to support JTCM, and look forward to your future participation and contribution."
+"Introduction {#sec1-1}\n============\n\nAmarnath shrine is a holy place of Hindus. It is situated at an altitude of 3888 m (12,756 feet) and is visited by more than 6,00,000 devotees each year. Climbing to these heights (\\>10,000 feet) by individuals living in plains, requires a moderate physiological adaptation. The stress of this adaptation may not be tolerable by all. In individuals with sickle cell disease, the enlarged spleen can develop splenic infarcts. As the only difference between the sickle cell trait and the sickle cell disease is the proportion of hemoglobin S (HbS) in the blood; one can assume that this complication can also occur in the trait condition. And yes, there are case reports where no cause for splenic infarction other than the trait condition could be found. The hypothesis that sickle cell trait predisposes to splenic infarction becomes stronger with our description of simultaneous splenic infarct in two members of a family. We searched the literature for the evidence of this hypothesis and tried to find the reasons for its rarity.\n\nCase Reports {#sec1-2}\n============\n\nCase 1 {#sec2-1}\n------\n\nA 55-year-old man from Ganjam (Odisha, India) presented to the casualty with a chief complaint of pain in the"
+"Peaks and valleys in protein translation prepare one set of immune cells for duty, according to findings from Lelouard et al. With the ebb and flow of translation, antigen-presenting dendritic cells (DCs) adjust the origin of their antigens.\n\nFigure 1Overall translation levels (black bars) peak several hours after DCs are activated and then decline.\n\nDCs are professional immunity activators that alert T cells to the presence of invaders by displaying antigens on their surface. This display is ramped up by a maturation program initiated when a DC encounters inflammatory stimuli such as pathogenic components. Scientists have identified an abundance of transcriptional changes that take place during maturation. The new results show that a boost in translation is necessary to put the new transcripts into action.\n\nTranslation peaked in DCs about 4 hours after their activation. During this stretch, translation---and the PI3K/AKT/mTOR signaling pathway that activated it---was needed for maturation-associated changes in the DCs. These changes include producing T cell-activating cytokines and activating the antigen-presenting machinery.\n\nAfter 4 to 8 hours, protein synthesis levels declined, due at least in part to proteasome-mediated cleavage of the eIF4GI translation initiation factor. At 16 hours, overall translation levels were even lower than they were"
+"Background\n==========\n\nSpatial patchiness of forage often results in uneven livestock grazing, with potential implications for patterns of forage intake, resource degradation, and plant community composition and invasibility \\[[@B1]\\]. Grazing concentrated in patches of preferred forage can lead to patch degradation over time. Improved grazing uniformity and the prevention of heavy, uneven grazing in patches of preferred forage is a primary goal of sound grazing management \\[[@B2]\\]. However, a better understanding of the mechanisms governing forage preference and selectivity in patchy, heterogeneous environments is needed to inform new management approaches that enhance grazing distribution at spatial sales ranging from bites to patches \\[[@B3]\\].\n\nPreference and selectivity are related but different terms that describe patterns of forage selection. Preferences are traditionally determined by offering equally accessible amounts of alternative forage and comparing forage intake. Thus, preference is a term that describes the individual\\'s forage intake in the absence of any constraints on availability or accessibility \\[[@B4]\\]. Selectivity, on the other hand, is a measure of forage intake under patchy, heterogeneous conditions where alternative forages are not equally available or uniformly distributed \\[[@B5]\\]. In this context, selection of preferred forage can often be constrained by environmental and physiological trade-offs \\[[@B4],[@B5]\\]. Thus, depending"
+"Introduction\n============\n\nRecurrent vulvovaginal candidiasis (RVVC) refers to the attack of mycologically-confirmed symptomatic VVC for 4 times or above within 1 year, whose incidence rate is about 5% ([@B1]). It is manifested as pruritus vulvae, increased vaginal secretions, soybean curb-like or curd-like secretions, burning pain, dyspareunia, dysuria and other VVC symptoms. Due to repeated attack or ineffective treatment, RVVC brings serious troubles to the patient's mental health, sexual life and social functions, affecting daily life and family relationship and causing a heavy psychological burden to patients. RVVC has always been a difficulty and hot spot in VCC research, but the research on RVVC nursing has not been paid enough attention to.\n\nAt present, clinical treatment methods of RVVC include intensive therapy and consolidation therapy, in which the consolidation therapy is performed for 6 months after mycological cure via intensive therapy ([@B2]). However, there are some problems, such as longer treatment cycle, poor compliance of patients, unsatisfactory results and high recurrence rate.\n\nThe concept of holistic nursing development in modern nursing has been expanded to physical, psychological, family, social, spiritual and cultural levels, but the research on RVVC nursing has not been paid enough attention to. In this study, RVVC patients"
+"Introduction {#s1}\n============\n\nWe have recently identified mutations in the mitochondrial x-prolyl aminopeptidase, *XPNPEP3*, in families that have a rare autosomal recessive form of renal failure [@pone.0077234-OToole1]. The renal histopathology includes interstitial fibrosis, tubular atrophy and tubular basement membrane disruption. *XPNPEP3* is conserved through evolution and its enzymatic function is inferred from studies performed with the *E. coli* ortholog, showing that it cleaves the amino-terminal residue of a peptide chain when proline appears in the second position [@pone.0077234-Yoshimoto1]. Subsequent studies with the *S. cerevisiae* ortholog, intermediate cleaving peptidase 55 (Icp55p), confirmed that it has an aminopeptidase function, but the presence of proline in the second position of the peptide chain was not invariably required for cleavage of the amino-terminal residue [@pone.0077234-Naamati1], [@pone.0077234-Vogtle1].\n\nBoth, XPNPEP3 in the human and Icp55p in yeast have been localized to the mitochondria [@pone.0077234-OToole1], [@pone.0077234-Naamati1]--[@pone.0077234-Reinders1]. The large majority of mitochondrial proteins are encoded by nuclear genes, which is the case for *XPNPEP3*/*ICP55*. After translation in the cytosol many of these proteins are designated for mitochondrial import by an amino-terminal mitochondrial targeting signal. Following mitochondrial import, the mitochondrial targeting signal is removed by the mitochondrial processing peptidase (MPP) leaving a nascent amino-terminal residue [@pone.0077234-Mossmann1]. Icp55p has recently"
+"Summary\n=======\n\nDevelopmental genes (DG) may be useful tools for promoting transformation. DGs, which can act through a wide variety of developmental mechanisms to promote regeneration of transgenic cells, have been widely employed in model plants to promote embryogenesis and in some cases organogenesis. Following initial experimental demonstration in dicots, the DGs *WUSCHEL* and/or *BABY BOOM* have formed the basis of a high efficiency method for a variety of monocot genotypes and species. However, in dicots the utility of these genes as the basis of a robust transformation system has not been demonstrated. Many additional DGs appear capable of promoting regeneration that have not been systematically explored as transformation tools.\n\nBecause *in vitro* plant transformation systems are costly and must be customized for each new genotype and species, *in vivo* approaches to transformation hold much appeal. It is possible to produce stable transgenic plants by agro-inoculation of seeds or vegetative/floral buds, but as yet these approaches have not been used routinely in any plant species except for the Arabidopsis floral dip. We will discuss how the Arabidopsis system, and other *in planta* techniques, may be tailored for forest trees, taking into account variations in biology of different taxa.\n\nDevelopmental Genes"
+"S\u00e3o Paulo, November 17, 2014\n\nDear Editor\n\nThe fine structure of apoptotic HeLa cells from cultures contaminated with mycoplasma in early and in advanced stages of the cell demise process differs from those so far described in apoptotic cells. The observed changes are enhanced after exposure of the cells to staurosporine. At low microscopic magnifications cells that have apparent normal cytoplasm and nuclei, actually may be harbouring cystic-like profile(s) of parasitic origin in an altered cytoplasm. The membranes of the transitional elements of the endoplasmic reticulum (TER) appear fragmented in irregular branching stripes of the smooth component of the TER ([Fig. 1](#f01){ref-type=\"fig\"}, white asterisks in L delimited area). The concentration of the rough endoplasmic reticulum (RER) membranes is less than in normal HeLa cells. Near to the smooth ER tubule-saccular elements lie groups of 50 nm microvesicles aside stacked, thin, various sized profiles of Golgi saccules ( \\] ). The 50 nm microvesicles bud off mainly from the periphery of the stacked Golgi elements ([Fig 1](#f01){ref-type=\"fig\"} thin arrow heads inside line U) and also from the extremities of smooth ER tubules ([Fig. 1](#f01){ref-type=\"fig\"} small arrows). Small groups of compacted microvesicles are noted in cells still maintaining normal nuclear appearance (not"
+"Introduction {#sec0005}\n============\n\nLa pand\u00e9mie li\u00e9e au COVID-19 (Coronavirus Disease 2019) d\u00e9clar\u00e9e par l'Organisation mondiale de sant\u00e9 le 11\u00a0mars\u00a02020 [@bib0255] met le syst\u00e8me de soins face \u00e0 de nouveaux d\u00e9fis lourds \u00e0 assumer avec des d\u00e9cisions majeures \u00e0 prendre en urgence. L'afflux massif de patients \u00e0 prendre en charge en hospitalisation avec pour certains d'entre eux une prise en charge en r\u00e9animation avec assistance respiratoire conduit \u00e0 une saturation intrahospitali\u00e8re et la s\u00e9curit\u00e9 des soins apport\u00e9s aux patients non COVID-19\u00a0en est directement menac\u00e9e. C'est pourquoi l'objectif de la gestion de ces patients est double\u00a0: d'une part, retarder au maximum les prises en charge non urgentes afin de d\u00e9sengorger au maximum l'h\u00f4pital et de rendre mobilisable au maximum le personnel soignant et, d'autre part, r\u00e9duire autant que possible la perte de chance chez ces patients dans ce contexte. C'est dans ce sens que l'ensemble de la communaut\u00e9 des chirurgiens digestifs et visc\u00e9raux \u0153uvre comme l'illustrent les recommandations \u00e9mises sur la prise en charge chirurgicale des cancers digestifs durant cette p\u00e9riode [@bib0260]. Alors que chacun de nous diff\u00e8re autant que possible la chirurgie programm\u00e9e, la chirurgie d'urgence peine \u00e9videmment \u00e0 \u00eatre r\u00e9duite.\n\nL'appendicite aigu\u00eb non compliqu\u00e9e concernant environ"
+"Sensation-seeking is a personality trait reflecting the desire to pursue novel or intense experiences, even if risks are involved[@b1]. Questionnaire measures of sensation-seeking ask people whether they would like to try adventurous activities, such as extreme sports or travelling to remote places; whether they enjoy loud parties and speaking in front of groups; and whether they dislike dull or repetitive activities, such as standing in queues[@b2][@b3]. People who score high on self-report measures of sensation-seeking have a higher propensity to misuse drugs, engage in risky sexual activities, and suffer accidental injuries than low sensation-seekers[@b4]. Understanding individual variation in sensation-seeking is therefore useful in creating targeted interventions to improve health and wellbeing[@b5].\n\nMen tend to have higher average scores than women on questionnaire measures of sensation-seeking, such as Zuckerman\\'s widely used Sensation Seeking Scale, version V (SSS-V)[@b1][@b3], and this sex differences has been reported across populations. For example, studies conducted in the USA, Europe, Australia and China have all reported higher average scores in men than women on three of the four sensation-seeking subscales, namely Thrill and Adventure Seeking (TAS; interest in physically challenging activities), Disinhibition (Dis; favourable attitudes to uninhibited social interactions), and Boredom Susceptibility (BS; dislike for repetition and"
+"G[lobal]{.smallcaps} organization of the cell and the coordination of its physiology requires interaction between different cytoskeletal systems. During interphase, a typical eukaryotic cell has microtubules emanating from the centrosome located near the nucleus, which extend to the periphery of the cell, presumably interacting with the cortical actin filament meshwork. Microtubules during interphase are thought to be mainly required for the organization of the membrane systems (e.g., vesicular traffic and organelle movement). The actin-rich cortex is important for maintaining cell shape and for cellular movement.\n\nThere is increasing evidence of coordination between the actin and the microtubule cytoskeletons ([@B29]; [@B27]). Data from a number of systems suggests that many cell types use a combination of microtubule and actin filament--based transport in vesicle and organelle trafficking. It is well established that microtubules are required for long distance transport of cellular components. In contrast, the actin cytoskeleton is thought to be required for more local traffic. The best evidence for transport along both cytoskeletal systems is in neurons. Vesicles appear to be transported along actin filaments in mammalian growth cones ([@B14]). Furthermore, gelsolin, which promotes depolymerization of actin filaments, has been shown to inhibit fast axonal transport in this system ([@B6]). In extruded"
+"Introduction {#s1}\n============\n\nOrganisms that live in different environments during ontogeny are faced with the constraint that it might be difficult to optimise responses, via adaptation, to the various selection pressures that operate in each habitat. Thus, trade-offs between physiological, morphological or behavioural traits might be constrained and so limit adaptation when ontogeny occurs across different environments [@pone.0011680-Moran1]. It is therefore of interest to examine if and how phenotypic induction early in ontogeny affects later phenotypes. Such knowledge is important if we want to predict how changes in one environment affect phenotypes in another environment. For example, a rise in global temperature might affect the rate at which pools dry out, which in turn could affect the growth and development rates of aquatic insects and amphibians inhabiting these pools [@pone.0011680-Brooks1]. Frogs provide an excellent system in which to study how morphological and behavioural traits are related across life stages. This is because most frogs spend the first stage of their life in an aquatic environment, which selects for a different suite of traits than do the terrestrial or amphibious environments occupied by adults. While several studies have examined the relationship between morphological traits across life stages in frogs e.g. [@pone.0011680-Blouin1],"
+"Introduction {#Sec1}\n============\n\nSimple fabrication routes represent a major advantage of hybrid organic-inorganic perovskites for the manufacturing of efficient yet low-cost solar cells. Solution-based methods are the most widespread approach to prepare perovskite thin films, being at the same time reliable and cost-effective^[@CR1]--[@CR5]^. However, even optimized solution-process methods are affected by shortcomings. One is a lack of control over the low-temperature crystallization process, which is affected by many factors such as solvents and precursors, surface properties of the substrate, solvent evaporation during the deposition and annealing conditions, often leading to poor reproducibility of films morphology, thickness, crystallinity, and crystal size, properties that in turn have crucial influences on the photovoltaic performance. The second major shortcoming, more fundamental than the first one, is that sequential film deposition from solution cannot produce perovskite-perovskite heterostructures, since the solvent employed in depositing subsequent layers washes away the underlying ones. As a consequence, multijunction tandem solar cells and *p-n* junctions all perovskite based are advancing very slowly.\n\nA very promising alternative to solution-based methods are the vapor-based deposition techniques, which started in the last few years to attract significant interest as a possible route to overcome the aforementioned problems^[@CR6]--[@CR9]^. In general, these methods are expected"
+"Occupational consciousness emerged as a construct from my doctoral work on intergenerational play within families in post-apartheid South Africa. It refers to ongoing awareness about the dynamics of hegemony and recognition that dominant practices are sustained through what people do every day, with implications for personal and collective health (Ramugondo, [@cit0046]). The emergence of the construct in this context signifies an ongoing struggle with negotiating long-standing dynamics of power that were laid down during colonialism, and maintained under black majority rule. Occupational consciousness provides a language through which people can describe how their individual and collective everyday doing can resist and challenge hegemonic practices that sustain all forms of unequal power relations. In providing a theoretical foundation to occupational consciousness as a construct in occupational science, this discussion advances the theorizing practice of the discipline in promoting understandings of human occupation.\n\nThe first three sections of the paper introduce theorizing as a distinct scholarly practice, outline the genesis of occupational consciousness as a construct and provide both theoretical and philosophical foundations to the construct. This is followed by an analysis of synergies between occupational consciousness and other related constructs. Occupational consciousness is then advanced as a critical notion that frames"
+"Introduction\n============\n\nInherited thrombocytopenias are a heterogeneous group of disorders characterized by a reduced number of blood platelets which can result in a bleeding tendency of variable severity. Although inherited thrombocytopenias are rare, recent improvements in the knowledge of these conditions have indicated that, taken together, their prevalence is higher than previously thought. In fact, based on a registry of patients with thrombocytopenia, the prevalence of inherited thrombocytopenias in the Italian population is estimated to be 2.7 cases per 100,000 population.^[@b1-1050820]^\n\nMost patients with an inherited thrombocytopenia have mild or no spontaneous bleeding: however, even patients who do not have spontaneous hemorrhages often require platelet transfusions prior to surgery or other invasive procedures because their platelet count is below the safe threshold for the specific procedure.^[@b1-1050820]--[@b5-1050820]^ Platelet transfusions have several drawbacks, as they expose patients to the risk of acute reactions, transmission of infectious diseases, and alloimmunization with consequent refractoriness to subsequent platelet transfusions.^[@b3-1050820],[@b6-1050820],[@b7-1050820]^ The last is a particularly critical event in these patients with lifelong thrombocytopenia. Moreover, the availability of platelet units is conditioned by the scarceness of blood donors. Less commonly, some patients with inherited thrombocytopenias have frequent episodes of spontaneous bleeding that affect their quality of life,"
+"1. Introduction {#s1}\n===============\n\nBenchmarking is a notoriously difficult task. Benchmarks are often created by the creators of the tools being benchmarked, resulting in biased comparisons favoring their tool. Benchmarking can be an inefficient process, as the tool being benchmarked may need changes to collect certain performance metrics. Even once that effort is undertaken, benchmarks are often run a few times and then forgotten, quickly becoming obsolete. However, benchmarks can spur progress as tool developers have an objective metric to maximize or minimize.\n\nPrior work benchmarking neural simulators and neuromorphic hardware has focused on low-level neural performance. For example, Sharp and Furber ([@B18]) showed that SpiNNaker can simulate a recurrent network of leaky integrate-and-fire neurons with similar firing rates and inter-spike intervals as the NEST neural simulator, but around six times faster. Stromatias et al. ([@B22]) showed that SpiNNaker\\'s power consumption varies between 15 and 37 Watts (0.5--0.8 Watts per chip) depending on the number of neurons being simulated. Goodman and Brette ([@B14]) showed that Brian simulated a randomly connected network of 4000 leaky integrate-and-fire neurons twice as fast as an equivalent Matlab implementation, but around three times slower than a C implementation. In all of these cases, none of"
+"INTRODUCTION {#s1}\n============\n\nGene expression profiles differ among different cell types and change as stem cells differentiate ([@BIO044222C8]; [@BIO044222C26]; [@BIO044222C34]). Genome-wide Cytosine-phosphate-Guanine dinucleotide (CpG) methylation, an epigenetic regulation and modification process, has been shown to exhibit similar dynamic behaviour during differentiation ([@BIO044222C7]; [@BIO044222C5]). Usually, these two changes (i.e. gene expression and CpG methylation) have been shown to correlate negatively with each other, depending upon the location of the methylated CpG relative to the gene body ([@BIO044222C39]; [@BIO044222C9]; [@BIO044222C19]; [@BIO044222C51]). Overall, changes in methylation patterns between cell types and tissues throughout life work to either activate or shut down specific cellular processes ([@BIO044222C42]), making cells exhibit different phenotypic characteristics. Acting as a shutdown mechanism, DNA methylation reinforces gene silencing, when expression is not required in a particular cell type ([@BIO044222C29]).\n\nNormal myeloid cell differentiation occurs within the bone marrow, where stroma cells secrete cytokines to help activate myeloid-specific gene transcription ([@BIO044222C10]). Further differentiation can occur in the peripheral tissues or blood, dependent upon exposure of the myeloid precursors to cytokines and other factors, such as antigens ([@BIO044222C1]; [@BIO044222C15]). The first direct committed step toward myeloid cell development is the differentiation of multipotent progenitors (MPP) cells into common myeloid progenitor cells (CMP)"
+"Introduction {#s1}\n============\n\nDespite the immediate and seemingly far reaching devastation that follows intense natural disturbances, there is an extensive literature showing that such events can ultimately generate environmental conditions favourable to the survival, growth and diversification of living organisms and ecosystems, at least as measured by species diversity [@pone.0028645-Connell1]--[@pone.0028645-Holt1]. Recently, studies have shown parallel responses to disturbance between species and genetic diversity with variation between-sites (beta diversity) increasing and within-sites (alpha diversity) decreasing [@pone.0028645-Vellend1]--[@pone.0028645-Evanno1]. However, within species the impact of catastrophes which result in severe reductions in population sizes are neither predicted nor known to result in the promotion of genetic diversity. Rather, the outcome of such population bottlenecks is usually the loss of genetic variation, the severity of which depends on both the intensity and duration of the crash and the subsequent rate of recovery and immigration [@pone.0028645-Wright1]--[@pone.0028645-Vignieri1]. Furthermore, while genetic diversity has been shown to enhance species and even ecosystem resilience to catastrophic disturbances [@pone.0028645-Hughes1]--[@pone.0028645-Reusch1], the reverse i.e. catastrophes enhancing genetic diversity, is yet to be demonstrated.\n\nCircumstances allowing for testing the impact of catastrophes on any aspect of ecosystem and evolutionary dynamics are highly unusual due to the longitudinal nature of the work required combined with"
+"The United States is rough terrain for those aiming to stake health-related human rights claims on domestic soil. Less than a decade ago, the passage of the 2010 Patient Protection and Affordable Care Act (ACA), which was designed as a massive expansion of insurance-based health coverage, led some health and human rights scholars to wax optimistic. The ACA---the Obama administration's signature piece of legislation---passed by a razor-thin margin in US Congress. For human rights optimists, this legislation deserved praise for adopting \"significant national reforms consistent with human rights norms\" in a manner \"Corresponding with international law, \\[and\\] following both the spirit and substance of the UDHR \\[Universal Declaration of Human Rights\\] and ICESCR \\[International Covenant on Economic, Social, and Cultural Rights\\].\"[@r1] As pessimists were quick to point out, however, the ACA's protections have always been \"inherently unstable.\"[@r2] First, this market-based arrangement grounds access to health care in a statutory right---in other words, a right that can be modified or revoked. In addition, it sidesteps international norms and commitments precisely \"by avoiding the specific language of rights and obligations of international law.\"[@r3]\n\nEarly predictions of the ACA's promise from a human rights standpoint are thus difficult to reconcile with current realities."
+"1. Introduction {#sec1-dentistry-04-00003}\n===============\n\nCaries is the most common cause of pulp-periapical disease. When the pulp tissue involved in caries becomes irreversibly inflamed and progresses to necrotic, the only treatment option is root canal therapy because the infected necrotic pulp in the root canal system is not accessible to the host's innate and adaptive immune defense mechanisms and antimicrobial agents. Therefore, the infected necrotic pulp tissue must be removed from the canal space by pulpectomy to prevent development or persistence of apical periodontitis.\n\nIt was the most acceptable treatment strategy for teeth with infected or non-infected necrotic pulps that the disinfected root canal space should not be left empty and should be filled with biocompatible material to prevent reinfection of the canal space for many decades. The root canal filling was expected to prevent coronal leakage, retard bacterial penetration from the canal space into the periapical tissues, and hopefully entomb bacteria in the canal space. Unfortunately, root canal filling is not able to achieve these desirable expectations in all endodontically treated teeth \\[[@B1-dentistry-04-00003]\\].\n\nAs our knowledge in pulp biology advances, the concept of treatment of pulpal and periapical disease appears to change accordingly. Endodontists have been looking for biologically based"
+"Introduction {#s1}\n============\n\nPlant lectins are specific carbohydrate-binding proteins classified into various families. Jacalin-related lectins (JRL) are further subdivided into the galactose- and mannose-specific groups [@pone.0004854-Peumans1]. On the basis of their carbohydrate-binding characteristics, plant lectins are also divided into \"classical\" and \"non-classical\" lectins [@pone.0004854-VanDamme1]. Classical lectins are usually abundant proteins with protein storage and plant defense properties in some plant tissues. In contrast, non-classical lectins induced by exogenous or endogenous stimuli are involved in specific protein-carbohydrate interactions and are suggested to play specific endogenous roles in plant tissues or cells [@pone.0004854-VanDamme1].\n\nJacalin-related mannose-specific lectins have been reported in monocotyledonous plants. Orysata, a mannose-specific jacalin in rice, is a potent mitogen of T lymphocytes and is involved in stress defense-related protein-carbohydrate interactions in plants [@pone.0004854-Zhang1]. Recently, horcolin, a new jacalin-related lectin specific to mannose, from *Hordeum vulgare*, was proposed to perceive and transfer environmental stress signaling [@pone.0004854-Grunwald1]. Despite the well-characterized carbohydrate-binding activity of plant lectins, cellular signaling and regulation mediated by the specific interaction of plant lectins with glycosylated proteins and glycoconjugates remains to be clarified. Nictaba, a tobacco lectin, is localized in the cytoplasm and nucleus, and the nuclear distribution of the protein is directed by a nuclear localization signal"
+"The Arnolfini portrait (Fig.\u00a0[1](#Fig1){ref-type=\"fig\"}a) remains one of the most puzzling yet alluring paintings of pre-renaissance western art. Painted by Jan van Eyck in 1434, it represents a prominent Italian cloth merchant (most probably Giovanni di Nicolao Arnolfini) who was based in Bruges with his wife.Fig.\u00a01Arnolfini portrait, Jan Van Eyck (1434), **a** complete portrait; **b** close-up of the face of Arnolfini\u00a9 The National Gallery, London\n\nThe painting is renowned for its exactitude in brush strokes, textures, and the distinctive morphology of the main characters, specifically Giovanni di Nicolao Arnolfini himself. A little progress, however, has been made in understanding some core features in the painting. These include: (a) the abnormal facial morphology of Arnolfini and (b) the reason why he is wearing lavish and heavy insulating clothes (particularly as the painting is likely in the summer as the trees outside are bearing summer fruits).\n\nAssessing Arnolfini's features (Fig.\u00a0[1](#Fig1){ref-type=\"fig\"}b), the following can be discerned: (a) he has a positive Hertoghe's sign (loss of outer third of the eyebrow), (b) bilateral ptosis is present, and (c) there is melasma of the forehead. Together, these support a diagnosis of hypothyroidism. Finally, although we do not get a view of his neck,"
+"Introduction\n============\n\n\"It is striking how quickly the assumption that the angel is analogous with Hungary has gained ground,\" Hungarian Prime Minister Viktor Orb\u00e1n wrote. \"I, for instance, see in the angel the innocent victims and not some kind of innocent state.\" The Hungarian Prime Minister was talking about the controversial German occupation memorial which was erected during the night of 20 July, 2014. The Nazi German occupiers are represented by a tympanum with a bronze eagle. Below it, there is a bronze statue of the Archangel Gabriel, holding an orb, which is one of the Hungarian national symbols. It is easy to see the intended message of the monument: above there is the perpetrator eagle and below there is the Hungarian angel, the victim. The monument has provoked opposition in Hungary, as many said that it whitewashes the role the Hungarian government and Hungarian people had in the murder of more than half a million Jewish, Romani and gay people during the Holocaust.\n\nThere is a growing body of research about the misdeeds committed by the members of the in-group ([@B6], [@B6],[@B7]; [@B54]; [@B48]). One important question is how innocent group members react to such misdeed? This is particularly"
+"INTRODUCTION\n============\n\nEndosonography was initially used in the staging of gastrointestinal tract malignancies.^(^ [@B01] ^)^ In the 1990s, it was adapted for use in bronchial diseases. In patients with lung disease, its uses now include tumor staging; the diagnosis of central (parenchymal) masses; and the detection of mediastinal or hilar lymphadenopathy. Endobronchial ultrasound (EBUS) enables the visualization of lymph node structure, thus allowing the pulmonologist to evaluate and sample lymph nodes. Consequently, minimally invasive staging of lung cancer has advanced considerably. In addition, tumor invasion of the tracheobronchial wall can be assessed more accurately with EBUS than with CT. The accuracy of EBUS in making this distinction is 94%, compared with 51% for CT.^(^ [@B02] ^)^ Lymph node stations 2, 4, 7, 10, and 11 can be sampled by EBUS. If EBUS is combined with esophageal ultrasound, lymph node stations 5, 8, and 9 can also be sampled. Therefore, the combination of esophageal ultrasound and EBUS can be seen as the first and best test in patients with suspected lymph node metastasis. ^(^ [@B03] ^)^ There are studies showing that this is a good alternative to mediastinoscopy.^(^ [@B04] ^,^ [@B05] ^)^\n\nIn patients with malignant disease or granulomatous diseases such"
+"How long a single eruption lasts is one of the most intriguing questions concerning volcano activity. We know that volcanic eruptions can last from less than a day to thousands of years. In 1977, the lava lake at Nyiragongo drained in less than an hour. By contrast, Stromboli has had a low-level of activity since 450 BC (about 2,400 years)[@b1]. Although the median duration of historic eruptions is \\~8 weeks[@b1], this value is largely meaningless because of its considerable variance and its non-normal distribution as we demonstrate in the following.\n\nImportant factors governing a single eruption are the volume of melt accumulated in the magma reservoir and its degree of over-pressure, but also the possible contribution of new magma from depth. An eruption will normally last until the local melt has been depleted, or until the pressure level of the gas inside the magma reservoir reaches the pre-eruption pressure conditions. Nonetheless, this is a rather simplified overview. The internal plumbing system of an active volcano can be quite intricate, though recent monitoring efforts involving geodetic, seismic and geochemical measurements are helping at improving the estimations of size, depth, and activity of magma chambers under active volcanoes[@b2][@b3][@b4].\n\nIn recent decades, different"
+"Background\n==========\n\nWith the growth in the health and fitness industry, sports footwear has shown technological advances and diversification. The introduction of footwear such as the MBT shoe (manufactured by Masai Barefoot Technologies) is an example of this diversification. MBT have based their shoe design on observations of the Masai, a semi-nomadic tribe from Africa who are well known for their posture and for walking long distances on uneven terrain. The MBT shoe construction is based on a mid-sole pivot with a rounded sole in the anterior-posterior direction, and a soft heel pad. It is claimed that the effect of the angled soft sole not only creates anterior/posterior facilitation of movement, by purposefully creating medial and lateral instability in the shoe \\[[@B1]\\].\n\nAccording to Romkes et al \\[[@B2]\\], MBT shoes have been used to treat foot problems such as hallux valgus, pes planus, heel and tendo-achilles pain as well as circulatory problems. Nigg et al \\[[@B3]\\] found that MBT shoes may be useful as a training device for stability and muscle strengthening adding another dimension to their use. However, New et al \\[[@B4]\\] and Nigg et al \\[[@B3]\\] found that subjects from many of the studies conducted using MBT shoes"
+"Geoffrey Schild was one of the great influenza virologists of his generation, being largely responsible for the nomenclature system in use to categorise natural strains today and for the development of the method for assessing influenza vaccine potency that is one of the few fixed points in influenza vaccines. He also played a big part in the way the World Health Organisation dealt with influenza, particularly in the selection of vaccine strains, where he encouraged the involvement of the vaccine manufacturers in the annual meeting. His first degree was from Reading after which he spent time in Sheffield before joining the MRC National Institute for Medical Research in Mill Hill. He became the Head of the Division of Viral Products at the National Institute for Biological Standards and Control (NIBSC) in the late 1970s.\n\nThe NIBSC emerged from the MRC NIMR and was set up in 1976 as the laboratory arm of the National Biological Standards Board, a quango established to provide independent scientific advice on reference materials and other issues in the control of biological medicines. Typically, biological medicines are made in biological systems, such as cell culture, or by fractionation of starting materials, such as human blood. Initially"
+"Introduction {#sec1-1}\n============\n\nThe Western Pacific region contains a diverse range of countries that differ in terms of culture, population size, and health care facilities.^[@ref1]^ Pacific island communities, even those that remain territories of European nations, such as French Polynesia, do not reach the same standards of psychiatric care as available in urban western centers.^[@ref2]^\n\nFrench Polynesia includes over 113 islands, scattered over an area larger than Europe. Out of the 268,270 inhabitants counted in the 2012 census of French Polynesia,^[@ref3]^ only the 178,174 inhabitants of Tahiti (the main island) have access to psychiatric and psychological care (*e.g*. Centre Hospitalier de Polyn\u00e9sie Fran\u00e7aise). The geographical remoteness of the other 112 islands of the country makes treatment of mental conditions difficult. Suicide standardized rates remarkably increased in recent years:^[@ref4]^ from 9.7 per 100,000 in the 1999-2004 period to 11.3 per 100,000 in 2005-2010, with a peak in 2008 of 13.7 per 100,000. Increased suicide rates have elicited a number of suicide prevention activities moduled around the geographical and socio-cultural context of the country.^[@ref5]^ With regards to non-fatal suicidal behavior, one of the strategies suggested to mitigate the risk of recurrance is reinforcement of social support by maintaining long-term contact with suicidal"
+"The competently performed and thoughtfully reported postmortem examination remains a vital component of today's autopsy practice. The integral role which autopsy plays in documenting diseases and injuries that cause death is well recognized. Of equal importance, however, is that in revealing anatomic pathology (and in some cases microbiologic and biochemical alterations, as well), an autopsy enables morbid anatomy to be correlated with clinical signs and symptoms, thereby enhancing an understanding of the decedent's ailments. The artful practice of clinical-pathologic correlation, advanced by Giovanni Battista Morgagni in 1761,[@B001] takes time to master, but becoming skillful at assisting clinicians in understanding a decedent's medical history or in explaining the cause of a decedent's symptoms to family members remains one of the most rewarding aspects of autopsy practice.\n\nIn order to provide meaningful clinical-pathologic correlations, autopsy pathologists should be aware of relevant issues that exist prior to, or arise during, an autopsy, and they should effectively address those issues in a satisfactory manner with the postmortem examination. For example, when pulmonary thromboembolism is identified at autopsy, deep veins of the legs and, if necessary, the arms should be dissected. (N.B. In consented autopsies additional permission(s) for the procedure(s) from next of kin may"
+"INTRODUCTION {#sec1-1}\n============\n\nThe radiological examinations in dentistry can be classified into intraoral (with film or the sensor placed in the mouth) and extraoral imaging techniques. Extraoral imaging includes (1) panoramic X-ray showing a curved section of the whole-maxillo-facial block (more or less mandible shape), and (2) cephalometric X-ray showing a projection, as parallel as possible, of the whole skull. The cephalometric X-ray may be achieved from the lateral side or from the anterior--posterior view.\n\nThere is no doubt that having an exact and noiseless view of such images can offer an invaluable help to the dentist in better diagnosis and treatment. Most of prevalent techniques of dental imaging are going to be acquired, processed, and even evaluated in digital form; however, the low contrast and the noise pollution are inevitable problems. The proposed method tries in reduction of noise level in different kinds of the mentioned dental image types and provides a better visualization for the dentist and a good contrast to the noise ratio by numerical computation. Furthermore, the method is of benefit to real-time image processing due to its fast response.\n\nSeveral papers reported current methods in dental noise reduction, first of which proposed by Goebel\\[[@ref1]\\] in"
+"The emerging of SARS-CoV-2 and COVID-19 pandemia with a high mortality rate in older subjects with one or more known cardiovascular comorbidities [@b0005] has prompted the question of \"sharing bio-molecular targets\" between coronaviruses and Renin Angiotensin Aldosterone System (RAAS), a system that is involved, at multiple levels, in the control of the cardiovascular function and, also, is a favorite drug target in cardiovascular diseases [@b0010]. Indeed during treatment with Angiotensin-Converting Enzyme inhibitors (ACEi) and Angiotensin Receptor Blockers (ARBs) the known up-regulation of ACE2/Ang 1-7/MasR axes might be very useful to treat arterial blood pressure, ischemic heart disease and heart failure but, at the same time, detrimental since during COVID-19 it might open the route to SARS-CoV-2 that have been proven to use the ACE2 as functional receptor to enter the human cells [@b0015]. This evidence at the bimolecular level has generated several commentary-style articles that claim it is more prudent to replace ACEi/ARBs during COVID-19 [@b0010], [@b0020], [@b0025], [@b0030]. The main scientific societies have taken a critical position towards any therapeutic change in the absence of supporting data [@b0035] and this is dictated by prudence. Nonetheless it should be said that switching can be done safely in arterial hypertension if"
+"1. Introduction {#sec0001}\n===============\n\nCurrently, with the significant advancement of nanotechnology, a variety of nanomedicines have been developed and introduced into the field of cancer treatment, including inorganic nanocrystals [@bib0001], polymer nanoparticles [@bib0002], biomimetic nanomaterials [@bib0003], and nanohybrids [@bib0004]. Most of the common nanomedicines incorporate nanocarriers such as nanoMOFs [@bib0005], 2D nanosheets [@bib0006], and nanogels [@bib0007] as anticancer drug-delivery nanoplatforms for oncotherapy. Typically, most of the nanomedicines, especially drug delivery nanoplatforms, suffer from the bottlenecks of low efficiency, serious side effects, and limited target efficiency to tumor tissues, which usually limit clinic translation potential. To overcome these disadvantages, the stimuli-responsive nanomedicine has been developed to precisely release drugs at specific sites for noninvasive cancer therapy [@bib0008]. Prodrug based nanomedicines are one of the typical representatives of stimuli-responsive nanomedicines that controllably release drug under external stimulations.\n\nThe prodrug (drugs conjugated to the precarrier), an inactive compound that can be enzymatically degraded into the parent bioactive drug in vivo, has gained wide attention as a practical approach to reduce off-target toxicity in cancer treatment. Due to its unique structure, most prodrugs can self-assemble into nanoparticles through simple chemical modifications. The prodrug exhibits several significant advantages, including high drug loading efficiency, ameliorative drug"
+"The last few years have witnessed the emergence of several high-throughput (HTP) platforms that are based on the evolution of omic science through transcriptomics, proteomics, and metabolomics. With the huge data accumulation, the informatics and computational methods have become essential to understand the complexity of biomedical data. We lunched the special issue to address the demand for statistical models, biological omic data analyses, and meta-analysis of biomarker for complex diseases.\n\nStatistical models are always important for the understanding of complex data; in this issue, Y. Liang et al. proposed a new adaptive L1/2 shooting regularization method for variable selection based on the Cox\\'s proportional hazards mode. Simulation and the real gene expression dataset analysis showed that the method is more accurate for variable selection than Lasso and adaptive Lasso methods. L. Tian et al. employed a nonlinear model to analyze time course gene expression data. They firstly developed a method for estimating the parameters in the nonlinear model and then utilized the model to perform the significance analysis of individually differentially expressed genes and clustering analysis of a set of gene expression profiles. The simulation and real-life biological data analyses showed that their methods outperform some existing methods.\n\nFor the"
+"Electromuscular incapacitating devices (EMDs) are frequently used by law-enforcement officers or private persons worldwide. They are high-voltage (peak voltage, 1200 V), low-current (peak current, 3 A) stimulators that cause involuntary muscle contractions in combination with sensory response. The electrical stimuli are in the form of high short-duration (10--100 \u03bcseconds) and repetitive (10--19 per second) pulses.^[@R1]^\n\nExisting data concerning adverse cardiac events of EMD including incidental deaths are still inconclusive. A number of animal^[@R2]^ and human^[@R3]--[@R7]^ studies have reported relative safety of EMD exposure. In contrast, some reports of severe adverse events including ventricular fibrillation^[@R8]--[@R13]^ or other effects on myocardium^[@R14]^ from EMD application exist.\n\nHeart rate (HR) acceleration before and after TASER exposure has been repeatedly described.^[@R4],[@R5],[@R15],[@R16]^ However, it is difficult to determine exact HR dynamics during exposure and whether the EMD application caused cardiac electrical capture owing to the fact that EMD discharge causes substantial electrical interference with the electrocardiographic (ECG) recording. Although clearly visible abnormalities in ECG after EMD application have not been described,^[@R15]^ very little is known about subtle repolarization changes in relation to EMD. Such changes could be revealed by using microvolt T-wave alternans (MTWA). This method allows us to reveal a subtle ECG pattern in which"
+"Introduction {#sec1-2470547016687996}\n============\n\nThe stress response is composed of cognitive, behavioral, and physiological processes that restore homeostasis and ensure survival. Cognitive appraisal of perceived threats and environmental stressors is mediated by the brain to determine cardiovascular, immune, and neuroendocrine processes, all of which can be adaptive or maladaptive.^[@bibr1-2470547016687996],[@bibr2-2470547016687996]^ Brain areas involved in the stress response include the hippocampus and hypothalamus, both targets of glucocorticoids (e.g., cortisol); the brain stem, which mediates autonomic stress responses; the prefrontal cortex (PFC), which downregulates neurobiological stress responses; the amygdala, which regulates threat appraisal and coordinates automatic neurophysiological and behavioral responses to threat; and the striatum, which mediates threat appraisal value. Acute stress resulting from a specific event or situation and chronic stress resulting from repeated exposure to stressful situations increases risk for the development of psychopathology, as well as social dysfunction that can maintain psychopathology.^[@bibr3-2470547016687996]^ Posttraumatic stress disorder (PTSD) can develop following exposure to trauma, a specific type of acute stressor that includes actual or threatened death, serious injury, or sexual violation and results in trauma-related intrusions, avoidance of trauma cues, changes in cognitions and mood, and hyperarousal.^[@bibr4-2470547016687996]^ Major depressive disorder (MDD), which is characterized predominantly by sad mood and loss of interest, has"
+"Introduction\n============\n\nQuestions of cost containment resolve into two distinct sorts of question. One sort is normative: For example, what are the right level and growth rate of health care costs? This question in welfare economics is appropriately discussed in terms of the value of the beneficial outcomes that health services produce in relation to the value of what is necessarily forgone. The other sort is positive: For example, given the available technology, what resources are necessary in order to produce any given level of outcome? These questions can be tackled at either the microeconomic or the aggregate level. In microeconomic analysis, the focus is on cost effectiveness, cost utility, and cost-benefit analysis ([@b9-hcfr-89-supp-021]). The aim is to make cross-program comparisons of marginal costs and benefits in order to determine both the optimal mix of programs and the payoff to increased spending (or the marginal lost benefits of reduced spending). A dense jungle must be hacked through here, and, although the methodology that ought to be used seems clear, its empirical implementation is underdeveloped. (A pioneering study is [@b36-hcfr-89-supp-021].) In aggregate analysis, the emphasis is on total spending, its share in gross domestic product (GDP) and its principal components, the"
+"Introduction {#s1}\n============\n\nThe evolution of sexual isolation during speciation depends on a joint change in male sexual traits and female preference for those traits [@pone.0017358-Ritchie1]. Theoretical work has identified several genetic conditions favouring this process, such as sex linkage and spatial clustering of genes underlying species-specific sexual signalling systems, [@pone.0017358-Kirkpatrick1]--[@pone.0017358-Via1]. Our empirical knowledge of the genetics underlying male secondary sexual traits is increasing [@pone.0017358-Qvarnstrm1], but the genetics underlying female choice mechanisms, causing biases in male fertilization success [@pone.0017358-Kokko1], remain largely unexplored. Sex linkage of the genes underlying female choice mechanisms should lead to increased potential rate of sequence divergence in response to selection [@pone.0017358-Charlesworth1] and favours processes such as reinforcement [@pone.0017358-Hall1] and good genes sexual selection [@pone.0017358-Kirkpatrick1], but not Fisherian runaway selection [@pone.0017358-Kirkpatrick1]. The spatial clustering of mate choice genes affects inter-taxon recombination during periods of contact and gene exchange and can mitigate the homogenising effects of gene flow [@pone.0017358-Via1]. Therefore taxa whose female choice genes are more sex-linked and/or more highly clustered are expected to be more prone to speciation, other things being equal.\n\nBiases in male reproductive success may be caused by multiple female choice components ([Fig. 1](#pone-0017358-g001){ref-type=\"fig\"}; [Text S1](#pone.0017358.s001){ref-type=\"supplementary-material\"}) that together can have an overriding influence"
+"Introduction {#s1}\n============\n\nThe regulation of microtubule dynamics is an essential requirement for all cells and in many aspects of their daily function. The ability to precisely regulate microtubule number, the assembly of networks, and the rate of microtubule assembly and disassembly underpins cellular processes including division, differentiation and migration. Male gamete development in particular relies upon the co-ordinated development and rapid remodelling of complex microtubule structures, such as the mitotic (spermatogonia) and meiotic (spermatocyte) spindle; flagella formation needed for sperm motility; and the manchette, which determines sperm head shape and contributes to tail structure. Approximately one in 20 men of reproductive age is sub-fertile or sterile, of which 60% of cases are due to intrinsic defects in spermatogenesis. This heterogeneous disorder manifests clinically as diminished sperm number, or abnormal motility or morphology, or commonly combinations thereof, in the ejaculate [@pgen.1002698-McLachlan1]. All of these clinical presentations may be underpinned by defective microtubule dynamics.\n\nMicrotubule severing is emerging as a key regulator of microtubule dynamics [@pgen.1002698-McNally1], [@pgen.1002698-Quarmby1], [@pgen.1002698-Baas1], [@pgen.1002698-Baas2], . The most well characterized microtubule severing enzyme is the katanin complex [@pgen.1002698-McNally2], the severing function of which is carried out by an ATPase enzymatic subunit, named p60, encoded by the *Katna1*"
+"A 66-year-old man with imatinib-resistant metastatic liver tumors of gastrointestinal stromal tumor started chemotherapy with sunitinib. Baseline computed tomography showed sporadic aortic calcifications and liver tumors (*A*). His systolic blood pressure increased to 160\u00a0mm Hg during chemotherapy[@bib1] and decreased to 130\u00a0mm Hg with administration of antihypertensive medication. During his sixth cycle of chemotherapy, he developed an acute aortic dissection (AAD, Stanford A) with thrombosed false lumen of the ascending aorta despite good control of blood pressure and reduction of the liver tumors (*B*). The entry site of the AAD was already calcified before chemotherapy as in *A*.\n\nThe presumable mechanism of the onset of AAD during chemotherapy with sunitinib is interruption of vascular endothelial growth factor function, which could be related to vascular stability.[@bib2] In this case, the AAD was considered to have developed on the basis of simultaneous hypertension due to sunitinib and vascular fragility due to both calcification and sunitinib presence. In daily practice, careful attention should be paid to the onset of AAD in patients with sporadic aortic calcifications during chemotherapy with sunitinib.\n\nAuthor conflict of interest: none.\n\nThe editors and reviewers of this article have no relevant financial relationships to disclose per the Journal"
+"SELEX is a powerful tool for identifying nucleic-acid--based ligands, or aptamers ([@r1][@r2]--[@r3]), to a wide range of molecular targets. However, the utility of aptamers in research, diagnostic, and therapeutic applications has been constrained by the limited chemical diversity of the nucleic acid libraries. Compared with protein-based ligands, like antibodies, natural nucleic acids are composed of fewer building blocks (four bases vs. 20 amino acids), have a polyanionic backbone with relatively hydrophilic character, and possess a smaller repertoire of functional groups available for target recognition. This limitation is partially compensated for by the sheer size of the random libraries available for screening (\u226510^15^ molecules).\n\nSeveral attempts have been made to increase the functional diversity of nucleic acids either with modified nucleobases or sugar-phosphate backbone modifications aimed at generating ligands with improved binding properties and metabolic stability. One approach has been to expand the four-letter genetic alphabet to include an additional base pair with a unique hydrogen bonding pattern ([@r4]). This six-letter library has been shown to be compatible with the required synthetic, PCR amplification, and sequencing steps of SELEX, resulting in the successful identification of aptamers to cell surface targets ([@r4]). Whereas the information density of such libraries is clearly higher,"
+"On page 929, Ashton et al. report that an intracellular parasite regulates its own growth and exploits the inflammatory environment within its host to continue its survival and mediate long-term damage.\n\nFigure 1*T. cruzi* (blue dots) thrives in cells lacking (bottom) TXA~2~ receptors.\n\n*Trypanosoma cruzi*, the bug that causes Chagas\\' disease, initiates a short-lived acute infection in humans. A third of those infected, however, develop chronic cardiac disease that sets in after a long asymptomatic period. The mechanism by which the parasite facilitates this long-term pathology is still unclear.\n\nAshton et al. now show that the parasite infects vascular endothelial cells and secretes a bioactive lipid called thromboxane (TXA~2~). When produced by human cells, TXA~2~ has pro-inflammatory effects and can cause cardiac injury by triggering platelet aggregation, clotting, and vasoconstriction.\n\nThe parasitic TXA~2~ also promotes cardiac injury, the team finds, yet it somehow mediates an anti-inflammatory immune response in the host. Mice that lack cell surface receptors for TXA~2~ had increased inflammatory damage.\n\nThese mice also had a higher parasite load than wild-type mice, suggesting that the parasite suppresses its own replication by a negative feedback through the TXA~2~ receptor. The group is now dissecting TXA~2~ receptor signaling within infected"
+"Introduction\n============\n\nEndogenous fungal endophthalmitis, especially caused by *Candida*, is usually seen in patients under intravenous hyperalimentation (IVH) or with indwelling lines. Apart from catheter-related factors, supposed risk factors include abdominal operations, major cardiopulmonary vascular surgery, diabetes mellitus, other compromising conditions, immunocompromised status, and neutropenia.[@b1-imcrj-10-189],[@b2-imcrj-10-189] These significant conditions continue to be of concern to medical personnel, including ophthalmologists. Some patients continue to experience poor visual prognoses despite the prescription of systemic anti-fungal drugs.[@b3-imcrj-10-189] However, early detection and treatment generally allow the progression of the distinctive cholioretinitis to be controlled.\n\nUsually, fungal endophthalmitis is identified via systemic examination (a blood culture positive for a fungus \\[i.e., fungemia\\] in those with prolonged fever). A recent report indicates that the frequency of fungal endophthalmitis among patients with fungemia is relatively low; it was speculated that anti-fungal treatments had already been administered prior to ophthalmic examination.[@b4-imcrj-10-189]\n\nIn the early stage of the disease, a chorioretinal lesion is evident upon fundus examination. Next, a small circle of yellowish-white spots (an exudate) appear on the retina. If the anterior chamber becomes inflamed, this may trigger the development of anterior synechiae, iris rubeosis, and (secondary) glaucoma.\n\nHere, we report a case of *Candida* fungemia in a 92-year-old"
+"Introduction\n============\n\nNature has created numerous examples of intriguing materials with different functionalities, which is an important source of inspiration for materials design and other associated disciplines.^[@cit1]--[@cit6]^ The structural hierarchy in these materials plays a vital role in contributions to their exceptional performances. Compared to conventional materials exhibiting a unitary (non-hierarchical) structure, new materials with multiple levels of structural hierarchy can provide positive synergies between each organization, thus leading to multiple benefits including valuable improvements in mechanical, transport, responsive and other properties.^[@cit7]--[@cit10]^ As one of these new materials, novel carbon materials with hierarchical porosity or frameworks are particularly appealing. This is motivated by their exceptional electrical conductivity, high surface area, and excellent physicochemical stability. Potential applications range from energy storage, catalysis, gas adsorption to molecular separation.\n\nWith the recent development of nanotechnology, significant advances have been attained in construction of hierarchical pore structures for hierarchical carbons.^[@cit11]--[@cit21]^ However, these current hierarchical carbons with various hierarchical pore structures generally possess a purely amorphous framework. In addition, there are rare examples of hybrid carbons with an amorphous/graphitic framework, but these carbon materials lack a hierarchical micro--meso--macroporous structure.^[@cit22]--[@cit30]^ Moreover, explicit control over the nanoscale and mesoscale architectures of hierarchical carbons remains challenging. Therefore, well-controlled"
+"Introduction {#s1}\n============\n\nIndonesian fisheries are among the largest and most productive worldwide, and are critical to the nation\\'s economic development and in providing food resources to millions of people. In 2004, production from marine capture fisheries in Indonesia was approximated at 4.5 million tonnes with an estimated gross value of US \\$3.13 million [@pone.0109182-FAO1]. The total marine capture fisheries production in Indonesia increased to 5.4 million tonnes in 2010 [@pone.0109182-FAO2]. The high level of employment, which in 2003 was estimated at 3.3 million people directly employed in marine capture fisheries [@pone.0109182-FAO1], is an important indicator of the value of fisheries to Indonesia. This places Indonesian marine capture fisheries among the top five worldwide in terms of fisheries production. The level of fishing effort in Indonesia is also increasing rapidly, with the number of motorised marine vessels increasing from an estimated 348,425 in 2007 to 390,770 in 2009 [@pone.0109182-FAO3].\n\nThe majority of Indonesia\\'s capture fisheries are considered to be fully or overexploited despite the fact that marine capture production in Indonesia is increasing annually [@pone.0109182-Mous1]. One of the greatest problems facing Indonesia\\'s Ministry of Marine Affairs and Fisheries is the quality of fishery statistics available. Since Indonesia\\'s fisheries are both"
+"1. Introduction\n===============\n\nVarious methods are used to examine vessels, while color Doppler sonography is preferred over other methods for numerous reasons. Doppler sonography consists of integration of B-mode images and Doppler wave form analysis. The old systems of Doppler sonography were limited to conventional black-and-white images; however, the possibility of creating color images has promoted the Doppler sonography to a powerful device in assessing vascular disturbances ([@b1-epj-08-2855]). The most common venous graft for CABG is the use of GSV. The saphenous graft is also used for other surgeries; yet, due to the unpredictable idiopathic morphology of the vein and the need for a long incision, many complications may result, including wound infection, hematoma, edema, and reduced mobility. To prepare the saphenous vein, a surgical incision is made along its long course, which may lead to various major problems for the patient. Incomplete healing of the wound most often causes a long hospital stay for the patient and increased costs. Various studies have reported various complications of lower extremity wound at the site of the great saphenous vein in 2% to 24% of cases ([@b2-epj-08-2855], [@b3-epj-08-2855]). To reduce the complications of lower extremity venous graft excision, the extent of the"
+"Introduction {#Sec1}\n============\n\nBeing lightweight metal, beryllium finds numerous technological applications ranging from aerospace and nuclear industry to mobile phones due to its exceptional physical properties such as high strength, electrical conductivity and high melting point. It has an anisotropic hexagonal close packed crystal lattice structure, which controls the complex properties of irradiation-induced self-point defects and dissolved foreign atoms^[@CR1],[@CR2]^. Their dynamic interplay with dislocations and grain boundaries (GBs) determines the microstructure evolution under irradiation. Therefore, investigations of beryllium microstructure after irradiation allow not only qualification of material properties for its prospective nuclear fusion reactor applications^[@CR3]^, but also contribute significantly to the physical understanding of the underlying mechanisms of microstructural changes in hexagonal closed packed metals under irradiation or high temperature aging in general. In addition, such investigations provide by analogy better understanding of the microscopic processes occurring in materials with other lattice structures.\n\nIn nuclear fusion technology, beryllium is considered as a \"First Wall\" material in ITER, presently one of the largest mankind projects worldwide^[@CR3]--[@CR5]^, but also as a neutron multiplier material in different tritium-breeding blanket concepts for the future demonstration fusion power plant DEMO^[@CR6],[@CR7]^. In one of the blanket concepts, called helium-cooled pebble bed (HCPB), interchanged layers of a"
+"Dear editor\n\nI don\\'t fully agree with point of view that Dr. P. Ravi Shankar has mentioned in an article entitled \\'Undergraduate medical education in Nepal: one size fits all?\\'\\[[@B1]\\]. Of course diversity of students, variations in curriculum, and different teaching approaches may influence the outcomes of health care delivery systems and may lead to inequality in health status. Nevertheless, the curriculum impact assessment is currently under debate, and so far it has not been concluded that one curriculum is fit for all. Therefore, curricula may differ among countries, and even among different contexts in the same country. Certainly the characteristics of different curricula affect performance during medical school and eventually these characteristics are reflected in their practice. This issue is not as straightforward as it appears to be since medical education encompasses different domains.\n\nContrary to Dr. Shankar\\'s view, I believe that it is already established and evidenced that the core curriculum of basic medical education should be the same for all; however, medical educators should understand that institutions have a responsibility to ensure the production of health personnel who have the knowledge, attitudes, and skills to meet the requirements of their own communities. This educational prerequisite is particularly"
+"The word pain is thought to derive from the Latin word poena, meaning punishment. An emotional reaction to a punishment might have been what Aristotle experienced, as he defined pain as an emotional event. Ren\u00e9 Descartes, the seventeenth-century philosopher and scientist, pictured a pain pathway consisting of a thread with two ends: one end is in a peripheral part of the body, for example a toe, and the other end is a bell in the brain. According to this picture, fire touching a toe pulls the thread, and rings the bell to sound a warning in the brain. Over the past decades, and in the current Decade of Pain Control and Research (2001--2010), pain research has undergone major changes, from a system level to cellular, subcellular and molecular levels. A new era of molecular pain research is now emerging, and the journal *Molecular Pain*is dedicated to this modern phase of pain research.\n\nRecent advances in pain research are in large part due to the rapid progress in neuroscience, molecular biology, and other fields in the life sciences. Breakthroughs in biomedical technologies have allowed us to address many important issues about pain, enriching our knowledge about the mechanisms by which sensory"
+"Introduction {#s1}\n============\n\nThe maintenance of animals in captivity as part of a larger program to ensure a particular species\\' survival is becoming increasingly commonplace [@pone.0009791-Teixeira1]. Within the realms of species reintroduction and translocation, individuals or groups of some species are routinely bred and/or held in captivity prior to being released into the wild. Animals are often housed under conditions which may not be representative of their preferred social structure, and this is particularly likely during transportation to the release site [@pone.0009791-Morgan1]. Although much research has been conducted into social group size and optimal housing conditions in, for example, zoos [@pone.0009791-Price1] and for some species groups, specifically primates [@pone.0009791-Bond1], and felids [@pone.0009791-Price1], little attention has focused upon those animals being housed or transported for the purposes of reintroduction or translocation. In many cases housing conditions are defined by convenience for the establishment, rather than animal welfare considerations [@pone.0009791-Olsson1]. It is, however, known from observed changes in cortisol levels that wild animals can become stressed after exposure to captivity for short periods of days or even hours [@pone.0009791-Coddington1], [@pone.0009791-Gregory1].\n\nIn this paper, we follow Moberg\\'s [@pone.0009791-Moberg1] definition of stress as being 'the biological response elicited when an individual perceives a threat"
+"Inanimate objects worn and used by health care workers (HCW), such as neckties and stethoscopes, have been shown to be reservoirs for potential pathogens.[@bib1] Of particular concern in the pediatric setting are identity (ID) badges and lanyards. Many pediatric HCWs use them not only for identification but also as a distraction tool during examination or procedures. Children have an increased tendency to place these items in their mouth as HCWs lean over to examine or care for them, with children up to 6\u00a0years old having a hand-to-mouth frequency of 9.5 contacts per hour.[@bib2] This therefore completes the chain of transmission for a potential nosocomial infection.\n\nKotsanas et\u00a0al have demonstrated that ID badges and lanyards worn by HCWs may harbor pathogenic bacteria; however, such colonization has not yet been implicated in a bacterial outbreak.[@bib3] Similar findings have been described in the United Kingdom, which has already implemented a bare below the elbows policy in an attempt to reduce opportunistic pathogen transfer.[@bib4], [@bib5] There is a paucity of comparative data suggesting that ID badges may be similarly contaminated with viral pathogens. However, given the higher incidence of viral infections in pediatrics---up to 50% of preterm infants screened during their hospital"
+"Problem\n=======\n\nThe handover of patient care has been described as one of the most perilous procedures in medicine. Professor Sir John Lilleyman from the National Patient Safety Agency describes this as \"a major contributory factor to subsequent error and harm to patients\" in a recent document produced by the British Medical Association (BMA). The junior doctors working in Yeovil District Hospital (YDH) echoed these concerns regarding the weekend handover system.\n\nThe current system required the ward doctors to compile a list of jobs for the on-call Foundation Year 1 (FY1) doctor. This was usually handwritten on a blank piece of paper and left for collection in one of the medical wards on a Friday evening. The junior doctors reflected on their experiences and felt that a lack of structure lead to an inconsistency amongst each handover and often a lack of detail. A typical example of a job being handed over was:\n\n\"Ward 4, Mrs Bloggs: UTI, check bloods\". Due to a lack of adequate information (eg patient identifiers, relevant past medical history) it was often very difficult to initiate a plan to complete each job. It was felt that this had often compromised the safety of patients, was"
+"Introduction {#s1}\n============\n\nA century after the first contributions giving birth to mathematical epidemiology, and after 20 years of fast growth since the first public health oriented contributions [@pcbi.1001021-Dietz1]--[@pcbi.1001021-Anderson1], infectious diseases modeling has recently received a further dramatic impulse from pandemics threats. The Bio-terrorism and SARS first, the fear of a potentially devastating pandemic of avian flu then, and finally the recent pandemic of A/H1N1 influenza, have all fostered the development of more and more detailed predictive tools. These range from traditional models to network analysis, to highly detailed, large scale, individual-based models (IBM) [@pcbi.1001021-Halloran1]--[@pcbi.1001021-Merler1]. IBM are highly flexible tools for policy makers as they allow to define intervention measures at the finest possible levels (e.g., the contact network of single individuals during a specific activity). For the first time, a pandemic model on a continental scale has been proposed [@pcbi.1001021-Merler1].\n\nA critical aspect common to all such models, is the parameterization of social contact patterns, i.e. how people socially mix with each other [@pcbi.1001021-Wallinga1]. Social contact patterns are the key factors underlying the transmission dynamics of directly transmitted close-contacts infectious diseases [@pcbi.1001021-Wallinga1]. Different models, independently of their level of complexity or geographical scale, are sensitive to the parameterization of"
+"We read with great interest the \"IFSO Endoscopy Committee Position Statement on the Practice of Bariatric Endoscopy during the COVID-19 Pandemic,\" and we would like to report our experience in a European endoscopy private tertiary center performing advanced therapeutic and bariatric interventional endoscopy.\n\nAs a private center, we received a \"call to arms,\" asking us to contribute to the management of the pandemic. Following the recommendation of the French Society of Digestive Endoscopy (SFED) (<http://www.sfed.org/professionels/covid19-et-endoscopie>), we interrupted all elective endoscopic activities from 11 March 2020 onwards. Moreover, we dedicated 80 beds to COVID-19 patients. Furthermore, we upgraded 10 beds for post-surgical critical care to fully equipped intensive care unit beds. Nonetheless, our Unit continued to perform semi-urgent and urgent interventional procedures such as follows: EUS and ERCP for biliary acute pancreatitis and cholangitis and management of the few surgical adverse events.\n\nWe fully agree with the authors, when they affirm the importance of withholding elective procedures, but we would like to share our experience in two clinical cases, which we find to offer perspicuous insights, on the one hand, on how to rethink the new standard of care for patients \"in the world after COVID-19\" and, on the other, on"
+"Background\n==========\n\nFor any material, microclimate changes are recognised as main responsible for speeding up their degradation. An indoor environment would reach an equilibrium that generally includes circadian cycles with, at different extent, smaller variation, similar frequency and a certain delay with respect to the outdoor climate (macroclimate). Many examples of how such equilibrium, as defined by Banham's \\[[@B1]\\], must be considered the ideal conservation conditions for artefacts rely on the huge Cultural Heritage Patrimony that survived for hundred and hundred centuries even if in thermohygrometric condition that surely cannot be considered ideal (buried, dived). Unfortunately such equilibrium is incompatible with the enjoying of Cultural Heritage (CH) as all is needed to expose them to public, as well the visitors themselves, create environmental perturbation; so, a compromise must be reached to ensure the longest life of artefacts, as well as of the building containing them, that, in many cases as our one, can constitute the main CH. An accurate microclimate monitoring of such buildings must be the first step in a conservation project both to individuate the spontaneous condition and to design an eventual heating/cooling system (HVAC); the last must be set taking into account the CH safety and not"
+"With over 200,000 procedures performed in 2012, liposuction continues to be one of the most common elective cosmetic procedures performed as both a stand-alone intervention or as a contouring modality in combination with other procedures.^[@R1]^ When proceeding with fully elective procedures, patient safety and minimizing risk are of utmost importance. To this end, principals for effective liposuction technique and clinical end points have been well established to increase operative efficiency.^[@R2]^ Furthermore, achieving outstanding initial results and obviating the need for secondary revision surgeries are the major components of patient safety and satisfaction.\n\nThe components of a lipoplasty system for suction-assisted liposuction include the suction pump, suction tubing, a collection canister, and the suction cannula. Although all components contribute to the overall efficiency of the system, the magnitude of each individual piece is not equal. Small variances in vacuum (\\<2 in Hg) and tubing length (\\<2 feet) do not appreciably change overall efficacy during clinical liposuction. Proper selection of suction tubing and canister size based on planned lipoaspirate volume (larger volume = larger tubing internal diameter \\[ID\\] and canister) along with fine adjustments to maintain the manufacturer recommended pump settings provides consistently similar liposuction efficiency.\n\nThe most vital and variable component"
+"Introduction {#H1-1-ZOI180256}\n============\n\nAlthough antidiscrimination laws and policies have improved the position of women over time, gender-based compensation disparities for women in science have persisted.^[@zoi180256r1],[@zoi180256r2],[@zoi180256r3],[@zoi180256r4]^ From the available reports, compensation for men exceeds that for women by approximately 7% to 8% among US physician researchers,^[@zoi180256r2],[@zoi180256r3]^ nearly 20% among Japanese surgeons,^[@zoi180256r5]^ and 25% to 40% between scientists in public sectors in Europe^[@zoi180256r6],[@zoi180256r7]^ even after controlling for other factors such as years of experience and rank.\n\nWith increasing attention on such inequities faced by female scientists, the Johns Hopkins University School of Medicine (JHUSOM) reviewed institutional data and noted that there was a lag in promotion of women to full professorship despite the presence of a significant proportion of women at the lower faculty ranks. In response, the JHUSOM created the Committee on Faculty Development and Gender in 2002. The committee first investigated barriers to career promotion by (1) reviewing faculty representation, attrition, and promotion rates for women; (2) conducting faculty surveys and departmental director interviews to identify sources of differences in career progression; and (3) performing annual faculty salary analyses (FSAs) to track salary inequities. The committee then offered specific recommendations, summarized in the [Box](#zoi180256b1){ref-type=\"boxed-text\"}.\n\n###### Summary of Recommendations From the"
+"Background {#section1-1073274817729043}\n==========\n\nIn 1907, Halsted published his results for radical mastectomy in the treatment of breast cancer.^[@bibr1-1073274817729043]^ Depending on the type of cancer, his cure rate results ranged between 25% and 75%. The surgery itself was morbid but remained the standard for many years to come. Since the advent of the radical mastectomy, an effort has been made to treat breast cancer effectively not only oncologically but also aesthetically. The radical mastectomy gave way to the modified radical mastectomy that followed with the simple mastectomy. Today, if a surgeon can maintain the breast form, the standard has become the partial mastectomy operation when operating for breast cancer. Large volume displacement oncoplastic surgery allows the surgeon the ability to resect large volumes of breast tissue and achieve the advantages in large volume resection which include fewer positive margins,^[@bibr2-1073274817729043],[@bibr3-1073274817729043]^ while maintaining and possibly improving the aesthetics of the breast form using mastopexy and breast reduction designs. Patients who would have been previously thought to be mastectomy candidates can now have breast-sparing procedures with improved aesthetics.\n\nThe oncoplastic surgical team typically consists of a breast surgeon and a plastic surgeon who work together in designing mastectomy skin incision patterns to best access"
+"Citation\n========\n\nScallion ML, Gibson GAP, Sharanowski BJ (2016) Revision of *Paranastatus* Masi (Eupelmidae, Eupelminae) with descriptions of four new species. ZooKeys 559: 59--79. doi: [10.3897/zookeys.559.6134](10.3897/zookeys.559.6134)\n\nIntroduction\n============\n\n*Paranastatus* Masi, 1917 (Eupelmidae, Eupelminae) is one of 33 currently recognized genera within Eupelminae ([@B5]). This genus was initially established for two species based primarily on the distinctive triangular shape of the head of females. Four species have been described to date: *Paranastatus egregius* Masi, 1917 and *Paranastatus violaceus* Masi, 1917 from Seychelles, and *Paranastatus verticalis* Eady, 1956 and *Paranastatus nigriscutellatus* Eady, 1956 from Fiji ([@B11], [@B3]). No new specimens of either *Paranastatus egregius* or *Paranastatus violaceus* have been reported since their original description and their biology remains unknown. However, [@B13] and [@B14] subsequently reared *Paranastatus nigriscutellatus* and *Paranastatus verticalis* from the eggs of the walking stick, *Graeffea crouanii* Le Guillou (Phasmatodea: Phasmatidae). Males are known only for *Paranastatus egregius*, *Paranastatus nigriscutellatus*, and *Paranastatus verticalis*. A key to these males was provided by [@B3].\n\nEupelmidae is likely a grade-level taxon ([@B4]) rather than being monophyletic ([@B8]), though Eupelminae is supported as monophyletic ([@B4]). The subfamily is characterized in part by its extreme sexual dimorphism, and species and higher level taxonomy is based"
+"Introduction\n============\n\nDuring the product announcement for Google Glass (GG) at the 2012 Google I/O conference, a team of skydivers flying above San Francisco used the device to livestream their jump to co-founder Sergey Brin, who was standing on the stage at the Moscone Center \\[[@b1-jeehp-15-05]\\]. This dramatic introduction of a wearable computer with an optical head-mounted display inspired attention to a new form factor for mobile computing. GG displays information in a smartphonelike hands-free format that can respond to both voice commands and touch. It contains an on-board processor running the Android operating system, memory, display, WiFi, Bluetooth, and a camera with high-definition video capabilities. While GG itself cannot make phone calls, it can pair to an Android or iOS phone for calls and messaging. GG also comes equipped with some basic productivity apps including messaging, web browsing, and maps/directions.\n\nGG is worn like a pair of glasses, making it an ideal device to support augmented reality and improving the degree to which the first-person perspective (1PP) can be shown by enabling photos and video to be captured from the perspective of the device wearer. These abilities of GG have led to much speculation about their potential application in"
+"Background\n==========\n\nThe Maastricht Treaty from 1992 marked the beginning of the health mandate of the European Union (EU) as enshrined today in Article 168 of the Lisbon Treaty (TFEU, Treaty on the Functioning of the European Union) \\[[@B1]\\]. The original EU health mandate focused primarily on stimulating cooperation between member states and supporting national actions (Art. 129 (1), Treaty of the European Union (TEU)) \\[[@B2]\\]. It embodied the Union with only limited legislative powers on health matters. Although this initial mandate was enhanced through subsequent Treaties, today Article 168, still gives the EU relatively circumscribed power in areas of public health (Art. 168 (4), TFEU). Healthcare continues to remain a national competence and in this regard, the EU *\"shall respect the responsibilities of the member states for the definition of their health policy and for the organization and delivery of their health services\"* (Art. 168 (7), TFEU). Despite the restricted Treaty-based mandate for health, the EU has a relevant role to play in national public health and health systems policies and has expanded its remit in areas beyond the Treaty \\[[@B3]\\]. Areas affected by EU provisions are extensively described in the literature \\[[@B4]-[@B11]\\]. To illustrate the main developments in"
+"Introduction {#s1}\n============\n\nAn enduring question in object recognition is what defines expert perceptual processes and how different they are from regular, everyday object recognition. This question was amply explored in the domain of face processing, a domain of natural expertise in all human adults. Faces form a highly homogenous set of stimuli with a very similar spatial configuration of parts. Therefore, discriminating between individual faces and extracting other relevant information from them should be, in theory, a difficult perceptual task. Nonetheless, humans are extremely adept in recognizing individual faces and categorizing faces along many other subordinate dimensions such as race or gender. This remarkable ability has been attributed by some to specifically tuned neural mechanisms distinguished by behavioral [@pone.0067024-Maurer1], electrophysiological [@pone.0067024-Bentin1], and neuroimaging [@pone.0067024-Kanwisher1]--[@pone.0067024-Puce1] markers. Others considered face perception as an extreme manifestation of perceptual expertise [@pone.0067024-Carey1]--[@pone.0067024-Tarr1], which may be generalized to objects other than faces, specifically to objects that form a visually homogenous category with a prototypical part configuration [@pone.0067024-Diamond1]--[@pone.0067024-Gauthier1]. The latter view challenges face specificity suggesting that processing characteristics usually attributed to faces are a general expression of expert visual processing rather than a peculiarity of face recognition. The present study addresses this contended issue by investigating"
+"Proprioceptive neurons of the peripheral sensory ganglia innervate muscle spindles, Golgi tendons and joints, playing an essential role in motor control by providing information about the body's position, its movement and balance[@b1]. In a recent study, two mouse Cre lines (*Pvalb*-*Cre* and *HoxB8-Cre*) were used to target a population of sensory neurons that included proprioceptive neurons and a subset of cutaneous mechanoreceptors[@b2]. In these animals, mechanical stimulation of these peripheral neurons evoked non-selective, cationic, rapidly adapting (RA) currents that were dependent on Piezo2 expression, as well as intermediately adapting (IA) currents that were independent of Piezo2. Indeed, Piezo2-deficient mice develop deficits in peripheral proprioception, reflected by their abnormal movement and limb position, supporting a significant role for Piezo2 in proprioception.\n\nIn order to clearly define the role of Piezo2 in proprioception, we have characterized the mechanically activated (MA) currents in neurons of the mesencephalic trigeminal nucleus (MTN), a unique population of purely proprioceptive neurons in the brainstem[@b3][@b4][@b5][@b6]. The homogeneous population of neurons in this nucleus represents a much cleaner system to analyze proprioception than the peripheral sensory ganglia that contain mixed populations of sensory neurons, including proprioceptors, touch receptors, nociceptors and thermoreceptors[@b7][@b8][@b9][@b10][@b11]. These functionally homogeneous trigeminal mechanosensory neurons extend axons"
+"Research in contextEvidence before this studyThe compendium of transcriptome datasets either from laboratory or clinical isolates showed divergent functional responses associated with variation in strain genotype, host pre-existing immunity and *in vitro* culture conditions. The functional importance of transcriptome variation during infection is unclear due to the underlying complexity in a natural human malaria infection, but is central to our understanding of parasite adaptation in the human hosts. Thus, the the establishment of controlled human malaria infection (CHMI) trials provide a unique experimental model to study parasite adaptation upon transmission and infection.Added value of this studyHere, we identified a unique transcriptional signature of a single strain malaria infection in a non-immune background. Transcriptional changes between sporozoite route of infection (intradermal *versus* intravenous), sporozoite dose (high *versus* low) and before-after mosquito passage (CHMI-derived strain *versus* pre-mosquito strain) reveal intriguing functional gene clusters associated with host immune evasion and parasite transmission. We applied and showed significant association of the variable transcriptome component from this study into the transcriptome component of parasites obtained from acute human infections from Africa, Bangladesh, Mekong, Myanmar and Cambodia.Implications of all the available evidenceParasites derived from CHMI studies can yield novel insights into the adaptation process in different"
+"At a glance commentaryScientific background on the subjectA noninvasive tomographic imaging technique with high spatial resolution is an accurate measuring method for high-resolution fluid flow velocity and structural images for biological tissue.What this study adds to the fieldIn our study on laser thermal injury tissue models, the feasibility and potential application of a noninvasive tomographic imaging technique to characterize and image blood flow has been demonstrated.\n\nLaser surgery involves high stability and low diffusivity which generates an influx of high energy in a short period of time, and therefore holds a highly important position in studies requiring constancy and precision [@bib1], [@bib2], [@bib3], [@bib4], [@bib5]. The increasingly rapid development and progress of laser techniques have been successfully and broadly applied to surgery. However, biological tissues react differently to the absorption and scattering of different light waves, and each wavelength of a laser beam can be used to treat different pathological changes.\n\nNoninvasive techniques for imaging *in\u00a0vivo* blood flow are of great value for biomedical research and clinical diagnostics [@bib6]. In plastic surgery, the superficial dermal plexus alone is particularly affected by the presence of cutaneous disease (e.g., eczema, scleroderma), vascular lesions (e.g., port-wine stain, hemangioma, telangiectasia), or trauma (e.g.,"
+"Background\n==========\n\nTo gain knowledge on the existence or not of protocols for the application of coercive measures in Spanish general hospitals, and to gain knowledge of the measures that are actually applied in practice and to analyze ethical, medico-legal and legal problems generated, especially in relation to the rights of the ill citizen.\n\nMethods\n=======\n\nAn exhaustive revision of the effective legal norms and specialized literature has been done. A naturalistic and prospective observation has been carried out at chosen services of five big general hospitals. Two complementary methods were used: quantitative and qualitative.\n\nResults\n=======\n\nNihil volitum quem prae cognitum. Information on intrinsic elements of the consent of the patient for the medical act showed the physician\\'s high importance in the definition of lex artis ad hoc. According to the High Court, other actions not specified habitually in texts should be considered as coercive measures (e.g. no information to patients from health staff). The catalogue should be opened to: involuntary admission, non-wished stay, non-wished medication or treatment, seclusion, chemical coercion and no information. The profile of the patient subject to coercion has been studied previously. We developed a complementary profile: age 71--80, lives alone, confused state, with neurological"
+"Introduction {#coy046s2}\n============\n\nThe measurement of biochemical and haematological parameters can serve as a valuable tool for evaluating and monitoring the health of wild reptile populations ([@coy046C45]; [@coy046C11]). However, a major obstacle to conducting wildlife health assessments is a lack of baseline data against which new data can be compared ([@coy046C10]). Without an understanding of typical species-specific (or taxon-specific) variation in biochemical and haematological parameters, researchers are unable to identify potential effects of disease, injury, pollutants or other changing environmental conditions ([@coy046C35]). This issue is particularly important for regions with large numbers of endemic species that are experiencing rapid change, such as the Galapagos Archipelago.\n\nThe Galapagos Archipelago has nine endemic species of lava lizard in the South American genus *Microlophus* (Family: Tropiduridae) ([@coy046C4]; [@coy046C32]). *Microlophus bivittatus* (Fig. [1](#coy046F1){ref-type=\"fig\"}), which is restricted to the island of San Crist\u00f3bal and nearby Islote Lobos, inhabits xeric, low-elevation areas, such as coastal scrubland and rocky beaches. This lizard is listed as near threatened ([@coy046C38]) and is particularly vulnerable to predation by feral cats ([@coy046C12]; [@coy046C13]). At present, no blood chemistry or haematology data have been acquired for the genus *Microlophus*, which complicates efforts to evaluate or monitor the health of wild lava lizard"
+"Citation {#SECID0E3G}\n========\n\nC\u00e9sar E, Bandala VM, Montoya L, Ramos A (2018) A new *Gymnopus* species with rhizomorphs and its record as nesting material by birds (*Tyrannideae*) in the subtropical cloud forest from eastern Mexico. MycoKeys 42: 21--34. [https://doi.org/10.3897/mycokeys.42.28894](10.3897/mycokeys.42.28894)\n\nIntroduction {#SECID0EVH}\n============\n\nThe Santuario de Bosque de Niebla (SBN) is a secondary-growth subtropical cloud forest, persisting as the main peri-urban natural forested area (ca. 30 ha) at southwest Xalapa City, Veracruz (east coast of Mexico). Part of it was a shade-grown coffee plantation abandoned several years ago and nowadays, the SBN (formerly called Parque Ecol\u00f3gico Francisco Javier Clavijero) is a forest ecosystem whose canopy is dominated mostly by trees of *Quercus*, *Carpinus*, *Clethra*, *Oreopanax*, *Ostrya* and *Turpinia*, amongst others. It is an area under conservation and protection by the Instituto de Ecolog\u00eda A.C. and the forest is functioning as an important refuge and reservoir of biological diversity. Permanent systematic field observations carried out on the site are allowing us to document the macrofungal community with special attention to the diversity and ecology of mushrooms (agarics, boletes and milk caps) and it has given us the opportunity to discover new or unusual species of different taxonomic groups, for example *Crepidotus*, *Crinipellis*,"
+"1.. Introduction {#s1}\n================\n\nLand salinization is a serious problem and leads to desertification \\[[@RSOS200637C1]\\]. Saline-alkali soils have important effects on plants. Most plants cannot or hardly survive on saline-alkali soils, since low osmotic potential of soil, imbalanced organic composition and salty toxicity inhibit plant growth and reduce land productivity \\[[@RSOS200637C2]--[@RSOS200637C4]\\]. Due to poor water condition, increased water table, seawater erosion and human activities \\[[@RSOS200637C5]\\], approximately 954 million hectares worldwide and 99.13 million hectares of lands in People\\'s Republic of China have been salinized \\[[@RSOS200637C6]\\], which are still increasing every year.\n\nRegarding bioremediation of saline-alkali, most studies focused on utilization of salty soil for agricultural production. To bioremediate saline-alkali lands, hundreds of halophyte species (such as seawater-cultivated vegetables) have been domesticated to reduce soil salinity \\[[@RSOS200637C7],[@RSOS200637C8]\\] and high-tolerant cultivars of non-halophytes have been bred to adapt to saline-alkali soils \\[[@RSOS200637C9]--[@RSOS200637C11]\\]. These studies paved an effective way to resolve saline-alkali agricultural lands.\n\nWith development of economic and living standards, requirements of landscape construction in urban areas are increasing. Worldwide, there are lots of cities built on saline-alkali lands, such as Cangzhou, Yancheng, Daqing and Chifeng in People\\'s Republic of China, the State of Victoria in Australia and California in America. Obviously,"
+"Introduction {#s1}\n============\n\nWhenever retrieving a key or lipstick from the bottom of a purse, we usually identify the searched object by hand-finger exploration in the absence of vision [@pone.0069931-Lederman1]--[@pone.0069931-Revesz1]. Despite our proficiency at haptic perception and our reliance on it in every day life, the neuronal mechanism behind this somato-motor process remains largely unclear.\n\nIn both humans and non-human primates, the secondary somatosensory cortex (area SII) and the adjacent posterior insular cortex (pIC) is believed to play a pivotal role in high-level haptic perception [@pone.0069931-Hsiao1]--[@pone.0069931-Mishkin1]. Neuropsychological studies revealed that unilateral damage to parieto-temporal cortices in either hemisphere, possibly including SII, induces tactile agnosia [@pone.0069931-Caselli1] and tactile apraxia [@pone.0069931-Valenza1]. In fact, both types of patients exhibit abnormal hand-manipulation [@pone.0069931-Roland1], frequently accompanied by impairments of tactile object recognition in the absence of more basic somesthetic dysfunction [@pone.0069931-Reed2], [@pone.0069931-Reed3]. Furthermore, the degree of recovery of manual dexterity in stroke patients revealed that it more positively correlates with the activation of SII than of the primary somatosensory cortex (SI) [@pone.0069931-Forss1]. This evidence suggests that fine manual control and haptic perception closely tie to each other in area SII. In favor of this interpretation, neuroimaging studies also demonstrate that human SII and ventral premotor"
+"Background\n==========\n\nCellular activities of genes and gene products represented in gene regulatory networks (GRN) provide a basis for signal transduction pathways. Since the signal transduction is transient, the study of dynamics of the transduction is essential. Further, the *distributed*nature of cell fate regulation events manifest\\'s itself as intense crosstalk between the nominal pathways. States of gene networks are often presumed to be stable, meaning that slight changes in the state of a few parents do not change the expression state of the child gene. This phenomena relates to the redundancy of biological systems which are to ensure that the system retains functioning inspite of the perturbations.\n\nIn this work, we use Bayesian networks (BN) in the stochastic framework to represent GRN. Pathways have a natural representation of BN, where genes are nodes in the network and edges are causal interactions among them. The causal dependencies are given as conditional probabilities which infer \\'cause and effect\\' relationships among genes in the network. A BN being acyclic is not able to model feedbacks and self-regulation events. The dynamic Bayesian network (DBN) is defined by a pair of structures (*S*~*t*~, *S*~*t*+1~) each corresponding to time instances *t*and *t*+ 1 and a transition"
+"At present, Iran has been known one of the up-warding countries in the world in regenerative medicine using stem cells therapy. In fact, the outcomes of some clinical trials on stem cell therapy of myocardial infarction, vitiligo, decompensated cirrhosis, and osteoarthritis narrate the feasibility of stem cell-based therapy for treatment of human diseases [@B1], [@B2]. However, in a similar manner with global configuration, the commercialization and translation of tissue engineering products into clinical phase has been restricted. It might be due to weak collaboration of different specialties for technology transfer of the multidisciplinary projects of tissue engineering field into clinical phase. Basic tissue engineers mostly prefer elegant studies, whereas physicians have tendency to solve medical problems with products indicating efficiency, easy to use, and cost benefit. Actually, a surgeon encountered with a dilemma between a partially effective tissue-engineered product that is both expensive and difficult to apply and a more traditional approach may choose the latter option. Therefore, a coherent teamwork between basic sciences and medicine as well as acquisition of competent knowledge about target tissue is necessary to conduct tissue engineering in the clinic. Moreover, it should be considered that in developing countries including Iran the high cost of"
+"Prof. Aurelio Bairati passed away in Milan, in December 2017.\n\nHe was Professor of Histology and Human Anatomy at the University of Milan. His interest in research began in 1951, when, still a freshman in the medical school, he had the chance to work in Berne in the laboratory of Prof. F.E. Lehmann, who was, at that time, a pioneer of biological electron microscopy. In the 60s' of the last century, Aurelio Bairati was at the forefront of ultrastructural research in Italy, studying the organization of a variety of cells and tissues.\n\nHe published extensively on the ultrastructure of the male reproductive apparatus of *Drosophila melanogaster*, thus providing the basis for future studies which proposed this insect as a model for studying male gametogenesis. Later, he extended his scientific interest to the study of the structure of the human testis and spermatozoa in infertile patients. He made influential contributions to the study of the extracellular matrix of connective tissues in vertebrates and invertebrates from the structural and comparative point of view, combining polarized light microscopy, electron microscopy, immunocytochemistry, morphometry, and biochemistry. He was a mentor for a large number of students in the field of electron microscopy and published over"
+"Plant functional genomics have come of age, not only because rice and the model *Arabidopsis thaliana* are fully DNA sequenced and hundreds of thousands of expressed sequence tags (ESTs) are available on data bases, but because of the isolation of genes defined by mutations controlling plant-microbe interactions, flowering, plant architecture, and hormone perception. Through this, we learnt that many processes in plants actually share common genetic determinants with bacteria and animals. Yet, public perception and government funding favor biomedical research in the myopic pursuit of our species\\' seemingly central position in the universe.\n\nThere is much excitement as, concurrent with the development in the human genome projects, computing, and robotics and related high throughput technologies, plant biotechnology in the last ten years has made significant advances that will benefit the life on this planet. Sadly, there is no Nobel Prize for plant science, preventing the popular press from featuring achievements in this area (NB, since the inception of Nobel Prizes one century ago, only three were awarded for plant-related research).\n\nWe all accept that plants are important in economical, environmental, and ecological terms. Imagine a world without flowers, shade trees, wooden furniture or floors, riverbanks without trees, mountains without meadows,"
+"**Effects of low-moisture, sugarcane molasses-based block supplementation on growth, physiological parameters, and liver trace mineral status of growing beef heifers fed low-quality, warm-season forage**\n\nPhilipe Moriel,^\\*,1^ Lu\u00eds F. A. Artioli,^\u2020^ Matheus B. Piccolo,^\\*^ Miguel Miranda,^\\*^ Juliana Ranches,^\\*^ Vitor S. M. Ferreira,^\u2021^ Lorenzo Q. Antunes,^\u2021^ Amanda M. Bega,^\u2021^ Victor F. B. Miranda,^\u2021^ Jos\u00e9 F. R. L. Vieira,^\u2021^ and Jos\u00e9 L. M. Vasconcelos^\u2021^\n\n\\*University of Florida -- Range Cattle Research & Education Center, Ona, FL 33865-9706; \u2020De Heus MBU Brazil Animal Nutrition Industry, Guararapes, S\u00e3o Paulo 16700-000, Brazil; and \u2021Department of Animal Production, S\u00e3o Paulo State University, Botucatu 18168-000, Brazil\n\nTable 5 included a typo for the concentrations of glucose. The correct unit for plasma concentrations of glucose is mg/dL."
+"Introduction\n============\n\nThe implementation of quality programs^[@r01]^ in public and private health services, as well as its increase in those that are already in course, is growing in Brazil. The adoption of indicators as tools for control of programs is necessary in this context, but the institutions, due to their complexities and multiple subdivisions, not always present specific indicators for each one of their areas. The search for quality requires that assessment tools should exist in each subdivision of a complex of health. Except for clinical laboratories and pathology anatomy that for years have indicators in their processes, there is a shortage of them to other areas of diagnostic medicine^[@r02]^. Particularly, in the context of the ergometric tests, it was not possible to find the proposition of indicators for this area in indexed publications. Whereas examination is noninvasive, but of risk, and it requires the informed consent form for its conduction, one deducts that tools of quality control can be useful and should be implemented.\n\nIn recent years, publications of Guidelines for medical practice, by specialty societies, have been increasing. The adoption of its recommendations has been strongly encouraged by representing the synthesis of reviews and analyzes of the available"
+"Fukushima et al. recently published research on the relationship between cost sharing policies and medical spending by the elderly (Fukushima et al., [@B6]). Japan, as the nation in the most advanced stage of population aging, is indeed the best place to search for answers (Ogura et al., [@B23]). The authors provided us with a valuable contribution on the effects of such policies on the demand for medical services and costs within the subpopulation of senior citizens. The study has been conducted within a sound methodological framework and significantly expands our knowledge on the oldest among the world\\'s large nations. I would like to complement their revealing findings with few additional facts crucial for understanding these issues.\n\nOne of the baseline results of the study claims: \"lower cost sharing significantly increases medical spending.\" This actually follows the natural logic that a patient is likely to consume more care if it is effectively free at the point of usage. Three decades ago policy makers believed it should be possible for a cost sharing mechanism to contain costs and induce net savings (Keeler and Rolph, [@B15]). It appears that the final balance is highly dependent on prevailing governing practices and legislative framework within"
+"Severe hyperbilirubinemia can induce devastating and permanent neurodevelopmental handicaps in infants. The occurrence of hyperbilirubinemia is higher in late preterm than in term infants, ranging from 8 to 40% of the formers according to different definitions of hyperbilirubinemia. The mechanisms by which this occurs is not completely understood, however an increased bilirubin load on hepatocyte, as result of decreased erythrocyte survival and increased erythrocyte volume, increased enterohepatic circulation of bilirubin, decreased hepatic uptake of bilirubin from plasma, defective bilirubin conjugation, and diminished serum bilirubin binding capacity play a relevant role.\n\nHyperbilirubinemia in late preterm infants is not only more prevalent than in term neonates, but also it occurs later and is more severe and protracted. In fact, Maisels et al. (Pediatrics 2006;117:1169) demonstrated that at 72 hours of life the value of 50\u00b0 percentile of trans-cutaneous bilirubin (TcB) is 9 mg/dl in 35-37 wks infants, while is \\<6 mg/dl in \u226540 wks infants. Moreover, they found that the decrease of TcB is slower in 35-37 wks infants than in \u226540 wks infants, since at 96 hours of life the value of 50\u00b0 percentile of TcB is 9 mg/dl in 35-37 wks infants, while is \\<3 mg/dl in \\>40 wks infants."
+"Introduction {#section1-1477370816677620}\n============\n\nEver since the 1980s there has been considerable debate about [@bibr30-1477370816677620] offender-based approach to offending. According to Sutherland, who was one of the first to recognize the importance of studying a white-collar crime category, white-collar criminals are defined by high social status and occupation, providing them with opportunities to commit types of crime that are out of reach for the 'common' criminal (see also [@bibr31-1477370816677620]). In addition, white-collar offenders were typically thought of as one-shot offenders, with few prior convictions and at low risk of developing a diverse crime pattern ([@bibr41-1477370816677620]). This profile supposedly distinguished white-collar offenders, who commit their crimes in the course of their occupation, from the typical street criminal, whose disadvantaged social background, low self-control and criminal history put them at risk of a prolonged and versatile criminal career.\n\nIn sharp contrast to the 1940s however, when most financial crimes were out of reach for ordinary people, in modern-day society the opportunity structure for white-collar crime has dramatically changed. The growth of the credit economy, the increase of the service sector, increased urbanization, and the advent of the internet -- to name but a few factors -- have increasingly democratized the phenomenon of financial"
+"This special journal issue was devised to solicit original manuscripts on current research findings, review studies, or conceptual papers pertaining to clinical or community level interventions, innovative treatment approaches, and discussions of cross-cultural issues pertinent to reducing ethnic disparities while improving care provided to patients with depression. Envisioning a collection of quality studies that encompassed a range of diverse topics reflecting the complexity of this issue, we broadly sought papers on areas including, but not limited to health beliefs, stigma, the care-seeking process, genetics and pharmacodynamics, financial barriers or other access problems, informal sources of care, healthcare reform and policy implications for mental health parity, the contribution and burden of medical comorbidities and care coordination, therapeutic alliance and cultural views of clinical power dynamics, unique issues regarding age, gender, and religious or sexual orientation, treatment retention and medication adherence, familial or social dynamics, specific treatment modalities, and special concerns of community patients and large insured populations alike.\n\nAlthough older national epidemiology surveys, such as the National Comorbidity Study and the Epidemiological Catchment Area study, found relatively similar prevalence rates for all mental health conditions across ethnic groups, \\[[@B1]\\] some evidence from recent studies like the National Survey of American Lives"
+"INTRODUCTION\n============\n\nGenomic DNA lesions are formed continually by environmental agents and toxic intermediates of metabolism. Some of this damage escapes removal by DNA repair and is encountered by the DNA replication apparatus, which can block replication fork progression. Mechanisms are available that allow cells to temporarily tolerate such DNA damage ([@gks054-B1]). One major tolerance mechanism uses specialized DNA polymerases to incorporate a nucleotide opposite a damaged template base in a process called translesion synthesis (TLS). TLS permits continued replication, but may cause mutations. At least 7 of the 15 DNA polymerases in mammalian cells have a capacity for TLS ([@gks054-B1]).\n\nIt is important to understand the cellular function of each DNA polymerase. DNA polymerase \u03b6 (pol \u03b6) is unique among TLS polymerases in mammalian cells, because inactivation of the gene encoding its catalytic subunit (*Rev3L*) leads to embryonic lethality in the mouse. This was not anticipated from extensive studies of budding yeast, as *Saccharomyces cerevisiae* containing a deletion of the homologous *REV3* gene are viable.\n\nThe inviability of *Rev3L-*defective mice suggests that pol \u03b6 performs one or more irreplaceable functions in proliferation of at least some cell types. Mouse models for conditional deletion of pol \u03b6 show that cells"
+"Introduction\n============\n\nAs of 2005, the world is confronted by 338 generic infectious diseases, scattered in a complex fashion across over 220 countries and regions. Each new day confronts health care workers with unexpected outbreaks, epidemics and heretofore unknown pathogens. Over 2,000 named bacteria, viruses, fungi and parasites are known to cause human disease; and are confronted by 328 anti-infective agents and vaccines. Experts working in Health Geographics share an obvious and immediate need for comprehensive and timely data on the status of infection around the globe. A recent outline of GIDEON addressed uses for the Infectious Diseases clinician \\[[@B1]\\]. This review will focus on the Global Health aspect of the program.\n\nIn 1990, we initiated a project to design computer systems to follow all diseases, outbreaks, pathogens and drugs. The initial DOS-based program was written in Paradox for floppy disks, later evolving through a compact disk-based program in Windows. A commercial web-based program was eventually released under the name, GIDEON (Global Infectious Diseases and Epidemiology ON-line, Gideon Informatics, Inc, Los Angeles, California) at <http://www.GideonOnline.com>. The current version is available on CD (updated every three months) or web subscription (updated every week).\n\nThe program consists of four modules: Diagnosis, Epidemiology,"
+"Background {#s1}\n==========\n\nOur current biological knowledge is spread over many independent bioinformatics databases, containing both novel and redundant data. Many different types of gene or gene product identifiers (IDs) are selectively used by these different databases and platforms. To leverage heterogeneous annotations across different bio-sources during data analysis, one of the immediate tasks is to convert users\\' IDs from one type to another as required by the individual source. For example, after an Affymetrix microarray experiment, one must typically translate Affymetrix IDs to gene names, GenBank accessions, RefSeq accessions, UniProt IDs, etc. for further analysis. While this is a time-consuming and tedious process, more importantly, an incomplete or inaccurate translation may easily result in the loss of key information during data analysis.\n\nNCBI's Entrez Gene \\[[@R01]\\] is a popular bioinformatics source for the translation of gene IDs from one type to another. In addition, several ID translation tools also offer this service in a high-throughput fashion \\[[@R02]-[@R06]\\] (supplementary file 1), based either on Entrez Gene or on the UniProt/PIR mapping databases \\[[@R07]\\]. The research goal of the DAVID Gene ID Conversion Tool (DICT), one of the components in the DAVID Bioinformatics Resources \\[[@R08],[@R09]\\], is to provide a more comprehensive"
+"The Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak in South Korea in 2015 has drawn public attention and inspired political debate regarding the regulation of infectious disease control in Korea. The discussion of the appropriateness of the regulatory system must take into account the interpretation arguments of and the legislative concerns regarding the Infectious Disease Prevention and Control Act (hereafter, 'Infectious Disease Prevention Act'), its ordinance and enforcement regulations as well as public statements from the relevant administrative agency. The Infectious Disease Prevention Act of 2015 has been much improved through two successions of amendments; through the amendments, there has been great progress in the regulation of quarantine measures in infectious disease control. The initial amendments on July 6, 2015 give the government the legal authority to immediately and actively order medical institutions to follow property quarantine measures when the infectious disease enters the epidemic phase. Following the amendments in December 29, 2015, financial compensation for losses incurred due to property quarantine enforcement has been established for the high effectiveness of the authority of the measures.\n\nAccording to the current Infectious Disease Prevention Act, quarantine measures can be classified into five types of personal quarantine and two types of property"
+"\"Vessels in the elderly restrict the transit of blood through thickening of the tunics.Leonardo da Vinci, 1452--1519.\"\n\nIntroduction {#Sec1}\n============\n\nLeonardo da Vinci presented perhaps one of the first known descriptions of atherosclerosis. In his collection of notes from post-mortem observations of human anatomy and poorly understood pathology, da Vinci merged what were the distinct disciplines of art and science to describe and depict human development and physiology.[@CR1] Five-hundred years later, significant advances in technology enable non-invasive visualization of atherosclerosis using multiple imaging modalities, moving beyond anatomical characterization toward directly imaging disease processes and pathophysiology. The current challenge for imaging scientists lies in identifying high-risk atherosclerotic lesions that could lead to coronary or cerebrovascular sequelae prior to adverse vascular events such as myocardial infarction and stroke, and thereby enable personalized therapy while mitigating risk.\n\nHerein, we present a general introduction to advanced non-invasive imaging of atherosclerosis with particular emphasis upon \\[^18^F\\]fluorodeoxyglucose (FDG) positron emission tomography (PET). We will discuss the role of FDG PET for the identification of the high-risk \"vulnerable plaque\" across the arterial tree and its potential for monitoring disease progression and response to therapy.\n\nAtherosclerosis {#Sec2}\n---------------\n\nAtherosclerosis is the most common underlying pathology responsible for adverse"
+"Introduction\n============\n\nPreoperative assessment of the axillary nodal status in primary breast cancer using ultrasonagraphy is now established practice and mandated by the NHSBSP. However, the criteria for nodal biopsy are based on the morphological appearance of the imaged nodes. This study\\'s poster proposes that the tumour and grade stage of the primary tumour should also influence the threshold for nodal biopsy with the intention of improving preoperative assessment and thus decreasing morbidity associated with further surgical intervention to the axilla following positive sentinel lymph node biopsy.\n\nMethods\n=======\n\nA retrospective analysis of final nodal status of the 296 surgically treated patients diagnosed with primary breast cancer in 2011 was performed. Data including preoperative assessment of tumour size, grade, axillary node status (preoperative and postoperative) and final outcome was collected. Patients with negative preoperative axillary node status were compared with postoperative node status and the proportion requiring further treatment was ascertained.\n\nResults\n=======\n\nA total of 207 had negative axillary preoperative assessment and underwent sentinel lymph node biopsy (SLNB). Fifty-one had positive sentinel lymph nodes, and of these 9% required further surgery. Sensitivity at the identification of positive axillary nodal disease preoperatively was 0.49 and specificity calculated at 0.99. Preoperative"
+"Introduction {#s1}\n============\n\nChromatin structure serves as a central regulator for DNA-associated cellular processes in eukaryotic cells, including transcription, replication, and repair. The primary components of chromatin are the highly conserved histone proteins, which provide the structural foundation for the organization of DNA. Molecular genetic, biochemical and genome wide studies have elucidated many aspects of the structural and functional roles of histones in genome organization. Here we investigate a set of nucleosome surface mutants in yeast with respect to their potential impact on chromatin structure, silencing and DNA repair.\n\nEukaryotic genomes are folded in arrays of nucleosome cores connected by linker DNA and further condensed into compact fibers and additional levels of higher order structures. While nucleosome cores are formed by intranucleosomal histone-histone and histone-DNA contacts, the close proximity of nucleosomes in arrays and higher order structures may require internucleosomal interactions of histones and DNA as well as a contribution of non-histone chromosomal proteins [@pone.0026210-Bassett1], [@pone.0026210-Li1]. Nucleosome cores are cylindrical particles containing of about 147 bp DNA wrapped around an octamer of core histones, two each of H2A, H2B, H3, and H4. The histones are folded in the centre of the core and have flexible N-terminal tails that protrude from"
+"Introduction {#s1}\n============\n\nStudies on improvisation in music and motion have mostly focused on a single improviser [@pone.0087213-Brown1]--[@pone.0087213-Limb1]. When people improvise together, special phenomena can arise. Experienced musicians, actors and dancers that improvise together report special moments of high performance and synchrony [@pone.0087213-Berliner1]. These are moments of creativity that arise out of the interaction between people, seemingly without a leader and a follower. As musicians often describe it, 'The music played us'. These moments can be defined as moments of togetherness. This may relate to concepts such as 'being in the zone' in theatre and sports, described as \"a state of unselfconscious awareness in which every individual action seems to be the right one and the group works with apparently perfect synchronicity\" [@pone.0087213-Seham1]. In anthropology, togetherness relates to communitas [@pone.0087213-Turner1] and interpersonal synchrony in meaningful rituals [@pone.0087213-Konvalinka1], and in psychology it may relate to the concept of group flow [@pone.0087213-Csikszentmihalyi1], [@pone.0087213-Sawyer1] and dyadic states in parent-infant interaction [@pone.0087213-Fogel1].\n\nRecently, building on the growing field of joint action research [@pone.0087213-Sebanz1]--[@pone.0087213-Hari2], a paradigm to experimentally study togetherness was presented [@pone.0087213-Noy1]. This paradigm is based on the mirror game, a theatre exercise whose purpose is to help actors experience moments of togetherness [@pone.0087213-Schechner1],"
+"Introduction {#s1}\n============\n\nThe birth and death of neurons and the growth and retraction of their axonal and dendritic arbors are critical features that mediate adult plasticity of the vertebrate brain. These processes, accompanied by changes in the electrophysiological properties of neurons, permit the brain to adapt to both short term and long term environmental changes, allowing the organism to survive and successfully reproduce. One useful model system for investigating adult neural plasticity within the context of a behaviorally-relevant brain circuit is the seasonally breeding songbird.\n\nSeasonally breeding songbirds show dramatic plasticity in adult brain and behavior between the breeding and nonbreeding seasons [@pone.0035119-Brenowitz1]. In these species, photoperiod-induced changes in circulating levels of steroid sex hormones induce changes in the neural structure [@pone.0035119-Nottebohm1], neuron number [@pone.0035119-Nottebohm2], and electrophysiological properties [@pone.0035119-Meitzen1] of the brain regions that control behaviors related to reproduction. In songbirds, this includes song, a learned behavior used for defending territories and attracting females [@pone.0035119-Catchpole1], and the song control system, a network of discrete brain nuclei that control song learning and production [@pone.0035119-Zeigler1].\n\nSeasonal changes in song behavior and the song control system have been studied using largely morphometric and electrophysiological techniques. Little is known, however, about how breeding"
+"Introduction {#s1}\n============\n\nIn the sports injury aetiology and prevention research field, the use of the 'complex systems approach' has been recently promoted.[@R1] Inspired by previous work that questioned the routine application of reductionist scientific methodologies and statistical techniques,[@R2] Bittencourt and colleagues[@R1] argued for an alternative causal approach. This approach recognises that sports injury is a 'complex emergent phenomenon', resulting from the interactions among different factors (ie, a web of determinants), which may produce regularities (ie, a risk profile) that are antecedent to the emerging pattern (ie, sports injury). In brief, the theoretical assumptions underpinning the complex systems approach can be traced back to general systems theory,[@R5] which identifies several characteristics of complexity as a general philosophical precept. These include, but are not limited to, adaptation and learning, tight coupling, causal feedback, non-linear relations, sensitivity on initial conditions, threshold effects, stochasticity and historical dependency. Those characteristics have featured across multiple discussions in the sports injury scientific literature[@R1]; however, no study has yet applied a recognised method that has the capability to dynamically simulate and better understand complex systems causal patterns and processes. One computational modelling method that has been suggested as a suitable approach for sports injury research[@R1] is agent-based"
+"Introduction {#s1}\n============\n\nThe Mediterranean fish fauna is unique, characterized by a history of isolation and connectivity [@pone.0036443-Coll1] resulting from tectonic movements and changes in ocean circulation. Isolation of the Mediterranean is reflected in its rich marine flora and fauna, with an estimated total of 17,000 species [@pone.0036443-Coll1]. 619 fish species have been inventoried in the Mediterranean, among which 13% are endemic, 2% are introduced, and 67% are non-endemic natives. 85% of these fish are teleosts [@pone.0036443-Lasram1]. General geological and oceanographic processes such as those involved at the origin of the Mediterranean Sea have been shown to influence regional histories of fish diversity globally [@pone.0036443-Friedman1],[@pone.0036443-Hurley1]. Studying the Mediterranean region may therefore illustrate mechanisms contributing to diversification of teleosts and help us understand the current distribution of diversity in the region.\n\nDuring the Cretaceous (145--65 Mya), the Mediterranean was part of the Tethys Sea and was connected with the Atlantic as well as with the Indo-Pacific oceans. At this time, Africa, Europe and the Adriatic plates were coming closer together, making this ancestral Mediterranean Sea smaller and smaller, and drastically changing its shape and connectivity. By the Miocene (23--5 Mya), the Mediterranean Sea was isolated from the Indo-Pacific. Subsequently, circa 7--5"
+"It is well known that the nucleic acids (NAs) ingested from food are metabolized in the digestive tract by endonucleases, phosphodiesterases and nucleoside phosphorylase into oligonucleotides, nucleotides, and even free bases. Some of these metabolites can be absorbed by intestinal endothelial cells and are utilized for the salvage synthesis of NAs throughout the body, a process important for infant nutrition[@b1] and for individuals with metabolic abnormalities[@b2]. Recently, it has been reported that ingested microRNA can regulate mouse gene expression *in vivo*[@b3]. This aroused our interest in the study of NA metabolism. The digestion of NAs is thought to start in the intestine and to be mediated by endonucleases[@b2][@b4][@b5]. Most textbooks and research papers describe a process in which histones are separated from DNA by pepsin and the acidity of the cellular environment, but few reports mention the role of the stomach in DNA metabolism. We noticed that much of our understanding of NA metabolism comes from studies conducted more than 30 years ago. However, it is well known that gastric juice is acidic, with a pH as low as 1.5 in some cases, and that depurination of DNA occurs to some extent under such acidic conditions. It is surprising that"