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-"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"
-"INTRODUCTION {#sec1-1}\n============\n\nCord lipomas (CL) are another form of spina bifida. They are covered by skin and are less frequent than myelomeningoceles (MMCL) \\[[Figure 1](#F1){ref-type=\"fig\"}\\].\n\n![Cord lipoma covered by skin](SNI-5-23-g001){#F1}\n\nIt is a fatty tumor that frequently is in continuity with the subcutaneous adipose layer. Some times through a raquischisis attaches to the cord and even infiltrates it \\[[Figure 2](#F2){ref-type=\"fig\"}\\].\n\n![Cord lipoma, with perianal anomalies](SNI-5-23-g002){#F2}\n\nAnatomically a CL resembles an intramedullary tumor albeit its symptoms are secondary to the tethering of the cord as it is an axis that connects the cord with the subcutaneous tissue.\n\nMany patients come to the consult without any symptoms. My experience has thought me that eventually the majority will develop some form of neurological or urological impairment.\n\nThere is controversy regarding the indications for preventive treatment. The French School favors operating only when there are symptoms related to tethering of the cord.\n\nThe association between CL and perianal malformations has been described having been observed between 1.8% to 5.1% of patients with CL. In a retrospective study at the Department of Neurosurgery Hospital de Ninos Ricardo Gutierrez we observed that over 82 patients with CL 4 (5%) presented perianal malformation. The clinical picture"
-"Background\n==========\n\nA hallmark of cancer cells is their limitless proliferative potential, which is sustained by the activation of a telomere maintenance mechanism (TMM) \\[[@B1]\\]. In a high percentage of human tumors (\\> 85%), proliferation-dependent telomere shortening is counterbalanced by the synthesis of telomeric DNA, which is catalyzed by telomerase \\[[@B2]\\]. However, in few cancers that lack telomerase, an alternative lengthening of telomeres (ALT) mechanism is used \\[[@B3]\\]. There may be more than one ALT mechanism, but in at least some ALT-positive human cancer cells telomere length is maintained by recombination-mediated replication of telomeric DNA \\[[@B4]\\].\n\nCharacteristics of ALT-positive tumor cells include an extreme heterogeneity of telomere length, with telomeres ranging from very short to extremely long within the same cell, as well as the presence of subnuclear structures termed ALT-associated promyelocytic leukemia (PML) bodies (APB), which contain telomeric DNA, telomere binding proteins and proteins involved in DNA recombination and replication \\[[@B5]\\]. Assays to detect telomere length and APB have been developed and alternatively used to screen human tumor specimens for the occurrence of ALT. Available results indicate that ALT is more common in tumors of mesenchymal and neuroepithelial origin, including osteosarcomas \\[[@B6]\\], soft tissue sarcomas \\[[@B7]\\] and glioblastoma multiforme"
-"1. Introduction {#sec1}\n===============\n\nOne of the animals which represent Pakistan and India throughout the world is cobra; in particular it is rearing out of a wicker basket and dancing to the sound of turban-wearing snake charmer music. In fact, they are deadly venomous among all species of the snakes due to high rate of mortality which strongly reasoned for their notoriety \\[[@B1]\\]. At the end of the nineteenth century, all cobra populations have been merged into single species naja (formerly known as naia); however, subsequently ten subspecies of*Naja naja* were identified \\[[@B1]\\]. Later on, Deraniyagala classified*Naja naja* (India) into several subspecies and considered*Naja naja karachiensis* one of them widely distributed in Southern Punjab province of Pakistan \\[[@B2]\\]. They are extremely toxic due to their severe side effects in the victims. Major signs and symptoms of cobra envenomation are edema, necrosis, pain, respiratory paralysis, vomiting, headache, hypotension, cardiac arrest, coagulopathies (elevated PT, aPTT, and TT), bleeding wounds, hematuria, mucus discharge, proteinuria, and increased creatinine and urea levels along with altered consciousness \\[[@B3], [@B4]\\].\n\nIndeed snake venom is a complex mixture of various sizes of polypeptides \\[[@B5], [@B23]\\] (\\<1.5\u2009kDa, 5 to 10\u2009kDa, and 10 to 150\u2009kDa), carbohydrates, lipids,"
-"1. Introduction\n===============\n\nThe relationship between hypertension and short sleep duration has raised concerns of cardiologists in recent years. Dozens of cross-sectional \\[[@B1-ijerph-12-00488],[@B2-ijerph-12-00488]\\] and longitudinal studies \\[[@B3-ijerph-12-00488],[@B4-ijerph-12-00488],[@B5-ijerph-12-00488]\\] have been conducted in populations of different ages, genders or races to investigate the potential association of short sleep duration in relation to hypertension and most of them indicated short sleep duration was related with the prevalence and incidence of hypertension. However, a few studies noted that sleep had quantitative and qualitative aspects \\[[@B6-ijerph-12-00488],[@B7-ijerph-12-00488]\\] and it may be not comprehensive to assess sleep only by sleep duration in those studies. Particularly, Bansil*et al.*'s study, which investigated the role of sleep duration and sleep quality in hypertension development separately, found that sleep duration alone failed to affect the hypertension prevalence, whereas the combination of short sheep duration and sleep disorders could influence hypertension \\[[@B7-ijerph-12-00488]\\]. Furthermore, the literature documented that poor sleep quality was associated with obesity \\[[@B8-ijerph-12-00488],[@B9-ijerph-12-00488]\\], metabolic syndrome \\[[@B10-ijerph-12-00488]\\] and glucose metabolism \\[[@B11-ijerph-12-00488]\\] which share many common risk factors with hypertension. Those findings suggested a possible link between sleep quality and hypertension which, however, has not been fully elucidated in the current literature. Therefore, it is necessary to investigate the potential relationship between"
-"1. Introduction {#sec1}\n===============\n\nSimulation of blood circulation in large capillary networks is a challenging task. Realistic modeling of microvessel structures should take into account not only sophisticated topologies of blood vessel networks but also correct hydraulic resistance of microvessels. The latter is characterized by the apparent blood viscosity which depends on the vessel diameter as well as the discharge and tube hematocrit. The discharge hematocrit is the volume fraction of the red blood cells (RBCs) in the blood delivered by the flow in the vessel. The tube hematocrit is the volume fraction of RBCs that are inside the vessel at a given time instant. The discharge hematocrit is larger than the tube one because the velocity profile in the radial direction is nonuniform; namely, the RBCs velocity is higher than the mean bulk flow speed, which is called the F\u00e5hraeus effect \\[[@B1], [@B2]\\]. The velocity profile in the radial direction is affected by the presence of the endothelial surface layer (ESL) \\[[@B1]\\].\n\nThe importance of accounting for the hematocrit level in blood flow simulations attracts attention of many researches. Animal models are utilized, for example, to measure and analyze the distributions of cell velocity and cell flux in the"
-"Background\n==========\n\nDefenses against pathogens and diseases have been remarkably well conserved across species, from invertebrates to vertebrates \\[[@B1],[@B2]\\]. In particular, the innate immune system, which responds to bacteria, fungi, viruses and other parasites, is very similar even at the molecular level in such diverse phyla as mammals, insects, and even plants \\[[@B3],[@B4]\\]. However, while molecular responses to pathogens have been the main focus of research, it has been demonstrated that behavioral responses could also serve a critical role in supporting the immune response to infection \\[[@B5]-[@B7]\\]. Research in mammals suggests that immune-stimulated individuals withdraw from their healthy social mates \\[[@B8]\\], which would represent an adaptive strategy to protect non-infected conspecifics \\[[@B7]\\]. However, it is still unclear whether alterations in social interactions represent a general and conserved mechanism implicated in the control of disease transmission within social groups.\n\nSocial insects, such as honey bees, ants and termites, are ideal models for studying mechanisms regulating disease transmission in social groups. Social insects provide an ideal environment for transmission of pathogens, since nests are typically environmentally controlled and there are hundreds if not thousands of potential hosts with frequent interactions, allowing for relatively easy dissemination \\[[@B9]-[@B12]\\]. Furthermore, based on modeling \\[[@B13]-[@B15]\\] and"
-"1. Introduction {#sec1-medicina-56-00269}\n===============\n\nAfter the initial presentation by Longo in 1998, the stapled haemorrhoidectomy (SH) has gained widespread popularity as a safe and effective surgical procedure for the treatment of grade III--IV hemorrhoids \\[[@B1-medicina-56-00269]\\]. In this new technique, Longo suggested a circumferential rectal mucosectomy for a mucosal lifting \\[[@B2-medicina-56-00269]\\].\n\nThe overall rate of complications is often underestimated \\[[@B3-medicina-56-00269]\\], and bleeding is the second most common complication in patients with SH and is twice higher than in classic haemorrhoidectomy \\[[@B4-medicina-56-00269]\\]. According to the most extensive series, the overall bleeding rate is 4.3%, and most frequently occurs immediately after surgery \\[[@B5-medicina-56-00269]\\]. In half of them, it stops spontaneously, whereas only 0.43%, required re-intervention for surgical hemostasis under anesthesia \\[[@B5-medicina-56-00269]\\]. This complication is associated with a more extended hospital stay, particularly in critically ill patients \\[[@B6-medicina-56-00269]\\].\n\nPostoperative bleeding can be intraluminal or perirectal \\[[@B7-medicina-56-00269]\\]. In the significant number of cases, the postoperative bleeding is intraluminal from the submucosal vessels \\[[@B8-medicina-56-00269]\\]. The reason is probably the large thickness of the visceral wall fold cut by the stapler, so the staples cannot adequately create adequate hemostasis \\[[@B9-medicina-56-00269]\\]. Fortunately, this bleeding is effectively treated through an overstitching of the mechanical suture line at the time"
-"introduction\n============\n\nSelection of efficacy end points for randomized controlled trials (RCTs) of non-Hodgkin\\'s lymphoma (NHL) depends largely on histology and treatment goals. In untreated aggressive histology lymphomas, primary treatment with chemotherapy is undertaken with curative intent, so the development of new treatments to increase the rate of overall survival (OS) remains an important goal for this patient population. In contrast, indolent histology lymphomas have a very long natural history and are generally incurable, and systemic treatment is generally directed at improving symptoms and prolonging progression-free survival (PFS).\n\nAlthough OS is an unambiguous measure of efficacy in clinical trials, its use as a primary end point requires a long duration of follow-up and may prolong the process of identifying novel and potentially beneficial therapy. Surrogate end points for OS have been explored in breast \\[[@bib1], [@bib2]\\], lung \\[[@bib3]\\], and rectal cancers \\[[@bib4]\\] but only have been validated in colon cancer \\[[@bib5]--[@bib7]\\]. Nonetheless, there is emerging acceptance of such end points by the oncology community and by regulatory agencies \\[[@bib8]--[@bib10]\\].\n\nWhile there is great interest in developing validated surrogate end points for OS, there is no consensus on the necessary validation process \\[[@bib5],[@bib11]--[@bib14]\\]. Prentice et al. proposed that the surrogate marker"
-"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"
-"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\n============\n\nSchizophrenia is a disorder of the brain which affects how a person thinks, feels, and perceives reality[@cky231-B1] and significantly decreases the quality of life of patients.[@cky231-B2] In the European Union population, the estimated prevalence of all psychotic disorders is around 1.2%, and the incidence of schizophrenia is 15.2 per 100 000 persons. People with schizophrenia have 2 to 3 times higher risk of death compared to the general population,[@cky231-B3] and the lifetime risk of schizophrenia morbidity is 7.2 per 1000 persons.[@cky231-B4] This disease is also associated with the social stigmatization of patients.[@cky231-B5]\n\nIndividuals with schizophrenia use a substantial amount of healthcare services. This condition imposes a significant economic burden on both the patients and their families, and on the society as a whole.[@cky231-B6] The quantifiable costs associated with human diseases and illness are typically categorized into two unique components, direct and indirect cost components, the general focus in the scientific literature is on direct cost component. However, to conduct thorough analyses on the effects of schizophrenia on society, the assessment of indirect costs is equally important.[@cky231-B7] In published cost-effectiveness analyses, many analysts continue to claim a societal perspective, while they collect and analyse data only from a payer"
-"Introduction {#s1}\n============\n\nSarcomas although rare in adult patients account for up to 20% of all paediatric malignancies ([@bib10]). These are often aggressive diseases which do not respond well to conventional therapeutic interventions ([@bib2]). As such the cure rates for many of these diseases are unsatisfactory and patient prognoses remain poor. The molecular pathology of many of these cancers is associated with recurrent chromosomal rearrangements; leading to the generation of chimeric fusion proteins. Significantly, many fusion protein generating aberrations occur in a genomic background with few co-occurring genetic alterations ([@bib18]; [@bib9]; [@bib51]; [@bib15]; [@bib40]; [@bib41]). This has led to the prevailing notion that these gene fusions are often the primary driver of disease development. These chromosomal rearrangements often effect genes involved in transcriptional/chromatin regulatory mechanisms; with the resulting fusion proteins thought to drive disease development by altering the dynamics of transcriptional control. Excitingly, recent work has highlighted the therapeutic potential of targeting mechanisms of transcriptional control in cancer cells ([@bib8]). However, effective means of blocking oncogenic transcriptional mechanisms in fusion gene driven sarcomas are currently lacking.\n\nSynovial sarcoma is a fusion gene driven malignancy, which accounts for\u00a0\\~10% of soft-tissue sarcomas. Synovial sarcoma is a poorly differentiated malignancy with an"
-"INTRODUCTION\n============\n\nDNA encodes not just the gene but also the program for expression. At the level of transcription, a given gene\\'s program consists of the promoter sequences necessary for recruiting RNA polymerase along with *cis*-regulatory sequences specific for different transcriptional activators and repressors ([@B1]). In bacteria, these regulatory proteins bind specific DNA sequences, also known as operator sites, typically proximal to the promoter. The sequence of the operator site determines which activators and repressors regulate the activity of the promoter. In order for this regulation to work, the proteins regulating a given promoter must bind specifically to the associated operator sites, otherwise aberrant regulation will occur. Understanding the molecular basis for this recognition and specificity has been the focus of innumerable studies \\[cf. ([@B2; @B3; @B4])\\]. This information can potentially be used to change the DNA-binding specificity of transcription factors, enabling the reprogramming of gene expression in cells with applications, for example, in synthetic biology and metabolic engineering ([@B5; @B6; @B7; @B8; @B9; @B10; @B11]). As a result, an active area of protein engineering has been to identify mutations that alter the DNA-binding specificity of these transcription factors ([@B12]). While a number of experimental methods exist for generating such"
-"INTRODUCTION {#S5}\n============\n\nPersistent pulmonary hypertension of the newborn (PPHN) represents a failure of the normal postnatal adaptation that occurs at birth in pulmonary circulation. It is characterized by decreased blood vessel density in the lungs ([@R1]) and impaired pulmonary vasodilatation at birth, both of which lead to postnatal persistence of high pulmonary vascular resistance (PVR). The increased PVR can result from a decrease in vasodilator signals, or increase in vasoconstrictor signals by pulmonary artery endothelial cells (PAEC) in PPHN. Nitric oxide (NO) and prostacyclin (PGI~2~) are two key mediators involved in pulmonary vasodilatation at birth ([@R2]--[@R4]). Although alterations in NO-cGMP system have been extensively studied in PPHN, the role of altered prostanoid signaling in PPHN remains unclear. Inhaled NO therapy has improved the outcomes in PPHN; however, some neonates do not respond to this therapy ([@R5]). Impaired vascular growth in the lung may contribute to this failure of response to NO ([@R6]).\n\nPGI~2~ is a prostanoid synthesized from arachidonic acid through cyclooxygenase (COX) - PGI~2~ synthase (PGIS) pathway. PGH~2~, the catalytic end product of COX activity and a vasoconstrictor itself, is further metabolized by PGIS to PGI~2~. PGI~2~ is synthesized primarily in vascular cells, especially in the vascular endothelium"
-"1. Introduction {#sec1}\n===============\n\nExtracorporeal life support (ECLS) or extracorporeal membrane oxygenation (ECMO) is used to support patients with cardiac or respiratory failure, or both, which is refractory to conventional therapy \\[[@B1]\\]. Indications for ECMO are expanding, and perioperative use of venoarterial (VA) and venovenous (VV) ECMO systems has been implemented increasingly for candidates of heart or lung transplantation as bridge therapy to transplant or for recovery in patients in whom early severe graft failure develops after transplantation \\[[@B2]\\].\n\nAlthough no consensus exists on whether ECMO support is an indication for solid-organ transplantation other than heart and lung, this practice continues to be limited. To the authors\\' knowledge, there are no reports of perioperative ECMO support during kidney transplantation. The authors present the case of a 55-year-old man who was placed on VA-ECMO during heart transplantation because of acute graft failure and then underwent single-kidney transplantation while on VA-ECMO, with no complications.\n\n2. Case Report {#sec2}\n==============\n\nA 55-year-old Caucasian male was admitted to our hospital with a history of biventricular systolic heart failure due to ischemic cardiomyopathy and chronic stage IV kidney disease due to diabetic nephropathy; one month earlier, he had been approved for combined heart-kidney transplant. He"
-"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"
-"I. Introduction\n===============\n\nTemporomandibular joint ankylosis (TMJA) is a joint pathology caused by bony and/or fibrous adhesion of the joint apparatus, resulting in partial or total loss of function[@B1][@B2]. Since the temporomandibular joint (TMJ) is unique in that it requires the synchronous motion of two joints for function, any pathology in one or both joints results in functional problems that can lead to low self-esteem and poor quality of life. The aetio-pathogenesis of TMJA includes trauma (e.g., forceps delivery)[@B3], fall on the chin[@B4][@B5], middle ear infection, and cancrum oris. Recent reports have established a progressive ankylosis gene that controls osteoblast differentiation[@B6].\n\nSeveral classifications of TMJA have been proposed to determine the difficulty of surgical treatment[@B7]. Currently, TMJA is classified simply as true or false ankylosis. Sawhney[@B8] further classified true ankylosis into types I, II, III, and IV. The management of TMJA poses a great challenge due to technical difficulties in investigating and treating the disease, as well as the high incidence of recurrence[@B9]. Several techniques have been reported in literature; however, no single method has produced a uniform success rate[@B2][@B10][@B11]. Such technical difficulties are further aggravated in resource- and personnel-scarce countries. Healthcare funding in sub- Saharan Africa, especially Nigeria, has"
-"Introduction {#s1}\n============\n\nBacteria have an extraordinary capacity to adapt to changes in their external environment. The histone-like nucleoid-structuring protein (H-NS) plays a key role for many Gram-negative bacteria by integrating a complex range of environmental signals such as temperature and osmolarity \\[[@ppat-0020081-b001],[@ppat-0020081-b002]\\]. Consequently, H-NS acts as a pleiotropic regulator of gene expression \\[[@ppat-0020081-b003]\\]. Deletion of *hns* resulted in altered gene expression of almost 5% of Escherichia coli genes, of which more than 80% were up-regulated \\[[@ppat-0020081-b004]\\]. H-NS also influences the major DNA transactions, such as replication, transposition and recombination \\[[@ppat-0020081-b005]\\]. The modular nature of the H-NS protein is reflected by the three distinct domains, involved in DNA binding, dimerisation, and the formation of high order oligomers \\[[@ppat-0020081-b003],[@ppat-0020081-b006]\\].\n\nUnlike classical regulatory repressor and activator proteins, H-NS does not recognise particular sequences of DNA; however, a number of in vitro studies have shown that the protein has a small preference for curved DNA \\[[@ppat-0020081-b007]--[@ppat-0020081-b009]\\]. It has been proposed that after binding to a preferential site, H-NS oligomerizes cooperatively along the DNA to cover a larger region \\[[@ppat-0020081-b010]--[@ppat-0020081-b012]\\]. This idea is supported by the observation that mutant H-NS proteins that are unable to oligomerize no longer repress the expression of some promoters"
-"Introduction\n============\n\nBone fractures are a very common clinical problem affecting of 3.6% of the UK population every year (Donaldson *et\u00a0al*, [@b25]). While the majority of fractures heal uneventfully, they are particularly problematic in certain subgroups of patients, including high-energy open fractures which represent limb-threatening injuries prone to delayed and non-union, and fractures in osteoporotic bone, which represent the greatest unmet clinical need. Although addition of exogenous bone morphogenetic proteins (BMPs) results in improved healing in animal models, clinical trials of BMPs for tibial non-union (Friedlaender *et\u00a0al*, [@b28]) and fracture healing (Govender *et\u00a0al*, [@b34]) have failed to achieve the efficacy anticipated (Lane, [@b50]; Lieberman *et\u00a0al*, [@b54]). This is probably because a single supraphysiological dose of BMP does not induce the complex pattern of growth factor and cytokine production required for optimal fracture repair. Currently, there is no approved therapy to enhance healing of fragility fractures in osteoporotic bone (Kanakaris *et\u00a0al*, [@b43]). Antibodies to endogenous inhibitors of the Wnt/\u03b2-catenin signaling pathway, including sclerostin and dickkopf-1, have shown early promise but are limited to systemic administration, leading to non-specific bone deposition. Furthermore, these are associated with safety concerns, including carcinogenesis and closure of osteal foramina (Baron &"
-"All relevant data are within the paper and its Supporting Information files.\n\nIntroduction {#sec001}\n============\n\nFlavor is an important determinant of both food selection \\[[@pone.0169583.ref001],[@pone.0169583.ref002]\\] and rejection \\[[@pone.0169583.ref003]\\]. Though agreement is not uniform, a widespread view is that the flavor of food reflects the summation of all of its sensory properties \\[[@pone.0169583.ref004]\\]. The relative contribution of each sensory property varies with the food system and concentration of the contributing stimuli. Stimuli that are rated as unpleasant when sampled alone (e.g., a bitter compound in water) may make an important positive contrition to the flavor profile of a food when present at an appropriate low concentration. For example, bitterness adds to the appeal of popular items such as chocolate, coffee, and wine. Fatty acids may resemble bitter compounds in this regard.\n\nEvidence now strongly indicates that humans can detect non-esterified, long chain fatty acids (NEFA) in the oral cavity, referred to as fat taste or, more recently, \"oleogustus\" \\[[@pone.0169583.ref005]\\]). This evidence includes a growing body of human psychophysical work, e.g. \\[[@pone.0169583.ref006]--[@pone.0169583.ref017]\\] as well as identification of receptors in human lingual epithelium \\[[@pone.0169583.ref018],[@pone.0169583.ref019]\\] and transduction mechanisms \\[[@pone.0169583.ref020]\\]).\n\nGiven that fats are especially energy dense, special attention has been given to their role"
-"INTRODUCTION {#omy034s1}\n============\n\nCellular and humoral immunity towards distinct onconeural antigens is the hallmark of PNDs \\[[@omy034C1]\\]. Stable formation of IgG antibodies to particular onconeural antigens occurs in the majority of cases, whereas persistent coexistence of antibodies specific for multiple onconeural antigens is a relatively rare phenomenon of certain malignant tumors like SCLC \\[[@omy034C2], [@omy034C3]\\]. However, onconeural antigen spreading, i.e. the dynamic appearance and disappearance of distinct onconeural antibodies during the course of PNDs in individual patients has not yet been described.\n\nCASE REPORT {#omy034s2}\n===========\n\nA 70-year-old Caucasian male with a long history of smoking and surgically treated urothelium carcinoma 2 years ago, presented 08/2013 with radicular neuralgia and hypesthesia of the legs, disturbed fine motor skills of the hands and extinction of knee and ankle jerks on both sides, accompanied by abnormal posture and ataxic gait. Nerve conduction studies revealed severe demyelinating and axonal polyneuropathy fulfilling the Inflammatory Neuropathy Cause and Treatment (INCAT) criteria for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Initial MRI of the brain and entire spinal cord showed moderate contrast enhancement in fibers of the cauda equine an radices only (not shown). Cerebral (as part of a whole-body) FDG-PET/CT was normal (Fig. [1](#omy034F1){ref-type=\"fig\"}A). Cerebrospinal fluid (CSF)"
-"Case Report {#cesec10}\n===========\n\nA 38-year-old male presented to the emergency room (ER) with a chief complaint of abdominal pain. Onset of pain was three days prior, when he sustained an occupational accident. The patient was a tree cutter, and upon cutting down a large tree, his safety strap became entangled with the superior aspect of the falling tree trunk. The patient was pulled flush against the stump with the majority of the tree suspended from his safety strap, torquing his abdomen and back. He complained of nausea and a single episode of vomiting. He denied fever, chills, and dysuria. He did complain of a single episode of dark stool, although his stool was heme negative. Abdominal exam revealed focal tenderness in the peri-umbilical region without evidence of guarding or rebound. His laboratory data, which consisted of serum electrolytes and white blood cell counts, was normal. A computed tomography (CT) scan ([Figure 1](#fig1){ref-type=\"fig\"}) was obtained which revealed a focal loop of thickened bowel alongside mild vascular congestion. However, the oral contrast was not impeded. He was admitted for observation based on his history and presenting symptoms; however, his constellation of clinical and radiological findings precluded him from emergent laparotomy.\n\nThe"
-"INTRODUCTION {#s1}\n============\n\nThe diseases that affect calves can have a substantial economic impact on beef and dairy farms, and most cases concern animals that are less than 1 mo old. The two most frequent diseases are diarrhea and respiratory disease ([@CIT0033]; [@CIT0038]). Umbilical infection is the third most common disease during the first few months of life, affecting between 1.3% ([@CIT0037]) and 29% of newborn dairy calves ([@CIT0040]). As well as the costs of treating sick calves and the time this requires, the economic losses resulting from calf diseases may also include increased mortality ([@CIT0033]), reduced weight gain ([@CIT0040]) or longevity ([@CIT0003]), and older age at first calving ([@CIT0036]). Previous studies had demonstrated the genetic component of diseases affecting calves ([@CIT0017]; [@CIT0016]). Genetic and genomic selection therefore represent a potential strategy to increase resistance to these diseases, but necessitate the collection of additional phenotypic data beyond what is included in most of the national databases used for genetic evaluation. In addition, little research has been dedicated to the health of beef calves when compared to studies on dairy (and particularly Holstein) calves. Because French breeders were interested in improving the viability of Charolais beef calves, 16 herds were recruited"
-"Introduction {#s1}\n============\n\nHIV-1 infection is characterized by progressive CD4+ T lymphocytopenia. The mechanisms driving this progressive loss of CD4+ T-cells are not completely understood. Several studies have found that increased T cell activation [@pone.0030306-Leng1]--[@pone.0030306-Ribeiro1] and turnover [@pone.0030306-Kovacs1]--[@pone.0030306-Sieg1] predicts risk of disease progression in HIV infection [@pone.0030306-Giorgi1]--[@pone.0030306-Choudhary1].\n\nPotential drivers of cellular activation and turnover in chronic HIV infection include the type I interferons. Type I interferons play an important role in innate and adaptive immune defenses against viral replication and in immune cell maturation [@pone.0030306-LeBon1], [@pone.0030306-Biron1]. In HIV infection, although interferon levels in blood have been difficult to detect and may vary with the stage of infection [@pone.0030306-vonSydow1], interferon exposure is implicated, as microarray studies have shown substantial upregulation of interferon stimulated gene expression [@pone.0030306-Hyrcza1]--[@pone.0030306-Asmuth1]. Type 1 interferons can induce cellular resistance to HIV propagation as well as enhanced cytolytic defenses [@pone.0030306-Levy1]--[@pone.0030306-Tomescu1].\n\nThe antiviral activities of type I interferons have been exploited for the systemic treatment of hepatitis B and C infection [@pone.0030306-Levin1]. AIDS Clinical Trial Group (ACTG) Study 5192 was designed to evaluate the safety and antiretroviral activity of type I interferon administration in chronic HIV infection. We decided to use this opportunity (through ACTG New Works Concept Sheet"
-"Matrix metalloproteinases (MMPs) play a role in many physiological processes, have additional roles in reorganization of tissues during pathological conditions such as inflammation\\[[@ref1][@ref2]\\] and in immunosurveillance by leukocytes against infections.\\[[@ref3]\\] This classical paradigm was further developed by tumor biologists who discovered that an increased expression of proteinases, including MMPs, is a marker of invasion and metastasis of cancer cells. At that time, the hope was to use MMP inhibitors (MMPIs) to halt the spreading of cancer cells. However, during clinical trials of metastatic cancer, severe side effects were observed, thus leading researchers to reappraise the use of MMPIs for the therapy of invasive cancer.\\[[@ref4][@ref5]\\] The positive effect of these cancer researches and clinical studies is that the marker functions of MMPs have been refined in several ways. In this review, we discuss important biological aspects of MMPs in view of the uses of MMPIs in inflammatory periodontal disease.\n\nMMPs - Redundancy, Expression Patterns, and Balances {#sec1-2}\n====================================================\n\nMMPs are multidomain enzymes containing a zinc ion, which are coordinated by three histidine residues in their active site. Although all MMPs possess different primary structures, they are composed of shared modules, known as protein domains. The hallmark of the MMP family is"
-"Background\n==========\n\nWith the advent of large gene expression experiments, new methods of analysis have become necessary to extract relevant information from the data. Exploratory data analysis methods like cluster analysis are regularly used to examine the expression profiles \\[[@B1]-[@B3]\\]. Other methods use annotation information and look for overrepresentation in sets of significantly regulated genes \\[[@B4]-[@B6]\\]. A next step would be to associate relevant profiles with annotation information and experimental variables simultaneously. In this paper we will show advances in finding associations between annotation categories and experimental variables in microarray experiments.\n\nOne of the most extensive and systematic methods of categorizing information about genes is the Gene Ontology (GO) database \\[[@B7]\\]. A problem when relating GO classes with expression profiles is the fact that the genes in these functional classes can have diverse expression profiles. This could mean that a class is not responding to the experimental factors and is not related to the specific biological settings. However, a second possibility is that interesting subgroups are silenced by other heterogeneous or anti-correlated expression profiles present within the class. This may obscure interesting relations. To address this problem, we propose to cluster the expression profiles of genes in every category, and"
-"1. Introduction {#sec1-diagnostics-06-00027}\n===============\n\nMost men will develop prostate cancer (PCa) if they live long enough \\[[@B1-diagnostics-06-00027]\\]. Indeed, population-adjusted figures show that PCa is the fifth most common cause of cancer-related death for males worldwide \\[[@B2-diagnostics-06-00027],[@B3-diagnostics-06-00027]\\]. PCa is a disease of the elderly, as the likelihood of developing it is associated closely with advancing age \\[[@B4-diagnostics-06-00027],[@B5-diagnostics-06-00027],[@B6-diagnostics-06-00027],[@B7-diagnostics-06-00027]\\]. In the last 20 years, a man's lifetime risk of being diagnosed with PCa has increased considerably, and this is attributed largely to the introduction of PSA screening in the early 1990s \\[[@B8-diagnostics-06-00027],[@B9-diagnostics-06-00027]\\]. On the other hand, the number of men dying from PCa has decreased over the same 20 year period as the disease can now be treated more effectively through a wide range of treatment options and at an earlier stage \\[[@B10-diagnostics-06-00027]\\]. When a man is diagnosed with PCa, his concerns are likely to include; (i) will I survive? (ii) how will I be treated? and (iii) what effect will treatment have on my lifestyle? From a clinical perspective, the main questions following a diagnosis of PCa are; do the prognostic data provide clear guidance of which treatment option(s) may be best for the individual patient? and, how does this align with"
-"Churg--Strauss syndrome (CSS) is an uncommon systemic disease characterized by bronchial asthma, hypereosinophilia, and granulomatous small vessel vasculitis. Ocular involvement is unusual in CSS. There have only been a few case reports of CSS associated with central retinal artery occlusion (CRAO) and most of the patients had a poor visual outcome.\\[[@ref1][@ref2][@ref3][@ref4]\\] Here, we report a patient with CSS and unilateral CRAO that responded to steroid pulse therapy.\n\nCase Report {#sec1-1}\n===========\n\nA 58-year-old man had been diagnosed with CSS from bronchial asthma, eosinophilia, polyneuropathy, and infiltration in lungs 2 years before. Bilateral foot drop and hypereosinophilia developed 2 weeks before the present condition and he was treated with oral prednisolone (15 mg/day). On referral to the Department of Neurology of our hospital, he had a diagnosis of peroneal nerve paralysis by CSS and steroid pulse therapy (methylprednisolone at 1 g/day) was started. The following day, he experienced acute painless loss of vision in his right eye and was immediately admitted to the Department of Ophthalmology.\n\nOn initial examination, the best corrected visual acuity was hand motion on the right side and 20/20 on the left. Slit-lamp examination revealed bilateral early cataracts. There was marked pallor of the retina with a"
-"INTRODUCTION {#s1}\n============\n\nLung cancer is a major cause of cancer deaths with approximately 80% of cases accounting to non-small cell lung cancer (NSCLC) \\[[@R1]\\]. In NSCLC target therapy, epidermal growth factor receptor (EGFR) is a promising candidate \\[[@R2]\\]. The frequency of EGFR mutation among Asian NSCLC populations is approximately 30% compared with approximately 10% in Caucasians \\[[@R3]-[@R5]\\]. EGFR TKIs like gefitinib, erlotinib, and afatinib are used for EGFR targeted therapy in NSCLC \\[[@R6], [@R7]\\]. The mode of action of tyrosine kinase inhibitors is to inhibit the kinase activation and signal transduction downstream by binding to the ATP binding site of the kinase domain of EGFR \\[[@R7]\\]. This targeted therapy has shown 56 to 74% of response rate with median of 10-14 months of progression free survival (PFS) \\[[@R8], [@R9]\\].\n\nMost common mutations of EGFR gene include in-frame deletions of exon 19 and heterozygous mutations of exon 21 \\[[@R7]\\]. The correlation between EGFR mutations and EGFR TKI sensitivity has shown prognostic potential as demonstrated from various clinical trials \\[[@R10], [@R11]\\]. Although, patients respond well, initially to EGFR TKIs, majority of them acquire resistance due to the emergence of secondary T790M resistance mutation which abrogates the TKIs inhibitory action \\[[@R12]-[@R15]\\]. This"
-"Introduction {#s1}\n============\n\nAcute kidney injury (AKI) is a syndrome characterized by the rapid loss of the kidney excretory function [@pone.0093297-Bellomo1]. It is strongly associated with increased early and long-term patient morbidity and mortality, as well as subsequent development of chronic kidney disease [@pone.0093297-Li1]. AKI is typically diagnosed by the accumulation of end products of nitrogen metabolism (urea or creatinine) and/or decreased urine output [@pone.0093297-Bellomo1]. Although these traditional markers are reliable, they lack the sensitivity and specificity that are necessary for early diagnosis. Multiple novel protein markers of AKI have been proposed and tested. However, early diagnosis of AKI in clinical conditions by using new serum and urinary biomarkers remains cumbersome [@pone.0093297-Vanmassenhove1].\n\nChallenges for developing new protein-based biomarkers include the complexity of protein composition in blood, diversity of post-translational modifications, low relative abundance of many proteins of interest, and the difficulties in developing suitable high-affinity detection agents [@pone.0093297-Etheridge1]. Circulating microRNA might provide a reasonable alternative. MicroRNAs are recognized as crucial regulators of gene expression. MicroRNAs are short non-coding RNAs that regulate gene expression by binding to specific mRNA targets and promoting their degradation and/or translational inhibition [@pone.0093297-Pritchard1]. Importantly, microRNAs have been found in plasma and urine [@pone.0093297-Rayner1]. They are stable"
-"Introduction {#ccr3921-sec-0001}\n============\n\nThe duodenum is the most frequent site of diverticulum next to the large bowel [1](#ccr3921-bib-0001){ref-type=\"ref\"}, [2](#ccr3921-bib-0002){ref-type=\"ref\"}. Duodenal diverticulum around the ampulla of Vater is referred to as juxta\u2010papillary diverticulum. Perforation of diverticulum at the large intestine is quite common, requiring surgical treatment for panperitonitis or retroperitoneal abscess. On the other hand, perforation of diverticulum at the duodenum is relatively rare. Duodenal diverticulum is one of the causes of obstruction to the outflow of pancreatic juice or bile, resulted in Lemmel\\'s syndrome. In this case report, we describe the patient with retroperitoneal abscess caused by perforation of juxta\u2010papillary diverticulum.\n\nCase Report {#ccr3921-sec-0002}\n===========\n\nA 52\u2010year\u2010old woman was admitted to our hospital due to sudden onset of pain at right hypochondriac region. The patient had undergone total mastectomy for left breast cancer 10\u00a0years ago. Results of blood tests were normal except increased number of white blood cells (WBC) (12,900/mm^3^). CRP was within normal range (0.11\u00a0mg/dL). Computed tomography (CT) scans showed significant dilation of the descending part of duodenum, mural edema, and accumulation of fluid and air (Fig.\u00a0[1](#ccr3921-fig-0001){ref-type=\"fig\"}). As abdominal CT suggested retroperitoneal abscess (40\u00a0\u00d7\u00a027\u00a0mm) caused by perforation at juxta\u2010papillary duodenal diverticulum, the patient"
-"Case report\n===========\n\nA 36-year-old man visited the emergency department of Inje University Haeundae Paik Hospital with severe pain in both lower limbs for 1 day. A physical examination revealed pale, pulseless, and cold lower limbs. He had sensory changes and foot drop of the right lower limb.\n\nOne year ago, he had been diagnosed with Kimura disease (KD) after excision of a right upper limb mass ([Fig. 1](#f1-kjtcvs-50-114){ref-type=\"fig\"}) at another hospital. He had been taking oral steroids but stopped doing so 6 months ago.\n\nThe initial laboratory findings were as follows: leukocyte count of 45.5\u00d710^9^/L with 74% eosinophils, elevated serum fibrinogen degradation product (FDP) level (18.7 \u03bcg/mL), elevated D-dimer level (5.1 \u03bcg/mL), and extremely elevated serum immunoglobulin (Ig) E (\\>2,500 IU/dL). A computed tomography (CT) angiogram showed total occlusion of both popliteal arteries (PAs) ([Fig. 2A](#f2-kjtcvs-50-114){ref-type=\"fig\"}).\n\nUnder the presumptive diagnosis of acute limb ischemia (ALI), the patient underwent an emergency thrombectomy of both femoral arteries using a Fogarty catheter (Edwards Laboratories, Santa Ana, CA, USA). After the operation, the pain and color changes resolved, but the right foot drop remained. To prevent thromboembolic events, he was treated with low-molecular-weight heparin followed by warfarin.\n\nThe patient was evaluated to determine"
-"A fundamental goal of biological research is to understand the functions of genes. One common strategy for studying gene function is to observe the phenotypes of mutants to deduce the biological processes in which a gene participates and, sometimes, details of its mechanism of action. This basic idea is the foundation of classical genetics and also underlies reverse genetic approaches including RNAi. A second strategy is to observe the localization and dynamics of a gene\\'s protein product within a cell or animal, either by antibody staining or by expressing a fluorescent protein (FP) fusion. Together, these two basic strategies form the backbone of much research in *Caenorhabditis elegans* and other model systems.\n\nThe use of the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 system for genome engineering ([@bib24]) has greatly facilitated the study of gene function in *Caenorhabditis elegans* and other organisms. By making precisely targeted mutations in endogenous genes, an investigator can examine the relationship between gene function and phenotype. By inserting coding sequence for a fluorescent protein, the expression and localization of endogenous proteins can be monitored. In both cases, one avoids the caveats of overexpression and silencing that are associated with conventional transgenes. Moreover, for fluorescent protein"
-"Dimethyl fumarate (DMF), marketed commercially as Tecfidera, is a twice-daily, oral disease-modifying therapy approved for the treatment of relapsing-remitting MS. While the exact mechanism of action is not entirely understood, DMF is known to cause reductions in white blood cell (WBC) count and absolute lymphocyte count (ALC) values. Mean ALC reductions of approximately 30% were previously observed within the first year of treatment.^[@R1]^ Significant ALC reductions were also described, resulting in grade III lymphopenia (ALC \\<500 cells/\u03bcL) in approximately 5% of patients.^[@R1]^ Recent studies have also reported reductions in T cells and B cells.^[@R2],[@R3]^\n\nSeveral cases of progressive multifocal leukoencephalopathy (PML) have occurred in DMF-treated patients with sustained lymphopenia (\\>6 months). While most cases have occurred in patients with ALC \\<500 cells/\u03bcL, fumarate-related PML has developed with ALC values as high as 792 cells/\u03bcL, highlighting the need for careful surveillance.^[@R4][@R5][@R6]^\n\nLike many immunomodulatory treatments, DMF influences several targets, having anti-inflammatory and immunomodulatory properties along with neuroprotective effects.^[@R7],[@R8]^ However, this does not completely explain reductions in ALCs and lymphocyte subsets.^[@R2],[@R3]^\n\nAs T cells and B cells contribute to MS pathogenesis, it is conceivable that some degree of therapeutic effect could be related to decreases in these cell counts. This investigation aimed"
-"Introduction {#S1}\n============\n\nPost-translational protein modification by tyrosine sulfation, first discovered in bovine fibrinogen^[@R1]^, is now known to have a widespread occurrence among proteins in multicellular eukaryotic organisms^[@R2],\\ [@R3]^. While the functional involvement of protein tyrosine sulfation remains to be fully elucidated, it has been implicated in the alteration of biological activity of proteins, proteolytic processing of bioactive peptides^[@R4]^, change in half-life of proteins in circulation^[@R5]^, and modulation of extracellular protein-protein interactions including inflammatory leukocyte adhesion^[@R6],\\ [@R7]^. The recent discovery of the tyrosine sulfation of chemokine receptors suggests an even broader role in inflammatory response^[@R8]-[@R9]^. In the case of the chemokine receptor CCR5, the sulfated tyrosine residues located in its N-terminal extracellular region have been shown to be crucial in mediating HIV binding/infection^[@R10]-[@R12]^.\n\nTPSTs catalyze the transfer of a sulfonate moiety from 3'-phosphoadenosine-5'-phosphosulfate (PAPS) to the hydroxyl group of protein-bound tyrosine residue to form a tyrosine *O*-sulfate ester and PAP ([Fig. 1a](#F1){ref-type=\"fig\"}). TPSTs are integral membrane glycoproteins located in the *trans*-Golgi network^[@R2]^. In humans, two TPST isoforms, designated TPST1 and TPST2, have been identified^[@R13]-[@R15]^. The two enzymes consist of 370 and 377 amino acid residues, respectively, sharing 64% amino acid sequence identity ([Fig. S1](#SD1){ref-type=\"supplementary-material\"}). They have been shown to display"
-"Introduction\n============\n\nHepatitis C virus is a member of the *Flaviviridae* family which has a positive-sense single-stranded RNA genome ([@B27]). The HCV genome encodes the viral structural and non-structural proteins, which are required for the HCV life cycle ([@B27]). In addition to HCV proteins, a number of host factors have been discovered on which HCV critically depends ([@B27]). Though most of these host factors are cellular proteins, a liver-specific micro-RNA (miR-122) has been identified which is mandatory for HCV replication and which is (at least partially) responsible for the hepatotropism of this virus ([@B27]).\n\nChronic infection with HCV is not only a major cause of liver cirrhosis and hepatocellular carcinoma, but also associated with metabolic traits including insulin resistance and dyslipidemia ([@B22]; [@B48]; [@B4]). While the effects of HCV infection on glucose metabolism are clearly documented *in vivo* and *in vitro*, the benefit of these alterations for the virus remains largely unclear ([@B41]; [@B38]), although insulin resistance was identified as a negative predictor of outcome of interferon-based therapies ([@B46]; [@B8]; [@B15]; [@B37]; [@B23]; [@B14]).\n\nGglycogen synthase kinase 3 is a serine/threonine protein kinase that exists in two isoforms, GSK3\u03b1 and GSK3\u03b2, which are encoded by two different genes. Approximately 100"
-"1. Introduction {#sec1-pathogens-09-00094}\n===============\n\nInfectious pancreatic necrosis (IPN) is a well-known disease originally named acute catarrhal enteritis by M'Gonigle in 1951 \\[[@B1-pathogens-09-00094]\\], but soon after Wood et al. \\[[@B2-pathogens-09-00094]\\] changed its name to IPN, based on a histopathological study of brook trout (*Salvelinus fontinalis*) suffering an infectious disease resembling a catarrhal enteritis. The virus causing the disease, the IPN virus (IPNV), was the first fish virus isolated in vitro \\[[@B3-pathogens-09-00094]\\] and belongs to the family *Birnaviridae* and the genus *Aquabirnavirus.* Although originally isolated from brown trout and considered a disease of great impact on cultured salmonids worldwide \\[[@B4-pathogens-09-00094]\\], it has also been isolated from non-salmonid diseased fishes, as well as from a wide range of fish species from natural environments \\[[@B5-pathogens-09-00094],[@B6-pathogens-09-00094],[@B7-pathogens-09-00094]\\]. In fact, the term IPNV is strictly used for those strains affecting salmonid fish which develop specific symptoms (see below). In those cases where the virus affects non-salmonids, with different symptoms, the term IPN is substituted by IPNV-like, and in general terms the name aquabirnaviruses is employed.\n\nThe disease mainly affects very young fry; salmonids are mostly susceptible immediately after yolk sac absorption and the first feeding. The clinical symptoms of the disease, described by many researchers since the"
-"1. Introduction {#sec1}\n===============\n\nNew observations regarding carcinogenesis and signal transduction pathways that regulate tumor growth, differentiation, angiogenesis, invasion, and metastasis have led to the identification of potential therapeutic targets and have accelerated molecular targeted drug development. In particular, the success of imatinib in chronic myeloid leukemia (CML) patients has strongly promoted the development of small-molecule tyrosine kinase inhibitors (TKIs). Since the United States Food and Drug Administration\\'s approval of rituximab (Rituxan; anti-CD20 antibody) and imatinib (Gleevec; Bcr-Abl TKI), several anticancer drugs have been approved each year in the US, European Union, and Japan \\[[@B1]\\].\n\nThe antitumor mechanisms triggered by molecular targeted drugs differ from those of conventional chemotherapeutic agents. Therefore, the estimation of target molecule expression in entire tumor is required to predict therapeutic efficacy. Target molecule and target gene expressions can be evaluated using immunohistochemical, polymerase chain reaction (PCR) and fluorescence in situ hybridization (FISH) analyses of biopsy samples. However, biopsy samples contain tissues from limited regions only, whereas tumor tissue is heterogeneous. Thus, it is possible that the expression observed in biopsy samples is not representative of that in entire tumor \\[[@B2], [@B3]\\]. This can lead to a misunderstanding with respect to tumor characterization. Moreover, expression levels"
-"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"
-"Introduction\n============\n\nMany investigations into the effect of ocean acidification (OA) on coral reefs have been conducted ([@B2]), and results indicate that that marine organisms which inhabit the carbonate structures of coral reefs are important and sensitive to OA ([@B40]). [@B1] and [@B47] found that changes to pH in the seawater surrounding natural coral reefs in the southern Great Barrier Reef can significantly affect calcification rates, suggesting that OA may already be altering the growth of coral reefs. By decreasing the ocean pH, OA can affect the calcifying rates of calcifying creatures such as coralline algae with carbonate skeletons ([@B29]; [@B1]). However, seagrasses can increase the pH of the ambient environment via high photosynthesis rates ([@B38]; [@B29]). Moreover, [@B39] found that seagrass in coral reef ecosystems can reduce disease levels twofold in comparison with the corals located adjacent to seagrass meadows and corals at paired sites without seagrass.\n\nSeagrass is highly productive and of great ecological importance in the marine environment. For instance, it can provide food, nursery and breeding habitats for other marine organisms inhabiting the ecosystem and nutrients for coral reefs. Nonetheless, available nitrogen is usually the main factor limiting the primary productivity of seagrass because coral reef"
-"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"
-"All relevant data are contained within the paper.\n\nIntroduction {#sec005}\n============\n\nInfection with specific types of high risk human papillomaviruses (HR-HPVs) is proved to be the principal etiologic agent for the development of cervical cancer which is the most predominant cancer in Indian women. Several well known risk factors such as early age of sexual intercourse, poor genital hygiene, multiple sexual partners, multiple pregnancies, high parity are associated with the development of cervical cancer \\[[@pone.0125693.ref001]--[@pone.0125693.ref003]\\]. More than 80% of Indian women with cervical cancer harbor HR-HPV types 16 and 18 \\[[@pone.0125693.ref004]--[@pone.0125693.ref007]\\]. Following establishment of causal link between HPV infection and cervical cancer, two vaccines Gardasil (MSD Merck & Co., Inc. Whitehouse station NJ, USA) and Cervarix (GlaxoSmithKline Biologicals, Belgium) have been developed against the two most common cancer causing genotypes HPV16 and HPV18 and are highly effective in preventing above HPV infection \\[[@pone.0125693.ref008]\\]. The vaccines are preferably given to adolescent girls or females aged between 9--26 years \\[[@pone.0125693.ref009]\\] before acquiring HPV infection.\n\nAdolescent girls are unique and vital group for investigating socio-demographic and sexual factors responsible for acquisition of HPV infection as their cervix is immature having larger area of ectopy and sexual exposure predisposes them to various reproductive tract"
-"1. Introduction {#sec1}\n===============\n\nAs the diet and life styles of the industrialized Western countries are adopted globally, the incidence of colorectal cancer (CRC) is increasing worldwide \\[[@B1]\\]. It becomes a second most common cancer and the third leading cause of cancer death in Taiwan. Fifty percent of patients diagnosed with CRC will eventually die from the disease, and less than 10% of patients with metastatic CRC survived more than 5 years \\[[@B2]\\]. Lots of studies have been carried on to search for effective therapeutics targeting on the molecular pathogenesis of CRC. Nowadays, several effective chemotherapeutics and molecular targeting agents, such as bevacizumab and cetuximab, which target VEGFR and EGFR, respectively, had been introduced into current colon cancer therapy. However, most of the advanced patients encountered inevitable relapse. Searching for new therapeutics targeting on other molecular pathway to improve the clinical outcome is urgently needed.\n\nThe Wnt/*\u03b2*-catenin signaling pathway plays an important role in both embryogenesis and tumorigenesis. Most sporadic colorectal cancer (CRC) and familial adenomatous polyposis (FAP) have mutated adenomatous polyposis coli (APC) gene. Normal APC protein could downregulate the Wnt signaling pathway through its binding to *\u03b2*-catenin and Axin, but most mutated APC proteins in colorectal tumors fail"
-"Introduction {#Sec1}\n============\n\nSevere acute respiratory syndrome (SARS) and avian influenza are two examples of recent emerging infectious diseases that may cause severe threats to population health, large economic losses, as well as fear and dread \\[[@CR1], [@CR2]\\]. The behavior of the general population or specific risk groups can play an important role in both the spread and control of infectious diseases. The SARS epidemic showed the impact of worldwide travel on the rapid spread of an epidemic, as well as the possible merits of strict hygiene and quarantine measures in halting that epidemic \\[[@CR3]\\]. In case of an infectious disease pandemic, public health authorities will be dependent on the willingness and ability of the general public to adhere to recommendations regarding personal hygiene, vaccination and/or prophylaxis, quarantine, travel restrictions, or closing down of public buildings such as schools \\[[@CR4], [@CR5]\\]. Compliance with recommended precautionary behaviors is not self-evident \\[[@CR6]\\]. Specific attention to factors influencing behavioral change during outbreaks of infectious diseases is, therefore, necessary.\n\nOne of the factors that may influence willingness and motivation to adopt precautionary behaviors is risk perception \\[[@CR7]--[@CR10]\\], i.e., the perceived personal vulnerability or likelihood of a disease or health threat. Perceived vulnerability, combined with"
-"Introduction\n============\n\nCOPD, a progressive respiratory condition, is among the leading causes of death in the West.[@b1-copd-12-529] COPD becomes more common with age[@b2-copd-12-529] and has been shown to have a substantial impact on health outcomes such as health status and health-related quality of life,[@b3-copd-12-529],[@b4-copd-12-529] health care resource use,[@b5-copd-12-529] and work productivity.[@b5-copd-12-529]--[@b7-copd-12-529] Indeed, the total cost of COPD in the US alone is nearly 50 billion dollars annually.[@b8-copd-12-529] Although forced expiratory volume in 1 second (FEV~1~) has been a standard marker for physiological change in COPD, research has suggested only a modest association between FEV~1~ and a patient's symptoms, which primarily include dyspnea, cough, and sputum production.[@b9-copd-12-529] As a result, understanding the symptom experience is an important part of proper COPD management as symptoms may relate more strongly to certain patient outcomes than standard clinical markers.[@b9-copd-12-529] Past research has suggested significant relationships between symptoms and health outcomes.[@b10-copd-12-529]--[@b13-copd-12-529] For example, an Internet survey conducted by Partridge et al[@b11-copd-12-529] found that dyspnea was among the most common symptoms and adversely affected patients' ability to perform their normal daily activities. However, these studies have generally focused on a broad COPD sample and may have included those not receiving proper treatment. As a result, the"
-"1. Introduction {#sec1}\n===============\n\nUpper gastrointestinal cancer is surgically treated by means of esophagectomy or gastrectomy. A feared complication of these complex procedures is the postoperative development of anastomotic leakage. The incidence of leakage of the esophagogastrostomy after esophagectomy has been reported to be in the range of 5--26% in tertiary referral centers \\[[@B1], [@B2]\\]. The leakage rates of the esophagojejunostomy after total gastrectomy vary between 4 and 15% \\[[@B3], [@B4]\\]. Leakage may result in spill of gastrointestinal contents, followed by the development of fistula, wound infection, abscess, mediastinitis, empyema, and sepsis. This results in an extended postoperative course in the majority of patients due to prolonged hospital stay, admission to the intensive care unit, and reinterventions \\[[@B5]\\]. It is hypothesized that additional sealing of the anastomosis with a fibrin patch (TachoSil) containing a human fibrinogen and thrombin may improve mechanical strength and might potentially prevent anastomotic leakage. Its application on esophageal anastomoses in rats was associated with increased mechanical strength \\[[@B7]\\]. However, whether its additional application on human esophageal anastomoses is possible has not yet been investigated. The aim of this study was to evaluate the technical feasibility of the application of a sealant patch in esophageal surgery.\n\n2."
-"Data contain potentially sensitive information. The Clinical Research Centre of the Hospital District of Southwest Finland has specified that legal and ethical restrictions prevent public sharing of deidentified individual participant data. Requests for data are handled by the directory board of the STEPS Study and can be sent to Hanna Lagstr\u00f6m (<hanlag@utu.fi>).\n\nIntroduction {#sec005}\n============\n\nRespiratory tract infections (RTIs) are the most common reason for medical care and antibiotic prescriptions in children \\[[@pone.0203650.ref001]\\]. Given the substantial disease burden to children, families, and society \\[[@pone.0203650.ref001]\\], new insights in how to reduce childhood RTIs are needed.\n\nIdentified risk factors for childhood RTIs include age, gender, number of siblings, day care attendance, exposure to smoking, genetic factors, socioeconomic status, and parents' long-term illnesses \\[[@pone.0203650.ref002],[@pone.0203650.ref003]\\]. Parental psychological factors, such as maternal stress during pregnancy, can also have an influence on the burden of infectious diseases in the offspring \\[[@pone.0203650.ref004]--[@pone.0203650.ref006]\\]. In the Norwegian Mother and Child Cohort Study, prenatal stressful life events, as well as relationship dissatisfaction, were associated with a higher frequency of infectious diseases in the infants \\[[@pone.0203650.ref007]\\]. To our knowledge, only one previous study has investigated the association between prenatal depression and the risk of childhood respiratory infections \\[[@pone.0203650.ref008]\\]. In this population-based"
-"This study was supported by funding from NSF CHE-0547940 to GER, and from NIH P30 CA022453 and NIH P30 ES020957 to P.M.S.\n\nIntroduction {#sec1}\n============\n\nCalcineurin (CN) is a Ca^2+^/calmodulin (CaM) activated serine/threonine phosphatase that is widely distributed in mammalian tissues.^[@ref1]^ CN functions in signal transduction pathways to regulate gene expression and participates in a wide variety of physiological processes including skeletal muscle differentiation and regeneration, cardiac hypertrophy, and neuronal signaling.^[@ref2]\u2212[@ref6]^ CN is a heterodimeric protein complex comprised of a \u223c60 kDa catalytic subunit, CNA, and a \u223c19 kDa regulatory subunit, CNB. As shown in Figure [1](#fig1){ref-type=\"fig\"}, there are four well-established domains in CNA: (i) a catalytic domain (14~A~-342~A~, where the number and subscript letter indicate the residue number and the corresponding subunit (i.e., CNA), respectively), (ii) a CNB binding domain (343~A~-373~A~), (iii) a CaM interaction region (390~A~-414~A~), and (iv) an autoinhibitory (AI) motif (469~A~-486~A~).^[@ref1],[@ref7]^ In addition, a section of the unstructured region within the CNA subunit that is important for stabilizing the interactions within CNA upon calmodulin binding has recently been identified.^[@ref8]\u2212[@ref10]^ The CN active site, which is located in the catalytic domain, contains a binuclear metal center that is critical for phosphatase activity. The two metals have been"
-"Sir,\n\nThe Burkitt's lymphoma-type chromosomal translocations such as t (8; 14), t (8; 22) or t (2; 8) are rarely seen in chronic lymphocytic leukemia (CLL) and their significance remains poorly understood. On reviewing the literature, t (8; 14) and t (8; 22) were reported in eight CLL cases each; and t (2; 8) has been reported in two CLL cases.\\[[@CIT1]\\]\n\nA 65-year-old male presented with leukocytes, in October 2003, at the time of the routine check-up for weakness and fatigability. Peripheral blood cell count showed WBC: 82.6 \u00d7 10^9^/l, Hb: 8.1 g/dl, platelets: 93 \u00d7 10^9^/l with mature lymphocytes, which accounted for 86% of the differential. The bone marrow aspirates (BMA) were hypercellular with 63% of morphologically mature lymphocytes. Immunophenotyping revealed that such cells were positive for monotypic Ig\u0138 light chain, CD5, CD19, CD20, CD23 and negative for CD10 and FMC7. Cytogenetic analysis performed on BMA showed normal karyotype. Physical examination revealed bilateral cervical lymphadenopathy and ultrasonogram of abdomen showed no hepatosplenomegaly. A diagnosis of CLL was made and according to modified Rai classification, his stage was IV (high risk). The patient was given chlorambucil orally and he obtained complete remission about 12 months later. He was on regular"
-"INTRODUCTION {#sec1-1}\n============\n\nVarious methods of surgical closure of muscular ventricular septal defects (mVSDs) have been described; however, the risk of ventricular dysfunction due to ventriculotomy and residual VSD is always present.\\[[@ref1][@ref2][@ref3]\\] Transcatheter closure of mVSD is a well-established procedure, but technically demanding, due to larger sheaths and a need for the formation of arteriovenous loop.\\[[@ref4][@ref5][@ref6]\\] Perventricular device closure has become an alternative option with minimal complications in infants with mVSD.\\[[@ref7]\\] We report our experience of the difficulty we faced during perventricular device closure, which necessitated modification of the technique.\n\nCASE REPORT {#sec1-2}\n===========\n\nAn eight-month-old infant (6.5 kilograms) presented with congestive heart failure. Transthoracic echocardiography (TTE) revealed a 10 mm apical mVSD \\[[Figure 1a](#F1){ref-type=\"fig\"}\\], two small additional mVSDs, and a 2 mm patent ductus arteriosus (PDA). The perventricular device closure of the mVSD was planned in view of the associated comorbid condition (gastroesophageal reflux disease with recurrent aspiration pneumonia). The procedure was performed in the Operating Room under TEE monitoring. After a mini sternotomy, the anterior free wall of the right ventricle (RV) was punctured using a 16G cannula. A 0.032\" angulated glide wire (Terumo Corporation, Japan) was negotiated into the left ventricle (LV) and exchanged for an 8Fr"
-"1. Background {#sec1}\n=============\n\nPatients with advanced heart failure commonly experience acute and/or chronic moderate to severe pain related to disease, treatment, or both \\[[@bib1], [@bib2], [@bib3]\\]. By definition, patients with American College of Cardiology/American Heart Association (ACC/AHA) Stage C or Stage D heart failure are significantly limited in function and quality of life due to disease progression \\[[@bib4]\\]. Compared to patients with cancer, patients with advanced heart failure may experience similar or more pronounced acute or chronic pain syndromes \\[[@bib5]\\]. While other common symptoms such as shortness of breath or fatigue may readily improve with heart failure disease management, pain usually does not, making pain management compelling to study in this heart failure population.\n\nPalliative care is a medical subspecialty that aims to relieve pain and suffering of such patients through pharmacologic and non-pharmacologic therapies. Those receiving inpatient palliative care consultation for pain management typically only receive drug therapies for analgesia. Many of these drug therapies, such as opioids, non-steroidal anti-inflammatory drugs (NSAIDs), or acetaminophen carry risk of significant side effects. Additionally, the current nationwide opioid epidemic highlights serious risks associated with prolonged opioid use in non-cancer populations. Many non-pharmacologic pain management strategies are not reimbursed by insurance, limiting"
-"Three-part question\n===================\n\nIn (adult patients with supraventricular tachycardia)\u00a0does (putting them in trendelenburg position) help (in cardioverting to sinus rhythm)?\n\nClinical scenario\n=================\n\nA 48-year-old male presents to the ED with a history of 45\u2009min of palpitations. He is otherwise well and his only medical history is of paroxysmal supraventricular tachycardia\u00a0(SVT). His ECG confirms SVT on this occasion. You are going to attempt the Valsalva manoeuvre and wonder whether the patient should stay sitting or whether the trendelenburg position would be better.\n\nSearch strategy\n===============\n\nDatabase: Ovid MEDLINE(R)\u00a0(1946\u2009to week\u00a02\u00a0November 2016)\n\n\\[exp Tachycardia, Supraventricular OR tachyarrhythmia.mp. OR svt.mp. OR . OR tachyarrhythmia\\$.mp. OR exp Tachycardia OR narrow complex tachycardia.mp. OR supraventricular arrhythmia.mp.\\] AND \\[exp Head-Down Tilt OR exp Supine Position OR modified valsalva.mp. OR trendelenburg.mp. OR trendelenburg tilt.mp.\\]\n\nSearch outcome\n==============\n\nFifty-four search results. Three were relevant and of high enough quality to include (see table 2).\n\nTable\u00a02\u00a0Relevant papers\n\n**Author, year, country of publicationPatient groupStudy type (level of evidence)OutcomesKey resultsStudy weaknesses**Appelboam\u00a0 *et al,*\\\n2015,[@R1]\\\nEngland428 patients presenting to the ED with SVT, randomised into two groups (214 patients each): a modified Valsalva (supine and legs raised) and a sitting valsalva groupPostural modification"
-"Introduction\n============\n\nLung cancer continues to be the leading cause of cancer related mortality worldwide, accounting for over one million deaths annually.[@b1-btt-4-237] The majority of patients present with metastatic disease, with a median survival of six months.[@b2-btt-4-237] Approximately 85% of lung cancers are classified as non-small cell lung cancer (NSCLC), which can be further subdivided in adenocarcinoma, squamous cell carcinoma and large cell carcinoma histology. Chemotherapy remains the cornerstone of treatment in advanced NSCLC; however, a plateau of effectiveness with such therapy has been reached. Molecularly targeted agents have further improved outcome over the last decade, and several additional targeted agents are being developed.\n\nTo date, three targeted agents have been approved by the US Food and Drug Administration (FDA) in advanced NSCLC. The first to receive FDA approval was gefitinib, a small molecule inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase, a transmembrane receptor whose activation leads to intracellular signaling involved in cancer cell proliferation and survival. Gefitinib was later restricted to use only in those who were previously benefiting, as a Phase III trial comparing gefitinib to best supportive care did not ultimately find a survival advantage.[@b3-btt-4-237] The second drug to be granted approval was erlotinib,"
-"1. Introduction {#sec1-sensors-17-00421}\n===============\n\nIn recent years, Wireless Sensor Networks have tended to be deployed in a wide area such as forests \\[[@B1-sensors-17-00421]\\], cities \\[[@B2-sensors-17-00421]\\], and underwater \\[[@B3-sensors-17-00421]\\]. With the development of unmanned vehicles, sensors now can be mounted on them to extend their exploring scope. Normally, these vehicles are far from each other and require data collectors to hand in their data. For example, Autonomous Underwater Vehicles (AUVs) have been deployed in the deep sea \\[[@B4-sensors-17-00421],[@B5-sensors-17-00421]\\] to do data collection and event detection. They will appear frequently for data reporting to avoid underwater acoustic transmission, which suffers from very significant signal attenuation \\[[@B6-sensors-17-00421]\\]. When they are underwater, their exploration work is often with a fixed schedule since the trajectory and working spots are predetermined. After these AUVs surface, a moving mobile sink will come to collect the data via wireless communications. UGVs are also favorable for sensor network applications \\[[@B7-sensors-17-00421]\\]. The mobile sink cruises in the area and visits each unmanned vehicle in a timely manner and uploads collected data via a satellite communication. In these scenarios, a unique problem is how to maximize the data collected via the trajectory planning of the mobile sink.\n\nTo deploy a stationary"
-"1.. Introduction {#S0001}\n================\n\nPorous ceramics are used in a variety of applications where high permeability is required, such as filtration of gases and liquids or catalytic supports.\\[[@CIT0001]\\] The main processing methods are extrusion, ceramic replication of an organic template, and direct foaming of a ceramic suspension. The final properties of porous ceramics are dependent on the processing technique and the resultant microstructure.\n\nIn general, ceramics processed by the replica method exhibit accurate porosity control and the pore size is relatively large (200--3000 $\\mathit{\\mu}$m), although the hollow struts characteristic of the replica method have a deleterious effect on strength.\\[[@CIT0002]\\] In contrast, materials obtained by direct foaming have higher mechanical properties compared to the replica method but larger pore size distribution and consequently a lower permeability.\\[[@CIT0003]\\] The microstructural effects on permeability of porous ceramics have been extensively studied in different cellular structures. Innocentini et al. \\[[@CIT0003]\\] compared the effect of pore volume (50--90%) and size (100--900 $\\mathit{\\mu}$m) in materials processed by replica and gel casting. Biasetto et al. \\[[@CIT0004]\\] conducted a similar study on porous ceramics obtained by organic burn out in a porosity range of 80--90% and pore size 10--150 $\\mathit{\\mu}$m. In both cases, permeability is increased by increasing porosity"
-"INTRODUCTION {#s1}\n============\n\nThe Ras superfamily control many cellular functions including cell growth, differentiation, motility and survival \\[[@R1]-[@R6]\\] and play a major role in cell transformation. They alternate between a GDP-bound (inactive) and a GTP-bound (active) state through the action of guanine nucleotide exchange factors (RasGEFs) and GTPase activating proteins (RasGAPS). Active Ras was found to interact specifically with two members of the galectins family; galectin-1 and galectin-3. \\[[@R7]-[@R9]\\].\n\nGalectins are a phylogenetically conserved family of lectins that share consensus amino-acid sequences and the carbohydrate recognition domain responsible for \u03b2-galactoside binding \\[[@R10]\\]. They are located within the cells (cytoplasm and nucleus) and are also secreted into the extracellular space. Although originally considered only as extracellular structural elements, a large body of evidence testifying to their role in intracellular signaling has accumulated over the last decade. Galectins have been implicated in several cellular processes, including apoptosis, cell survival, cell adhesion, immune response, and gene expression (reviewed in \\[[@R11]\\] and \\[[@R12]\\]).\n\nOverexpression of galectin-1, a prototype member of this family, has been documented in many different tumor types \\[[@R13]-[@R15]\\], and in various aspects of tumor biology including migration and invasiveness, chemoresistance \\[[@R16]\\], angiogenesis \\[[@R17]\\], immune escape \\[[@R18]\\] and malignant progression \\[[@R19]-[@R21]\\]. Galectin-1"
-"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"
-"Introduction\n============\n\nComparative genomics adopts the assumption that important biological processes are often conserved across related species. Based on that, scientists use animal models to infer human physiological and genetic properties.[@b1-ebo-2009-081]--[@b3-ebo-2009-081] Sequence comparison is the most popular tool for comparative genomics. However, sequence similarity is not necessarily proportional to functional similarity.[@b4-ebo-2009-081] The biological functions of a gene not only rely on its molecular functions but also its spatiotemporal expression pattern. Changes in gene expression often mean changes in function.[@b5-ebo-2009-081] One example is that, for duplicate genes, which are usually associated with highly consistent coding sequences but diverse biological functions, there is only a weak correlation between rates of sequence divergences and rates of expression divergences.[@b6-ebo-2009-081] It is urgent to make the details of gene expression evolution clear for the aim of making proper functional inferences across species.\n\nMicroarrays, which can characterize the transcriptional profiles of tens of thousands of genes simultaneously, have been widely used in biomedical[@b7-ebo-2009-081]--[@b9-ebo-2009-081] and comparative genomic[@b10-ebo-2009-081]--[@b12-ebo-2009-081] studies. In the latter applications, studies of gene expression levels in different species often rely on cross-species hybridization.[@b13-ebo-2009-081]--[@b16-ebo-2009-081] This method is limited to closely related species as it is based on the hybridization of target RNA and gene probes designed"
-"###### 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 {#s1}\n============\n\nWhile the negative effects of heat exposure on physical performance are well known (Drust et al., [@B9]; Morris et al., [@B26]), data regarding the effects of heat exposure on cognitive performance are less well understood. It is important to understand the effects of heat exposure across a range of domains of cognition, given that the components of cognition will interact to affect overall performance in sport, however also in professions such as firefighting and the military (Allard and Burnett, [@B1]; Hemmatjo et al., [@B17]). Gaoua et al. ([@B12]) has recently provided valuable insight into the mechanisms associated with changes in cognition in response to passive heat exposure, however an understanding across a broad range of cognitive domains is still lacking.\n\nThe impact of heat exposure on cognitive function remains equivocal, largely due to a number of methodological discrepancies across the research, such as the cognitive domain tested. Heat exposure has been reported to have a positive effect on attention (Simmons et al., [@B33]; Lee et al., [@B20]; Watkins et al., [@B39]; Schlader et al., [@B32]) and working memory (Bandelow et al., [@B2]; Lee et al., [@B20]), but a negative effect on working memory capacity (Racinais et al.,"
-"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"
-"1. Background\n=============\n\nThe currently favoured explanation for the origin of Mendel\\'s dominant and recessive traits is untenable \\[[@B1]\\]. The primary error in this current attempted explanation is the assumption that there is a direct, proportional, relationship in a diploid cell between a series of allegedly dominant and recessive alleles written as (*AA*+ 2*Aa*+ *aa*) and the dominant, hybrid and recessive traits written as (*AA*+ 2*Aa*+ *aa*). This assumption (Figure [2](#F2){ref-type=\"fig\"}, in reference \\[[@B1]\\]) incorporates four fundamental faults:\n\n![Accounting for Mendel\\'s observation of a 3(dominant):1(recessive) trait ratio in his F2 populations of plants. Mendel\\'s notations for a dominant trait, a hybrid and a recessive trait were (*A*), (*Aa*) and (*a*) respectively. For reasons given in the preceding paper \\[1\\], a hybrid trait is represented in Figure 2 by (*H*). The molecular components of all traits are synthesised by a metabolic pathway. When the activity of any one enzyme in a metabolic pathway is changed in discrete steps, the flux to a trait component responds in non-linear (non-additive) fashion \\[3\\]. If the flux response is quasi-hyperbolic, as shown here, the hybrid trait (*H*) will be indistinguishable from the trait (*A*) expressed in the wild-type cell or organism, even when the enzyme"
-"1. Introduction {#s0005}\n===============\n\nThe urinary bladder has an important role storing urine formed by the kidney and preventing systemic reabsorption of urine components from the bladder cavity until urination ([@b0045]). Different diseases such as interstitial cystitis ([@b0010]), overactive bladder syndrome ([@b0015]), urinary tract infection ([@b0105]), and bladder cancer ([@b0035]) affect the bladder's normal function. Patients with these diseases have symptoms that affect the bladder and cause discomfort such as urinary storage problems and pain. Treatment of urinary bladder diseases with systemic drug administration suffers from several limitations such as poor bioavailability and first pass metabolism leading to a low drug concentration in bladder tissue and the subsequent need for high drug doses which may increase side effects ([@b0095]).\n\nIntravesical drug delivery systems (IDDS) can be delivered via urethral catheter as an alternative route of drug administration. Intravesical administration of drugs leads to high drug concentrations in bladder tissue which increases the efficacy of treatment ([@b0025]). However, the drug will be washed out within 2\u202fh after intravesical administration by urination ([@b0055]). Repeated administration of the drug via frequent catheterization increases risk of infection and causes patient discomfort. Therefore, developing an IDDS that can be retained in the bladder cavity"
-"List\u2009of\u2009editors {#Sec58587}\n===============\n\nEdited by Mizaton Hazizul Hasan, Kalavathy Ramasamy, Lim Siong Meng, Aisyah Hasyila Jahidin, Gurmeet Kaur Surindar Singh, Kamran Ashraf, Nor Hayati Abu Samah, Neoh Chin Fen and Fazlin Mohd Fauzi\n\nSponsorship {#Sec1581}\n===========\n\nPublication charges for this supplement were funded by the conference.\n\nNumbering\u2009format {#Sec1587}\n================\n\nI - Introduction\n\nKN -- Keynote Lecture\n\nPL -- Plenary Lecture\n\nIL -- Invited Lecture\n\nOPT -- Oral Presenter Pharmaceutics\n\nOPP -- Oral Presenter Pharmacology\n\nOPL-- Oral Presenter Life Sciences\n\nOPC -- Oral Presenter Chemistry\n\nPPT -- Poster Presenter Pharmaceutics\n\nPPP -- Poster Presenter Pharmacology\n\nPPL-- Poster Presenter Life Sciences\n\nPPC -- Poster Presenter Chemistry\n\nPPR -- Poster Presenter Pharmacy Practice\n\nINTRODUCTION {#Sec1}\n============\n\nAsian Conference on Pharmaceutical Sciences (Asia Pharm) is an international conference dedicated to promoting advances in pharmaceutical sciences. Asia Pharm was first held in Vietnam, from July 10-12 2016, with the theme of \"*Advances in Pharmaceutical and Biosciences*\". Asia Pharm I was co-organised by Ton Duc Thang University, Vietnam and Seoul National University, South Korea. Following the success of Asia Pharm I, Asia Pharm II was hosted from July 20-22 2017 at Seoul National University with the theme of *\"Education and Science in Pharmacy*\"."
-"Introduction\n============\n\nInfectious diseases are ailments caused by pathogenic viruses and microorganisms such as bacteria and fungi. Infections can spread directly from person to person and from animal to human, or indirectly via contaminated water and food. This can result in small local outbreaks and epidemics, like the plague, syphilis and SARS, or pandemics affecting several countries, of which the flu is one of the best-known examples. In times of globalization and climate change, infectious diseases are spreading more rapidly than ever before, and new ones continue to emerge. Even though they are a global health burden, inhabitants of developing countries especially suffer from infections. Accordingly in 2010, worldwide, roughly one quarter of deaths was due to infectious diseases, while in low-income countries, nearly 60% of fatalities could be attributed to them ([@B37]). This is primarily because in these regions often hygienic measures are insufficient, diagnostic tools are lacking and therapeutic options are not available.\n\nExisting medications are categorized into antivirals used to combat viral diseases, antibiotics contradicting bacterial infections and antifungals inhibiting the growth of fungi. In addition, multiple vaccines preventing viral and bacterial diseases exist, which has already led to the successful eradication of smallpox. However, countermeasures are"
-"J Diabetes Investig 2019; 10: 1012--1021\n\n**Clinical Trial Registry**\n\n*UMIN Clinical Trials Registry* UMIN000018839\n\nIntroduction {#jdi12985-sec-0005}\n============\n\nBodyweight (BW) gain is a major disadvantage of insulin treatment. Previous reports have suggested that achieving sufficient glycemic control with insulin in inadequately controlled type 2 diabetes patients results in BW gain[1](#jdi12985-bib-0001){ref-type=\"ref\"}, [2](#jdi12985-bib-0002){ref-type=\"ref\"}.\n\nSodium--glucose cotransporter 2 (SGLT2) inhibitors improve glycemic control and induce BW reduction by creating a negative energy balance through urinary glucose excretion. Previous studies have reported BW reduction of approximately 3 kg at 24 weeks after initiation of SGLT2 inhibitors[3](#jdi12985-bib-0003){ref-type=\"ref\"}. This BW reduction is thought to result from fluid loss and dehydration in the initial phase, and from fat and muscle mass reduction in the late phase of treatment[4](#jdi12985-bib-0004){ref-type=\"ref\"}. Fat mass reduction is a favorable feature of SGLT2 inhibitors. However, reduction in skeletal muscle mass might have negative effects, especially in elderly or lean patients with type 2 diabetes.\n\nSarcopenia is a serious condition that affects quality of life and mortality among elderly people[5](#jdi12985-bib-0005){ref-type=\"ref\"}, [6](#jdi12985-bib-0006){ref-type=\"ref\"}. Diabetes is a risk factor for sarcopenia, probably because of the negative energy balance caused by glucosuria or insulin resistance[7](#jdi12985-bib-0007){ref-type=\"ref\"}. Bone mineral density is another concern related to SGLT2 inhibitors. Previous studies have shown a"
-"Severe exacerbations of asthma are responsible for a large burden of illness in Australia and throughout the world. Viral infection is the main cause of asthma exacerbation requiring hospitalization,[@bib1]with respiratory viruses being isolated from 81% of patients with asthma exacerbations requiring hospitalization in adults and children.[@bib2]The mechanisms driving viral asthma exacerbations are clearly different from the well-characterized pathogenesis of allergen-induced asthma, which is driven by an interleukin (IL)-5-mediated eosinophil infiltrate.[@bib3], [@bib4], [@bib5]Viral asthma exacerbations involve a marked neutrophil infiltration together with eosinophil degranulation.[@bib2], [@bib6], [@bib7], [@bib8], [@bib9], [@bib10]The chemokine RANTES (or regulated on activation, normal T cell expressed and secreted), which promotes eosinophil degranulation, and the cytokine IL-10, which suppresses eosinophil cellular infiltration, may be important in this inflammatory response, as the gene expression of these mediators is up-regulated in patients with virus-induced asthma.[@bib11]\n\nDespite optimal medical therapy, incomplete recovery of airway function occurs in a relatively high proportion of people after an acute asthma exacerbation. Corne et al[@bib12]observed that in people with asthma who were infected with human rhinovirus (RV), lower respiratory tract symptoms were experienced more often, were more severe, and were of longer duration than in nonasthmatic people. Persistent lower respiratory symptoms in people with asthma extended"
-"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"
-"We described rescue behavior in *Megaponera analis* focused on ants that got injured while raiding termite prey.[@cit0001] These ants had termites clinging to them or had lost extremities during the fight ([Fig.\u00a01](#f0001){ref-type=\"fig\"}). After the hunt the injured \"called for help\" with a pheromone consisting of the compounds dimethyldisulfide (DMDS) and dimethyltrisulfide (DMTS), stored in their mandibular glands. They were then picked up by their nestmates and able to recover within the nest, thereby reducing their mortality risk. After some hours the injured became functioning members of the colony again. This behavior allowed a predatory species to reduce their foraging costs when hunting prey capable of inflicting injuries. Figure 1.*Megaponera analis* minor with 2 clinging termite soldiers. Notice the loss of the tarsus on the mid leg.\n\nAntecedents of behavior {#s0001-0001}\n=======================\n\nThere are certain antecedents to this behavior in ants. In the closely related species *Paltothyreus tarsatus*, ants that were covered in soil (because of a cave in) send a distress call using the same substances (DMDS and DMTS) from their mandibular glands, thereby triggering attraction and digging behavior in their nestmates.[@cit0002] For this response to change toward attraction and picking up an injured ant should not require many"
-"1. Introduction {#s0005}\n===============\n\nChemo-mechanical cleaning and shaping of the root canal system and three-dimensional obturation are mandatory to fulfill the main aim of root canal treatment (RCT) that is preventing and/or treating apical periodontitis ([@b0100], [@b0105]). Presence of anatomical difficulties will affect the process of chemo-mechanical cleaning and shaping which ends up in a potential reduction in the success rate of RCT ([@b0085]). Therefore, clinicians should be thoroughly aware of the common root canal morphology and their possible variations in order to improve the predictability of RCT. In this context, the past few decades witnessed development of many techniques that implemented to evaluate anatomy of the teeth and their root canal systems including injection of plastic resin, conventional radiograph, histological examination, clearing and dye injection, conventional and micro-computed tomography ([@b0030], [@b0045]). Certainly, these methodological approaches provided very useful information to the practitioners. However, essential limitations of these techniques inspired us to search for newer methods that help in depicting the anatomy more accurately. Recently, cone beam computed tomography (CBCT) has been widely used with a wide range of applications in dental practice. Briefly, CBCT enables the clinicians to observe the three dimensions of the relevant area. The use of"
-"1. Introduction {#sec1-sensors-20-02014}\n===============\n\nElectrochemical immunosensors are a type of integrated devices that provide selective quantitative or semi-quantitative analytical information using biorecognition phenomenon between an antibody (Ab) and antigen (Ag) with an electrochemical transducer \\[[@B1-sensors-20-02014]\\]. Due to the stable, strong and specific binding between these biomolecules, electrochemical immunosensors are characterized by high selectivity and sensitivity \\[[@B2-sensors-20-02014]\\]. These analytical devices have found application in different fields, including food, environmental, agricultural analysis, clinical diagnosis and others \\[[@B3-sensors-20-02014],[@B4-sensors-20-02014],[@B5-sensors-20-02014]\\].\n\nThe interactions between Ab and Ag can be observed using different labels, such as radioactive, chemiluminescent and fluorophore compounds. Enzymes are another group of labels, including horseradish peroxidase (HRP), alkaline phosphatase (ALP), laccase and glucose oxidase (GOx), which need some substrates added to the testing solution, such as hydroquinone, catechol, o-aminophenol, naphthyl phosphate, p-aminophenol phosphate, ferrocene and glucose \\[[@B3-sensors-20-02014]\\].\n\nIn the past few years, the enzyme-linked immunosorbent assay (ELISA) used for specific detection of different analytes has become very popular and commonly used in laboratory practice. This method, depending on the format of the assay (i.e., direct, sandwich or competitive) could be equally useful for the detection of both antigens and antibodies. It uses the secondary antibodies conjugated with a specific enzyme. After addition of"
-"Key Messages\n============\n\nSystemic inflammation is hypothesized as a major underlying biological mechanism linking particulate matter (PM) air pollution and cardiovascular disease, but current evidence is limited and inconsistent.We observed positive association between long-term PM exposure and C-reactive protein (a sensitive marker of systemic inflammation and a valuable predictor of cardiovascular events) in an Asian population experiencing high-level PM air pollution.The PM~2.5~ concentrations remained stable over the study period. For those participants with repeated CRP measurements, no significant changes were observed between the first and last measurements.Our findings substantially advance understanding of the mechanism linking air pollution and cardiovascular disease, supporting the global efforts towards air pollution reduction in prevention of cardiovascular disease.\n\nIntroduction\n============\n\nCardiovascular disease is one of the leading causes of death worldwide, contributing to an estimated 17.5 million deaths in 2012.[@dyx069-B1] In addition to traditional risk factors such as obesity, tobacco smoking and physical inactivity, there has been growing evidence supporting a causal link between exposure to particulate matter (PM), especially fine PM (PM with an aerodynamic diameter less than 2.5\u2009\u03bcm, PM~2.5~), and cardiovascular morbidity and mortality.[@dyx069-B2] Systemic inflammation, which plays an important role in the development of atherosclerosis, has been hypothesized as the potential"
-"This retrospective study was based on pretreatment records and cbct images of the patients who received treatment between 2012 and february 2018 in delhi ncr region. Forty two male and 58 female patients between the ages of 19 and 72 years (mean, 45.5 years) were selected according to the following criteria: atleast 18 years of age at the time of the cbct scan; all maxillary anterior teeth (canine to canine) were present, with at least two occluding posterior teeth (premolar and/or molar) in each quadrant; no radiographic evidence of infection, with no internal resorption.. The cbct images were evaluated and the relationship of the sagittal root position of the maxillary anterior teeth to its associated osseous housing was recorded as class i, ii, iii, or iv. The overall percentage of sagittal root position observed in ncr indian population was compared with overall percentage kan's srp classification... An understanding of the clinical relevance of sagittal root position will provide adjunct data for the treatment planning of immediate implant placement and provisionalization in the anterior maxilla."
-"Published: May 27, 2010\n\nIntroduction {#sec1}\n============\n\nViruses rely on their host for viability and replication. During infection, the virus and host become engaged in a dynamic duet, lasting from several hours to potentially years (in persistent infections), in which the virus initiates spatio-temporally ordered sequences of subcellular events, along the way dramatically altering cellular architecture and physiology. The host cell not only provides building blocks such as nucleotides and amino acids for viral metabolism but also can provide a structural platform for replication and viral assembly ([@bib48]). Many RNA viruses and even some DNA viruses such as the poxviruses rely on host intracellular membranes for replication ([@bib35], [@bib41]). In particular plus-strand RNA virus families, so called because upon infection their RNA can be directly translated into protein by host machinery, replicate and assemble on modified intracellular membranes ([@bib35], [@bib41]). The group of plus-strand RNA viruses includes many important human pathogens like picornaviruses (such as the enteroviral genus members poliovirus \\[PV\\] and Coxsackievirus B3 \\[CVB3\\], rhinovirus, and hepatitis A), coronaviruses (SARS), and flaviviruses (hepatitis C virus \\[HCV\\], Yellow Fever virus, Dengue Fever virus, West Nile virus).\n\nCells infected with plus-strand RNA viruses undergo\u00a0a dramatic remodeling of their intracellular membranes,"
-"INTRODUCTION\n============\n\nHuman papillomavirus (HPV) is the most common sexually transmitted virus in the human population. Although the vast majority of these HPV infections are cleared by the immune system within a year after infection, HPVs may in rare cases persist and cause cancer ([@gkt803-B1]). HPV is present in 99.7% of all cervical cancers and is tightly associated with several other anogenital cancers and head and neck cancers ([@gkt803-B2]). Nearly half of the human cancers, which are caused by viruses are attributable to HPVs, and cervical cancer is one of the main causes of death in women in the developing world ([@gkt803-B3]). A subset of the sexually transmitted HPV types has been associated with cancer and is termed high-risk HPV types. HPV type 16 is the most common high-risk type in HPV-induced cancers as well as in the human population ([@gkt803-B4],[@gkt803-B5]).\n\nThe HPV-16 DNA genome is small, but it contains at least six early genes and two late genes under control of at least two promoters ([@gkt803-B6]). The early promoter p97 is located upstream of the E6 gene, and the late differentiation-dependent promoter named p670 is located upstream of the E1 AUG ([@gkt803-B7],[@gkt803-B8]). The early region encoding E1, E2, E4,"
-"Introduction\n============\n\nPhosphoramidate and phosphonamidate moieties are common motifs in medicinal chemistry. Nucleoside phosphoramidates are developed as antiviral prodrugs with great success.[@cit1] In protease inhibitors they serve as peptidomimetics replacing the carbonyl carbon in the amide bond.[@cit2] They can be seen as transition-state analogues of the enzyme reaction and coordinate to the active site metal ion in metalloproteases.[@cit3] In natural products, however, N--P bonds are comparably rare and little is known about their biosynthesis.[@cit4] Phosphoramidon ([Fig. 1](#fig1){ref-type=\"fig\"}; **1**) and its stereoisomer talopeptin (**2**) have been isolated from *Streptomyces* culture broths and are potent inhibitors of metalloendopeptidases including thermolysin, *Pseudomonas* elastase LasB, neutral endopeptidase and endothelin-converting enzyme.[@cit5]--[@cit7] Phosphoramidon was extensively investigated in animal models and pilot clinical studies for its effects on various diseases.[@cit8]--[@cit10] Today, this compound is still a widely used pharmacological tool in cell biological research. The inhibitory activity of **1** and **2** has been attributed to the metal-chelating properties of a phosphoramidate moiety which uniquely links a deoxysugar to the N-terminus of a [l]{.smallcaps}-Leu--[l]{.smallcaps}-Trp dipeptide backbone.[@cit11] The deoxysugar consists of [l]{.smallcaps}-rhamnose in the case of **1** and 6-deoxy-[l]{.smallcaps}-talose in the case of **2**. The two molecules belong to a small group of structurally diverse natural products with N--P"
-"1. Introduction {#sec1}\n===============\n\nThe five lemur families are amongst the world\\'s most imperiled groups of vertebrates with at least 94% of 101 species identified as threatened by the International Union for the Conservation of Nature ([@bib25]). Endemic to the biodiversity hotspot of Madagascar, lemur diversity is particularly remarkable considering that Madagascar represents only a small fraction of tropical landmass ([@bib15]). Threats to lemurs primarily include habitat loss and bushmeat hunting ([@bib1]; [@bib3]; [@bib2]) which result from non-sustainable land use and resource extraction driven by poverty and a legacy of political instability ([@bib29]). Today the forests of Madagascar cover 92,200\u202fkm^2^ (approximately the size of Portugal), approximately 10% of the original forested area. Between 2000 and 2010 the country lost 9,700\u202fkm^2^ of forest, which is almost three times the area of loss in the previous decade ([@bib26]; [@bib6]; [@bib13]).\n\nIntroduced predators also have the potential to devastate lemur populations, but this has not received sufficient research attention ([@bib6]). Globally, free-ranging domestic dogs affect wildlife through predation, competition, hybridization, and disease transmission ([@bib30]; [@bib14]; [@bib28]; [@bib17]; [@bib23]; [@bib12]). To date, little attention has been paid to the threat of dogs as disease vectors. In Madagascar, free-roaming dog populations have been"
-"1. Introduction {#sec1}\n===============\n\nTotal knee replacement surgery for osteoarthritis has been shown to be successful in relieving pain and improve function and quality of life for the majority of patients. However, continued efforts are directed to further optimise the functional outcome of total knee surgery by attempting to improve implant design \\[[@B1], [@B2]\\] and more recently the type of surgical approach used. The term \"minimally invasive surgery\" covers a variety of approaches including midvastus and mini-parapatellar approaches with or without computer navigation. Several authors have compared the effects on outcome of the midvastus (MV) approach compared to the more traditional medial parapatellar (MP) approach and their results have been summarised by reviews \\[[@B3]--[@B5]\\] concluding some early benefits on mobility milestone and muscle strength. However, only few studies \\[[@B6]--[@B9]\\] included in the above reviews and more recent studies \\[[@B10], [@B11]\\] were prospective randomised controlled trials and only few reported a double blind design. A recent study comparing the midvastus approach with the medial parapatellar approach in bilateral TKA, by Nestor et al. \\[[@B10]\\], was the only one to standardise incision length allowing both the patient and the assessor to be blind to group allocation.\n\nJarvis et al. \\[[@B12]\\] compared the"
-"Introduction {#s1}\n============\n\nAntibiotics are chemotherapeutic agents used for the clinical management of infectious diseases in humans, plants and animals. However a sizeable fraction of antibiotics produced every year all over the world is used for non-therapeutic purposes. In US alone, about 24.6 million pounds of antibiotics are used in animal agriculture annually and a substantial portion of this is used as growth promoters and not for the treatment of infections (Oliver et al., [@B21]). According to a recent report, out of 13 million kg of antibiotics administered to animals in 2010, the major portion was meant for promoting the growth of the livestock (Spellberg et al., [@B24]). The ability of low doses antibiotics to promote growth of animals and birds was discovered serendipitously in the 1940s (Gustafson and Bowen, [@B14]). Subsequently, it was widely exploited and by this time, addition of antibiotics to the animal feed to stimulate growth has turned into a global practice.\n\nThe basis of growth-promoting effect of antibiotics is not clearly known. It is postulated that microorganisms present in the animal feed consume a considerable portion of nutrients in the feed. They also inhibit absorption from the intestine and produce toxins having adverse effect on"
-"1. Introduction {#sec1-sensors-17-01607}\n===============\n\nAutonomous Underwater Vehicles (AUVs) and underwater gliders have found important applications in ocean exploration, oil and gas production, environmental monitoring, underwater infrastructure monitoring, weather services, and coastal surveillance \\[[@B1-sensors-17-01607],[@B2-sensors-17-01607],[@B3-sensors-17-01607]\\]. Typically, these vehicles are programmed to visit a number of predetermined targets, perform some tasks at the target locations, and then return home. With the increased demand and commercial success of the AUVs and gliders, it is of increasing interests to employ a fleet of vehicles simultaneously and cooperatively to perform a mission. Therefore, multi-vehicle task assignment and path planning become an important research topic in recent years.\n\nDue to the size, weight, and fuel constraints, these vehicles have strong limitations in underwater missions, such as limited mission length, stringent nonholonomic motion constraints, and limited communication with each other or with the home base. A nonholonomic motion constraint requires that the vehicle motion is along a smooth curvature without reversing direction. This often requires that the vehicle paths satisfy geometric continuity to support their kinematic constraints \\[[@B4-sensors-17-01607],[@B5-sensors-17-01607]\\]. For point-to-point path planning, Dubins curves have been widely utilized to achieve $G^{1}$ continuity and shortest path length \\[[@B6-sensors-17-01607],[@B7-sensors-17-01607]\\]. Recent literatures on Dubins vehicles also consider environmental conditions such as"
-"INTRODUCTION\n============\n\nSnoring is the sound of turbulence and vibration of the upper respiratory tissues which is caused by complete or partial obstruction of the upper respiratory tract. Snoring during sleep can be a sign or an alarm of obstructive sleep apnea (OSA), which is defined as episodes of repetitive hypopnea or apnea with desaturation and awakening while sleeping. OSA is known to be associated with increased risks of major systemic illness such as cardiovascular disease \\[[@b1-kjim-2017-110],[@b2-kjim-2017-110]\\], stroke \\[[@b2-kjim-2017-110]\\], diabetes \\[[@b3-kjim-2017-110]-[@b5-kjim-2017-110]\\], high blood pressure \\[[@b5-kjim-2017-110],[@b6-kjim-2017-110]\\], and postoperative cardiovascular or respiratory complications as well as daytime somnolence, and decreased concentration and quality of life \\[[@b7-kjim-2017-110]\\]. Although snoring causes significant systemic illness, patients with habitual snoring are sometimes unaware of breathing difficulties even while having repetitive episodes of oxygen desaturation when awake. In the Unites States, a population-based study conducted by The National Sleep Foundation found that 59% of participants reported snoring. Of the 895 respondents, 54% reported snoring more than three nights per week and 11% reported having respiratory pause more than three nights per week. Of the 1,506 respondents, 26% (31% of men and 21% of women) were at high risk for OSA \\[[@b8-kjim-2017-110]\\]. Another population-based study from India found"
-"**Cite this article as:** Momeni H, Tabatabaei Fard SF, Arefinejad A, et al. Composition, production rate and management of dental solid waste in 2017 in Birjand, Iran. *Int J Occup Environ Med* 2018;9:52-60. doi: 10.15171/ijoem.2018.1203\n\nTAKE-HOME MESSAGE {#home1}\n=================\n\n-   About one-third of the dental waste is infected.\n\n-   A significant portion of dental waste is consisted of recyclable materials such as nylon, paper, and cardboard.\n\n-   Most of the non-used amalgam materials are finally disposed to sewage or trash bin.\n\n-   Most of the tiny and coarse particles of amalgam separated from patients\\' teeth are disposed to sewage and trash bin, respectively.\n\n-   Almost in half of the clinics, radiographic film packets and fixing solutions are directly disposed in trash bin and sewage, respectively.\n\n-   Dental tools are sterilized using autoclave, oven, or disinfectant solutions, or a combination of them, while autoclave was the most common one.\n\nIntroduction {#s1}\n============\n\nWaste management is one of the major issues and management challenges in Iran. Each year, a significant portion of the municipals budget is allocated to this issue. Special waste products including medical waste are of particular importance. Medical waste disposal management requires the correctness of the statistics and accurate"
-"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"
-"1. Introduction {#sec1}\n===============\n\nBreast cancer is the most abundant malignant tumor in women worldwide \\[[@B1]\\]. Early detection methods and the establishment of improved treatment strategies reduced breast cancer mortality \\[[@B2]\\]. According to the German S3-guideline for early detection, diagnosis, therapy, and follow-up of breast cancer, adjuvant chemotherapy (CTX) is indicated for HER2-positive tumors, non-endocrine (or unclear) sensitive tumors, lymph node-positive disease, grade 3 tumors, luminal B tumors, and for patients aged \\<\u200935 years \\[[@B3]\\]. Decisions about adjuvant CTX in women with early stage breast cancer are often challenging \\[[@B4]\\]. Uncertainty about benefits versus evolving side-effects complicates decision-making. The factors that influence the treatment decisions are complex and involve issues regarding access to health care, concerns for cancer recurrence, and the impact of cancer therapies on health-related quality of life (HRQL). HRQL has gained growing importance in clinical oncology \\[[@B5], [@B6]\\]. Numerous questionnaires have been developed, to objectify and standardize HRQL analysis \\[[@B7]\\]; among them the mainly utilized is the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) \\[[@B8]\\] and the Functional Assessment of Cancer Therapy (FACT) scale \\[[@B9]\\]. Beyond those captured dimensions of HRQL, other relevant aspects such as the"
-"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\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"
-"Introduction {#S1}\n============\n\nTriterpenoids and triterpenoid glycosides constitute a major class of plant secondary metabolites, which are thought to be involved in defense against pathogens and pests ([@B17]). Compounds such as ginsenosides and glycyrrhizic acid have also been shown to possess health benefits in humans ([@B7]). However, access to these compounds is limited due to their low levels in plants and difficulties in their purification and chemical synthesis. Unraveling the biosynthetic pathways used for their production might provide the possibility of improving their availability through synthetic biology ([@B24]).\n\nOver the past several decades, tremendous interest and progress in the understanding of the biosynthesis of triterpenoids and triterpenoid glycosides have been observed. Generally, triterpenoid glycoside is assembled from six isoprene units followed by cyclization and scaffold modifications. The cyclization reaction mediated by oxidosqualene cyclases (OSCs) is the first diversifying step in the biosynthetic pathway. So far, more than 100 triterpene scaffolds have been reported, primarily including lupane, dammarane, oleanane (derived from \u03b2-amyrin), and ursane (derived from \u03b1-amyrin) ([@B16]). Recently, a novel triterpene orysatinol was identified, which even widen the potential scape of triterpene scaffolds that could exist in nature ([@B22]; [@B18]). The subsequent site-specific oxidation and glycosylation of the cyclic scaffold"
-"Introduction\n============\n\nPostharvest \"blue mold\" is the most common and economically deleterious pome fruit rot worldwide ([@ref-24]; [@ref-36]). Many *Penicillium* species (*P.\u00a0auarantiogriseum, P. carneum, P. commune*, *P. brevicompactum, P. crustosum, P.\u00a0solitum, P.\u00a0verrucosum* and *P.\u00a0expansum*) cause blue mold during long-term storage of apples, pears, quince and sometimes other fruits ([@ref-22]; [@ref-25]; [@ref-26]; [@ref-19]). The fungus gains access to stored fruits primarily through stem punctures/wounds and bruises. On apples, *P.\u00a0expansum* is the most cosmopolitan and aggressive species ([@ref-19]) while *P.\u00a0solitum* is less aggressive and causes significantly less decay in storage ([@ref-20]).\n\nIsolates of *P.\u00a0expansum* regularly produce patulin, a regulated mycotoxin, while all tested *P.\u00a0solitum* isolates are non-toxigenic ([@ref-9]; [@ref-12]). Comparisons of the patulin biosynthetic pathway have been conducted between *P.\u00a0expansum*, *P.\u00a0italicum* and *P.\u00a0digitatum* but not other blue mold causing fungi ([@ref-15]). By comparing the genomes of the aggressive and toxigenic *P.\u00a0expansum*, the less aggressive and nontoxigenic *P.\u00a0solitum*, and other closely related *Penicillium* species, we sought to identify differences that provide insights into blue mold decay of stored pome fruits. With the aim of devising novel strategies for management of these economically important fungi, it is important to understand the"
-"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."
-"Background\n==========\n\nA key step in planning a randomized clinical trial is the determination of the smallest difference in the primary outcome that should be detected between the study arms. This difference determines the sample size to be used in the study together with the type I error, power and variance of the primary outcome. In principle, this determination should be made a priori by the researchers \\[[@B1]\\] based on scientific and public health arguments; only then should the sample size be calculated. In reality, researchers often start with a small difference to be detected, which they subsequently revise until an achievable sample size is obtained \\[[@B2],[@B3]\\]. The danger of such practice is that trials may end up being sufficiently powered to detect convenient differences, but underpowered to detect clinically meaningful differences. On the other hand, there is currently no objective, scientific method for determining the smallest difference that is important for Science and Society. Given this uncertainty, the description of current practice can provide a useful framework for judging what differences are large or small.\n\nStating the smallest difference to be detected is necessary in planning a superiority trial. Planning an equivalence or noninferiority, trial (henceforth called noninferiority trial)"
-"Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is still rapidly spreading worldwide. The authors focus a spotlight on the injured skin as a reservoir of SARS-CoV-2 to decrease the infection rate. Angiotensin-converting enzyme-2 (ACE2) receptor has been identified as the functional receptor of SARS-CoV-2. ACE2 receptor is expressed in many tissues, including alveolar epithelial type II cells in lungs. When the spike protein of SARS-CoV-2 binds with the ACE2 receptor on the lung cells, the lungs then serve as a reservoir for viral invasion and replication. The oral mucosa and intestine act also as alternative routes of viral transmission.[@bb0005] In the skin, immunoreactivity for ACE2 receptors was detected in the basal cell layer of the epidermis and hair follicles, eccrine glands, blood vessels and capillaries, sebaceous glands, and its surrounding smooth muscle cells. As such, skin cells expressing ACE2 receptors can act as home cells and are prone to SARS-CoV-2 invasion, facilitating cellular viral entry and replication.[@bb0005]\n\nCOVID-19 not only is airborne through aerosols formed during medical procedures but also can be transmitted through saliva directly or indirectly even between patients without coughing or other respiratory clinical manifestations. The virus can also"
-"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 {#sec1-1}\n============\n\nSausage is one of the oldest forms of processed food which is usually made from minced meat, animal fat, salt, spices, and sometimes aromatic herbs.\\[[@ref1]\\] It often forms a significant part of diet and its consumption is increasing because of several reasons (i) increase in young population, (ii) increase in women\\'s employment, (iii) decrease in purchasing power of families, (iv) need for an appropriate substitute for meat, (v) a gradual tendency toward simple living, and (vi) simple, fast, and cheap industry of sausage production.\\[[@ref2]\\]\n\nNitrate/nitrite is a common ingredient in sausage formulation with clear and distinct functions; it is a microbial preservative particularly against anaerobic ones such as *Clostridiums* also it acts in the development of specific pink color, taste, and smell of sausage.\\[[@ref3]\\] However, its usage in sausage formulation is controversial as carcinogenic. Nitrosamines can be created as a consequence of acid nitrous with secondary amines. This reaction may take place in both foods or stomach.\\[[@ref4]\\] Production of nitrosamines could be accelerated through the activity of intestine flora, acidic conditions, and high heat over the storage period.\\[[@ref5]\\] Accordingly, minimizing the use of sodium nitrate as a preservative and replacing it with natural and less toxic alternatives"
-"Introduction {#sec1_1}\n============\n\nHuggins et al. first reported the effectiveness of surgical castration for prostate cancer in 1941 \\[[@B1]\\]. Since then androgen deprivation therapy still plays an important role in advanced prostate cancer.\n\nGnRH agonist treatment is associated risks in that it takes approximately 2 weeks to reduce the serum testosterone level to castration level, and it is also associated with a flare effect \\[[@B2]\\]. Degarelix is a GnRH agonist that came into clinical use in Japan in 2012. Degarelix treatment is not associated with a surge in serum testosterone and rapidly reduces the serum testosterone level to a castration level. Klotz et al. reported degarelix was more effective than a GnRH agonist in the treatment of high-risk prostate cancer patients \\[[@B3]\\]. On the other hand, degarelix is associated with a higher rate of injection site reaction than GnRH agonist drugs, including leuprorelin acetate and gosereline acetate \\[[@B4]\\].\n\nMiller et al. reported a case in which changing from leuprorelin acetate to degarelix resulted in PSA control \\[[@B5]\\]. Until now, there have been no reports about changing from a GnRH agonist to an antagonist for the treatment of CRPC in a Japanese patient. We herein report a case in which changing"
-"All data files are available from the Harvard Dataverse: <https://doi.org/10.7910/DVN/YCQB1A>.\n\nIntroduction {#sec005}\n============\n\nIn Niger, one-fourth of girls are married by age 15 years and three-fourths by age 18 years \\[[@pone.0237512.ref001]\\]. Studies have shown that child marriage can lead to negative sexual and reproductive health (SRH) outcomes for girls \\[[@pone.0237512.ref002], [@pone.0237512.ref003]\\]. Marriage being a central expectation of Nigerien life \\[[@pone.0237512.ref004], [@pone.0237512.ref005]\\], entering into a union helps both men and women fulfill their roles and thus, this practice has endured. In Hausa communities, the predominant ethnic group in Niger \\[[@pone.0237512.ref006]\\], these gender norms ascribe to women the role of bearing and raising children while men's roles are as providers and strictly not as homemakers \\[[@pone.0237512.ref005], [@pone.0237512.ref007], [@pone.0237512.ref008]\\]. Further, social status in Hausa communities has been shown to be largely determined by gender, age, and wealth, thus placing young married girls in particularly disadvantaged positions \\[[@pone.0237512.ref007]\\]. In the context of such societal structures where inequitable gender norms prevail, male dominance over decision-making remains prevalent, preventing girls from negotiating for their SRH. Ethnographic research in the Maradi region of Niger has demonstrated the continuing hold that men have over decisions at all levels from political leadership to household assets and extending to matters"
-"1. Introduction {#sec1-microarrays-04-00407}\n===============\n\nOver the past decade there have been a large number of studies that have explored the biological impact of constitutional (inherited and *de novo*) copy number variants (CNVs) in the human genome \\[[@B1-microarrays-04-00407],[@B2-microarrays-04-00407]\\]. CNVs are structural rearrangements that increase or decrease DNA content at regions larger than 50 base pairs (bps) in size \\[[@B1-microarrays-04-00407],[@B2-microarrays-04-00407]\\], accounting for a majority of genetic variation in humans based on bp coverage. These variants are estimated to cover 5%--10% \\[[@B2-microarrays-04-00407]\\] of the human genome which is at least an order of magnitude greater than the number of bps (\\~15 Mbps; dbSNP Human Build 142) encompassed by the more commonly studied single nucleotide polymorphisms (SNPs).\n\nMolecular technologies used to profile DNA copy number, such as microarrays (SNP-based arrays and comparative genomic hybridisation) and next-generation sequencing, have led to the identification of more than 300,000 CNVs, or 21,757 unique CNV loci in the human genome \\[[@B3-microarrays-04-00407]\\] . These technologies have also revealed the extent to which constitutional CNVs partially overlap or fully encompass genes and/or regulatory sequences. Concomitant gene expression analyses have shown a strong relationship between copy number dosage and mRNA levels with hundreds of genes \\[[@B4-microarrays-04-00407],[@B5-microarrays-04-00407]\\]. This functional effect can play"
-"Introduction\n============\n\nPatients with debilitating knee osteoarthritis (OA) refractory to conservative treatments are often referred for total knee arthroplasty (TKA). However, due to the invasive procedure, extended recovery period, and complication risk, only 9% to 33% of patients are willing to consider TKA.[@b1-imcrj-5-091]--[@b3-imcrj-5-091] Consequently, an estimated 3.6 million knee OA patients in the United States linger in the treatment gap, characterized by failure of conservative therapies and refusal to undergo TKA.[@b4-imcrj-5-091]\n\nThe KineSpring\u00ae Knee Implant System (Moximed, Inc, Hayward, CA) is a unique, joint preserving, unloading implant with potential to fill the therapeutic void between conservative and surgical knee OA treatments. The key component of the KineSpring System is a covered cobalt/cobalt-chrome alloy absorber that reduces the load carried by the affected medial compartment by up to 13 kilograms during the stance phase of gait. The clinical utility of the KineSpring System is postulated since excessive knee joint loading is a known potent stimulus for knee OA development[@b5-imcrj-5-091]--[@b7-imcrj-5-091] while therapies that reduce loading forces across the knee joint may halt OA progression[@b8-imcrj-5-091],[@b9-imcrj-5-091] or even allow healing.[@b10-imcrj-5-091] The KineSpring System absorber resides in the subcutaneous tissue and is attached to titanium alloy femoral and tibial bases ([Figure 1](#f1-imcrj-5-091){ref-type=\"fig\"}). The entire device"
-"Background {#S0001}\n==========\n\nThe construct of birth order has been extensively discussed over the last century in both public and academic spheres, with the aim of dissecting how the order in which children are born into a family may impact psychological or social outcomes. Theories of birth order stress the differing psychosocial environment experienced by each ordinal birth position, emphasising the quest of children to court the attention and approval of their parents and find a 'niche' amongst their siblings (Adler [1928](#CIT0001); Sulloway [1996](#CIT0040)). Such processes are thought to\u00a0account for the differences by birth order in measures such as achievement (Booth and Kee [2009](#CIT0005)) and conformity (Becker and Carroll [1962](#CIT0004); Bragg and Allen [1970](#CIT0006)).\n\nIn spite of the proliferation of birth order literature, studies assessing the impact of birth order on sexual health outcomes are limited in number, and have mostly focussed on one outcome such as age at first sex (Miller et al. [1987](#CIT0029); Rodgers, Rowe, and Harris [1992](#CIT0034)) or on sexual health in the context of risk-taking behaviour (Argys, Rees, Averett, and Witoonchart, [2010](#CIT0002)). Although research into aspects of birth order as they relate to sexual health is lacking, by extrapolating from existing birth order theories it"
-"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"
-"Background {#Sec1}\n==========\n\nMosquitoes (Diptera:Culicidae) are known to be vectors of a large number of pathogens around the globe and are considered as prime candidates for transmitting (re-)emerging vector-borne diseases (VBDs) in Europe \\[[@CR1]\\]. The increased mobility of humans, that has also increased the mobility of livestock and pathogens, as well as environmental modifications and climate changes can contribute to the (re-)emergence of vector-borne diseases \\[[@CR2]\\]. Furthermore, mosquito bites can cause a considerable nuisance for humans and mammals. Severe nuisance can have negative economic consequences (e.g., in tourism, work productivity outdoors, meat and dairy production) \\[[@CR3]\\]. These nuisance situations can eventually lead to autochthonous VBD cases, when in non-endemic areas infectious reservoirs, either humans (travellers, temporary workers) or animals (livestock, migrating animals) come in contact with high density of mosquito vectors.\n\nIn 2010, in the Netherlands, the Centre for Monitoring of Vectors (CMV) started a nationwide inventory of indigenous mosquitoes to acquire basic information on the composition, geographical distribution, biodiversity and environmental preferences of mosquito species. In this survey, the nuisance mosquito species and potential malaria vector *Anopheles plumbeus* (Stephens, 1828) (Figure\u00a0[1](#Fig1){ref-type=\"fig\"}) was one of the most frequently collected mosquito species \\[[@CR4]\\]. This species has been proven to be"
-"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"
-"Introduction {#Sec1}\n============\n\nCardiovascular (CV) diseases are the leading cause of death and morbidity in developed countries^[@CR1]^. The underlying cause of the most serious CV events is atherosclerosis, which is defined as a chromic inflammatory disease characterized by the build-up of subendothelial cholesterol deposits and the formation of leukocyte-rich plaques in the intimal layer of arteries. The fibrous cap is an atheroprotective layer of vascular smooth muscle cells (VSMCs) that covers the atherosclerotic plaque^[@CR2]^ and induces acute thrombo-occlusive events, such as myocardial infarction and stroke^[@CR3]^. Immune cells and inflammation play a key role in promoting the disruption of the fibrous cap^[@CR2]^. Full comprehension of the mechanisms of atherosclerosis is linked to revealing the role of the paracrine mediators released by the heterogenous cell populations involved in the development, progression, and complications of atherosclerosis.\n\nCardiotrophin-1 (CT-1) is a member of the interleukin (IL)-6 family of cytokines, and was initially cloned based on its ability to induce hypertrophy in neonatal cardiomyocytes^[@CR4]^. CT-1 is highly expressed in the cells of the cardiovascular system -- cardiomyocytes, cardiac fibroblasts, vascular endothelial cells, vascular smooth muscle cells (VSMCs), macrophages^[@CR5]--[@CR8]^, as well as in other organs^[@CR9],[@CR10]^. Factors like mechanical stretching, hypoxia, angiotensin II, aldosterone, growth factors, insulin,"
-"The food we eat has long been linked to the rate we age. Selective pressures in times of food abundance and scarcity have influenced our very genetic makeup, instilling in our genome genes believed to control the delicate balance between metabolism and aging. However, this balance has been disrupted in western societies with developments in agriculture and technologies that have promoted the intake of high-calorie diets and sedentary lifestyles. We are witnessing an alarming increase in the rate of metabolic syndrome, which consists of a collection of abnormalities including obesity, type 2 diabetes, dyslipidemia, fatty liver, and a pro-inflammatory and prothrombotic state \\[[@R1],[@R2]\\] Currently, one in four adults in the United States suffers from metabolic syndrome and worldwide estimates are over 2.1 billion \\[[@R3],[@R4]\\]. Ultimately, this epidemic threatens human life-span projections and puts great pressure on our already overburdened health care system.\n\nThe sirtuin family of proteins appears to be at the crossroads between nutritional status and longevity. Sirtuins are highly conserved NAD^+^-dependent protein deacetylases and/or ADP ribosyltransferases that target histones, transcription factors, and co-regulators to adapt gene expression in response to the cellular energy state \\[[@R5]\\]. Many members of this family, including the founder Sir2, have been shown to"
-"Introduction {#s1}\n============\n\nLate access to antiretroviral therapy (ART) substantially increases the incidence of opportunistic infections and mortality associated with HIV infection. In low income countries in 2005--2006, an estimated 51% to 78% of people who needed life-sustaining ART presented late to ART clinics [@pone.0051289-The1]. Vietnam is no exception in this regard. Despite a WHO recommended threshold for ART initiation at a CD4 cell count of 350 cells/mm^3^ [@pone.0051289-World1], and a rapid increase in the number of sites providing free ART from 74 in 2005 to 287 in 2009 [@pone.0051289-Vietnam1], an estimated 41% of people living with HIV (PLHIV) in Vietnam in 2010 initiated ART very late, at a median CD4 cell count below 50 cells/mm^3^, placing them at high risk of premature mortality [@pone.0051289-Vietnam1]. Consistent delay in the initiation of ART is a major factor currently hindering the scaling up of ART to the national level.\n\nART clinics in Vietnam are organized in parallel with the HIV treatment system. These clinics serve as access points for HIV patients to receive HIV care and treatment. Free ART is provided on a monthly or bi-monthly basis. HIV clinics are located inside central hospitals in Hanoi in the North and Ho Chi"
-"Background {#Sec1}\n==========\n\nGlobally, more than 30 million people are estimated to suffer from sepsis each year \\[[@CR1]\\]. Recently redefined as organ dysfunction resulting from an exaggerated systemic immune response to an underlying bacterial, fungal, or viral infection, the syndrome sepsis belongs to the ongoing challenges of modern intensive care medicine \\[[@CR2]\\]. Steady improvements of treatment bundles resulted in a gradual decline in mortality over the past years, remaining anyhow on an unacceptable high level of 20--50% \\[[@CR3]\\]. Sepsis not only does affect elderly persons but also can strike all ages, including patients before or within the onset of their sexual activity \\[[@CR4]--[@CR6]\\]. During the immune response in the early stage of sepsis, a systemic activation of immune cells leads to an uncontrolled release of cytokines, chemokines, and other mediators, e.g., reactive oxygen species \\[[@CR7]\\]. The consequence is an avalanche-like forward amplifying response, impacting in its severity not only cells of the immune system but also, e.g., endothelial cells, cardiomyocytes, or skeletal muscle cells \\[[@CR8]--[@CR10]\\]. Furthermore, changes in progenitor cells like hematopoietic stem cells (HSC) of the bone marrow have been hypothesized to occur during inflammation \\[[@CR11]\\], with recent proof of this concept during chronic inflammation in diabetes \\[[@CR12]\\] as"
-"Introduction {#Sec1}\n============\n\nThe trade-off between parental reproductive effort and survival may lead to negative fitness consequences for adults (Williams [@CR72]; Trivers [@CR68]; Dijkstra et al. [@CR14]; Stearns [@CR65]). The basis for this relationship is, however, still poorly understood. Survival is an attribute of fitness, which may be difficult to quantify. In contrast, reproduction is a clearly defined physiological event with a starting and an ending point, which can be evaluated by measuring parental effort and costs (Lochmiller and Deerenberg [@CR32]). Previous explanations of the trade-off focussed on physical deterioration during breeding attempts (Drent and Daan [@CR15]) or accelerated senescence of an organism (Partridge [@CR49]). Physiological explanations assume that reproduction and survival compete for limited energy and nutrients (Harshman and Zera [@CR22]). However, external factors may also interact with this trade-off. Increased predation risk of parents, protecting offspring, as well as frequent infections during the breeding season may affect the parents' survival (Magnhagen [@CR34]; Gustafsson et al. [@CR18]; Saino et al. [@CR57]).\n\nIt is worth emphasising that immunity is one of the major physiological mechanisms, which determine host survival (Lochmiller and Deerenberg [@CR32]). The immune system is a defence mechanism to control and fight any parasitic or pathogenic infection, and"
-"1. Introduction {#sec1}\n===============\n\nArsenic is a kind of toxic metalloid which mostly exists in inorganic or organic form in the environment \\[[@B1]\\]. Arsenic can be absorbed by the body through skin, drinking water, and other ways and then reach all parts of the body through blood circulation. At present, arsenic poisoning in drinking water has become a global public health problem. Among them, arsenic poisoning in China, India, and other countries is more serious. According to the report, 26 million people in India have been affected by arsenic poisoning in drinking water \\[[@B2]\\]. A large number of studies have found that arsenic can be metabolized through methylation in the body \\[[@B3]\\]. However, Pratheeshkumar et al. \\[[@B4]\\] found that arsenic exposure can induce the production of a large number of reactive oxygen species and NOS and promote consumption of antioxidants such as glutathione, inducing oxidative stress. Epidemiological investigation shows that arsenic exposure is closely related to cardiovascular disease, skin cancer, and liver cancer, in which oxidative stress plays an important role \\[[@B5], [@B6]\\].\n\nGlutathione (GSH) is an important redox molecule in cells, which can be used not only as a major antioxidant molecule to relieve arsenic-induced ROS \\[[@B7]\\] but also"
-"Tuberculosis (TB) is a leading cause of death worldwide. According to a recent report by the World Health Organization (WHO), TB killed 1.5 million and caused illness in 9.6 million people in 2014. Bacille Calmette-Gu\u00e9rin (BCG) is the only licensed vaccine against TB. Although it is effective at reducing disseminated forms of TB (e.g., miliary TB and tubercular meningitis) in children[@b1][@b2], BCG has highly variable efficacy (0--80%) against adult pulmonary TB[@b3][@b4], the most contagious form of the disease. Another concern with BCG is its safety in immunocompromised individuals. Disseminated BCG disease has been observed in HIV-infected children following BCG vaccination[@b5], and the risk outweighs the benefit of TB prevention[@b5][@b6]. In 2007, the WHO revised its recommendation and declared that HIV infection is a contraindication for giving BCG[@b7]. In light of this, there is an urgent need to develop a more effective and safe TB vaccine.\n\nOne hypothesis to account for the highly variable protective efficacy of BCG observed in clinical trials concerns the heterogeneity of BCG strains[@b8]. Although colloquially referred to as BCG, there are a number of BCG substrains that have been used in different vaccination programs[@b9][@b10]. Genetic differences including deletions and duplications of genomic regions and single nucleotide"
-"1. Introduction {#sec1-jcm-09-00331}\n===============\n\nThe hepatitis E virus (HEV) is the leading cause of acute viral hepatitis worldwide. HEV, which is mainly transmitted enterically, is responsible for outbreaks in developing countries and zoonotic cases in both developing and developed countries \\[[@B1-jcm-09-00331]\\]. HEV genotypes 1 (HEV1) and 2 (HEV2) are mainly found in developing countries and are restricted to humans. Other genotypes, including HEV3 and HEV4, have been detected in both humans and animals, with pigs being the main reservoir. While most infections are asymptomatic, they can cause acute hepatitis, including severe forms in patients with pre-existing liver disease and in pregnant women living in developing countries. An HEV infection may also trigger extra-hepatic manifestations and can lead to chronic infections in immunocompromised patients. Its pathogenesis is still unclear but our knowledge has greatly improved in the past few years.\n\n2. HEV Genome and Classification {#sec2-jcm-09-00331}\n================================\n\nHEV is a small virus with the positive-sense, single-stranded \\~7.2 kb RNA genome that contains three open reading frames (ORF), ORF1, ORF2 and ORF3 ([Figure 1](#jcm-09-00331-f001){ref-type=\"fig\"}). ORF1 encodes a non-structural protein about 1693 amino acids (aa) long, with at least four putative functional domains: methyltransferase, cysteine protease, helicase and RNA-dependent RNA polymerase (RdRp). Other"
-"1. Background\n=============\n\nNon-pharmacological treatments such as transcutaneous electrical nerve stimulation (TENS) and microcurrent electrical nerve stimulation (MENS) have been used to treat and manage muscle pain and dysfunction. TENS has appeared in many surveys compared to laser, ultrasound, hot pack, etc. while MENS is a new electrotherapy method that its efficacy has not been validated compared to TENS in patients with rotator cuff tears.\n\nThe rotator cuff (RC) assists in shoulder joint mobility and dynamic stabilization ([@A88327REF1]). The primary characteristic of a rotator cuff tear is pain induction while muscle weakness appears as a secondary feature ([@A88327REF2], [@A88327REF3]), leading to further reduction in mobility and functionality of the shoulder and arm ([@A88327REF2], [@A88327REF3]). Conservative treatment often works ([@A88327REF2], [@A88327REF4]) but in cases where the tear has expanded and functional problems are intense, a surgical procedure may be required ([@A88327REF2], [@A88327REF4]). Physiotherapy is normally the \ufb01rst line of management for shoulder pain ([@A88327REF3]). It involves a wide range of interventions and is highly recommended ([@A88327REF5]). Specifically, it helps reduce the pain and muscle spasm, maintain the tract in the joint, and prevent or eliminate functional difficulties ([@A88327REF6]). Physiotherapeutic interventions include the use of kinesiotherapy, electrotherapy (such as TENS and MENS),"
-"Introduction\n============\n\nMany physiological systems have underlying circadian rhythms. These rhythms are orchestrated by a central biological clock, situated in the suprachiasmatic nucleus (SCN). The mechanisms behind the innate rhythm of the biological clock and its adjustments to the photoperiod are being elucidated and it is becoming clear that abnormalities of circadian rhythms are linked to several common diseases.\n\nMajor depressive disorder (MDD) is a frequent disorder that poses a major handicap to patients. Understanding MDD is essential in order not only to treat acute episodes, but also to prevent recurrence. Several disorders are closely linked to MDD, and it is probable that several subtypes of MDD exist.[@b1-jcnsd-4-2012-015] Bipolar disorder is sometimes hard to distinguish from MDD due to infrequent episodes of elevated mood, and seasonal depression[@b2-jcnsd-4-2012-015] may rest undiagnosed as neither patients nor physicians have linked the onset of recurrence to changes in day length.[@b2-jcnsd-4-2012-015]\n\nLinks between depression and circadian rhythms have long been suspected due to the existence of seasonal depression, where the onset of low mood correlates with a reduction in daylength (also called the photoperiod).[@b3-jcnsd-4-2012-015] More recently, attention has focused on chaotic sleep wake cycles in patients suffering from bipolar disorder, where degradation in regular rhythms"
-"Introduction {#sec1}\n============\n\nDNA molecules have been widely explored as useful building materials because of their intrinsic characteristics, for example, base sequence design capability, self-assembly predicted by complementary binding, and simple adaptability with various functionalized materials. Various dimensional structures made of synthetic DNA oligonucleotides have been constructed with precise control of size, shape, and pattern.^[@ref1]\u2212[@ref9]^ DNA structures can serve as effective building platforms for arrangement of various nanomaterials to be used in specific target applications such as optoelectric devices, chemical sensors, drug delivery, and biocomputing.^[@ref10]\u2212[@ref14]^ DNA can be functionalized with various materials such as proteins, drugs, metallic and semiconducting nanoparticles, carbon-based materials, fluorescence dye molecules, and metal and lanthanide ions.^[@ref15]\u2212[@ref26]^ Similarly, natural DNA such as lambda and salmon DNA (SDNA) has also been used in the fields of biology, medicine, and bionanotechnology.^[@ref27],[@ref28]^ Such DNA can be easily obtained in large quantities at a relatively low cost, and these molecules can be easily incorporated with various functionalized nanomaterials.\n\nDNA structures embedded with individual nanomaterials such as quantum dots, gold nanoparticles, cobalt ions, and doxorubicin were fabricated, and their chemical, physical, and biological properties have been reported. However, there are certain limitations to construction of multiple function-embedded DNA complexes containing various types"
-"Introduction\n============\n\nNeural tube defects (NTDs) are among the most common birth defects resulting in infant mortality and serious disability, with around 500 pregnancies being affected in England and Wales each year.[@b1-cmwh-7-2014-009]\n\nNumerous countries including the UK recommend that all women planning to become pregnant should take 400 \u03bcg per day of folic acid for at least one month prior to conception and for up to 12\u00a0weeks postconception. This recommendation was based on the findings of the Medical Research Council Vitamin Study Research Group in 1991 that periconceptional folic acid intake reduces the risk of NTDs.[@b2-cmwh-7-2014-009]--[@b4-cmwh-7-2014-009]\n\nIn the UK, a campaign was launched in 1995 by the Health Education Authority (HEA) to improve folate status awareness in women. The three-year campaign also aimed to target health and other professionals, such as teachers and journalists.[@b5-cmwh-7-2014-009]\n\nVarious studies around the world have investigated the understanding of the importance of folic acid among women of child-bearing age, with some identifying associations between demographic and lifestyle variables with folate uptake.[@b6-cmwh-7-2014-009]--[@b10-cmwh-7-2014-009]\n\nTo our knowledge, there have been no surveys conducted to date to determine any differences in the understanding and use of folic acid among women before and after they had attended their first"
-"All relevant data are within the paper and its Supporting Information files.\n\nIntroduction {#sec001}\n============\n\nSince the onset of agriculture, cereals have played a crucial role in human nutrition. However, the needs of the growing human population, which is projected to reach 9.7 billion by 2050 \\[[@pone.0167099.ref001]\\], together with the changing climate represent a serious challenge for breeders and researchers to meet the growing demand for food. Despite the fact that barley represents only 5.2% of the total world production of cereals with 144 mil. tons harvested per year \\[[@pone.0167099.ref002]\\], this cereal ranks among major crops in many, especially European countries responsible for 59.7% of total world production. The Czech Republic has a long tradition in barley production mainly due to the brewery industry with 14.9% of sowing areas occupied by this crop and its yearly harvest representing as much as 22.4% of total cereal production \\[[@pone.0167099.ref003]\\].\n\nThe yield is constantly exposed to the risk of adverse effects due to different abiotic and biotic factors. An obligate biotrophic fungus *Blumeria graminis*, a causal agent of powdery mildew disease, is currently ranked among the Top 10 most important fungal plant pathogens \\[[@pone.0167099.ref004]\\]. *B*. *graminis* f. sp. *hordei* (*Bgh*) is responsible for"
-"Introduction {#Sec1}\n============\n\nInfantile cortical hyperostosis (ICH, OMIM 114000) was first reported by Roske \\[[@CR26]\\] and subsequently studied by De Toni who recognized the congenital and regressive aspects of this disorder \\[[@CR13], [@CR14]\\]. Caffey and Silverman \\[[@CR9]\\] and Caffey \\[[@CR8]\\] formally defined ICH, which is a neonatal and infantile familial disease, spontaneously healing in the first years of life. The disease is characterized by regressive subperiosteal hyperosteogenesis mainly affecting the long bones, mandible, clavicles, and ribs, which are remarkably swollen and deformed on X-ray. The presence of fever, inflammatory signs, and pain led clinicians to suspect different disorders, in particular those caused by infectious agents \\[[@CR2], [@CR22], [@CR25], [@CR30]\\]. Familial clustering has been reported by several authors who also outlined the autosomal dominant pattern of inheritance and a possible reduced penetrance \\[[@CR1], [@CR4], [@CR6], [@CR10], [@CR15], [@CR17], [@CR19], [@CR20], [@CR23], [@CR24], [@CR27], [@CR31]\\].\n\nA genome-wide analysis in three unrelated ICH families allowed Gensure et al. \\[[@CR18]\\] to map the disease locus on chromosome 17q21. All affected individuals were found to be heterozygous for a missense mutation (3040C\u2192T) in the *COL1A1* that altered residue 836 (R836C). Suphapeetiporn et al. \\[[@CR29]\\] and Cho et al. \\[[@CR11]\\] corroborated these results by confirming the"
-"Introduction {#sec1}\n============\n\nDislocation of the extensor tendons from their central position on the metacarpal heads is rare, especially in non rheumatoid patients. Four etiological factors are reported to be involved in extensor tendon subluxation. Dislocation of the extensor tendons can be traumatic (due to sagittal band rupture), congenital, spontaneous and degenerative.[@bib1], [@bib2], [@bib3], [@bib4] The patients with extensor tendon dislocations usually complain of discomfort and snapping with active finger flexion. However, we could not find any study reporting extensor tendon subluxation with pseudotriggering of the digits. In this study, we report a case of congenital extensor tendon subluxation of multiple digits with pseudotriggering of the left little finger. We aim to attract notice to pseudotriggering of the digits due to tendon dislocations and to discuss tendon reconstruction surgery for extensor tendon dislocations.\n\nCase {#sec2}\n====\n\nThis study is performed with an informed consent form signed by the patient and parents. A 16 year old female patient presented to our clinic with a complaint of triggering of her left little finger for about 2 years. She had a history of two surgical A1 pulley releases about a year and 5 months ago respectively. During the first surgical intervention, ulnar tunnel"
-"Introduction {#Sec1}\n============\n\nThe North American Multi-Model Ensemble (NMME) was established as a means of exploiting a highly useful and somewhat counter-intuitive property of seasonal forecast models. Multi-model ensemble means (MMEMs), where multiple instances of different models are combined, typically have higher forecast skill than the individual models they are composed of (e.g. Palmer et al. [@CR20]; Jin et al. [@CR13]; Kirtman et al. [@CR16]). This property has resulted in the pursuit of multi-model ensembles (MMEs) as a means of improving intraseasonal to interannual (ISI) prediction capabilities. The success of the MME methodology combined with the straightforward, but not simple, nature of its implementation led to the creation of the National (now North American) Multi-model Ensemble (Kirtman et al. [@CR16]). This initial effort consisted of an extensive hindcast dataset, as well as real-time forecasts, composed of integrations from numerous prominent North American models, including the current US operational seasonal forecast system (Coupled Forecast System version 2; CFSv2). Following the initial success of the NMME (sometimes referred to as Phase-1) a second effort, is ongoing, with updated models and an experimental design more closely in line with the needs of the operational community.\n\nThe NMME data represents one of the most"
-"1. Introduction {#sec1}\n===============\n\nIn recent years, studies of objectively measured physical activity (PA) using accelerometers have shown that not only low PA but also sedentary behavior (SB) predisposes to health hazards [@bib1], [@bib2]. Most studies of PA and cognition are based on self-reported PA. In such cross-sectional studies, PA has been associated with better cognition in the most robust studies (n\u00a0\\>\u00a02000 and a valid measure of PA and cognition) [@bib3], [@bib4].\n\nSo far, only four studies appear to have assessed associations of objectively measured PA profiles with cognition in a cross-sectional study of an elderly population [@bib5], [@bib6], [@bib7], [@bib8]. Kerr et\u00a0al. [@bib5] showed that moderate-to-vigorous physical activity (MVPA), measured using waist-worn accelerometers, was associated with a better processing speed and executive function performance (n\u00a0=\u00a0217). Light physical activity (LPA), regardless of the amount, was not associated with cognition when models were adjusted for demographic variables. Barnes et\u00a0al. [@bib6] did not distinguish between the intensity of PA but found that elderly women in the lowest PA quartile performed worse on cognitive tests. In their study, PA was measured using a wrist-worn accelerometer in a large sample (n\u00a0=\u00a02736). The most extensive cross-sectional study"
-"Percutaneous vertebroplasty (PVP) is a safe and effective procedure for the treatment of osteolytic vertebral metastases. In recent years, percutaneous osteoplasty (POP), as a technical extension of PVP, has been used as a method for the treatment of osteolytic lesions due to a malignancy in the skeletal system, including the acetabulum, sacrum, pubis, ischium, humerus and femur ([@B1]-[@B8]). POP has been demonstrated to be highly efficient to provide pain relief and functional improvement. Nevertheless, there are few reports on the use of POP for femoral head osteolytic lesions. Furthermore, the effectiveness of POP for the treatment of these lesions is not well known. In this report, we present a patient with osteolytic lesions of the femoral head due to a lung cancer who experienced sustained pain relief and improvement in quality of life following POP.\n\nCASE REPORT\n===========\n\nA 43-year-old man developed unremitting pain in the lower back and the right leg, which especially increased while walking. Subsequently, the patient was admitted to our hospital. The patient received bed rest for more than one month. Magnetic resonance (MR) and emission computed tomography (ECT) images demonstrated the presence of L3, S2 and S3 vertebral lesions that were metastatic tumors. Computed tomography"
-"Introduction\n============\n\nTrichomonas vaginalis is the causative agent of trichomoniasis, a non-ulcerative sexually transmitted disease. *T. vaginalis* is the protozoan parasite infecting the urogenital tract of both females and males ([@B1], [@B2]). It is reported to be 250 million new cases all over the world every year ([@B3]). Estimates of prevalence are differences between populations, but the range from 5--74% in women and 5--29% in men is observed ([@B1]). Women by the age of 16--53 are at greater risk of infection ([@B4]--[@B6]). Recently, different studies have shown that *T. vaginalis* has been associated with HIV, which increases the number of high-risk members ([@B7], [@B8]). Additionally, this pathogen has been associated with serious health consequences; including low-birth-weight in pregnant woman or premature infant and increased chances of cervical cancer. Women who are infected can be asymptomatic or have different symptoms, consisting a yellowish-green frothy discharge purities, dysuria, and the strawberry cervix which is recognized by punctuates hemorrhagic lesions. In general, infection is asymptomatic in men, although it can be associated with urethral discharge and dysuria ([@B1]--[@B4]). For diagnosis of trichomoniasis, different methods have been used, such as, wet mount, culture, Papanicolaou smear, Pap smear, polymerase chain reaction (PCR) and serological tests."
-"INTRODUCTION\n============\n\nPortal hypertension (PH) is the result of increased hepatic vascular resistance and portal blood flow. PH leads to serious complications, such as variceal bleeding, portal hypertensive enteropathy, ascites, spontaneous bacterial peritonitis, hepatorenal syndrome, and hepatic encephalopathy. PH is responsible for significant morbidity and mortality in patients with decompensated cirrhosis ([@B1], [@B2]). For patients with compensated cirrhosis, the diagnosis and grading of clinically significant portal hypertension (CSPH) enable the prediction of prognoses such as the possibility of progression to decompensated cirrhosis and mortality ([@B3]).\n\nThus, the precise grading of PH is essential for appropriate treatment and follow-up of patients with cirrhosis ([@B3], [@B4]). The measurement of the hepatic venous pressure gradient (HVPG) has served as the gold standard for assessing the degree of PH ([@B5]). This parameter reflects disease severity and has a strong prognostic value with regard to survival and decompensation in patients with compensated cirrhosis ([@B6]). However, the widespread routine clinical use of this method has been limited by the procedure\\'s invasive nature and the requirements for skilled expertise and special equipment ([@B7], [@B8]).\n\nTherefore, many investigators have undertaken efforts to diagnose and grade PH using non-invasive ultrasonography (US) in patients with cirrhosis to replace invasive HVPG"
-"Introduction {#Sec1}\n============\n\nAnimal development requires precise coordination among the cells of the embryo to balance cell division and patterning, and thereby ensure the generation of all adult organs and tissues in their proper locations and proportions. Extra-cellular signaling molecules mediate cell--cell communication to control fundamental embryonic processes such as formation of the primitive streak, gastrulation movements, and establishment of the anterior/posterior and dorsal/ventral axes. The WNT/\u03b2-catenin signaling pathway (commonly referred to as the canonical WNT pathway), which is highly conserved across all metazoan life forms, is essential for embryonic development and, later in life, for adult tissue homeostasis and regeneration. Deregulation of this pathway causes severe congenital defects, underlies multiple diseases and disorders, and frequently drives oncogenic transformation (reviewed in refs. ^[@CR1]--[@CR3]^).\n\nDevelopmental signaling pathways, such as the WNT/\u03b2-catenin pathway, initiate signaling cascades that culminate in the expression of many target genes that subsequently mediate developmental programs. To exert temporal control over these highly coordinated developmental processes, these same signaling pathways initiate negative feedback loops that act to desensitize the cell to the signal. Less understood and studied are the mechanisms by which the transcriptional program previously activated by a pathway are diminished and eventually terminated so that a"
-"**Chinese Library Classification No.** R446; R654.5+5; R741\n\nIntroduction {#sec1-1}\n============\n\nHypoxic ischemic encephalopathy (HIE) refers to a serious neurological syndrome that occurs in the earliest days of life because of placental insufficiency or umbilical cord occlusion in the perinatal period (Allen and Brandon, 2011). HIE is a major neuro-developmental disability in infants, with a prevalence of approximately 1 to 6 per 1000 births (Vannucci, 2000; Chau et al., 2014). Twenty-five percent of HIE patients suffer permanent neurological deficits (Graham et al., 2008). Additionally, worldwide, approximately one million newborns die from HIE each year (Lv et al., 2017). HIE can result in periventricular leukomalacia or developmental retardation, and can cause dysfunction in remote organs (Zeppellini et al., 2001; Wu et al., 2011; Zhao et al., 2012; Alaro et al., 2014; Khatri et al., 2014; Saeed et al., 2014). Despite numerous clinical trials, many neuro-protective strategies have failed to effectively treat HIE patients. The need to expand our understanding of HIE mechanisms and to develop novel therapies is therefore urgent (Ginsberg, 2008; Davies et al., 2019).\n\nA single-nucleotide polymorphism (SNP) is the substitution of a single nucleotide at a certain position in a genome. Generally, SNPs are present at varying percentages within"
-"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 {#Sec1}\n============\n\nSimulation has been a part of healthcare education for the past 50\u00a0years \\[[@CR1]\\]. A significant amount of research demonstrates its value in surgical training \\[[@CR2], [@CR3]\\] and health authorities have identified simulation as a medium to improve patient safety \\[[@CR1], [@CR4]\\].\n\nAviation was one of the first industries to use simulation \\[[@CR5]\\]. The philosophy was to create an environment as similar to the real one as possible. The pilots find themselves sitting within a cockpit, experiencing the same forces and audio-visual stimuli as in a real plane \\[[@CR6]\\]. Conversely, the recreation of human organs that look and feel realistic still proves to be highly challenging \\[[@CR7]\\].\n\nUnlike the legislation they replaced, the Human Tissue Act 2004 and Human Tissue Act 2006 allow for surgical procedures to be performed on human cadavers in Britain \\[[@CR8]\\]. This development opens up new horizons for high-fidelity surgical simulation. However, in a recent review, cadaveric surgical simulation was criticised, due to alteration of tissue quality caused by the embalming/preservation technique \\[[@CR9]\\]. Simulation of advanced surgical operations in traditionally embalmed cadavers is often impossible, due to the rigidity of the tissue. Using fresh frozen cadavers is a popular option for such training."
-"Background\n==========\n\nEndothelial dysfunction is supposed to be a key event in the development of several cardiovascular diseases. In the middle-aged, apparently healthy population, the endothelial function is frequently already impaired, representing the first step in the development of cardiovascular diseases. It seems reasonable to try to improve endothelial dysfunction in the mentioned population also by pharmacological approaches. It can be assumed that therapies that could improve the function of the vascular endothelium would lead to diminishing or slowing the onset of cardiovascular diseases. The aim of our study was to evaluate the protective pleiotropic effects of a combination of statin and angiotensin receptor blocker at sub-therapeutic doses in middle-aged volunteers with low risk for cardiovascular disease on the function of endothelium.\n\nMethods\n=======\n\nTen healthy volunteers (males) aged from 30 to 50 years without history of cardiovascular disease, diabetes mellitus, hypertension or hypercholesterolemia were recruited for the study. Subjects took a combination of statin (fluvastatin 10 mg) and angiotensin receptor blocker (valsartan 20 mg) daily for 30 days. Ultrasound measurements (Aloka Alfa 10 ProSound echo-machine) of flow-mediated dilatation (FMD) were repeated three times: at the beginning of the study, after 14 days, and at the end of the study."
-"Introduction {#Sec1}\n============\n\nSince the recent update of the World Health Organization (WHO) Classification of Tumors of the Central Nervous System^[@CR1]^, the revised classification now integrates histology and molecular features, particularly giving pivotal attention to the isocitrate dehydrogenase (IDH) mutation and 1p/19q co-deletion, which allow a prediction of the individual response to therapy^[@CR2]--[@CR4]^. Furthermore, the inclusion of the IDH mutation status enables an improved assessment of the individual prognosis, compared to the WHO grades defined by the 2007 classification^[@CR1],[@CR2],[@CR5]--[@CR7]^.\n\nIDH mutations (mut) are frequently observed in lower-grade gliomas (WHO grades II and III) and secondary glioblastomas (GBM)^[@CR8]^. In contrast, IDH mutations in primary GBM are rare^[@CR8]^. From a clinical point of view, most IDH wild type (wt) lower-grade gliomas are comparable to GBM^[@CR7],[@CR8]^. Furthermore, GBM patients with IDH mutations have a significantly longer overall survival compared to their IDH wt counterparts (31 months vs. 15 months)^[@CR7]^. Moreover, current guidelines recommend that treatment decisions should be based on the IDH status and 1p/19q co-deletion^[@CR9]^. However, to date tissue samples are inevitable if one wants to assess the IDH status. Hence, a reliable method for the non-invasive assessment of the IDH genotype is of great interest. Magnetic resonance spectroscopy has already been"
-"1. Introduction {#sec1}\n===============\n\nCarbon steel is very often applied in diverse industrial fields, including building; chemical processing; oil/gas storage and transportation; process vessel, equipment, and pipeline; and so forth, due to its low cost, incredible mechanical workability, and easy availability for constructing various vessels.^[@ref1],[@ref2]^ Nevertheless, any environment containing water has a notable potential to generate corrosive activity, since it can inevitably dissolve gases (e.g., O~2~ and CO~2~) and mineral salts. For instance, in petroleum and natural gas industries, oil field formation water always contains high-concentration chlorides, carbonates, sulfates, and dissolved gases, such as H~2~S and CO~2~, thereby causing massive economic loss. Also, in many industrial processes, acid solutions are widely used for cleaning, pickling, descaling, etching of metal, and oil well acidizing. Unfortunately, carbon steel is dramatically sensitive to being corroded in contact with various aggressive media, especially in the acidic environment.^[@ref3]^ To address acid corrosion, the use of inhibitors is one of the most effective and practical methods to prevent carbon steel from the corrosion and reduce the corrosive attack. In principle, inhibitors normally function by adsorbing on the metal surface and then forming a compact barrier layer, thereby protecting the metal against corrosion; moreover, the adsorption interactions"
-"Introduction {#Sec1}\n============\n\nOsteoarthritis (OA) is an important health concern and among the top 10 leading conditions in Europe with respect to its socio-economic burden to society \\[[@CR1]\\]. The knee joint is the largest joint in the human body and is the most commonly affected site in OA \\[[@CR2]\\]. Amongst other structural changes, OA is characterised by loss of cartilage thickness \\[[@CR3]\\] and MR imaging has previously been validated and shown to provide reliable measures of cartilage thickness \\[[@CR4], [@CR5]\\] and of cartilage loss in knee OA \\[[@CR6]\\]. Further, this methodology has been previously used to determine the magnitude of in vivo cartilage deformation of the patella \\[[@CR7]--[@CR9]\\] and of the femorotibial joint \\[[@CR10]\\] by comparing cartilage thickness before and after loading.\n\nHistochemical analyses have suggested that OA cartilage has a lower proteoglycan and collagen content \\[[@CR11], [@CR12]\\] and a reduced collagen fibril connectivity and fibril orientation than healthy cartilage \\[[@CR13], [@CR14]\\]. Further, it was shown that OA cartilage suffers from greater permeability and elevated water concentrations, potentially leading to cartilage swelling \\[[@CR15], [@CR16]\\]. OA cartilage also displayed a diminished compressive modulus \\[[@CR17], [@CR18]\\] and greater deformation upon loading \\[[@CR16], [@CR19]\\] in ex vivo studies, suggesting that OA cartilage is"
-"INTRODUCTION {#s1}\n============\n\nCoronary heart diseases cause a large number of deaths worldwide, and ventricular arrhythmia is a leading contributor to mortality from heart disease ([@CIT0015]). It is well established that hypertension, hyperglycemia, dyslipidemia, and sedentary lifestyle are the important risk factors for coronary heart disease ([@CIT0005]; [@CIT0011]). In recent years, alternative health care using diet and dietary components has become increasingly popular due to its beneficial effects discovered ([@CIT0004]; [@CIT0017]). In particular, the protective effects in metabolic diseases have been attributed to the consumption of wholegrain foodstuff, especially germinated brown rice (GBR; [@CIT0013], [@CIT0014]; [@CIT0012]). Germination is a natural process during the growth period of seeds; the germination process improves texture and increases the useful compounds of the grain ([@CIT0021]; [@CIT0010]). Germinated brown rice is a biotransformation product of brown rice; it is known that GBR showed excellent benefits on health promotion and disease prevention ([@CIT0008]).\n\nIn contrast to the extensive studies on the protective effects of GBR on central nervous system diseases, fewer studies on the health effect of GBR on coronary heart diseases have been published. According to several studies, GBR is a good source of phytochemicals with various pharmacological activities, such as antiatherosclerotic, antidepressant, anti-inflammatory, antidiabetic,"
-"INTRODUCTION\n============\n\nUnderstanding the principles of transcriptional regulation remains one of the greatest challenges in functional genomics, despite years of intensive investigations. Spectacular advances in experimental technologies, such as ChIP-seq ([@gks543-B1]), FAIRE-seq ([@gks543-B2]) and RNA-seq ([@gks543-B3]) represent obvious breakthroughs in this field, as they allow interrogating regulatory activity at the genome-wide scale, and are becoming available to most research groups ([@gks543-B4],[@gks543-B5]). However, interpretation of these genome-wide datasets, as well as their integration into a unified model of *cis*-regulation that includes computational motif predictions remains challenging for many biologists, given the amount of information and the lack of appropriate tools. Two typical situations are often encountered in genomics studies. First, given a set of co-expressed genes, an immediate question is whether these genes share regulatory motifs and, if so, which transcription factors (TFs) may co-regulate these genes, or a significant subset thereof. Secondly, given a set of genomic loci identified through DNase-Seq, FAIRE-seq, or ChIP-Seq, motif discovery can be applied in a similar fashion as to co-expressed gene sets, with the aim to confirm the presence of the targeted TF (for ChIP-seq against TFs), uncover novel co-factors, but also disentangle the noisy input set into direct target regions of different TFs."
-"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]"
-"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"
-"1. Background {#sec1}\n=============\n\nSince laparoscopic surgery was introduced in 1987 by Mouret and more frequently employed, it has rapidly evolved as a major innovation in the history of surgery \\[[@B1]\\], offering an important contribution to the reduction of all the typical complications related to open surgery. On the other hand, laparoscopic surgery can be associated with a specific type of incisional hernia through the trocar site causing complications such as small bowel obstruction. Trocar site hernia (TSH) is defined as an incisional hernia which occurs after minimally invasive surgery on the trocar incision site \\[[@B2]\\]; some authors also define this condition as a port site hernia.\n\nIn 2004 Tonouchi classified trocar site hernias into 3 types \\[[@B3]\\] as follows.\n\n\\(i\\) Early onset typeDehiscence of anterior and posterior fascial plane and peritoneum characterized by early onset after surgery. It usually occurs as a small bowel obstruction. An example of this type is the so-called Richter\\'s hernia.\n\n\\(ii\\) Late onset typeDehiscence of anterior and posterior fascial plane. Peritoneum constitutes the hernia sac. Hernias usually develop several months after surgery and they are not associated with small bowel obstruction. They appear as an asymptomatic swelling by the wound site.\n\n\\(iii\\) Special typeDehiscence"
-"Introduction {#S5}\n============\n\nThe prevalence of overweight and obesity has increased at an alarming rate ([@R1]). The World Health Organization projects that by 2015, approximately 2.3 billion adults will be overweight and more than 700 million will be obese ([@R2]). As the prevalence of obesity increases, the demand for research in this area has also increased, creating more articles in this topic area for clinicians and others to consider. Clinicians are expected to keep up to date and apply the current best evidence from health care research to their clinical care ([@R3]) but are challenged by more than two million new research articles published each year in medical and scientific journals ([@R4]). Retrieving high-quality and methodologically sound research articles in a given topic area is difficult ([@R5]), making it more important than ever for clinicians to carefully select which journals to read ([@R6]). A study by Burke et al ([@R7]) found that at least half of the surveyed residents in physical medicine and rehabilitation looked for important articles within one of six journals; four of the six were specific to their discipline. A study by Weiner et al ([@R8]) revealed that journal selection should not be based on intuition alone."
-"Introduction {#Sec1}\n============\n\nThe fermentative activity of yeast has been used to make bread and fermented beverages by mankind since its early settlement. Thus the physiological capabilities of yeast are directly linked to human development and culture. These processes depend fundamentally on the respiro-fermentative phenotype also called the Crabtree effect of some yeast species, most prominently baker's yeast (*Saccharomyces cerevisiae*).\n\nA similar phenomenon as the Crabtree effect can be observed in cancer cells which have high glycolytic rates and lactic acid fermentation, termed the Warburg effect^[@CR1]^. The Crabtree effect of *S. cerevisiae* is seen as a unicellular model to study the genetic and metabolic control of the Warburg effect^[@CR2]--[@CR6]^.\n\nBeing a fundamental feature of yeast metabolism, the Crabtree phenotype defines whether a yeast can perform simultaneous respiration and fermentation under aerobic conditions at high growth rates. Crabtree-positive (respiro-fermenting) yeasts, such as *S. cerevisiae*, *Vanderwaltozyma polyspora, Torulaspora franciscae, Lachancea waltii*, and *Lachancea kluyveri* (syn. *Saccharomyces kluyveri*) can exhibit alcoholic fermentation in the presence of oxygen until glucose reaches low concentrations^[@CR7],[@CR8]^. Nevertheless, rather few yeasts show this phenotype. In most cases, glucose uptake and glycolysis are strictly regulated to match the TCA cycle capacity, so the exclusive use of respiration leads to"
-"Introduction\n============\n\nIt comes as no surprise that the Internet has changed the way patients diagnosed with cancer and their caregivers seek information about their diagnosis. The influx of big data and the use of electronic health records (EHR) in the health care system \\[[@ref1]\\] have been instrumental in the evolution of the relationship between large datasets with both patients and providers. Even though the Health Information Technology for Economic and Clinical Health Act (HITECH), which was passed by Congress in 2009 \\[[@ref2],[@ref3]\\], is increasing the adoption and use of EHRs, the health care industry as a whole has not been as quick to adopt changes into their systems \\[[@ref4]\\], such as integrating decision support tools or predictive tools (known as nomograms) into physician workflow \\[[@ref5]\\].\n\nThe lack of uptake of tools into EHR systems, matched with the increase in tool development as it relates to cancer prognosis, has led to a number of cancer prognostic tools being housed outside of the health care setting. These cancer prognostic tools often use clinical or population datasets (or sometimes a combination of both) to tell a story about millions of patients and their health. On their own, population datasets are overwhelming and"
-"1. Introduction {#sec0001}\n===============\n\nModeling and simulation are eminently appropriate tools for optimizing malaria control strategies [@bib0001], helping elucidate their probable mechanisms of action, and optimizing intervention timing and coordination. To compare different methods of suppressing infection in a community with endemic disease, we extend an established Ross/Macdonald model variant for mosquito-born parasite transmission to simply incorporate time-dependent control interventions. In particular, we focus on mass drug administration (MDA) and indoor residual spraying (IRS), two strongly effective interventions which address, respectively, the human and the mosquito reservoirs of parasitemia. These interventions have direct and complementary effects on the transmission dynamics.\n\nThere is context and precedence for this investigation from a long history of both MDA and IRS campaigns, sometimes used in combination. In the post-WWII era, DDT and Chloroquine prompted large scale campaigns with the ensuing Global Malaria Eradication Programme of 1955--1969 [@bib0002], [@bib0003]. Subsequent eradication efforts both succeeded and failed [@bib0004], [@bib0005] and a legacy of this era is acquired resistance [@bib0006]. Both Chloroquine and DDT lost efficacy with successive sprayings and the regularly high chemical pressure stemming from frequent treatment with a single pharmaceutical. Later, from 1969 to 1976, the Garki project investigated and recorded many aspects of"
-"I[NTRODUCTION]{.smallcaps} {#sec1-1}\n==========================\n\nPalliative care is focused on providing relief of physical, psychological, social, and spiritual symptoms for patients with life-limiting illness and their families. There are 159 million people in Bangladesh, and the gross national income per capita is US\\$1080.\\[[@ref1]\\] Annual health expenditure per capita is US\\$16.20, 64% of this spending is out of pocket.\\[[@ref2]\\] In the past 20 years, Bangladesh has made remarkable progress in the field of maternal and child health, and in 2014, the majority (59%) of deaths were due to noncommunicable diseases.\\[[@ref3]\\]\n\nBangladesh is estimated to have more than 600,000 people in need of palliative care at any point in time.\\[[@ref4]\\] Annually, there are 140,000--200,000 patients newly diagnosed with cancer and 100,000 deaths attributable to cancer.\\[[@ref2][@ref5][@ref6]\\] Experience from a local cancer hospital (National Institute of Cancer Research and Hospital) found that 80%--90% of patients with cancer present to oncologists with incurable disease.\\[[@ref4]\\]\n\nPalliative care remains in a very early stage of development in Bangladesh. A recent global mapping exercise found that there are seven palliative care services (public and private) operating in Bangladesh.\\[[@ref7]\\] There is one specialized palliative care institution, the Centre for Palliative Care (CPC) at Bangabandhu Sheikh Mujib Medical University (BSMMU), which provides"
-"**Specifications Table**TableSubject area*Chemistry*More specific subject area*Physical chemistry*Type of data*Tables and figures*How data was acquired*Atomic absorption spectrometer 3110 (Perkin Elmer); Spectrophotometer with an ATR universal accessory (Spectrum 400, Perkin Elmer Cetus Instruments); Microcalorimeter \u03bcDSC 7 Evo (Setaram); Microtensiometer EZPiplus (Kibron) and spectrometer AVANCE-III 500 (Bruker)*Data format*Analyzed results*Experimental factors*Commercial forms were used without further purification*Experimental features*Physicochemical properties were determined for \u03ba-carrageenan and two surfactants (SSL and Tween 20) by using atomic absorption, infrared and nuclear magnetic resonance, calorimetry, and measurements of surface tension*Data source location*Authors' affiliation*Data accessibility*Data are presented in this article*\n\n**Value of the data**\u2022Intrinsic ions content is a key factor in mixtures of ionic components, like \u03ba-carrageenan and SSL, because interactions between them can be affected by the presence of salts.\u2022DSC analysis, IR and NMR spectra are used to identify the components and to determine their purity, which are relevant characteristics since the presence of distinct species could modify their behavior.\u2022Surface tension is useful to know the adsorption parameter of surfactants and how it changes in a mixture with other components.\n\n1. Data {#s0005}\n=======\n\nSSL had sodium as the primary ion and small quantities of other ions, whereas Tween 20 only had traces of ions. \u03ba-carrageenan was found mainly"
-"Background {#Sec1}\n==========\n\n*Campylobacter* species are the most important gut pathogens in developed countries. Campylobacteriosis occurs in 1% of the US population each year \\[[@CR1]\\] and costs the European Union alone an estimated \u20ac2.4 billion annually \\[[@CR2]\\]. In developing countries the disease is endemic but extensively unrecorded and it is prevalent in infants (\\<\u20091\u00a0year), with isolation rates of 8 to 21% of all diarrhoea samples \\[[@CR3]\\]. In developed countries the disease also occurs in older age groups. There is considerable pressure to reduce disease burden with government agencies having strategies to monitor disease. The public health burden, however, continues to rise. Illness is often associated with consumption of chicken \\[[@CR4]--[@CR9]\\] but this does not account for all cases \\[[@CR10]\\]. In temperate regions *Campylobacter* incidence is also predictably seasonal \\[[@CR10], [@CR11]\\] but the causes of this seasonality are not understood. *Campylobacter* is found in many animal species and these along with environmental exposures have been suggested to explain 20--40% of disease burden \\[[@CR12]\\]. The relative importance of different exposures to disease remains largely unquantified which renders effective intervention to reduce the disease burden difficult. Furthermore, understanding of the interaction between human host and pathogen is poor as seroconversion rates"
-"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"
-"Introduction {#s1}\n============\n\nWnt mediated activation of Frizzled receptors results in translocation of \u03b2-catenin to the nucleus where it binds to TCF/LEF transcription factors to induce expression of Wnt target genes. Wnt signaling proteins mediate a wide variety of biological processes during development, including maintenance of stem cell populations ([@bib13]; [@bib1]), and aberrant Wnt activation is linked to several diseases, including cancer ([@bib2]). Vermeulen and colleagues showed that high Wnt activity correlated with markers of colon cancer stem cells and enhanced clonogenic potential of cells ([@bib20]). They also showed that stromal myofibroblasts secreted factors such as HGF that enhanced Wnt activity and clonogenicity ([@bib20]). Further, treatment of more differentiated cells with myofibroblast conditioned medium (MFCM) enhanced Wnt activity in these cells and enhanced clonogenicity in vitro and in vivo, illustrating that colon cancer cell stemness can be modified by the microenvironment.\n\nTo assess Wnt activity in colon cancer cells, Vermeulen and colleagues utilized the TOP-GFP reporter system, a LEF-1/TCF responsive promoter driving expression of the enhanced GFP reporter ([@bib17]). In Figure 2F, colon cancer stem cells were isolated from human colon cancer specimens and transduced with the TOP-GFP reporter. Wnt activity was then assessed using fluorescence-activated cell sorting (FACS) in"
-"1. Introduction {#sec1}\n===============\n\nSkeletal muscle injury can be caused by a variety of conditions such as direct trauma, disuse, ischemia, exercise, toxins, and genetic diseases. To face these challenges, skeletal muscle has developed a remarkable regenerative capacity, which relies on muscle stem cells, named satellite cells. Skeletal muscle regeneration is a tightly regulated process during which quiescent satellite cells are activated and become proliferating myoblasts, which will differentiate and fuse to form multinucleated myotubes (newly formed muscle fiber) \\[[@B1]\\]. The coordination of the myogenesis process (formation of new muscle tissue) involves the cooperation of numerous other cellular and molecular components \\[[@B2]\\]. Particularly, the onset, development, and the resolution of the inflammatory response play an instrumental role in the regulation of myogenesis.\n\nMonocytes and macrophages are predominant myeloid cells that chronologically accumulate in skeletal muscle at the onset of injury-induced inflammation \\[[@B3]\\]. There are numerous evidences indicating that macrophages are key regulators of different biological processes involved during skeletal muscle regeneration, such as myogenesis, fibrosis, inflammation, and revascularization \\[[@B3]--[@B9]\\]. On the other hand, in chronic degenerative conditions, the excessive and disorganized influx of macrophages stimulates muscle necrosis, fibrosis, and defective muscle repair. Therefore, the spatiotemporal regulation of inflammation is vital"
-"1. Introduction {#sec1-biosensors-06-00028}\n===============\n\nEllington and Szostak \\[[@B1-biosensors-06-00028]\\] developed for the first time an in vitro selection technique that allowed the discovery of oligonucleotides or peptides that bind to specific targets with high specificity and affinity. Since then, the interest in aptamers has increased significantly \\[[@B2-biosensors-06-00028],[@B3-biosensors-06-00028],[@B4-biosensors-06-00028]\\] because of their advantages compared to other biological receptors. Among these properties, we can enumerate the size, the synthesis and the stability. Additionally, the aptamer-analyte bound might be disrupted by very small changes.\n\nWhispering gallery mode based resonators (WGMR) have attracted much attention in the biomedical sensing field \\[[@B5-biosensors-06-00028],[@B6-biosensors-06-00028]\\], including aptamer based sensors for thrombin detection \\[[@B7-biosensors-06-00028],[@B8-biosensors-06-00028]\\], vascular endothelial growth factor \\[[@B8-biosensors-06-00028]\\] and toxins such as aflatoxin M1 \\[[@B9-biosensors-06-00028]\\]. WGMR have different morphologies with particular spectral features such as including narrow linewidth, high stability, and tunability. Regarding sensing applications, the most important properties are the ultrahigh quality factor *Q* and long lifetime of WGMR, where the change in *Q* or the shift resonant wavelength is used for measuring the change of parameters in the surrounding environment or binding event on the WGMR surface. WGMR are a valid alternative to other evanescent wave (EW) sensors, such as surface plasmon resonators (SPR) \\[[@B10-biosensors-06-00028]\\]. The feasibility of"
-"Introduction\n============\n\nCervical cancer is the most common gynecological carcinoma in women worldwide [@B1]. In particular, locally advanced cervical cancer (LACC) accounts for a large proportion of patients in China, most likely because cervical cytologic screening methods have not been widely used in Chinese practice. The current standard treatment for patients with LACC is concurrent chemoradiotherapy (CCRT) globally. For LACC patients without para-aortic lymph node metastases, the standard radiation therapy treatment field is the pelvis. The para-aortic lymph node region is excluded from the treatment field, despite the fact that it plays an important role in cervical cancer metastasis and is one of the most common sites of tumor relapse [@B2], [@B3]. To reduce the incidence of para-aortic lymph nodes failure (PALNF) and improve the survival of cervical cancer patients without para-aortic lymph node, para-aortic lymph nodes region is included in the target volume of radiation therapy in some institutes. This is prophylactic extended-field irradiation in patients with cervical cancer.\n\nIt is controversial whether prophylactic extended-field irradiation is beneficial for patients with LACC who were treated with CCRT [@B4]-[@B10]. In our previous study, extended-field irradiation decreased para-aortic lymph node failure (PALNF) and distant failure rates in patients with cervical cancer."
-"Background\n==========\n\nAngiogenesis, or the formation of new blood vessels from the existing ones, is an essential biological process for maintaining numerous physiological functions ranging from cell growth, proliferation, repair of damaged cells to wound-healing *in vivo*\\[[@B1]-[@B3]\\]. Throughout the life of an individual and during embryonic development, various pro-angiogenic and anti-angiogenic factors (i.e. promoters and inhibitors of angiogenesis respectively) produced by various cell types maintain a balance between neovascularization and angiogenesis programs in a cyclic manner \\[[@B4],[@B5]\\]. Exactly how abnormal angiogenic signals are generated *in vivo*is not well-understood, but an imbalance in the production of one or more critical factors can alter the protein-protein interaction pathways and induce angiogenic anomalies including inflammation, vascular dementia, hemangioma, dysfunctional uterine bleeding, ovarian hyperstimulation and choroidal/intraocular disorders to name a few \\[[@B1],[@B6]\\]. Angiogenesis is also critical for cancer metastasis, diabetic blindness, age-related macular degeneration, rheumatoid arthritis, psoriasis, and for the development of new blood vessels that supply oxygen and nutrients to the body when aortas are clogged (thrombosis) \\[[@B2],[@B6]\\].\n\nIn both the neoplastic and non-neoplastic diseases, endothelial cells have been shown to express various isoforms of the vascular endothelial growth factors (VEGFs) which bind to their cognate VEGF receptors (VEGFRs), activate their associated protein"
-"Introduction {#s1}\n============\n\nThe healthcare systems in Eastern European countries in general, and Romania in particular, have been significantly affected by the political changes in the 1990s, de-centralisation, transition to market-orientated economies, as well as various political and economic crises [@pone.0097833-Bara1], [@pone.0097833-Holt1], [@pone.0097833-Krcmery1], [@pone.0097833-Lakey1].\n\nWith the public attention being focused mainly on HIV and tuberculosis, there are only few data available on other issues such as, *e.g.,* antibiotic resistance in various pathogens such as *Staphylococcus aureus*. Since its first description roughly 50 years ago, methicillin-resistant *S. aureus* (MRSA) has globally become a public health threat. While there is an abundance of epidemiological and typing data from Western Europe, the United States and Australia, relatively few data are available for other parts of the world. Unfortunately, this is also true for Eastern Europe including Romania. It is known that the MRSA rates are extremely high, ranging from approximately 30% up to 70% in recent Romanian studies [@pone.0097833-Dorneanu1], [@pone.0097833-Szekely1], [@pone.0097833-Dorobat1], [@pone.0097833-Ionescu1], [@pone.0097833-Kock1], [@pone.0097833-Nastase1], [@pone.0097833-Nica1], [@pone.0097833-Vremera1], thus reaching the highest prevalence levels reported anywhere in the world. According to the ECDC antimicrobial resistance surveillance (formerly EARSS), the MRSA rate among invasive infections was \"equal to or above 25%\" in 2008 and slightly above"
-"Introduction {#Sec1}\n============\n\nIn the past decade, the high-numerical-aperture (NA) focusing of a cylindrical vector beam has attracted considerable interest because of its novel focusing property^[@CR1]--[@CR5]^. A number of unique focal field distributions, such as spherical spot^[@CR6]--[@CR8]^, optical chain^[@CR9],\\ [@CR10]^, flattop focus^[@CR11]^, light cage^[@CR12]^ and so on. In particular, notable attention has been devoted to the generation of light needles with ultra-long depth of focus (DOF), narrow radial width, uniform intensity, and high-purity polarization state^[@CR13],\\ [@CR14]^. Many methods have been proposed to create optical needles with these properties. For example, by focusing a radially polarized Bessel--Gaussian beam with a high-NA lens and a diffractive optical element (DOE), a longitudinally polarized needle with 0.43\u03bb beam size and approximately 4\u03bb DOF was first obtained by Wang *et al*.^[@CR15]^. An ultra-long light needle (\\~14\u03bb) with a strong transversally polarized field, uniform intensity along the optical axis and a subwavelength beam size (\\~0.9\u03bb) was obtained by focusing hybrid polarized vector beams through a dielectric interface under an annular high-NA lens^[@CR16]^. A high-NA Fresnel zone plate (FZP) illuminated by a radially polarized vector beam was used to form a super-Gaussian optical needle with 0.366\u03bb beam size and a strong longitudinally polarized field^[@CR17]^. By modulating the"
-"The authors confirm that all data underlying the findings are fully available without restriction. All relevant data are within the paper.\n\nIntroduction {#s1}\n============\n\nBrain metastases are secondary brain tumors that result from the spread of malignant tumors from locations other than the brain, and they are more common than primary brain tumors [@pone.0109308-Bhangoo1]--[@pone.0109308-Tsao1]. According to statistics, 20--40 percent of malignant tumor cases will undergo brain metastases over the course of the diseases [@pone.0109308-Jenkinson1], [@pone.0109308-Tsao1]. Of these cases, only approximately 2/3 cases have symptoms, such as headache, seizures, nausea and vomiting, etc., or focal neurological signs that lead to the diagnosis. However, the optimal management strategy for these patients cannot be determined at the stage of their diagnosis [@pone.0109308-Bhangoo1], [@pone.0109308-Serres1]. Therefore, there is a clinical need for the development of effective modalities that can provide a reliable diagnosis of brain metastases at an early stage.\n\nOf the available diagnostic methods for brain metastases, imaging modalities play an important role in non-invasive diagnosis and treatment management [@pone.0109308-Bhangoo1], [@pone.0109308-Jenkinson1], [@pone.0109308-DeWever1]--[@pone.0109308-Bochev1]. Computed tomography (CT) has been widely used in the diagnosis, staging, monitoring, therapeutic effect evaluation and follow-up due to its accessibility and affordability [@pone.0109308-DeWever1], [@pone.0109308-Nomoto1]. Routine cranial CT and contrast-enhanced CT (CECT)"
-"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,"
-"Introduction {#s1}\n============\n\nEfforts to design a vaccine against Human Immunodeficiency Virus type 1 (HIV-1) have been disappointing. The principal empirical strategies that yielded successful vaccines against other viruses in the past have not provided protective immunity. The first unsuccessful attempts included strategies using inactivated whole virus or virus protein subunits, which would be expected to raise antibodies and HLA class II-restricted helper responses against HIV-1. When such approaches (including a phase III trial of the HIV-1 envelope-based \"AIDSVAX\") failed to produce protective humoral immunity, researchers turned to the idea that a vaccine to elicit HLA class I-restricted cytotoxic T lymphocyte (CTL) responses might provide protection against disease if not infection, given the increasingly clearly protective role of CTL in the immunopathogenesis of HIV-1 infection.\n\nThe attempts to generate HIV-1-specific CTL responses with a vaccine have focused heavily upon vector development for immunogenicity, as safety concerns precluded the classical empiric approach of using live-attenuated HIV-1. Although numerous strategies ranging from naked plasmid DNA to replication-competent vaccinia vector showed promise in animal models, to date only recombinant adenovirus serotype 5 (rAd5) has appeared to be reliably immunogenic for CTL responses in humans. Vaccination of HIV-1-uninfected persons with modified replication-incompetent rAd5 containing"
-"Dear Editor:\n\nBeh\u00e7et\\'s disease (BD), a chronic inflammatory disease, is characterized by oral apthae and genital ulcer, arthritis, cutaneous lesions, such as non-bacterial folliculitis, and erythema nodosum, as well as ocular, gastrointestinal and neurological manifestations. Although genital ulcers are histologically similar to oral aphthae, they are deeper than oral aphthous ulcers and are a major criterion for diagnosis. We present a case of scrotal squamous cell carcinoma (SCC) in a patient diagnosed with BD.\n\nA 39-year-old male patient was admitted to our clinic with recurrent oral aphthae and a deep ulcer, covering the scrotum and perineal regions. The patient had been suffering from recurrent oral aphthous lesions for almost 11 years, and he had been medicated with 1.5 mg/day of colchicine, with a diagnosis of BD. Over the preceding 2 years, the genital ulcer had gradually enlarged and deepened. During this period, the patient received topical treatment and systemic antibiotics therapy; however, he was lost to follow-up.\n\nDermatological examination revealed a large and painless ulcer, extending from the scrotum to perineal region, which was approximately 8 cm in diameter ([Fig. 1](#F1){ref-type=\"fig\"}). This ulcer had an indurated floor and also sharp and irregular edges. No growth was observed in the bacterial"
-"Introduction {#sec1}\n============\n\nBradycardia after left atrial surgery using a superior transseptal approach is common. However, the mechanism of bradycardia evaluated by electroanatomical mapping has rarely been reported.\n\nCase report {#sec2}\n===========\n\nAn 80-year-old woman without any past medical history was admitted to our hospital for gradually deteriorating episodes of dizziness on exertion over 12 months. The electrocardiogram was normal. A left atrial myxoma was detected by transthoracic echocardiography and its size was 51 mm \u00d7 32 mm and was growing on the left atrial septum. With a superior transseptal approach, the myxoma was resected along with the atrial septum. The defect of the atrial septum was closed with a pericardial patch. The diagnosis of a myxoma was confirmed by histology. The electrocardiogram after surgery showed junctional rhythm with retrograde P waves and an incessant atrial tachycardia with negative P waves in leads \u2161, \u2162, and aVF. She suffered from fatigue during junctional rhythm and palpitations during atrial tachycardia ([Figure\u00a01](#fig1){ref-type=\"fig\"}). As the bradycardia and tachycardia persisted for more than 3 weeks after the surgery, we decided to perform an electrophysiologic study.Figure\u00a01The electrocardiogram after surgery showing junctional rhythm with retrograde P waves and an incessant atrial tachycardia with negative"
-"All relevant data are within the manuscript and its Supporting Information files. Raw sequencing data is uploaded to the NCBI BioProject repository and accessible via the following URL: <https://www.ncbi.nlm.nih.gov/bioproject/PRJNA626000/>.\n\nIntroduction {#sec001}\n============\n\nSoil microbial communities are essential to the fertility of soil and success of agricultural crops, yet a substantial portion of microbial life within the soil remains uncultivated and under-explored \\[[@pone.0232453.ref001]\\]. The composition and diversity of these soil microbial communities are important indicators of the soil fertility. Within agricultural soils, microbes play essential roles in supporting plant development through processes such as nitrogen fixation, growth hormone synthesis and nutrient recycling of decomposed plant matter \\[[@pone.0232453.ref002],[@pone.0232453.ref003]\\]. An array of farming techniques has been developed with the purpose of manipulating the microbial composition within soil in an effort to promote soil health and enhance crop quality. An approach that has demonstrated much promise in recent years is cover cropping, which is the practice of planting specific species of crop(s) to maturity then, without harvesting, mowing the cover crop back into the soil. Utilized in both conventional and organic agriculture, this technique recycles nutrients back into the soil and has been found to contribute to both pest management and the development of"
-"Sir,\n\nWe appreciate the critical comments made by Dr. Agarwal.\\[[@CIT1]\\] The highlight of our article is that approximately 30% of patients in dialysis will not be diagnosed HCV+ve with the currently available 3^rd^ generation Elisa.\\[[@CIT2]\\]\n\nWe will try to clarify the points raised as they appear in the letter to the editor.\n\n1.  We agree that there is significant literature available on HCV from Indian centers. However, most of these do not utilize HCV RNA for diagnosis. We related our observations to studies using similar techniques based on PCR. Majority of the references quoted are out of context because of methodology,\\[[@CIT5][@CIT6][@CIT8][@CIT9][@CIT10][@CIT11][@CIT12][@CIT14]\\] non-relevant group studies\\[[@CIT7][@CIT15][@CIT16][@CIT17]\\] or review article.\\[[@CIT13]\\]\n\n2.  Duration of ESKD/ESRD, whether on HD or renal transplant, is a risk factor for HCV.\\[[@CIT3][@CIT4][@CIT18]\\]\n\n3.  On treatment, HCV patients are excluded because this may affect results of HCV PCR. In fact, some positive patients on treatment were HCV RNA negative at the time of our study. (These were not part of the study)\n\n4.  We do not separate HCV patients but follow universal precautions, while HCV dialyzers are reprocessed in a separate area. However, this has not been the focus of our article.\n\n5.  This study looks at point prevalence of"
-"Introduction {#Sec1}\n============\n\nApple is one of the four major fruits in the world. Its root system architecture constitutes an important part of apple seedlings, which is buried deep in the soil to fix plants as the main vegetative organ for plant growth and metabolism. The morphological parameters of root mainly include the morphological parameters of main root, lateral root and fibrous root of the seedling. The root of the diaphysis is the main root, and the branches on it are collectively referred to as lateral roots. The fine roots formed by several branches on the lateral roots are called fibrous roots. As the main factors reflecting the growth of roots, they have an impact on shoot and leaf growth aboveground, carbon assimilation, flower bud differentiation through absorption of water, nutrients and endogenous hormones. Neri et al. showed that lateral roots could be formed anywhere along the primary roots of strawberry plants from a few stem cells distributed along the pericycle close to the protoxylem arches \\[[@CR1]\\]. The tree body also establishes a close connection between matter and energy exchange through roots and soil during its life activities. The structure and form of root system is affected by the physical"
-"###### Strengths and limitations of this study\n\n-   This is a protocol for a scoping review that aims to provide evidence to inform the use of smartphone ophthalmoscopy in patients with diabetes mellitus.\n\n-   Our findings may be of particular relevance to clinicians in rural or resource-constrained settings with limited access to standard diagnostic approaches for diabetic retinopathy (DR) identification.\n\n-   We will employ a scoping review approach to perform a comprehensive search of the literature and thorough data analysis, with the aim of providing reliable findings on the accuracy of smartphone ophthalmoscopy for DR identification.\n\n-   While not a requirement of scoping reviews, our review will include a quality assessment of the included studies; a potential limitation of this scoping review is the possibility of missing relevant articles.\n\nIntroduction {#s1}\n============\n\nDiabetic retinopathy (DR) is the primary cause of impaired vision in patients 20--74 years of age.[@R1] It is a common microvascular complication of diabetes mellitus (DM): one-third of patients with DM have signs of DR and of these people, one-third possess sight-threatening DR.[@R2] DR is classified into proliferative DR (PDR) and non-proliferative DR (NPDR). PDR is characterised by neovascularisation, that is, angiogenesis in response to retinal tissue hypoxia."
-"All relevant data are within the paper.\n\nIntroduction {#sec005}\n============\n\nThe provision of safe, reliable healthcare has become a national and international priority for both the developed\\[[@pone.0138490.ref001], [@pone.0138490.ref002]\\] and the developing world\\[[@pone.0138490.ref003]\\]. It is now more than 20 years since the widespread recognition that the delivery of healthcare in complex systems which have not been carefully and rationally designed to minimise risk can and frequently does result in harm\\[[@pone.0138490.ref004]\\], with levels of risk equivalent to micro light aircraft flight\\[[@pone.0138490.ref005]\\]. Attempts have been made to improve the sustainable delivery of safe healthcare using a variety of approaches. It has been recognised that surgery is one of the most challenging areas of healthcare in which to provide safe and reliable care, with incident analysis studies consistently finding a higher level of harm than in medical specialities\\[[@pone.0138490.ref006]--[@pone.0138490.ref008]\\].\n\nThe concept of resilience demands consistent, safe delivery of output despite changing circumstances\\[[@pone.0138490.ref009], [@pone.0138490.ref010]\\]. Studies of high reliability organisations (HROs) have highlighted both the care with which processes are designed, defined and standardised, and the emphasis put on optimising human teamwork and communications. There have been attempts to translate concepts from HROs (aviation, nuclear, manufacturing and petrochemical) into the healthcare industry through improvement interventions of various"
-"Introduction {#sec1-1}\n============\n\nRuminants are poor candidates for general anesthesia because of the increased risk of complications such as regurgitation, bloating, and muscle damage \\[[@ref1]\\]. Therefore, surgical interventions under local anesthesia in standing animals are preferred \\[[@ref1]\\]. Paravertebral nerve block, local infiltration of anesthetic agents, intravenous regional limb perfusion, and epidural anesthesia are commonly used in ruminant surgery \\[[@ref1]\\]. Various obstetrical operations, surgical procedures of the anus, vulva, perineum, caudal udder, and scrotum are performed under epidural analgesia. Epidural analgesia is also used as an adjunct for the treatment and control of tenesmus \\[[@ref1],[@ref2]\\].\n\nCaudal epidural analgesia has received plenty of research over the last 10 years. Many anesthetic drugs and combinations thereof have been experimented in ruminants with variable successful results. By searching the current literature, however, no comprehensive review articles that summarize published findings regarding epidural analgesia in cattle, camels, and buffalos can be found. Therefore, the objectives of this article were to comprehensively review and summarize all scientific data available in the literature on techniques and drugs or drug combinations used for epidural anesthesia in cattle, camel, and buffalo. Databases - such as Google scholar, Pubmed, and ResearchGate - were used to find newly published articles. Keywords"
-"Background\n==========\n\nTraditional methods of genetic evaluation depend on the accumulation and analysis of phenotypic and pedigree information to produce estimated breeding values (EBV). For a given selection intensity, response to selection measured in genetic standard deviations is proportional to the ratio of the accuracy of EBV and generation interval. In practice, accuracy increases but the generation interval is extended by waiting until the individual or offspring phenotypic records are available to estimate genetic merit, usually decreasing selection response. Genomic selection is a recently developed technology \\[[@B1]\\] that is beginning to revolutionize animal breeding. It is currently possible to genotype cattle for at least 50 000 single nucleotide polymorphisms (SNP) using a variety of assays, such as the BovineSNP50 \\[[@B2]\\], BovineHD (Illumina, San Diego, CA) or Axiom BOS 1 (Affymetrix, Santa Clara, CA) assays. These SNP panels can be used to produce direct genomic values (DGV), as proposed by Meuwissen et al. \\[[@B1]\\], via the estimation of marker effects from the analysis of a population with SNP genotypes and trait phenotypes (training set). The resulting estimates of SNP effects are then used in conjunction with SNP genotypes and trait phenotypes from a new group of animals (validation set) to evaluate"
-"Background {#Sec1}\n==========\n\nIn Ontario, Canada, 98.9% of individuals access health care at least once in their last year of life costing the healthcare system, on average, CA\\$4.7 billion annually, or approximately 10% of the annual healthcare budget \\[[@CR1], [@CR2]\\]. Hospitalizations alone account for approximately 43% of those costs, with 20% of those costs as a result of at least one ICU visit. Current guidelines from the Society of Critical Care Medicine state that \"in general, ICUs should be reserved for those patients with reversible medical conditions who have reasonable prospect of substantial recovery.\" \\[[@CR3]\\]. A prospective cross-sectional study conducted in a Canadian teaching hospital in 2014 suggested that in 37% of patients admitted to the ICU, at least one member of the care team believed that a patient was being given excessive or inappropriate care in the ICU \\[[@CR4]\\]. Many studies suggest that advance care planning and palliative care interventions rather than ICU admissions in older, critically ill or dying patients reduce healthcare costs and provide patients with a better quality of life in the time they have left \\[[@CR3], [@CR5]--[@CR7]\\]. Despite this evidence, in both the USA and Canada, ICU use has been increasing over time \\[[@CR1], [@CR5]\\]."
-"1.. Introduction\n================\n\nMineral clays of the smectite group present a set of structural characteristics that make them attractive for the development of catalysts, sorbents, supports for drug or enzymes, and intercalation of organic molecules \\[[@b1-ijms-11-01546]--[@b5-ijms-11-01546]\\]. Organosilanes are widely used for the modification of silica surfaces. The silylation mechanism for the attachment of organosilane to amorphous silica and alumina surfaces has been commonly reported \\[[@b6-ijms-11-01546]--[@b8-ijms-11-01546]\\]. Recently, organosilanes have been employed for the modification of layered silicates, with smectites and vermiculites being the most commonly clays used to investigate the functionalization processes \\[[@b9-ijms-11-01546]--[@b12-ijms-11-01546]\\]. Organo-functional silanes, represented as RSiX~3~, are often used as coupling agents to enhance the adhesion between polymer and silica filler. The methoxy or ethoxy groups, represented by X, can be hydrolyzed with water. The silanol groups of hydrolyzed coupling agents can be condensed with other silanol groups on a glass or ceramic surface. The organo-functional group, R, can be bonded chemically to a polymer matrix. Thus, the adhesion between polymer and inorganic fillers was improved due to the chemical bonds that formed at the interface. To our best knowledge, how the interface inside organic--inorganic composite materials as well as the coupling agents affect the drug release property has"
-"Introduction\n============\n\nInvasive candidemia is a major cause of increased mortality among ICU patients. Antifungal agents like liposomale amphotericin B and azoles could not accomplish the claim to be first choice in the treatment of invasive fungal infection (IFI) because of side effects and effectiveness. Especially, cardiothoracic surgery patients as a group of high-risk patients are in a focus for new strategies and agents. A new class of antimycotic agents, the echinocandins, with a low profile of side effects, low interactive potential and high effectiveness in the treatment of candidemia, is a powerful option in the treatment of IFI. We report our single-center experience with a modified clinical treatment approach based on clinical score of Leon and using echinocandins as first-line therapy for proven and suspected fungal infection.\n\nMethods\n=======\n\nFrom May 2011 to October 2012, 2,844 patients were treated on our cardiothoracic ICU. We evaluated 37 cardiothoracic postoperative patients with proven or suspected IFI or prophylaxis (Figure [1](#F1){ref-type=\"fig\"}). The records were evaluated for cardiothoracic procedures, microbiological and yeast date, cardiothoracic surgery score (CASUS), ICU and clinical data.\n\n![**Cologne antifungal strategy**.](cc12023-1){#F1}\n\nResults\n=======\n\nMean age was 67.4 years with 64% male patients. Most patients had combined CABG and valve procedure"
-"Background {#Sec1}\n==========\n\nWell-designed observation studies permit researchers to assess treatment effects when randomisation is not feasible. This may be due to cost, suspected non-equipoise treatments or any number of other reasons \\[[@CR1]\\]. While observational studies minimise these issues by being cheaper to run and avoiding randomisation (which, although unknown at the time, may prescribe patients to worse treatments), they are potentially subject to issues such as unmeasured confounding and increased possibility of competing risks (where multiple clinically relevant events occur). Although these issues can arise in any study, Randomised Controlled Trials (RCTs) attempt to mitigate these effects by using randomisation of treatment and strict inclusion/exclusion criteria. However, the estimated treatment effects from RCTs are of potentially limited generalisability, accessibility and implementability \\[[@CR2]\\].\n\nA confounder is a variable that is a common cause of both treatment and outcome. For example, a patient with a high Body Mass Index (BMI) is more likely to be prescribed statins \\[[@CR3]\\], but are also more likely to suffer a cardiovascular event. These treatment decisions can be affected by variables that are not routinely collected (such as childhood socio-economic status or the severity of a comorbidity \\[[@CR4]\\]. Therefore, if these variables are omitted form (or"
-"Introduction {#s1}\n============\n\nMeiotic recombination occurs during prophase I when homologous chromosomes are synapsed along their entire length. Synapsis is defined as the close and stable association of homologous chromosomes through a proteinaceous structure called the synaptonemal complex (SC). In most organisms, this complex is composed of two main parts: lateral elements that attach along the axis of each homologous chromosome and transverse elements that span the central region of the SC and function to tether the homologs [@pgen.1001059-Page1], [@pgen.1001059-Zickler1]. At the leptotene/zygotene stages of meiotic prophase, these structural proteins begin to load onto the chromosome axes, and are completely assembled at pachytene, when homologous chromosomes are synapsed along their entire length.\n\nRecombination between the homologous chromosomes initiates with DNA double-strand breaks (DSBs) that are repaired as either crossovers or noncrossovers [@pgen.1001059-McKim1]--[@pgen.1001059-Keeney1]. Crossovers establish chromatin linkages called chiasmata, which, along with sister chromatid cohesion, hold homologs together after recombination has been completed and chromosomes have dissociated their SC proteins. Chiasmata help orient the homologous chromosomes on the metaphase I spindle and ensure their proper segregation at anaphase I. The failure to establish a crossover/chiasma can result in the nondisjunction of homologs and lead to aneuploid gametes.\n\nCrossover formation is a"
-"1. Introduction {#sec1}\n===============\n\nA long segmental bone defects repair is one of the challenging problems in orthopaedic surgery. Although allogenic bone grafts are a current major option \\[[@B1]--[@B3]\\], this technique is associated with problems of significant failure rates, poor mechanical properties, and immunological rejection \\[[@B2]\\]. Porous materials are of significant importance for bone tissue engineering applications because of the good biological fixation to surrounding tissue through bone tissue \\[[@B4]\\].\n\nPorous titanium and titanium alloys have been investigated as they provide favourable mechanical properties with an elastic modulus closed to that of natural bone under a load bearing condition \\[[@B5]\\].\n\nSurface characteristics of porous titanium are important determinants in its scaffold properties since the surface condition of titanium has been reported to play a critical role in bone formation associated with superior osteoblast adhesion and subsequent cell behaviors \\[[@B6]--[@B10]\\].\n\nRecent studies have raised a concern that degradation of biological ability with increase in adsorption of organic impurities on titanium-based biomaterials \\[[@B6], [@B7]\\]. This reduces hydrophilicity, adsorption of cell-binding proteins, and subsequent cell functions. Titanium-based biomaterials therefore need to be fabricated as clean surface without particular contamination such as titanium carbide.\n\nThere are a number of approaches in fabrication of porous"
-"1. Background {#sec1}\n=============\n\nSchizophrenia is a severe and chronic mental disorder characterized by a group of symptoms that include distortions of thinking and perception, cognition and psychomotor abnormalities, avolition, and apathy as well as emotional and communication and emotional difficulties \\[[@B1]\\]. It affects general health, functioning, autonomy, and subjective well-being and alters individuals\\' perception of reality \\[[@B2]\\]. The lifetime prevalence of schizophrenia has generally been estimated at approximately 1% worldwide, and it is about the same in men and women \\[[@B3]\\]. The World Health Organization (WHO) estimated that about 24 million people suffer from schizophrenia globally \\[[@B4]\\].\n\nIn treating and managing schizophrenia, clinicians often focus on treating psychotic symptoms and ignore factors that are directly related to quality of life and prognosis of disease even though evaluation of patient\\'s quality of life can help a lot in improving quality of care in patients with schizophrenia \\[[@B5]\\]. Thus, there was a shift in the concept of treatment with more emphasis on the aspect of the patient\\'s quality of life \\[[@B6]\\]. Schizophrenia affects many areas of functioning; people with the illness often lead an isolated and a marginalized existence in poor housing, with a low income, little education, and poor vocational"
-"All relevant data are available in the paper and its Supporting Information file.\n\nIntroduction {#sec001}\n============\n\nWireless Sensor Network (WSN) is a collection of sensor nodes with powerful sensing capabilities but limited resources. They consist of advanced network architectures and thus are used in a wide variety of applications \\[[@pone.0123069.ref001]\\]\\[[@pone.0123069.ref002]\\]. These sensors lack tamper resistance hardware because of cost considerations and are often deployed in tough and rough settings and vicinities, hostile scenarios and unattended environments. Thus, they antagonize the extortions from the invaders and muggers which can launch many attacks including the intention to acquire critical information from the WSN or to debilitate and enervate the tasks of the WSNs. Here, we particularly focus on more harmful attack which is known as *node replication attack* or *clone attack*. In this attack an adversary physically captures one or more sensor nodes and compromise all its secret credentials. The node compromise consequently allows an adversary to be capable of creating clones or replicas of the compromised nodes and then surreptitiously deploying them at strategic positions of the network.\n\nAn important distinctive behavior of clones or replicas is that they act as legitimate nodes or authorized participants in the network. These clones"
-"Introduction\n============\n\nDesiccation-tolerant (DT) plants can withstand the loss of up to 90--95% of the water of their vegetative tissues and revive when humidity is available, in contrast to the majority of plants ([@bib40]). Desiccation tolerance entails cellular, biochemical, and molecular changes during dehydration ([@bib54]), including the accumulation of carbohydrates ([@bib56]; [@bib47]), late embryogenesis-abundant (LEA) proteins ([@bib24]), and antioxidants ([@bib27]; [@bib35]; [@bib54]), as well as altered expression of target genes and transcription factors ([@bib13]; [@bib41]). Recovery from the desiccated state is much faster in homoiochlorophyllous DT (HDT) plants such as *Haberlea rhodopensis* ([@bib14], [@bib15]) than in poikilochlorophyllous DT (PDT) plants such as *Xerophyta scabrida* ([@bib49], [@bib50]). The former retain their chlorophyll (Chl), preserve their photosynthetic apparatus, and undergo morphological changes during drying that protect their tissues against oxidative stress ([@bib54]). In contrast, the latter lose all of their Chl and dismantle their photosynthetic apparatus during drying, and they resynthesize these molecules after rehydration ([@bib50], 1998*a*; [@bib46]). *Xerophyta scabrida* preserves most of its Chl when dried in the dark, so most of the loss seems to result from photooxidative degradation ([@bib53]). The PDT strategy evolved in plants that are anatomically complex and that include the largest in size of all DT"
-"Introduction\n============\n\nSince the coronary artery bypass grafting (CABG) procedure was introduced, ischemia/reperfusion (I/R) injury has become one of the most challenging problems in modern cardiac surgery. Hence, numerous solutions and techniques have been introduced to preserve the myocardium during this type of surgery.[@b1-ARYA-11-186]-[@b4-ARYA-11-186]\n\nCold cardioplegia reduces the oxygen demands of myocardial cells by keeping the heart in an arrested state.[@b5-ARYA-11-186] As a consequence, the saved energy results in greater preservation of the heart and less reperfusion injury.[@b6-ARYA-11-186] Terminal warm blood cardioplegia (TWBC) has proved to be effective in reducing I/R injury.[@b5-ARYA-11-186]-[@b7-ARYA-11-186] The mechanisms which are responsible for myocardial protection using (TWBC) remain uncertain.[@b8-ARYA-11-186] In addition, TWBC has a significant impact in decreasing the incidence of I/R injuries, especially during coronary artery bypass surgery.[@b9-ARYA-11-186] There have been a number of studies conducted on patients undergoing coronary artery bypass graft using widely differing cardioplegia techniques, but there are fewer studies that have focused on hot shot administration during CABG and its clinical impact.[@b8-ARYA-11-186],[@b10-ARYA-11-186],[@b11-ARYA-11-186]\n\nThe aim of this study was to compare the effect of intermittent antegrade cold blood cardioplegia with or without TWBC (hot shot) on different clinical indictors in patients undergoing CABG.\n\nMaterials and Methods\n=====================\n\nA total of 2488"
-"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"
-"All relevant data are within the paper and its Supporting Information files.\n\nIntroduction {#sec001}\n============\n\nThe global crop demand for human consumption and livestock feed is expected to increase by 60--110% between 2005 and 2050 \\[[@pone.0129487.ref001], [@pone.0129487.ref002]\\]. Changing dietary habits towards more affluent diets consisting of a larger share of animal products, vegetable oils, and sugar-sweeteners \\[[@pone.0129487.ref003]\\] as well as the growing world population are the main drivers of the global crop demand \\[[@pone.0129487.ref004]\\]. Increasing crop demand can be fulfilled either by expanding cropland and harvested area, and/or by increasing crop yields. Between 1985 and 2005, the global crop production has increased by 28% of which only 8% came from the expansion of cropland and harvested area, and 20% from increased crop yields \\[[@pone.0129487.ref005]\\]. However, yields of the four major crops (maize, rice, wheat, and soybean) have either stagnated or collapsed over the period of 1961--2008 across 24% to 39% of their cultivated areas globally \\[[@pone.0129487.ref006]\\]. Yield growths per year of these crops over the same period is substantially less than the annual growth rate of 2.4% that will be required for doubling crop production by 2050 \\[[@pone.0129487.ref007]\\]. Presently, crop yields vary across regions even within the same climatic zones"
-"1. Introduction {#S1}\n===============\n\nThe molecular basis for store-operated Ca^2+^ entry (SOCE) has been extensively investigated since the discoveries of the ER Ca^2+^ sensor, STIM1 (and its homologue, STIM2; \\[[@R1],[@R2]\\]) and the Ca^2+^-selective channel proteins, Orai1--3, which are activated by association with oligomerized STIM1 \\[[@R3]--[@R5]\\]. Depletion of Ca^2+^ from ER stores causes oligomerization of STIM1 \\[[@R6]\\], which is necessary for productive coupling to hexameric Orai \\[[@R7]\\]. Other studies provided evidence that, in addition to oligomerization, a conformational transition in the cytoplasmic region of STIM1 is necessary for functional coupling \\[[@R8]--[@R11]\\]. Several groups found that expression of a portion of this cytoplasmic region as a soluble protein spontaneously activates SOCE \\[[@R8],[@R9],[@R12]--[@R14]\\]. This minimal segment, commonly referred to as SOAR (human sequence 344--442) \\[[@R13]\\] or CAD (342--448; \\[[@R14]\\]) ([Figure 1A](#F1){ref-type=\"fig\"}), is not active when expressed as part of full length STIM1 in the absence of store depletion, suggesting that it is normally sequestered prior to STIM1 activation and oligomerization \\[[@R12],[@R14]\\].\n\nIn 2012, a crystal structure of the CAD/SOAR region yielded the first atomic-level resolution of this minimal active segment \\[[@R15]\\]. More recently, an NMR study revealed structural details for interactions between a trypsin-resistant STIM1 fragment that includes part of this region and"
-"Perception of body size throughout history {#Sec1}\n==========================================\n\nLife expectancy and survival throughout mankind's history was and remains dependent upon ability to cope with harmful stimuli. The human body itself developed very sophisticated defense mechanisms, which, however, are primarily based on rather primitive responses like inflammation, neurohormonal, and sympathetic nervous system activation. Vital for all processes is energy, which is derived from fat, proteins, and carbohydrates. Energetic efficacy of life organisms, although highest known in nature, is about 30% while the rest is lost primarily through heat production. Chronic food shortage and malnutrition have been the scourge of humankind throughout history. This has led to development of safety measures to accumulate energy when available to bridge over times of need. As a matter of fact, an evolutionarily conserved gene family important for fat depots, which store twice the amount of energy as carbohydrates or proteins, have recently been identified \\[[@CR1]\\]. Until about a century or two ago, this gene family served its purposes for the majority of the world's population. Nowadays, when abundant food is available all over the year, activation may be prolonged to lead to significant increase of body weight. It is therefore not surprising that attitudes of"
-"Background {#Sec1}\n==========\n\nIt is indisputable that an elevated blood pressure (BP) is one of the most important risk factors for cardiovascular disease, heart failure, strokes, chronic kidney disease, peripheral arterial disease, and atrial fibrillation \\[[@CR1]\\]. Many factors including the genetics, life style, medications, obesity, and dietary factors contribute to the development of hypertension in a complicated way.\n\nEpidemiological studies have revealed that excessive salt intake plays a major role in elevating the BP in the global population, leading to increased cardio- and cerebrovascular morbidity and mortality \\[[@CR2]--[@CR4]\\]. Also, many studies have demonstrated that salt itself has an impact on the aortic stiffness and coronary heart disease in a BP-independent manner \\[[@CR3], [@CR5]\\]. The global mean sodium intake in 2010 was about 4\u00a0g/d (salt \u2248 10\u00a0g/d) in adults, and is especially higher in Asian regions \\[[@CR4]\\]. In that year, the Korean population aged 20 and over had a high estimated sodium intake of 5.21 (4.98--5.48) g/d. WHO (World Health Organization) recommends a sodium reduction of \\<2\u00a0g/d in adults \\[[@CR6]\\] and also the current hypertension guidelines recommend reducing the sodium intake as a way of a lifestyle modification \\[[@CR7]\\].\n\nIf a high salt intake of the population has"
-"Background\n==========\n\nMedically unexplained symptoms (MUS) have been reported among both civilians and military personnel exposed to combat. These symptoms can be classified into different syndromes such as somatoform disorder, chronic fatigue syndrome, and conversion disorder. There is considerable overlap between these syndromes \\[[@B1]\\]. Symptoms such as abdominal distension, headache, and weakness are present in many such syndromes. The term, medically unexplained symptoms, is used when there is no objective evidence of an illness despite subjective complaints of symptoms. Only a small proportion, about one in four, seeks medical attention for their symptoms \\[[@B2]\\]. Factors that precipitate seeking medical help include perceived seriousness, functional impairment, and psychological distress \\[[@B1]\\].\n\nThere is overlap between multiple physical symptoms and psychological morbidity \\[[@B1],[@B3]\\]. Physical symptoms are associated particularly with anxiety and mood disorders. The likelihood of a psychiatric disorder increases with increasing numbers of physical symptoms \\[[@B4]\\]. In people with MUS, psychological morbidity increases risk of medical consultations and functional impairment \\[[@B1],[@B4]\\].\n\nA large number of military personnel deployed to the Gulf War in 1991 reported non-specific symptoms \\[[@B5],[@B6]\\]. These symptoms did not constitute a clearly defined syndrome. Initially, these symptoms were attributed to physical conditions such as exposure to chemicals or vaccination."
-"Introduction\n============\n\nThe etiological agent of Giardiasis, *Giardia* *duodenalis* (syn. *G. intestinalis, G. lamblia*) is one of the most prevalent intestinal protozoan flagellate of the human. The life cycle of *Giardia* species is simple and it is included of two active trophozoite and cystic forms.\n\nThis parasite transmits via fecal-oral route through direct or indirect ingestion of infectious cysts. The incubation period varies from 9 to 15 days after ingestion of cysts. Symptoms of infection are varied from the absence of symptoms to acute watery diarrhea, nausea, epigastric pain and weight loss ([@B1],[@B2]).\n\nGiardiasis has a global distribution and it is common in both children and adults. The prevalence of *Giardia* infection is higher in developing countries. More than 200 million cases of giardiasis are annually diagnosed worldwide. Since 2004, *Giardia* has been included in the \\\"neglected diseases initiative\\\" by World Health Organization ([@B3]). The infection rate in asymptomatic children has been reported from 8% to 30% in developing countries and 1-8% in industrialized regions ([@B4]). The occurrence of giardiasis is probably higher in individuals with diarrhea.\n\nThe prevalence of human giardiasis in different regions of Iran has been reported from 1.2% to 38% ([@B5]). In immunocompromised patients, *Giardia* is"
-"1. Introduction\n===============\n\nMethotrexate (MTX) is an anchor drug in the management of rheumatoid arthritis (RA). Lymphoproliferative disorder (LPD) occasionally develops in patients treated using MTX, and is termed MTX-associated LPD (MTX-LPD). The predominant primary site of MTX-LPD is the lymph nodes, followed by extra-nodal sites such as the gastrointestinal tract, skin, and lungs.[@R1] The pathophysiology of MTX-LPD is not well understood. The hyperimmune state of RA itself or the immunosuppressive state induced by MTX administration is thought to play a role in the development of LPD.\n\nThe increased risk of LPD in RA patients has been well established. The incidence rate of LPD is 2-times higher in Western RA patients and 6-times higher in Japanese RA patients than that in the general population.[@R2][@R3] However, LPD in the central nervous system (CNS) is rare because it accounts for less than 1% of LPD.[@R4] We present the rare case of an RA patient who developed lymphoma in the CNS and stomach during MTX therapy.\n\n2. Case report\n==============\n\nThe patient was a 75-year-old Japanese man with a 9-year history of seropositive RA. The disease activity of RA was controlled well by MTX at 14\u200amg/week and bucillamine at 100\u200amg/day. He"
-"1. Introduction {#sec1-materials-13-00258}\n===============\n\nAs a promising technology, the Additive Manufacturing (AM) technology offers a new strategy for producing customized parts with desired architecture, shape, pores and porosity \\[[@B1-materials-13-00258],[@B2-materials-13-00258]\\]. Based on the AM, the Fused deposition modeling (FDM) melts a spool of thermoplastic filament and extrudes it onto a platform to create tangible 3 dimensional parts \\[[@B3-materials-13-00258]\\]. Poly (lactic acid) (PLA) is the most extensively used material in FDM, and has been regarded as a promising material for its eco-friendly, biocompatible and processability \\[[@B4-materials-13-00258]\\]. However, its relatively hydrophobic and low degradable properties have limited its use \\[[@B5-materials-13-00258]\\].\n\nNatural biomass is known as being hydrophilic, biodegradable and recyclable \\[[@B6-materials-13-00258]\\]. Driven by the increasing environmental pollution and global energy crisis, natural biomass has been used as the reinforcements on the polymer-matrix composites \\[[@B7-materials-13-00258]\\]. Some biomass has been successfully used for PLA-matrix, including seeds (e.g., cotton and milkweed), fruit nutshells (e.g., coconut shell and peanut shell), basts (e.g., flax, lamp and jute), leaves (e.g., sisal and banana) and grass/cane/reed fibers (e.g., bamboo) \\[[@B8-materials-13-00258],[@B9-materials-13-00258]\\].\n\nSome researchers have combined the study of FDM and the PLA/natural biomass composites. Tao et al. \\[[@B10-materials-13-00258]\\] prepared the PLA/5 wt% wood flour composites using the FDM and enhanced the"
-"Introduction\n============\n\nA growing body of research indicates that symptoms of attention-deficit/hyperactivity disorder (ADHD) often persist into adulthood.[@b1-ppa-8-997]--[@b4-ppa-8-997] With increasing awareness of the need to treat adult ADHD, cost-effectiveness analyses are needed to demonstrate and compare the value of new and existing treatment options. A cost--utility model is a type of cost-effectiveness analysis that requires utilities, which are values on a scale with anchors of 1 (full health) and 0 (dead) to represent the strength of preferences for various health states.[@b5-ppa-8-997]\n\nAlthough utilities have been reported for childhood ADHD, including values associated with various levels of treatment response,[@b6-ppa-8-997]--[@b9-ppa-8-997] little is known about utilities associated with adult ADHD. Two recent reviews reported no published utility values representing ADHD in adults.[@b10-ppa-8-997],[@b11-ppa-8-997] Literature searches conducted for the current study also found no published work on adult ADHD utilities, but one conference presentation was located that reported adult ADHD utilities derived from SF-36^\u00ae^ (Medical Outcomes Trust, Hanover, NH, USA) responses via the SF-6D scoring algorithm.[@b12-ppa-8-997] However, the six items from the SF-6D do not assess attention or other constructs that are specifically relevant to ADHD,[@b13-ppa-8-997] which suggests that it may have limited content validity for this particular condition. Therefore, the purpose of this study"
-"1. Introduction {#sec1}\n===============\n\nChinese goldthread,*Coptis chinensis* Franch., is an important medicinal plant in the Ranunculaceae.*C. chinensis* is native to China and has been used in traditional Chinese medicine for centuries \\[[@B1], [@B2]\\]. The major active compounds of*C. chinensis* are protoberberine alkaloids \\[[@B1]\\], such as berberine, palmatine, jatrorrhizine, coptisine, columbamine, and epiberberine. These compounds have antiviral, anti-inflammatory, and antimicrobial activity, and they dispel dampness, remove toxicosis, and aid detoxification \\[[@B4]--[@B7]\\]. Despite the prominent roles of*C. chinensis* in medicine, understanding of its biology and evolution is limited due to a lack of genomic resources.\n\nChloroplast genomes in angiosperms are mostly circular DNA molecules ranging from 115 to 165\u2009kb in length \\[[@B8]\\]. They exhibit a conserved quadripartite structure consisting of one large single copy (LSC) region, one small single copy (SSC) region, and two copies of inverted repeats (IR). Due to their low levels of recombination and substitution rates compared to nuclear genomes, plant chloroplast genomes are valuable sources of genetic markers for phylogenetic analyses. Over 21 complete genomes of species within the Ranunculales have been sequenced and deposited in the NCBI database (as of August 2016), and these data can be used to study chloroplast genome evolution in the Ranunculales."
-"Abstract {#s1}\n========\n\nThe escalating global burden of cardiovascular disease (CVD) is related to the rapid health transition that developing countries are experiencing.[@R01] Adoption of high-energy, high-fat, Westernised diets and diminished physical activity contribute to the accelerating epidemic of CVD.[@R02] South Africa, an emerging economy, is currently undergoing a health transition, characterised by the triple burden of disease consisting of a high prevalence of under-nutrition-related infectious diseases, the emergence of non-communicable chronic diseases (NCDs), and the human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) pandemic.[@R03]\n\nThe rate of urbanisation in the North West province of South Africa has dramatically increased, characterised by high rates of rural-to-urban migration, increased numbers of industrial companies, improved economic activity and an increased population in urban settings. Concurrently these economic changes have led to changes in the quality of food intake, from the traditional prudent dietary patterns and nutrient intake to modern, imprudent fast foods, which seem to play a major role in increasing the rate of NCDs.\n\nThe THUSA study, conducted from 1996 to 1998 in the North West Province of South Africa, indicated that Africans with a higher socio-economic status (SES) had higher risk factors for CVD than those with a lower SES.[@R04] Many"
-"1. Introduction\n===============\n\nForsythiae Fructus (FF), the dried fruit of *Forsythia suspensa*, is widely used as an antipyretic, antidotal and anti-inflammatory agent in China, Japan and Korea for treating infections, such as acute nephritis, erysipelas and ulcers \\[[@B1-molecules-20-10065],[@B2-molecules-20-10065]\\]. It also suppresses vomiting, inhibits elastase activity, resists hepatic injury and exhibits diuretic, analgesic, antioxidant and antiviral effects \\[[@B3-molecules-20-10065]\\]. In addition to being a sore-effective medicine, FF is also a popular heat-clearing and detoxifying herb; indeed, more than 40 Chinese medicinal preparations containing FF are listed in the Chinese pharmacopoeia \\[[@B4-molecules-20-10065]\\]. Some components of FF include phenylethanoid glycosides, lignans, flavonoids, terpenes, alkaloids and volatile oils \\[[@B5-molecules-20-10065]\\]. Among them, phenylethanoid glycosides, lignans and flavonoids, which are phenolic compounds, have been reported to exhibit diverse biological activities \\[[@B6-molecules-20-10065],[@B7-molecules-20-10065],[@B8-molecules-20-10065],[@B9-molecules-20-10065]\\].\n\nDepending on the maturity stage of *F. suspensa*, two kinds of FF exist---green FF (GF) and ripe FF (RF). GF (called *Qingqiao* in Chinese) is usually harvested in early September, while the fruits are still greenish, but nearly ripe and indehiscent. As such, GF requires thorough steaming and drying under the Sun. RF (called *Laoqiao* in Chinese) is usually harvested in October, and its fruits are fully ripe, yellow, dehiscent and dried. Both GF and RF"
-"Introduction {#s1}\n============\n\n*Mycobacterium tuberculosis* (*Mtb*) is the causative agent of tuberculosis (TB), a disease that accounted for 1.7 million deaths in 2016 ([@B1]). Caseous granulomas which develop at the site of *Mtb* infection are considered a hallmark of pulmonary TB ([@B2]). Albeit specific for TB, these lesions are not pathognomonic, granulomas are triggered also by unrelated bacteria, fungi and parasites as well as by foreign bodies ([@B3]). The cellular composition of TB granulomas may vary with disease stage. Generally, lesions consist of macrophages, lymphocytes and transformed macrophages, including epithelioid and multinucleated giant cells as well as foamy macrophages ([@B4], [@B5]). Trajectories and the fate of granulomas are determined by a plethora of secreted factors, such as cytokines and eicosanoids, which are locally produced by immune cells ([@B6]), *in situ* changes in cellular composition, as well as viability, replicative and metabolic features of the mycobacteria ([@B7], [@B8]). Balanced abundances of the pro-inflammatory cytokines IFN-\u03b3 and TNF-\u03b1 are associated with bacterial clearance while regulatory cytokines like IL-10 offer limited protection to TB ([@B2], [@B9], [@B10]). Presence of selected immune cell subsets, their location, as well as their propensity to produce soluble mediators thus control stability of granulomas and TB progression.\n\nDespite"
-"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],"
-"1. Introduction\n===============\n\nInflammatory bowel disease (IBD) mainly manifests as ulcerative colitis (UC) and Crohn disease (CD). Abnormality of the immune system is observed in most IBD patients.^\\[[@R1]\\]^ Azathioprine (AZA) is a commonly used nonspecific immunosuppressant, and it was first introduced into the treatment of IBD about 40 years ago.^\\[[@R2]\\]^ Many studies have demonstrated its efficacy in the treatment of IBD. Currently, AZA is widely used to induce and maintain remission in IBD, especially in developing countries, because it is effective, much less expensive than infliximab, and can be orally administered. However, the initial indications for thiopurines have been progressively challenged by wider use of anti-TNF-alpha agents.^\\[[@R3]\\]^\n\nThe consensuses in Europe, Asia-pacific region, and China all recommend AZA as a first-line medicine for the maintenance therapy for IBD.^\\[[@R4]--[@R6]\\]^ The European Crohn\\'s and Colitis Organization (ECCO) recommends a dose of 2.0 to 2.5\u200amg/kg/d for the European population with IBD.^\\[[@R5]\\]^ The Asia-pacific consensus on Crohn disease states that AZA at a dose of 2 to 2.5\u200amg/kg/d is superior to 1\u200amg/kg/d.^\\[[@R6]\\]^ However, a lower dose of AZA (0.6--1.2\u200amg/kg/d) for the treatment of UC is recommended by another Asia-pacific consensus on UC and a Japanese study, ^\\[[@R7],[@R8]\\]^ which is quite"
-"Introduction {#s1}\n============\n\nPluripotent embryionic stem cells (ESC) derived from the inner mass of the pre-implanted embryos have the ability to self-renew indefinitely *in vitro* and in appropriate conditions can be enforced to differentiate into a diversity of specialized cell types. Recently, it has been shown that endodermal cell derivatives from ESC can be generated through the *in vitro* recapitulation of major developmental signalling pathways occurring *in vivo* [@pone.0054243-Murry1]. For instance, a conserved mechanism for mesoderm-endoderm lineage commitment involves Nodal, a TGF\u03b2 family member, and can be mimicked *in vitro* by activin A, yielding a high percentage of endodermal-like cells [@pone.0054243-Kubo1], [@pone.0054243-DAmour1], [@pone.0054243-Yasunaga1]. From this cell population, different studies have used instructive signals playing a role in pancreatic organogenesis and \u03b2-cell differentiation to commit ESC to similar fates *in vitro* in order to obtain a source of replaceable \u03b2-cells for diabetic patients [@pone.0054243-DAmour2], [@pone.0054243-Kroon1], [@pone.0054243-Sulzbacher1]. In addition to the endocrine compartment, the pancreas is composed by exocrine cells including ductal and acinar cells. Acinar cells are responsible for the synthesis of secretory digestive enzymes, and alterations in the acinar differentiation program have been linked to exocrine pancreatic diseases, such as chronic pancreatitis and adenocarcinoma [@pone.0054243-Rooman1]. Therefore, providing normal *in vitro*"
-"1. Introduction {#sec1}\n===============\n\nApart from thorough detection and diagnosis of dental caries, compiling a treatment plan is another important task of a dentist. The initial assessment of hard tooth tissue is normally visual and, depending on indication and availability, X-rays are used for further detection and treatment planning.\n\nThe visual classification system International Caries Detection and Assessment System (ICDAS-II) was developed to provide clinicians, epidemiologists, and researchers with an evidence-based method for standardized data collection in different settings and better comparison between studies \\[[@B1]\\]. Reproducibility and accuracy of ICDAS-II have already shown to be promising for occlusal caries detection \\[[@B2]\\]. ICDAS criteria have the potential to aid treatment planning \\[[@B3]\\]. Depending on the visual assessment, activity of a lesion, and patient\\'s risk status, the preferred care options might be tilted towards preventive or operative treatment.\n\nApart from purely visual and visual-tactile caries diagnosis, there are several other methods for the detection of dental caries on occlusal surfaces. This includes radiography, laser or light fluorescence-based methods, and electrical impedance measurements. It is well known that fluorescence-based methods make use of the phenomenon that carious lesions fluoresce more strongly than sound tissues when excited by light at specific wavelengths. The devices"
-"INTRODUCTION {#SEC1}\n============\n\nCellular senescence is defined as a stable cell cycle arrest elicited in response to a variety of stressors. Intense oncogenic signaling, telomere loss, radiation, chemotherapeutic drugs, bacterial toxins and oxidative stress have all been linked to the induction of the senescent phenotype through direct DNA damage or replication stress-induced DNA damage ([@B1]--[@B9]). Interestingly, oxidative stress has been shown to induce cellular senescence ([@B8],[@B10],[@B11]) and replication stress independently ([@B12],[@B13]). There is a lack of evidence to implicate replication stress-induced DNA damage as the driver for the initiation of cellular senescence in response to oxidative stress. The acquisition of cellular senescence is a dynamic process in which changes take place over an extended period of time ([@B14]--[@B17]). These changes are necessary for the permanent halt of proliferation, failing which cells might escape from senescence to a pro-oncogenic state ([@B5],[@B18]). The senescent phenotype is associated with the activation of the tumor suppressor p53 through its phosphorylation at Ser15 residue, which prevents cells carrying genomic lesions from progressing through the cell cycle ([@B19]--[@B22]) and the acquisition of persistent DNA damage foci or DNA segments with chromatin alterations reinforcing senescence (DNA-SCARS) ([@B5],[@B16],[@B21]). DNA-SCARS contain mediators of the DNA damage response (DDR) such"
-"INTRODUCTION\n============\n\nThe Glenn procedure (superior vena cava to right pulmonary artery anastomosis) is one of the stages of palliative care indicated for children diagnosed with univentricular heart. The postoperative mortality depends on preoperative and postoperative factors,[@B001] such as thrombosis, arrhythmias, and superior vena cava syndrome.[@B002]\n\nThe superior vena cava syndrome in patients submitted to Glenn surgery stems from inadequate flow from the superior vena cava to the pulmonary artery due to factors like pulmonary hypertension, vessel lumen narrowing at the surgical anastomosis, and pulmonary artery or vein stenosis. As a result, the patient can present facial and upper limb edema, which can lead to cerebral edema, low cardiac output syndrome, and death.\n\nHerein, we report on a child with the diagnosis of tricuspid atresia who was submitted to the Glenn procedure and evolved to death because of severe superior vena cava syndrome right after the procedure.\n\nCASE REPORT\n===========\n\nA one-month-old girl with postnatal diagnosis of tricuspid atresia, concordant ventricular-arterial connection, and patent ductus arteriosus, without pulmonary outflow tract obstruction, was submitted to a modified Blalock-Taussig shunt, ductus arteriosus ligation, and pulmonary artery amputation, with excellent postoperative recovery. The patient had unremarkable evolution, and the Glenn procedure was proposed"
-"Introduction\n============\n\nThe microorganisms causing nosocomial infections bring about several issues from the viewpoint of treatment failure as well as patients' mortality, this is particularly due to their antibiotic-resistant property. Among these bacteria, *Acinetobacter baumannii* is an important human pathogen which has recently gained much importance.[@b1-idr-10-455] *A. baumannii* is a Gram negative non-fermentative, anaerobic coccobacilli which is widely dispersed in the hospital environment. In addition, it is an important opportunistic pathogen and is responsible for various nosocomial infections.[@b2-idr-10-455] This pathogen has been considered among the six most dangerous nosocomial microorganisms by the Infectious Diseases Society of America (IDSA).[@b3-idr-10-455] *A. baumannii* generally infects intensive care unit (ICU) patients including those who have suffered stroke, injuries, burns, and need mechanical ventilation.[@b4-idr-10-455] One of the most interesting peculiarities of *A. baumannii* is that it can easily attain resistance toward different antibiotics. *A. baumannii* strains have shown resistance to most antibiotics so far.[@b5-idr-10-455] The factor which has led to fortification of this resistant system is the unnatural inherited abilities of *A. baumannii* during long-term viability in nosocomial environments, thereby causing nosocomial expansion of this bacteria.[@b6-idr-10-455]\n\nToday, this bacteria is resistant to all antibiotics; thus, some drugs have been excluded from treatment of *A. baumannii*"
-"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"
-"Introduction\n============\n\nThis paper is the continuation of a series of original research papers published by the authors on the topic of nutritionally driven organic cation transporter (OCT) functional status determination (herein referred to as OCT assay\\[s\\]). This paper correlates original research previously published by the authors on the topic of transporter-driven centrally acting monoamine observations with the monoamine hypothesis.[@b1-ijgm-5-135]--[@b12-ijgm-5-135]\n\nThe centrally acting monoamines serotonin, dopamine, norepinephrine and epinephrine (herein referred to as \"monoamine\\[s\\]\") exist in one of two states. The \"endogenous state\" is present when no supplemental amino acids are being administered, and the \"competitive inhibition state\" is found when significant amounts of serotonin and/or dopamine amino acid precursors are simultaneously administered.[@b1-ijgm-5-135]--[@b7-ijgm-5-135]\n\nPrevious literature described the competitive inhibition state as \"functionally meaningless.\" The basis for this assertion was the inability to alter monoamine levels with amino acid precursors and then objectively quantify the changes.[@b7-ijgm-5-135] With the perfection of the novel OCT assay analysis by the authors, the competitive inhibition state is no longer functionally meaningless.[@b1-ijgm-5-135]--[@b12-ijgm-5-135]\n\nSince the early 1960s, the monoamine hypothesis has been a reference point for understanding the etiology of the electrical defects associated with monoamine-related disease and the mechanism of action of reuptake inhibitors. The monoamine"
-"Introduction\n============\n\nMaxillary molar distalization is a nonextraction procedure normally used to gain space in the upper arch and to correct a Class II dental relationship (when there is a mesial migration of maxillary posterior teeth). Traditionally extraoral appliance, the headgear, is used for maxillary molar distalization ([@B1]). However, headgear needs patient compliance and it is esthetically unacceptable. Intraoral devices are then developed (eg. pendulum appliance, distal jet appliance) ([@B2]-[@B4]); these appliances do not require patient cooperation but cause, as a side effect, the mesial drift of the premolars and the incisors, namely anchorage loss ([@B2]-[@B4]). To prevent anchorage loss, intraoral distalization appliance supported by additional miniscrew anchorage can be used ([@B5],[@B6]).\n\nThe aim of the present study was to compare the amount of upper first molar distalization and the dentoalveolar side effects, obtained in six months, using a traditional distal jet appliance and a miniscrew-supported distal jet appliance. The results were analyzed at 6 months from the start of therapy. This endpoint was determined to avoid that different pattern of malocclusion influenced the results, but in all patients the therapy continued until a first molar relationship was achieved.\n\nIt was hypothesized that miniscrew-supported distal jet appliances achieve a greater"
-"Background\n==========\n\nMany medical schools, including Oklahoma State University -- Center for Health Sciences (OSU-CHS), have discontinued the Microbiology wet laboratory in light of cost, space issues, and curricular changes \\[[@B1]\\]. Initially, to circumvent potential deficiencies in student learning as a result of wet lab removal, faculty retained the lab\\'s time block and instead presented material typically conveyed in the laboratory session through a variety of mixed media presentations, lectures and physician-led case discussions. Student feedback was overwhelmingly negative in response to the lectures, mostly negative for the mixed media presentations and somewhat positive for the physician-led case discussions. Thus, to make more effective use of this time block, the course instructors introduced an interactive case-based tutorial in the Medical Virology module. Case-based learning has been shown to be effective for dental and allopathic medical programs in the U.S., Europe, and South America \\[[@B2]-[@B5]\\]. Problem-based learning was also considered but discarded because its use would require significantly greater faculty manpower. The interactive case-based session was designed to show students the value of basic science information in clinical applications, to provide a review of course material and to familiarize the students with differential diagnosis. Given that the majority of questions on"
-"1. Introduction\n===============\n\nCoronaviruses are positive-stranded RNA viruses recently classified in the order *Nidovirales*, mainly on the basis of their genomic organization and their replication strategy ([@BIB3]). The coronavirus genome consists of a large open reading frame (ORF) at the 5\u2032-end which encodes the replicase gene (ORF1a and ORF1b). Downstream from the replicase gene, there are smaller ORFs which encode the structural proteins S, E, M, the nucleocapsid (N) protein and a number of presumptive non-structural proteins of largely unknown function ([@BIB9]).\n\nMost research has focused on the S protein as a candidate antigen for coronavirus vaccines, since it is the major inducer of virus-neutralizing antibodies ([@BIB7]). The function of the M protein is still not clear. Although a major immunological role has been attributed to the S protein, both the amino- and the carboxy-termini of the M protein elicit strong immune responses ([@BIB5]), inducing antibody-dependent, complement-mediated, virus neutralization (VN) ([@BIB23]).\n\nThe role of CCoV in inducing enteric illness in canids has been the subject of active investigation for over two decades. The virus is responsible for mild to moderate enteritis in dogs; in young pups, or in combination with other pathogens, illness may be severe with diarrhoea, vomiting, dehydration,"
-"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"
-"Background {#Sec1}\n==========\n\nThe domestic dog is classified as a mono-estric, polytocous and aseasonal breeder, with an obligatory quiescence phase called anestrus \\[[@CR1], [@CR2]\\]. Although canine reproduction has already attracted some attention, still many of the species-specific peculiarities remain not fully understood. Unlike in livestock, the dog lacks placental steroidogenesis \\[[@CR3]\\]. Thus, luteal P4 is the only major source of circulating levels of this hormone, both in non-pregnant cycles and during pregnancy. The lifespan of corpora lutea (CL) in non-pregnant bitches often outlasts the luteal duration in pregnant animals \\[[@CR4]\\]. The luteal phase and P4 levels are almost identical in both situations until around day 60, i.e., prior to parturition when a steep decline of serum P4 is observed in pregnant dogs, indicating prepartum luteolysis \\[[@CR5], [@CR6]\\]. In contrast, in the non-pregnant dog a slow decline of P4 is observed, until basal levels of P4 reach \\<1\u00a0ng/ml, indicating the onset of anestrus \\[[@CR4], [@CR7]\\]. Moreover, at least in non-pregnant dogs, the function of CL is independent of a uterine luteolysin (PGF2alpha), and remains unaffected by hysterectomy \\[[@CR8]\\]. Also, a luteolytic function of intraluteally produced prostaglandins can be ruled out \\[[@CR9]\\]. In pregnant dogs, the prepartum decline of P4 is"
-"Introduction\n============\n\nHypoxic-ischemic brain damage (HIBD), a result of asphyxia in the perinatal period, seriously threatens the health and life of newborns. HIBD leads to apoptosis and necrosis of nerve cells, with a high mortality rate and poor outcome. Long-term nervous system sequelae, including disorders of recognition, language, sensation, movement, vision and memory function affect 25--30% of patients with HIBD. To date, there is no specific remedy for HIBD ([@b1-etm-05-02-0419]--[@b4-etm-05-02-0419]). Earlier interruption of the pathological and physiological changes of HIBD is the key point for decreasing case fatality and disability rate of newborn infants. In spite of the great progresses that have been made in treatment, the therapeutic efficacies remain unsatisfactory. Therefore, the absence of effective therapies for HIBD has provoked an intensive search for novel treatment strategies. A previous study demonstrated that mNGF may have a potential therapeutic efficacy for HIBD; however, little is known about its mechanism ([@b5-etm-05-02-0419]).\n\nGlial fibrillary acidic protein (GFAP), a skeleton protein generated from astrocytes, is crucial in the survival of neurons and formation of synapses following brain injury ([@b6-etm-05-02-0419]). In this study, using a neonatal mouse model of HIBD, we investigated the expression of GFAP in neonatal rats with HIBD when injected with"
-"Background\n==========\n\nYalla \\[[@B1]\\] remarked that progressive structural changes in the bladder of a spinal cord injured (SCI) patient usually depend on the level and completeness of the cord lesion, duration of the lesion and rehabilitative management strategies. Delnay and associates \\[[@B2]\\] studied histological changes associated with chronic indwelling urinary catheter in 208 spinal cord injured patients. These patients had indwelling urethral and/or suprapubic catheters for more than 8.5 years. Squamous cell carcinoma was found in 10, transitional cell carcinoma in five and adenocarcinoma in two. Non-malignant mucosal changes in bladder biopsies included inflammation in 89%, cystitis glandularis in 17% and cystitis follicularis in 10%. Janzen and associates \\[[@B3]\\] reviewed 94 urinary bladder biopsies in patients with spinal cord injury and found no correlation between the number of bladder infections per year, the period since injury, the neurologic level of the spinal cord lesion and the histopathology of the urinary bladder mucosa.\n\nPresentation of the hypothesis\n==============================\n\nWe propose a hypothesis that *the type of bladder drainage* in spinal cord injury patients may influence the histological changes in the mucosa of neuropathic bladder. This hypothesis implies that SCI patients with long-term indwelling urinary catheters develop certain histological changes in bladder"
-"Background {#Sec1}\n==========\n\nPreeclampsia has been a major cause of poor result in pregnancy and the category \"hypertensive diseases of pregnancy\" and is a leading cause of maternity in Africa \\[[@CR1]\\]. It is a common pregnancy disorder that correspond one out of the three cases i.e. obstetric morbidity, hypertension and/or proteinuria \\[[@CR2], [@CR3]\\]. Preeclampsia is the most public hazardous pregnancy complication affecting mother as well as foetus \\[[@CR4]\\]. It is assorted with an increased risk factor of cardiovascular diseases and type II diabetes in later life cycle of mother \\[[@CR5]\\]. Preeclampsia is responsible for approximately 50,000 maternal deaths worldwide annually out of which 25\u00a0% of cases are due to Intra Uterine Growth Restrictions (IUGR) and 15\u00a0% are outcome of preterm birth in developed countries \\[[@CR4]\\]. However, there is no known cure for preeclampsia apart from delivery of the baby and the placenta. Accordingly, early diagnosis of preeclampsia and close observation are assertive for controlling preeclampsia during pregnancy.\n\nThe strategy employed by high-income countries have successfully reduced both the incidence of eclampsia and the mortality associated with it by almost 90\u00a0%, utilizing a combination of early detection during Antenata Care and increased access to hospital care for women"
-"1. Introduction {#sec1-ijerph-17-05440}\n===============\n\nIn recent years, the way in which researchers' results, discoveries, and knowledge have been disseminated has changed significantly. The advancement of Internet technology has enabled the rise of social media platforms such as Facebook, Twitter, Reddit, and others to serve as channels where people interact, share opinions, and debate. These forums create communities where people establish relationships and interactions among themselves.\n\nThese online communities can influence and can be influenced by other online communities. This spread of influence plays a major role in the spreading of information, some of which may affect people's offline behavior \\[[@B1-ijerph-17-05440]\\].\n\nContent produced on social media can spread quickly throughout these communities, triggering rumors and cascading effects that can deeply influence political decisions, economic choices, social well-being, perceptions, and beliefs \\[[@B2-ijerph-17-05440]\\].\n\nThe use of social media text analysis and social network detection is not new in the public health field. Many studies have investigated the areas of forecasting clinical surveillance \\[[@B3-ijerph-17-05440],[@B4-ijerph-17-05440]\\] and misinformation within and across health communities \\[[@B5-ijerph-17-05440]\\]. These studies contain considerable evidence suggesting that technology has been useful in the health domain, generating considerable awareness on social media, and helping people who live in remote areas \\[[@B6-ijerph-17-05440]\\] or who"
-"Background {#Sec1}\n==========\n\nThe functional independence of individuals after stroke is directly influenced by the ability to perform reaching and grasping movements successfully \\[[@CR1]\\]. However, the performance of these motor activities is commonly affected after stroke, leading to slower and segmented movements, and these, in turn, may be associated with compensatory movements of structures such as the shoulder and trunk \\[[@CR2]\\].\n\nReach and grasp movements involve the coordination of the fingers and thumb, previously positioned according to the size, shape, and function of the object that are combined with the movement of the arm toward the object and the control of the force to hold the target and keep it in the hand during its transport \\[[@CR1], [@CR3]\\].\n\nSeveral conventional and standardized clinical measures aim to evaluate reach and grasp activities in post-stroke subjects \\[[@CR4]\\]. Instruments, such as the Fugl Meyer Functional Performance Scale (FM), Box and Blocks Test (BBT), and Action Research Arm Test (ARAT), aim to quantify movement changes through observational analyses, further classified on either ordinal or nominal scales \\[[@CR2], [@CR5]\\].\n\nThe assessment of reach and grasp through clinical tests, when applied by trained professionals, allows the verification of psychometric properties and their effects on daily activities."
-"Introduction {#Sec1}\n============\n\nThe prostate consists of the glandular epithelium and supporting stroma. This connective stroma is comprised of fibroblasts, myofibroblasts, smooth muscle cells, vascular endothelial cells, nerve cells, and inflammatory cells. While prostate cancer arises from the epithelial component of the gland, the surrounding stroma is increasingly recognized as an important contributor in the process of carcinogenesis^[@CR1],\\ [@CR2]^ and a driver of cancer progression. Experimental models demonstrate that altered stromal cells can induce tumor formation in non-cancerous prostate epithelial cells^[@CR2]^ and in cell lines derived from prostate cancer^[@CR3]^. Benign prostate epithelial cells are more proliferative and ultimately undergo transformation when combined with prostate cancer-derived fibroblasts^[@CR2],\\ [@CR4]^. It is also clear that the stroma can morphologically and functionally change in the presence of cancer and other insults. Compared to normal stroma, there is a switching of the cellular phenotype^[@CR5]^, remodeling of the extracellular matrix^[@CR6]^ increases in expression of growth factors and proteases^[@CR7]^ increased angiogenesis^[@CR8]^, and change in inflammatory cells^[@CR9]^. The bidirectional signaling between epithelial cells and stromal constituents during normal prostate homeostasis is disrupted early in tumorigenesis (reviewed in ref. ^[@CR10]^). The consequences are diverse and range from deposition of extracellular matrix, to recruitment of inflammatory cells, production of miRNA,"
-"See related commentary by Kovalaske and Gandhi, <http://ccforum.com/content/13/4/161>\n\nIntroduction\n============\n\nHyperglycaemia occurs frequently, even in patients without pre-existing diabetes \\[[@B1]\\], and adversely affects outcome \\[[@B2]\\]. For this reason, treatment with insulin is widely used; however, insulin therapy is associated with a substantial risk of hypoglycaemia, which is associated with both short- and long-term adverse events \\[[@B3],[@B4]\\]. Although the use of parenteral nutrition affords a stable caloric load, which minimises the incidence of hypoglycaemia \\[[@B2]\\], enteral feeding is the preferred method of nutrient delivery in critically ill patients \\[[@B5]\\]. Hence, there is a need for a therapy to manage hyperglycaemia in enterally fed patients without the risk of hypoglycaemia \\[[@B6]\\].\n\nExogenous administration of the incretin hormone, glucagon-like peptide-1 (GLP-1), has been shown to normalise blood glucose concentrations both in healthy patients and those with type 2 diabetes \\[[@B7]\\]. This occurs as a result of stimulation of insulin secretion, suppression of glucagon release and slowing of gastric emptying \\[[@B7],[@B8]\\]. Because the former effects are glucose dependent, the use of GLP-1 does not appear to be associated with hypoglycaemia \\[[@B9]\\]. The effect of GLP-1 on glycaemia in enterally fed critically ill patients has hitherto not been evaluated. The primary aim of this study"
-"Background {#Sec1}\n==========\n\nCoronary artery disease (CAD) is the most common cardiovascular disease \\[[@CR1]\\]. CAD is the leading cause of disability \\[[@CR2]\\] and mortality worldwide \\[[@CR3]\\]. Myocardial infarction (MI) is a common, acute manifestation of CAD \\[[@CR4]\\]. The case fatality rate of MI remains high, despite a reduction over time \\[[@CR4], [@CR5]\\]. Thus, MI constitutes a significant public health burden.\n\nAllopurinol is commonly used for the treatment of hyperuricemia \\[[@CR6], [@CR7]\\]. Allopurinol is a structural isomer of hypoxanthine, and its active metabolite, oxypurinol, competes with hypoxanthine for the enzyme xanthine oxidase, and leads to the lowering of uric acid production. In addition to its urate-lowering effect, recent studies have suggested other mechanisms of action, some dependent and some independent of this action \\[[@CR8]--[@CR15]\\]. Debate continues whether allopurinol use reduces the risk of MI and the magnitude of this effect.\n\nTwo studies that examined the association of allopurinol with MI provided contradictory results. In a population-based case-control study, de Abajo et al. \\[[@CR16]\\] reported that allopurinol was associated with a lower risk of MI with a hazard ratio (HR) of 0.52. This contradicts the finding of an increased HR of 1.25 for a cardiovascular event requiring hospitalization (including MI, stroke, hypertension,"
-"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"
-"1. Introduction {#sec0005}\n===============\n\nSince prostate cancer (PCa) has unfortunately become a common cancer in men in more economically-developed countries, it is significant to detect these lesions, especially in the transition zone (TZ) of prostate. It was reported that between 25% and 40% of these cancers were TZ cancers [@bib0005], [@bib0010], [@bib0015]. Because the TZ is commonly the site of origin of benign prostatic hyperplasia (BPH) [@bib0020], [@bib0025], which has a heterogeneous appearance, it is difficult to differential diagnose these lesions. Therefore, differentiation of PCa from BPH is always a major problem frequently missed during clinical evaluation.\n\nT2-weighted magnetic resonance (MR) imaging has been used widely for the evaluation of prostate cancer but with limited sensitivity and specificity [@bib0030], [@bib0035], [@bib0040]. More advanced functional MR imaging sequences in a custom multiparametric MR imaging (mpMRI) exam have been shown to significantly improve the performance of MRI in cancer diagnosis [@bib0045]. In addition, DWI has become a useful tool for differentiating malignant and benign prostatic tissue due to high contrast resolution and the quantitative apparent diffusion coefficient (ADC) [@bib0030], [@bib0050]. DWI reflects and measures the diffusion of water molecules within biological tissues due to thermal Brownian motion. However, because the monoexponential ADC"
-"Background\n==========\n\nOsteoarthritis (OA) is a disease characterized pathologically by articular cartilage loss in focal areas of the synovial joints, accompanied by various levels of synovitis, subchondral bone change, and osteophyte formation \\[[@b1-medscimonit-25-7488]\\]. Extracellular matrix (ECM) degradation and death of articular cartilage are the primary characteristics of OA. The ECM is responsible for the structure of chondrocytes, which is maintained by remodeling \\[[@b2-medscimonit-25-7488]\\]. An important cause of OA pathogenesis is cartilage homeostasis disorder \\[[@b3-medscimonit-25-7488]\\]. Chondrocyte apoptosis and ECM degradation occur due to increased expression of MMPs and ADAMTS (A Disintegrin And Metalloproteinase With Thrombospondin Motifs 5), which are the predominant matrix-degrading enzymes that degrade ECM components and hydrolyze aggrecan core proteins \\[[@b4-medscimonit-25-7488]\\]. Human articular cartilage is composed of chondrocytes and lacks blood vessels. Articular chondrocyte repair is generally considered a core component of OA treatment \\[[@b5-medscimonit-25-7488]--[@b7-medscimonit-25-7488]\\]. Although many risk factors have been identified and researchers have elucidated the chemical pathways associated with inflammation and wear, the pathological mechanism of OA is still controversial and not fully understood \\[[@b8-medscimonit-25-7488]\\]. The main symptoms of OA are joint pain and swelling and stiffness in the limbs. In the clinic, nonsteroidal anti-inflammatory drugs (NSAIDs) are the preferred alternative for OA therapy, even though these"
-"Introduction\n============\n\nOver the past decade, due to their good biocompatibility, ease of synthesis, monodispersity, and tunable surface functionality,[@b1-ijn-11-929] gold nanoparticles (AuNPs) have shown excellent potential for the delivery of a wide range of antitumor substances such as oxaliplatin,[@b2-ijn-11-929] cisplatin,[@b3-ijn-11-929] and paclitaxel.[@b4-ijn-11-929] Additionally, the synthesis of AuNPs can be easily controlled to obtain NPs of a wide range of sizes.[@b5-ijn-11-929] The size of NPs has been shown to be one of the most important factors affecting biodistribution, tissue uptake, and applications in the biomedical fields.[@b6-ijn-11-929] It has been reported that the cellular uptake of NPs ranging from 15 to 100 nm depends upon the particle size.[@b7-ijn-11-929] Considerable research has recently been carried out on the biodistribution, cellular uptake, and in vivo activity of AuNPs.[@b8-ijn-11-929] NPs of a particular size (\\<200 nm) show efficient extravasation into leaky tumor vasculature and accumulation in tumor tissues via an enhanced permeability and retention effect.[@b9-ijn-11-929] Particle size-dependent biodistribution and toxicity of AuNPs have been widely studied in vivo.[@b10-ijn-11-929] Generally speaking, a smaller particle size is characteristic of higher transvascular and interstitial transport.[@b11-ijn-11-929],[@b12-ijn-11-929] For example, 20 nm NPs showed significantly higher permeability in tumors compared with 125 nm NPs. Therefore, to be effective, a drug carrier"
-"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\n============\n\nMetabolic acidosis is associated with the progression of chronic renal failure (CRF) and can be a common consequence of CRF ([@B1]). Conversely, many clinical studies have shown that metabolic acidosis itself may be a cause of renal disease progression and that alkali therapy ameliorates its progression ([@B2], [@B3]). In experimental studies, several mechanisms for the effects of alkali therapy have been evaluated, such as the reduced activation of the alternative complement pathway ([@B4]), decreased cell proliferation and transdifferentiation ([@B5]), and the endothelin (ET) antagonism pathway ([@B6]). However, there are few reports of the role of renal acid-base transporters during alkali therapy in remnant kidney models.\n\nLuminal Na/H exchanger type 3 (NHE3) is responsible for a significant portion of renal Na^+^ and HCO~3~^-^ absorption ([@B7]). NHE3 is variably expressed depending on the pathologic condition and was increased in adriamycin-nephropathy models ([@B8]). NHE3 activation plays a role in the pathogenesis of ischemic acute renal failure ([@B9]). Under alkali loading, apical NHE3 expression in the kidney can be down-regulated ([@B10]). The inhibition of NHE3 may improve kidney function and structure in acute ischemic kidney injuries ([@B11]). However, there are few reports of the effects of alkali therapy on apical NHE3 expression"
-"Main {#Sec1}\n====\n\nThe lung is a complex organ consisting of at least 40 different cell lineages^[@CR1]^. Following postnatal growth, the lung epithelium slowly turns over under normal conditions, but its regenerative capacity can be activated substantially after injury^[@CR2]^. Resident lung stem/progenitor cells (referred to collectively as LSCs throughout this Article) are responsible for this epithelial repair and tissue homeostasis. Several stem cell niches have been identified as being located in terminal bronchioles or bronchoalveolar junctions^[@CR3],[@CR4],[@CR5],[@CR6]^. These putative LSCs are susceptible to infection by severe acute respiratory syndrome (SARS) associated coronavirus^[@CR6],[@CR7]^, leading to deterioration of lung tissue and loss of lung repair capacity. LSCs have also been found to be able to renew and proliferate to form epithelial cells *in vivo*^[@CR4]^. They are potentially useful in regenerative therapy, for example, in repairing damaged lung tissue in patients. The advances and obstacles of using various strategies and assays to establish the regenerative potential of endogenous LSCs have been reviewed recently^[@CR8],[@CR9]^.\n\nTo enable the aforementioned therapeutic applications of LSCs, it is crucial to determine their tissue-specific engraftment and regenerative capacity in animals. Achieving this goal requires the use of a highly sensitive imaging modality, together with a highly stable (both biologically and"
-"1. Introduction\n===============\n\n*Mycobacterium tuberculosis* (*Mtb*) can survive *in vivo* for prolonged periods of time (decades) in a clinically undetectable latent state called non-replicating persistence. *Mtb* is metabolically dormant in the latent state and is unresponsive to most antituberculosis drugs. Diverse stimuli, including hypoxia \\[[@B1-biosensors-03-00259]\\], exposure to nitric oxide \\[[@B2-biosensors-03-00259]\\], nutrient deprivation \\[[@B3-biosensors-03-00259]\\], and increased acidity of the microenvironment \\[[@B4-biosensors-03-00259]\\] are thought to trigger dormancy, which can be reversed when the host immune response is compromised, as in HIV co-infection \\[[@B5-biosensors-03-00259]\\].\n\nEarly evidence linked hypoxia to dormancy. Wayne established that tuberculosis bacteria settle into a non-replicating, persistent state when grown under low oxygen tension or hypoxia and, more importantly, that the bacilli developed resistance to clinical drugs \\[[@B1-biosensors-03-00259]\\]. Tuberculosis infections are normally localized in the oxygen rich regions of the lungs, which indicates that normal *in vivo* growth and survival requires oxygen. However, mycobacteria also experience hypoxic conditions *in vivo* inside macrophages. Thus, *Mtb* growth is inhibited when the bacilli are engulfed into granulomas, the inside of which is associated with low oxygen levels \\[[@B6-biosensors-03-00259]\\]. Similarly, oxygen depletion has been shown to inhibit the growth of *Mycobacteria bovis* BCG and to result in dormancy \\[[@B7-biosensors-03-00259]\\].\n\nGenetic analysis combined with studies"
-"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"
-"Introduction\n============\n\nThe understanding of the biology behind lipid-metabolism has increased exponentially in the past two decades, enabled by the vast interrogation of the human genome. To date, genome-wide association studies have identified over 170 candidate single-nucleotide variants (SNVs), with many residing in common regions of the genome ([@B26]; [@B9]). However, two major limitations exist in the current exploration for causal loci associated with lipid metabolism: (1) Identification of SNVs in non-coding regions or SNVs in large regions that span several candidate genes; and (2) missing detection of candidate genes altogether, particularly if population-specific ([@B3]). Exome-wide association studies naturally expand on findings from genome-wide association studies through their exploration of the functional region of the genome ([@B20]).\n\nExome-wide association studies have been extensively used to dissect the genetic architecture of complex diseases and quantitative traits ([@B14]). Exonic variants, particularly loss-of-function variants, tend to show the most dramatic effect sizes, yielding the greatest power for detection. Recent evidence on lipid traits provides support that rare variants can be ancestry-specific ([@B18]). Therefore, examining exonic variants across diverse ancestry groups likely augments the identification of novel loci.\n\nThe Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) cohort, recruited from families of European"
-"Introduction\n============\n\nRheumatoid arthritis (RA) is an autoimmune chronic inflammatory disease of unknown aetiology that is characterized by infiltration of monocytes, T cells and polymorphonuclear cells into the synovial joints. The pathogenesis of this disease is still poorly understood, and fundamental questions regarding the precise molecular nature and biological significance of the inflammatory changes remain to be answered \\[[@B1],[@B2]\\]. A powerful way to gain insight into the molecular complexity and pathogenesis of arthritis has arisen from oligonucleotide-based microarray technology \\[[@B3]\\], because this platform provides an opportunity to analyze simultaneously the expression of a large number of genes in disease tissues.\n\nThe earliest preclinical stages of human RA are not easily accessible to investigation, but a diverse range of experimental arthritis models are considered valuable tools for delineating mechanisms of inflammation and autoimmune phenomena. An animal model that shares some of the hallmarks of human RA is the reactivation model of streptococcal cell wall (SCW)-induced arthritis in rats. In this model, a synovitis with maximal swelling at 24 hours is induced by local injection of SCW antigen directly into an ankle joint. The initial response is reactivated by systemic (intravenous) challenge with SCW, which produces a more prolonged and severe inflammation"
-"Introduction {#S1}\n============\n\nMajor depression is a common but serious psychological disorder that affects more than 300 million people around the world ([@B1], [@B2]). Moreover, major depression is frequently associated with suicidal behavior ([@B3]). Since the diagnosis of major depression is based on the severity of depressive symptoms, the severity distribution of depressive symptoms in a general population has been of great interest to researchers ([@B4]).\n\nEpidemiological studies of depressive symptoms have been conducted intensively using a variety of depression screening scales ([@B5]--[@B7]). These studies have provided important information on depressive symptoms in the general population (e.g., the estimated prevalence of clinical depression). However, little has been reported regarding the distributional patterns of item responses on depression screening scales among the general population. Information about the mathematical patterns of item responses on depression screening scales is important for several reasons. First, it predicts how depressive symptoms distribute among the general population. If the mathematical pattern of item responses adequately approximates the empirical distribution, the pattern is useful for evaluating the scores of individuals in a population and verifying the survey results. Second, the mathematical pattern determines which statistical methods to use (e.g., parametric or non-parametric statistics) ([@B8]). Generally, parametric statistics,"
-"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,"
-"Introduction {#Sec1}\n============\n\nDiffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma with a high degree of heterogeneity in clinical and biological behavior and a poor prognosis in high-risk patients. With the development of molecular biology in recent years, 6--14% DLBCL have been found c-Myc gene translocation that often accompanied with bcl-2 or bcl-6 translocation, known as double-hit lymphoma (DHL)^[@CR1]^. The CR (complete response) to the traditional R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) regimen for DHL is only about 20%. Currently, most of DHL adopts the strong chemotherapy regimen combined with autologous hematopoietic stem cell transplantation^[@CR2],[@CR3]^, which however haven't benefit the treatment of DHL, reported by a multi-center comparative study^[@CR4]^.\n\nMost DHL arise from germinal centers, which are the main sites where B cells switch the class of their antibodies (CSR) in response to antigenic stimulation^[@CR5]^. Activation-induced cytidine deaminase (AID) in the germinal center induce the high mutation degree of B cells, which produce different-encoded antibody B cells to complete CSR, ultimately leading to the occurrence of proto-cancerous chromosomal translocation between immunoglobulin c-Myc and IgH in B cells^[@CR6],[@CR7]^. Several studies have shown that AID expression in DLBCL has a poor prognosis^[@CR8],[@CR9]^.\n\nAID is expressed in various types of"
-"Introduction {#S0001}\n============\n\nBreast cancer is recognized as one of the leading causes of cancer-related mortality in women worldwide.[@CIT0001] In spite of the development of aggressive interventions, the inevitability of relapse and metastasis result in severe mortality rate.[@CIT0002] While, the roots of breast cancer relapse and metastasis have remained elusive.\n\nCancer stem cells (CSCs) are a small but significant subpopulation of undifferentiated cells in tumor tissues.[@CIT0003]--[@CIT0005] Accumulating evidences indicated that CSCs drive cancer initiation, progression, spread and resistance to chemo- or radiotherapy.[@CIT0006],[@CIT0007] CSCs were also identified in breast cancer tissues, called breast cancer stem cells (BCSCs). BCSCs were characterized with the ability of self-renewal, differentiation, tumor initiation, invasion and resistance of conventional therapy, which indicated that BCSCs should be an effective target for breast cancer therapy.[@CIT0008]--[@CIT0012] However, our understanding of BCSCs still needs to be improved.\n\nThere are several signaling pathways that have been identified to be associated with the maintenance of breast cancer stemness, including Hippo/YAP, Notch, Hedgehog and Wnt pathways.[@CIT0013]--[@CIT0018] In addition, numerous miRNAs are identified to be dysregulated in BCSCs population, such as miR-200c[@CIT0019], miR-205,[@CIT0020] miR-141,[@CIT0021] miR-1,[@CIT0022] miR-34a[@CIT0023], miR-221,[@CIT0024] miR-21[@CIT0025] and Let-7.[@CIT0026]\n\nmiR-520b is a member of miR-302/372/373/520 family. Recently, several members in this family have been"
-"Introduction {#Sec1}\n============\n\nWorldwide, there are currently 425 million people estimated to suffer from type 1 and 2 diabetes, which results in a yearly healthcare expenditure of 727 billion USD. By 2045, the number of sufferers is predicted to increase to 693 million, which will further increase the economic burden of the disease \\[[@CR1]\\]. One of the most common and debilitating complications associated with diabetes is the development of diabetic eye disease associated with diabetic retinopathy (DR), diabetic macular edema and glaucoma \\[[@CR1]\\]. Over 90% of patients with type 1 diabetes and around 60% of patients with type 2 diabetes will suffer from a level of DR ranging from blurred vision to complete vision loss \\[[@CR2]\\]. Given the increasing incidence of diabetes, there is thus a significant need to understand the mechanisms which regulate DR, with the aim of developing effective therapeutic agents for the complication.\n\nEndothelial cell injury is a hallmark of the microvascular complications observed due to chronic hyperglycaemia in diabetes. Indeed, small improvements in glycosylated-haemoglobin directly correlate with a significantly reduced risk of developing DR \\[[@CR3]\\]. Hyperglycaemia increases metabolic disruption, inflammation and hypoxia in patients with diabetes, associated with the pathophysiology of DR \\[[@CR2]\\]. DR, characterised by"
-"Introduction\n============\n\nSystemic hypertension is the most common cardiovascular condition, affecting as many as 1 billion people worldwide and responsible for 1 million deaths.[@b1-vhrm-6-457] It affects about 72 million individuals in the United States.[@b2-vhrm-6-457] According to American Heart Association estimates, it is responsible for more than 54,000 deaths in 2004 in the US alone.[@b3-vhrm-6-457] The incidence of hypertensive emergency is disproportionately higher in the elderly, male, and African American populations.[@b4-vhrm-6-457] Approximately 1%--2% of all patients with hypertension are estimated to have hypertensive emergencies.[@b2-vhrm-6-457]\n\nThe Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure (JNC-7) publication defines hypertensive emergency as a severe elevation in blood pressure (BP) (usually \\>180/120 mmHg) complicated by evidence of impending or progressive target organ dysfunction,[@b5-vhrm-6-457] such as neurologic changes, hypertensive encephalopathy, cerebral infarction, intracranial hemorrhage, myocardial ischemia or infarction, acute left ventricular dysfunction, acute pulmonary edema, aortic dissection, renal insufficiency, or eclampsia.[@b6-vhrm-6-457] Hypertensive urgency is defined as \"severe elevations in BP without progressive target organ dysfunction.\"[@b5-vhrm-6-457] One study of emergency department admissions found that hypertensive crises accounted for 27.5% of all medical emergencies and urgencies in patients arriving at an emergency department, with 77% having a history of hypertension.[@b7-vhrm-6-457]\n\nHypertension in critical"
-"INTRODUCTION {#s1}\n============\n\nShoulder pain, which is experienced by 70--84% of patients with hemiplegic stroke, has become a dominant factor in delaying participation in a rehabilitation program[@r1], [@r2]^)^. The pain and limited range of motion (ROM) make ambulation more difficult. In addition to affecting physical activities owing to the compromised ability to maintain balance and restricting activities of daily living (ADL), this negatively impacts the desire and ability to engage in social activities because of feelings such as fear, frustration, and disappointment[@r3], [@r4]^)^. If the pain is not treated, it also causes edema, joint instability, joint contracture, and bone and soft tissue atrophy, as well as limits the ability to move the upper limbs[@r5]^)^. The goal of rehabilitation therapy for hemiplegic patients is to allow them to regain independence in activities and make it easier to perform such activities by improving the movement on the paralyzed side[@r6]^)^. Therefore, muscle strengthening is recommended to improve the ability to perform exercise[@r7], [@r8]^)^.\n\nKinesitherapy is essential for preventing muscle tonicity and atrophy in hemiplegic patients. With continuous exercise, it improves muscular strength and joint flexibility, which allows performing more physical activities. Most studies on exercise effects show that exercise contributes to the recovery"
-"Introduction {#s1}\n============\n\nThe incidence of cardiovascular disease (CVD) has increased in many countries, and CVD has been the leading underlying cause of death worldwide since 2000 ([@c45]). CVD contributed to one in every three deaths in the United States in 2008 ([@c26]) and to two in every five deaths in China in 2014 ([@c8]). More than 80% of CVD can be attributed to modifiable and nongenetic factors, and lifestyle choices such as smoking, diet, and exercise were considered as major environmental influences on CVD ([@c4]). Recent disparate lines of evidences together indicate that exposure to chemical pollutants plays a larger role in the etiology of CVD than previously thought ([@c3]). The adverse effects of fine particles present in ambient air and metal on CVD have been demonstrated in epidemiological and animal studies ([@c3], [@c4]; [@c6]). However, significant gaps remain in our understanding of the environmental factors that affect cardiovascular health ([@c2]).\n\nAtherosclerosis is a major cause of CVD. Foam cell (i.e., cholesterol-laden macrophages) formation within the artery wall can facilitate adventitia angiogenesis and the buildup of necrotic pools, thereby playing a key role in atherosclerosis pathogenesis ([@c35]). Liver X receptors (LXRs, including the $\\text{LXR}\\alpha$ and $\\text{LXR}\\beta$ subtypes) regulate foam"
-"Introduction {#Sec1}\n============\n\n*Riemerella anatipestifer* is a Gram-negative, non-motile, extracellular bacterium that belongs to the *Flavobacteriaceae* family, and infection of ducks with this pathogen causes acute and chronic septicaemia characterized by fibrinous polyserositis, and meningitis^[@CR1],[@CR2]^. Currently, at least 21\u2009*R*. *anatipestifer* strains that vary in virulence both between and sometimes within a given serotype have been identified and are characterized by a 5--75% mortality rate, depending on the virulence of the strain^[@CR2],[@CR3]^. Although *R*. *anatipestifer* infection is a contagious disease that has resulted in significant economic losses in the duck industry^[@CR2]^, little is known about the mechanisms of protective immune responses involved in *R*. *anatipestifer* pathogenesis.\n\nSeveral attempts have been made to understand the host immune responses to *R*. *anatipestifer*. Using an immunoproteomic approach, immunoreactive proteins have been identified in duck or rabbit antisera to *R*. *anatipestifer*^[@CR4],[@CR5]^. Upregulated host immunity was observed in ducks vaccinated with inactivated *R*. *anatipestifer* plus levamisole as an adjuvant^[@CR6]^ or with recombinant *R*. *anatipestifer* outer membrane protein A plus CpG oligodeoxynucleotides as an adjuvant^[@CR7]^. Furthermore, host genes involved in the immune response were identified in duck livers following *R*. *anatipestifer* infection^[@CR8]^. Recently, comparative expression analyses of immune-related genes in ducks and chickens indicated that duck"
-"Background {#Sec1}\n==========\n\n*Bean common mosaic virus* (BCMV) is a seed borne, aphid-transmitted virus with worldwide distribution \\[[@CR1]\\]. Common bean (*Phaseolus vulgaris* L.) is the main host of this virus, although it also infects other *Phaseolus* species \\[[@CR2], [@CR3]\\]. This virus can cause significant yield losses (50-100\u00a0%) in the host crop plants \\[[@CR4]--[@CR6]\\]. As a member of the family *Potyviridae*, it is a single-stranded, positive-sense RNA virus approximately 10\u00a0kb in length and encodes an open reading frame for a polyprotein containing 10 genes and a eleventh gene is created by ribosomal slippage in the P3 protein and is called PIPO \\[[@CR7]--[@CR10]\\]. Each of the 10 other proteins is cleaved out after polyprotein synthesis by one of three viral encoded proteases \\[[@CR7]\\].\n\nThere are 8 pathogenicity groups in the BCMV complex, identified by the virus response on a standard set of differential bean lines \\[[@CR11]--[@CR13]\\]. The differential bean lines contain either a single resistance gene, or none, or combinations of stacked resistance (*R*) genes \\[[@CR14], [@CR15]\\]. Seven resistance loci have been identified: a dominant *I* locus, and recessive loci, bc-u, bc-1, bc-1^2^, bc-2, bc-2^2^, and bc-3 \\[[@CR11], [@CR14], [@CR16]\\]. The *I* locus is associated with a cluster of *R*"
-"Background {#Sec1}\n==========\n\nBreast cancer is the commonest malignancy in women and a major cause of cancer-related mortality \\[[@CR1]\\]. While mastectomy is the primary treatment modality for these patients, it can have a profoundly negative impact on their lives, impairing personal, sexual and social relationships. Fifty percent of women post-mastectomy suffer from negative self-image with negative changes in their sexuality \\[[@CR2], [@CR3]\\]. The demand for reconstructive procedures has risen, not only as a consequence of advancing cancer treatment but also because of the demonstrated functional, psychological and social benefits for patients, overcoming the psychological trauma associated with mastectomy \\[[@CR4]--[@CR9]\\]. The rates of post-mastectomy breast reconstruction doubled from 13 to 26% between 1998 and 2007 \\[[@CR10]\\].\n\nA number of reconstructive techniques exist for breast reconstruction. The two most frequently employed techniques include the autologous deep inferior epigastric perforator (DIEP) flap and implant-based reconstruction \\[[@CR11]\\]. The choice of treatment is determined by combination of patient factors (individual preference, age, body image) and surgeon factors (team experience, availability of resources) \\[[@CR8], [@CR9]\\]. Despite this, many plastic surgery units worldwide regard autologous flap reconstruction as the superior technique as it follows the paradigm of replacing 'like with like' \\[[@CR10]\\]. Indeed, there is growing evidence"
-"*Sir,*\n\nAggrecan is a chondroitin sulphated proteoglycan encoded by the *ACAN* gene with essential structural functions in the extracellular matrix of cartilages \\[[@CR1]\\]. Heterozygous *ACAN* mutations have been associated with a broad spectrum of non-lethal skeletal dysplasias, called Aggrecanopathies, including spondyloepimetaphyseal dysplasia, Kimberly type spondyloepiphyseal dysplasia, autosomal dominant short stature, early onset osteoarthritis and recurrent osteochondritis dissecans (OCD) \\[[@CR2]--[@CR5]\\].\n\nHere, we present a child with severe inflammatory elbow involvement mimicking septic arthritis who carried a new missense variant of the *ACAN* gene.\n\nA 14-year-old boy developed swelling and pain at the right elbow after a physical effort. Symptoms were not associated to other systemic inflammatory signs and worsened during the following days, leading to a severe joint limitation. Laboratory tests and X-ray of the right elbow were normal. Non steroidal anti-inflammatory drugs (NSAIDs) were administered for a month without any improvement.\n\nThe patient was admitted to our Institute after 2 months of symptoms onset. On physical examination, acute arthritis of the right elbow was present: it appeared painful and warm, without local erythema. Laboratory tests showed slight elevation of the acute phase reactants (C reactive protein 1.7\u2009mg/dl, erythrocyte sedimentation rate 26\u2009mm/h). Ultrasound revealed a distension of coronoid and"
-"INTRODUCTION {#sec1-1}\n============\n\nOsteochondroma or osteocartilaginous exostosis is an exophytic lesion that arises from the cortex of the bone and is cartilage-capped. It is one of the most common benign tumors of the axial skeleton but extremely rare in the condyle. Forssell *et al*. reviewed 26 reported cases of osteochondroma and subsequently Henry also added a case to the literature.\\[[@ref1][@ref2]\\] They have excluded several case reports because of misdiagnosis and others due to lack of clinical details. Nwoku and Koch in a review of 3200 head and neck tumors in their institution included an osteochondroma of the mandibular condyle but have not given any histopathological or surgical details.\\[[@ref3]\\] Skull base, maxillary sinus, zygomatic region and mandible osteochondroma have been reported.\\[[@ref4]\\] The condyle or coronoid are the most common site in the mandible.\\[[@ref5]\\] Subsequently, we report a comprehensive case of a giant osteochondroma of the mandibular condyle removed via extended preauricular incision to the temporomandibular joint (TMJ).\n\nCASE REPORT {#sec1-2}\n===========\n\nA 23-year-old male presented with complaints of progressive facial asymmetry, difficulty in speech and mastication secondary to restricted movement of the mandible \\[[Figure 1](#F1){ref-type=\"fig\"}\\]. The patient also experienced intermittent pain in the right TMJ region. He reported progressive reduction in"
-"*Dedicated to Professor Yuri Grin on the Occasion of His 60th Birthday*\n\nIntroduction {#sec1}\n============\n\nIn 2013 more than 85\u2009% of the world energy consumption was covered by energy harvested from fossil fuel sources.[1](#bib1){ref-type=\"ref\"} Pollution, global warming as well as the foreseeable depletion of these resources thus demand for the further development of alternative energy sources. Thermoelectric materials can convert waste heat directly into electricity. Therefore, they might play an important role in a future world energy balance.\n\nThe efficiency of a thermoelectric material is benchmarked by the dimensionless thermoelectric figure\u2010of\u2010merit *ZT* = *S* ^2^/(*\u03c1*(*\u03ba* ~el~ + *\u03ba* ~ph~))*T*, where *S* is the thermopower, *\u03c1* is the electrical resistivity, and *T* is the absolute temperature. According to the Wiedemann\u2010Franz law, the electronic part of the thermal conductivity (*\u03ba* ~el~) is proportional to the inverse electrical resistivity. Therefore, *\u03c1* cannot be tuned without affecting the thermal conductivity (*\u03ba*). As a result, two main routes for improving *ZT* can be followed. On the one hand efforts to decrease the phonon thermal conductivity (*\u03ba* ~ph~) can be undertaken, on the other hand routes to increase the electrical power factor *\u03b1* = *S^2^*/*\u03c1* can be studied.\n\nOne possibility to impede the phonon transport"
-"THREE KEY POINTS {#SEC1}\n================\n\nImproved PHI-base 4 platform with increase in pathogen species and genotypic/phenotypic data content.On-line author curation tool called PHI-Canto for any pathogenic species and a PHIB-BLAST function.Cross-references for first plant host targets of pathogen effectors.\n\nINTRODUCTION {#SEC2}\n============\n\nWith an increasing world population and associated global trade, pathogens pose a constant threat to efforts focused on increasing crop yield, whilst safeguarding human and animal health and protecting natural ecosystems ([@B1]). Since the identification of the first bacterial avirulence gene in the plant infecting pathogen *Pseudomanas syringae* in the early 1980s ([@B2],[@B3]), many more research articles have been published describing the molecular analysis of pathogen gene mutations via experimentation and the functional characterization of these mutant alleles on one or more host organisms.\n\nThe pathogen--host interactions database ([www.phi-base.org](http://www.phi-base.org)) is a well recognized information resource cataloguing the phenotypes of experimentally verified pathogenicity, virulence and effector genes from a wide range of plant and animal pathogens and host species. The trained curation team manually extracts the information about gene function in pathogenesis from peer reviewed literature and transfers the data into a computable form. This enables immediate data access to guide further experimentation and enable comparative data analysis. Various"
-"Soft tissue sarcomas are a group of rare malignant tumors originating from connective tissues. They can occur at any age and in any anatomic site.^[@bib1]^ These tumors are challenging to diagnose and treat because of the high degree of malignancy, multiple pathological subtypes, and heterogeneity in biological properties; the disease may also relapse easily or show distant metastasis.^[@bib1]^ Regardless of the pathological type and grade, surgery is still the most effective method for the treatment of soft tissue sarcomas (STSs) except gastrointestinal stromal tumors and desmoid.^[@bib2]^ The presence of osseous, joint, nerve, and vascular invasion are largely determinant of the feasibility of limb sparing surgery. When STSs, especially deep tumors, involve the major vessels, limb salvage may not be possible for main surgical solutions.^[@bib3]^ The choice of the treatment strategy for STSs is often difficult, but standardized surgical resection can increase the local control rate of the STS and improve the limb salvage rate. Therefore, accurate delineation of the local extent of the neoplasm in bones, muscles, and joints is essential, especially by determining the presence and level of major vessel involvement by imaging before surgical treatment, which can contribute to the choice of treatment strategy.\n\nComputed tomography (CT) plays"
-"Cycloviruses (CyCVs) belong to the *Circoviridae* family and have recently been found in different sample types from different hosts, including mammals and insects[@b1][@b2][@b3][@b4][@b5]. Recently, we reported a new cyclovirus species, tentatively named cyclovirus-Vietnam (CyCV-VN), in cerebrospinal fluid (CSF) of two Vietnamese patients[@b6]. The virus was subsequently detected in 4% of 642\u2005CSF samples of patients with central nervous system (CNS) infections from 7 different provinces in southern and central Vietnam, but in none of 122\u2005CSF samples from patients with noninfectious CNS conditions[@b6]. Almost simultaneously, another novel CyCV (CyCV-VS5700009) was reported in CSF and serum from patients with paraplegia in Malawi[@b7], while other CyCVs have previously been reported in stool samples of patients with acute flaccid paralysis from Tunisia, Pakistan and Nigeria[@b3]. Together, these data suggest that cycloviruses may have a wide geographic distribution, and that specific CyCV species might be associated with specific clinical phenotypes, although it should be noted that associated pathology of cycloviruses has yet to be proven.\n\nResults\n=======\n\nTo explore whether CyCV-VN is circulating beyond central and southern Vietnam, we screened a total of 615\u2005CSF specimens from patients with acute CNS infections from northern Vietnam (n = 233), Cambodia (n = 123), Nepal (n"
-"Introduction\n============\n\nAccording to statistics, by October 2012, the number of cases of Acquired Immune Deficiency Syndrome (AIDS) and Human Immunodeficiency Virus (HIV) in Iran had reached 25041([@B1]); 22.2% transmitted sexually and 60% through intravenous drug use (IDU) ([@B2]). Evidence suggests that the most common transmission route for AIDS around the world is sexual contact, and in Iran, it is IDU ([@B3],[@B4]). Some identified factors that speed the spread of the disease in Iran include limited sex education, a high prevalence of sexually transmitted infections (STI) and a high proportion of young people in the population ([@B5]--[@B7]).\n\nStudies in Asian countries indicate increased HIV transmission through sexual contact in addition to IDU. According to a study in Central Asia, the increased prevalence of HIV in the countries in this region was due to the increased number of female sex workers and their clients ([@B8]). Similar studies in China, India, Pakistan, and Bangladesh have focused on the transmission of AIDS and factors that set the scene or increase the transmission. Even in Pakistan, which is culturally very similar to Iran, the most common transmission route is unsafe heterosexual contact ([@B9]--[@B11]). In Iran, research on knowledge, perception and sexual/reproductive behavior of adolescents"
-"Background {#Sec1}\n==========\n\nKnee pain is common complaint affecting people of all ages. In adult populations, the reported prevalence of knee pain has been 25--28% depending on the age of the examined persons and the level of pain chronicity \\[[@CR1]--[@CR3]\\]. In the younger age groups, knee pain is commonly secondary to increased activity, injury or contact sports \\[[@CR4]--[@CR6]\\]. In older people, however, knee pain that gets progressively worse over time is often sign of osteoarthritis (OA) \\[[@CR7], [@CR8]\\]. Knee OA in particular is associated with severe disability, owing to the weight-bearing function of the knee and the large range of movements it performs.\n\nTo be able to detect and treat individuals with a variety of knee problems effectively requires reliable and valid outcome measures, preferably at low cost. During recent decades, a few well-validated outcome measures have been developed for the assessment of symptoms and function in subjects with knee or hip OA \\[[@CR9]--[@CR11]\\]. In the elderly population, the Western Ontario and McMaster Osteoarthritis Index (WOMAC) is the self-administered instrument most commonly used to measure pain, stiffness and function in daily living. However, in younger and/or more physically active subjects, joint injuries cause knee problems more often than primary knee"
-"INTRODUCTION {#s1}\n============\n\nKidney cancer is one of the ten most frequently occurring cancers with substantial mortality estimates in Western societies \\[[@R1]\\]. Constant search for powerful biomarkers capable of prognostication and prediction of therapy response in this type of tumors is one of the priorities of modern medicine and science.\n\nImportantly, all tumors are considered to undergo certain metabolic changes to achieve high proliferation rates and sustain further growth. At that, lipid metabolism supposed to be seriously altered in many tumor types \\[[@R2], [@R3]\\]. Adipophilin is one of the important players in lipid metabolism, responsible for storage of lipid droplets in all types of cells \\[[@R4], [@R5]\\]. Some recent studies show that many tumors overexpress adipophilin \\[[@R6]--[@R22]\\], especially those with clear cell histology \\[[@R10], [@R11]\\]. Several small reports showed that renal cell carcinoma (RCC) cells also overexpress adipophilin \\[[@R10], [@R11], [@R23]--[@R27]\\] and one major study \\[[@R24]\\] reported the prognostic role of this biomarker in clear cell subtype on transcript level. However, an analysis on the protein level was pending, so far.\n\nIn this study we aimed to investigate the expression patterns of adipophilin using immunohistochemistry in patients with different subtypes of the renal cell cancer and to study the prognostic"
-"Introduction {#fsn3367-sec-0001}\n============\n\nAccording to Kenya Demographic Health Survey 2014 (KNBS and ICF Macro [2015](#fsn3367-bib-0020){ref-type=\"ref\"}), the proportion of stunted and wasted children in Kenya was 26% and 4%, respectively. Children aged 6--11\u00a0months had the highest wasting rates of 7%. These children fail to attain their full potential of growth and development, suffer long\u2010term deprivation of energy, nutrients, and consequently chronic protein energy malnutrition (PEM), often accompanied by micronutrient deficiencies. The period 6--24\u00a0months of age is one of the most critical periods in the growth of the infant. At this age, their demand for nutrients relative to their body size is high. However, there are limitations in the quality and quantity of available complementary foods (Dewey and Adu\u2010Afarwuah [2008](#fsn3367-bib-0009){ref-type=\"ref\"}; Owino et\u00a0al. [2008](#fsn3367-bib-0030){ref-type=\"ref\"}; Imdad et\u00a0al. [2011](#fsn3367-bib-0016){ref-type=\"ref\"}).\n\nSome of the challenges during this period include the use of plant\u2010based complementary foods that are too bulky for the weanling with a tiny stomach to eat the necessary quantities that provide adequate nutrients and energy to meet their requirements. Besides plant\u2010based foods notably unrefined cereals, legumes, and nuts contain high levels of phytates and at times polyphenols (Gibson and Ferguson [2008](#fsn3367-bib-0101){ref-type=\"ref\"}). These components vary in the degree to which they inhibit"
-"All relevant data are within the paper and its Supporting Information files.\n\nIntroduction {#sec001}\n============\n\nThe dentate gyrus (DG) is the primary interface between the neocortex and the hippocampus proper. It receives highly-processed information about the external environment via the entorhinal cortex and is believed to perform a pattern separation function whereby similar inputs are transformed into distinct neural codes \\[[@pone.0197869.ref001],[@pone.0197869.ref002]\\]. Behaviorally, this has been proposed to enable discrimination of similar sensory stimuli that are prone to interference.\n\nWhile physiological assays have confirmed a pattern separation function for the DG, these experiments are technically challenging \\[[@pone.0197869.ref003],[@pone.0197869.ref004]\\]. Thus, many have turned to behavioral tests of putative pattern separation-dependent, discrimination functions for the DG. In mice, deletion of DG NMDA receptors leads to impaired context discrimination in a fear conditioning paradigm \\[[@pone.0197869.ref005]\\]. DG-specific lesions and/or molecular manipulations also lead to impaired discrimination memory for object location and spatial geometry when stimuli are highly interfering \\[[@pone.0197869.ref006]--[@pone.0197869.ref008]\\]. Such a discrimination function is not limited to animals, as imaging studies indicate that the DG-CA3 region is specifically recruited when subjects are asked to distinguish visual stimuli that are distinct, but bear a high resemblance, to previously-studied items \\[[@pone.0197869.ref009]\\]. Notably, in conditions such as aging and"
-"1. Introduction {#sec1-materials-11-00148}\n===============\n\nThe development of new materials derived from renewable sources is an objective of high priority on a technological and environmental point of view to reduce dependence on non-renewable sources (oil). Currently, the global consumption of plastics is more than 200 million tons, with an annual increase of approximately 5% \\[[@B1-materials-11-00148]\\]. Although the use of oil for plastics is assessed at about 4% of global consumption, it is anyway important to try to replace them with alternative raw materials. Until now petrochemical-based plastic have been used as packaging materials. This kind of petrochemical plastics are preferred because they show good mechanical performances, heat stability, good barrier properties, high availability, and a relative low cost. Nevertheless, their end-life management is often not easy, because only some plastic items, e.g., those made of only one material, can be selectively collected and recycled \\[[@B2-materials-11-00148]\\]. Plastic films can be recycled but they have a low apparent density. The packages consisting of different materials, e.g., multilayer packages, cannot be easily recycled, but they usually can neither be composted.\n\nThe production of flexible films by using compostable plastics can be particularly important because they can be used for preparing low apparent-density packaging, such"
-"CASE REPORT\n===========\n\nA 65-year-old female visited Korea University Anam Hospital complaining of chest pain, palpitation, and dyspnea. On the basis of computed tomography, she was diagnosed with Takayasu's arteritis including a large aneurysm (58 mm) on the aortic distal arch ([Fig. 1A, B](#f1-kjtcvs-48-74){ref-type=\"fig\"}). Because the patient strongly refused surgery, we performed thoracic endovascular aortic repair (TEVAR) with left subclavian artery (LSCA) to left common carotid arterial transposition ([Fig. 1C, D](#f1-kjtcvs-48-74){ref-type=\"fig\"}). The thoracic duct was ligated due to injury during the LSCA dissection. After TEVAR, the patient's symptoms improved, and she was discharged on postoperative day 10 with a normal chest X-ray ([Fig. 2A](#f2-kjtcvs-48-74){ref-type=\"fig\"}).\n\nThe patient returned to the hospital complaining of moderate dyspnea on postoperative day 19, and the follow-up chest X-ray showed a severe left pleural effusion ([Fig. 2B](#f2-kjtcvs-48-74){ref-type=\"fig\"}). After the insertion of a chest tube, postoperative chylothorax was confirmed by a pleural fluid analysis. Conservative management with a fat-free diet and *nil per os* was attempted for 2 weeks, but there was no remarkable improvement. Chest tube drainage exceeded 300 mL/day despite the conservative management. Therefore, we administered a subcutaneous injection of octreotide (0.1 mg) every 8 hours for 2 weeks; however, even these injections had no"
-"Introduction {#s1}\n============\n\nEarly vigour or seedling vigour (i.e. the amount of leaf area produced early in the season) has been considered an important trait for rainfed (water-limited) wheat especially in Mediterranean climate regions such as southern Australia. In these regions, rainfall is winter dominant ([@CIT0031]; [@CIT0037]; [@CIT0032]) and coincides with early wheat growth (planted in mid-autumn to early winter). Wheat yield is often limited by insufficient rainfall around anthesis with a terminal drought during grain-filling ([@CIT0035]). More efficient use of soil moisture at early wheat growing stages (before canopy closure) is considered crucial for higher grain yields. Greater early vigour leads to faster leaf area development, reduces soil water loss via soil evaporation, increases competition with weeds ([@CIT0021]), and improves nutrient uptake ([@CIT0020]; [@CIT0039]). Consequently, it has been shown that genotypes with higher early vigour produced higher biomass and grain yield ([@CIT0048]; [@CIT0041]; [@CIT0031]; [@CIT0003]). However, greater early growth and water use may also reduce available soil water later in the season to worsen terminal drought, leading to reduced yields. Whether early vigour leads to increased or decreased yield will depend on local climate conditions. Despite the promise of benefits through greater vigour (e.g. [@CIT0003]), there is a lack"
-"1. Introduction {#sec1-pharmaceutics-12-00165}\n===============\n\nDry eye disease (DED) is the condition of having dry eyes, in which the eye surface is damaged due to lack of tears, excessive evaporation of tears, or irregularity of tear component \\[[@B1-pharmaceutics-12-00165]\\]. The symptoms include itching, redness, irritation, ocular fatigue, dryness, and foreign body sensation \\[[@B1-pharmaceutics-12-00165],[@B2-pharmaceutics-12-00165]\\]. DED can cause severe pain and limit daily activities such as reading books or using the computer for a long time \\[[@B3-pharmaceutics-12-00165]\\]. These detrimental effects can lead to psychological complications and reduce the quality of life for DED patients \\[[@B4-pharmaceutics-12-00165]\\].\n\n*Achyranthes japonica* is a perennial herb of *Achyranthes* genus \\[[@B5-pharmaceutics-12-00165],[@B6-pharmaceutics-12-00165]\\]. *Achyranthis radix*, the roots of *Achyranthes japonica*, has been used in traditional medicine for arthritis, menses, and edema \\[[@B7-pharmaceutics-12-00165]\\]. Recently, the protective effect of *Achyranthis radix* extract (USL) on the eye components has been reported \\[[@B8-pharmaceutics-12-00165]\\]. According to the literature, 1% USL improved the symptoms of dry eye syndrome caused by fine dust \\[[@B8-pharmaceutics-12-00165]\\]. However, the lack of information about the eye drop formulation of USL has limited its clinical application. Thus, the development of eye drop formulations of USL should be conducted prior to the application of USL in DED patients.\n\nTear deficiency is one of the most"
-"Introduction {#Sec1}\n============\n\nA series of caves which yielded an important record of Neanderthal remains, including an almost intact cranium^[@CR1]^, along with a number of artifacts featuring the outstanding occurrence of instruments made on shell^[@CR2]--[@CR4]^, occur at elevation ranging 5--10\u00a0m a.s.l. along the carbonatic reefs forming the coast of the Tyrrhenian Sea in southern Latium (Fig.\u00a0[1](#Fig1){ref-type=\"fig\"}b). Frequentation of these caves has been considered to be possible in a systematic manner after the sea-level drop following the Last Interglacial stage (MIS 5.5). In contrast, during the highstand, circa 125\u00a0ka, it was assumed that the seawater entered the caves, producing a series of sea-level markers, represented by tidal notches, horizontal stripes of lithodomus burrows, and characteristic biodetritic beach deposits (\\\"panchina\\\"). Based on inferences provided by these sea-level markers occurring a few meters above the present sea level, this region has been considered to be substantially stable from a tectonic point of view. This is consistent with the common assumption of a maximum sea level 4--8\u00a0m higher than in the Present during MIS 5.5^[@CR5]^. Moreover, the occurrence of \\\"Senegalese fauna\\\", including the most characteristic gastropod species *Strombus bubonius,* in these beach deposits was considered distinctive of the MIS 5.5"
-"Introduction\n============\n\nPrevious studies have shown that inflammatory response plays an important role in the progression and destabilization of atherosclerosis and cardiovascular disease (CVD).[@B1][@B2] Among the various inflammatory markers related to CVD neutrophil to lymphocyte ratio (NLR) and C-reactive protein (CRP) have recently been investigated as new predictors of worse cardiovascular outcomes.[@B3][@B4] NLR is an inexpensive, easily obtainable, and widely available inflammatory biomarker associated with CVD. High NLR is an important predictor of mortality in patients with acute coronary syndrome, and it also has been reported as a prognostic marker for poor outcomes of coronary artery bypass graft surgery and postoperative atrial fibrillation.[@B5][@B6] CRP is an inflammatory biomarker and is known as an independent predictor of adverse cardiovascular events in coronary artery disease (CAD) patients.[@B3] Although both NLR and CRP could be used as potential predictors of poor prognosis in acute myocardial infarction (AMI) patients, the combined usefulness of NLR and CRP in the prediction of adverse outcomes has not been investigated. Moreover, the combination of 2 biomarkers may increase the predictive ability of individual markers in AMI patients with multiple comorbidities. In previous studies, performed in other disease entities such as cancers, the combined use of NLR and CRP"
-"Introduction {#s1}\n============\n\nIt is well known that the human mind is limited in the conscious processing of relevant stimuli (*e.g.*, letters) when presented in close temporal proximity in a sequential stream of irrelevant stimuli (*e.g.*, digits). Most people show a reduced ability to successfully report a second target (T2) when presented within 200--500 ms of a first (T1), a phenomenon known as the attentional blink (AB) [@pone.0073415-Raymond1], [@pone.0073415-Martens1]. Although there are a diversity of models and theories of this phenomenon, they can roughly be divided in two types: limited-resource accounts [@pone.0073415-Chun1]--[@pone.0073415-Shapiro1] and attentional-control accounts [@pone.0073415-DiLollo1]--[@pone.0073415-Wyble1].\n\nIn limited-resource accounts of the AB, the common assumption is that there is a pool of resources available for processing targets and that this pool is limited. Whenever a target must be stored for later report, resources are drawn from the resource-pool in order to consolidate that target. Because this pool of resources is limited, there is a chance that the pool is still depleted due to the ongoing consolidation of T1 at the moment that T2 is encountered. Because there are not enough resources available for the processing of T2, an AB occurs. Thus, in these theories, a capacity-limitation of the attentional system"
-"1. INTRODUCTION {#acm212277-sec-0001}\n===============\n\nBrain metastases are an important source of morbidity for cancer patients. Whole brain radiation therapy (WBRT) is effective, but results in significant neurocognitive side effects for many patients, especially in terms of verbal memory. As survival for patients with metastatic brain disease increases,[1](#acm212277-bib-0001){ref-type=\"ref\"}, [2](#acm212277-bib-0002){ref-type=\"ref\"} approaches to spare neurocognition have become an intense area of study. Focal radiation with stereotactic radiosurgery (SRS) is one approach that results in less neurocognitive impairment,[3](#acm212277-bib-0003){ref-type=\"ref\"} but is not an option for many patients with more diffuse metastatic disease. One alternative that has gained popularity in the last several years has been hippocampal avoidance whole brain radiation therapy (HA\u2010WBRT), which uses advanced radiation techniques to reduce the dose to the hippocampus, an area important for memory formation and neurogenesis.[4](#acm212277-bib-0004){ref-type=\"ref\"} The RTOG 0933 phase II study showed evidence of improvements in quality of life and memory preservation compared to historical WBRT controls.[4](#acm212277-bib-0004){ref-type=\"ref\"} Hopkins Verbal Learning Test\u2010Revised Delayed Recall (HVLT\u2010R) revealed a 30% mean relative decline in WBRT without hippocampal avoidance (baseline 4 months) versus 7% utilizing HA\u2010WBRT along with no decline in Quality of Life scores (QOL).[4](#acm212277-bib-0004){ref-type=\"ref\"}\n\nIntensity modulated radiation therapy (IMRT) has been used as a practical delivery method for HA\u2010WBRT based"
-"Discussion\n==========\n\nSub-Saharan Africa\n------------------\n\nSub-Saharan Africa remains the region most heavily affected by the epidemic, accounting for 67% of all PLHIV and nearly 75% of all AIDS deaths in 2007. Almost 90% of the children with HIV worldwide live in sub-Saharan Africa, and HIV is the underlying cause of almost one-third of all child deaths in some high-burden countries \\[[@B1]\\].\n\nSouth Africa has the world\\'s largest national epidemic, with an estimated 5.7 million PLHIV. Approximately 500,000 people are newly infected each year and 1,000 people die every day from AIDS-related illnesses. Young women in South Africa face a substantially greater risk of becoming infected than men \\[[@B2]\\].\n\n22 million people live with HIV in sub-Saharan Africa. 1.5 million people died from AIDS-related causes in 2007. 1.9 million people were newly infected in 2007. The most vulnerable populations include women and girls, children and youth.\n\n### Lessons learned\n\nThe regional session on sub-Saharan Africa acknowledged the tremendous progress in national responses to AIDS in the past few years, including substantial increases in ART coverage \\[[@B3]\\]. Declining HIV prevalence has been observed in several countries, particularly in the smaller HIV epidemic of West Africa. In his overview of the regional response,"
-"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\nPoor ovarian response (POR) is observed in at least 10% of infertile women but the incidence rises with advancing age. Reproductive treatment in these patients remains a major challenge in fertility research ([@B1]), mainly because of the low live birth rate of approximately 6% per cycle in this population, irrespective of the treatment protocol used ([@B2]).\n\nAn important hurdle for improving outcomes in poor responders is the historical lack of consensus with regard to the diagnosis of POR, with studies using a variety of definitions, which could hamper the clinical value of inter-study comparison and meta-analysis in this group of patients ([@B3]). The introduction of the Bologna criteria in 2011 represents a major step toward proper identification of this group of women and the adoption of these criteria paved the way for studies using an unanimous and formal definition ([@B4]).\n\nDifferent treatment protocols for the management of Bologna poor responders have been evaluated so far, but currently no single stimulation protocol stands out as unequivocally effective ([@B5]). Corifollitropin alfa (CFA) is a long acting gonadotropin that has been designed as a sustained follicle stimulant with the ability to simplify ovarian stimulation, given that a single subcutaneous injection"
-" {#Sec1}\n\nImplementation gaps exist in understanding the factors that influence the scale-up of Treatment as Prevention (TasP), a strategy increasingly adopted worldwide to reduce HIV transmission.Using the Consolidated Framework for Implementation Research, this study identified the key implementation factors that influenced the scale-up of TasP in British Columbia (BC), Canada---one of the first jurisdictions to scale up to the population level.Our findings provide critical insights for other jurisdictions that are currently scaling up TasP, as well as offer contextualized understandings about how BC can effectively go to scale with other promising population-level interventions.\n\nIntroduction {#Sec2}\n============\n\nDuring the past decade, the role of antiretroviral therapy (ART) in preventing HIV has had a critical impact in reducing the transmission of HIV and reshaping the broader HIV continuum of care \\[[@CR1]\\]. Building on ecological data from observational research in the mid to late 2000s \\[[@CR2]--[@CR4]\\] in which the preventive benefit of ART was described, the landmark clinical trials HPTN-052 \\[[@CR5]\\] and Partners of People on ART---A New Evaluation of the Risks (PARTNER) \\[[@CR6], [@CR7]\\] established during the early to late 2010s and strengthened recently with new data that ART confers a protective benefit against HIV transmission among both heterosexual and male homosexual"
-"Introduction\n============\n\nFor the majority of individuals, facial signals of aggression are threatening, inducing anxiety or fear. For a smaller but significant proportion of society they are interpreted as provocative, evoking an aggressive response. Identifying the neurobiological factors that underlie this variation is one key factor in understanding of aggression. A large body of research has demonstrated that a personality trait linked to the motivation to gain reward (reward--drive or appetitive motivation) is associated with altered perception of facial signals of aggression, clinical disorders of aggression, and heightened tendency to experience and display anger but not other negative emotions, such as fear ([@bib13; @bib17; @bib19; @bib23; @bib36; @bib37; @bib38; @bib53; @bib58]). High reward--drive individuals also show increased attention to facial signals of aggression ([@bib53]), attributed to their increased tendency to interpret them as signals of provocation or social challenge ([@bib6; @bib62]); the same effect has also been observed in high trait anger participants ([@bib62]).\n\nIn recent research we have explored the neural basis of this effect. Functional Magnetic Resonance (fMRI) data have shown that reward--drive selectively modulates the responses of the amygdala and ventral anterior cingulate (ACC) to viewing facial signals of aggression ([@bib5]). These regions have a wider role"
-"1 INTRODUCTION {#SEC1}\n==============\n\nGenome-wide association studies (GWAS) are an increasingly popular approach for identifying associations between genotype and phenotype. A large number of such studies have been performed recently to try to identify the genetic basis of a wide variety of diseases, and explore how this genetic basis differs depending on the geographic origin of the studied population. High-throughput genotyping chips are used to obtain the genotype of an individual at several hundreds of thousands of single nucleotide polymorphisms (SNPs). These sets of SNPs are able to represent most of the variability at the single locus level that was identified by the HapMap project (Frazer *et al.*, [@B3]). In a GWAS study, several thousands of disease individuals, and several thousands of healthy controls are genotyped. Statistical tests are used to identify SNPs that show a strong association with the disease. Strong association between a SNP and a disease can be evidence that the SNP is related to the disease, or that it is in linkage disequilibrium with SNPs that are related to the disease. In both cases significant associations provide promising leads for further experimental investigation into the genetic etiology of diseases. These studies have led to the identification"
-"Introduction {#Sec1}\n============\n\nThe classic insect hormones, juvenile hormones (JH) and ecdysteroids, play critical roles in insect postembryonic development. In juvenile insects ecdysteroids trigger the moulting process, while JH will determine the nature of the moult^[@CR1]^. These lipophilic hormones, together with nutritional cues, as well as signalling mechanisms directed by regulatory peptides, such as insulin-related peptides (IRP) and neuroparsins (NPs) also control the reproductive physiology of adult insects. However, the exact interplay between hormones and nutrition in this regulation may distinctly differ depending on the insect's specific feeding habits and reproductive strategies^[@CR2],[@CR3]^. The role of JH as a master regulating gonadotropin in insect female reproduction is established in phylogenetically basal species, such as orthopterans (the insect order to which locusts belong), while ecdysteroids seem to have taken over this leading role in some lepidopteran and most dipteran species^[@CR3],[@CR4]^. In female locusts, JH, synthesized in the corpora allata (CA, part of the retrocerebral complex), stimulates vitellogenin (Vg) production in the fat body by activating *Vg* gene transcription^[@CR5]^. Furthermore, JH also binds to membrane receptor sites in the ovarian follicular epithelium to initiate events that cause cells to shrink^[@CR6]--[@CR10]^. This process, called patency, allows Vgs, which are mainly produced by the fat"
-"Background {#Sec1}\n==========\n\nWith continuing industrialization and urbanization, the number of older migrants in China has increased dramatically. Many of them move to cities to join their adult children and take care of their grandchildren. Immigration status is an important component in racial and ethnic disparities in access to healthcare \\[[@CR1]\\]. Immigrant populations can easily become vulnerable groups in health services use in both developed and developing countries. A study in Europe reported that the migrants had less usage of screening and outpatient services for specialized care \\[[@CR2]\\]. EU policy supports healthcare access for undocumented migrants, but practices remain haphazard \\[[@CR3]\\]. A Czech study found that migrants were more likely to remain excluded from the public health insurance system \\[[@CR4]\\]. Another study in Vietnam reported that the rural-to-urban older migrants had less access to health services \\[[@CR5]\\]. Equity in health services means everyone has a chance to enjoy a fundamental preventive treatment, healthcare, and rehabilitation in need. Reported issues on health services accessibility included the following: i) The current status of health services use. A study conducted in Shanghai reported a low usage of health services in the older \"floating\" population \\[[@CR6]\\]. ii) Accessibility to health services among vulnerable groups,"
-"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"
-"1. Introduction {#sec1-sensors-19-02537}\n===============\n\nRecently, with the rapidly increasing location-based service (LBS) \\[[@B1-sensors-19-02537]\\], such as positioning, tracking, navigation, and location-based security, the indoor localization has attracted wide attention. In outdoor environments, Global Positioning Service (GPS) \\[[@B2-sensors-19-02537]\\] and other satellite positioning methods can provide people with an acceptable accuracy of positioning services, which can basically meet the various needs of people. However, for indoor scenes, the GPS method cannot work due to a signal's dispersion and blocking. Thus, various indoor localization technologies have been proposed by researchers like Time Of Arrival (TOA) \\[[@B3-sensors-19-02537]\\], Angle Of Arrival (AOA) \\[[@B4-sensors-19-02537]\\], Time Difference of Arrival (TDOA) \\[[@B5-sensors-19-02537]\\], and Received Signal Strength (RSS) \\[[@B6-sensors-19-02537]\\]. Concerning factors such as positioning accuracy, technical complexity, electromagnetic interference, and construction cost, the WLAN (Wireless Local Area Networks) indoor positioning technology based on RSS fingerprints has become the principal method with an acceptable positioning accuracy.\n\nThe fingerprint-based method is widely used in a RADAR system \\[[@B7-sensors-19-02537]\\], a Nibble system \\[[@B8-sensors-19-02537]\\], and a Weyes system \\[[@B9-sensors-19-02537]\\] currently. Generally, the fingerprint-based positioning method is implemented in two phases: the off-line training phase and the online positioning phase. In the off-line training phase, the RSSs from different access point (APs) are measured at"
-"Introduction {#s1}\n============\n\nBorderline personality disorder (BPD) is a mental disorder marked by a pervasively unstable pattern in affective experience, interpersonal relationships, impulsive behavior, and self-image ([@B1]). Typical clinical symptoms include affective dysregulation, impulsive aggression, non-suicidal self-injury, and suicidal behavior ([@B2]). Besides these core symptoms, patients with BPD also often demonstrate disturbances in their bodily self-experience. These disturbances not only relate to a negative bodily self-image such as an increased body dissatisfaction and lowered self-appraised body attractiveness ([@B3], [@B4]), but also to more global body-perceptual distortions, such as dissociation phenomena or body-alienation symptoms, including experiences of disownership toward one's own body ([@B5], [@B6]).\n\nThe sense of ownership (SoO) is described as the experience of \"mineness\" toward one's body, and the sense of agency (SoA) relates to the experience of being the initiator and author of an action \\[for a review, see Braun et\u00a0al. ([@B7])\\]. It is not yet understood whether an altered SoO or SoA may contribute to the distorted bodily self-experiences in BPD patients. One current hypothesis is that, similar to patients suffering from schizophrenia ([@B8]--[@B10]), patients with BPD also have a weakened sense of self that manifests itself in a disturbed SoO experience ([@B11]) as well as"
-"MicroRNA (miRNA) is a group of small non-coding RNA that plays significant roles in multiple metabolic processes. Since its discovery in 1993 \\[[@CR1]\\], numerous studies have postulated and established a set of theories concerning miRNA biogenesis and functions,\u00a0with cross-species\u00a0researches initially focusing on translational repression in cytoplasm. After transcription, cleavage, and processing, mature miRNA is transported from the nucleus to cytoplasm to be loaded into RNA induced silencing complex (RISC).\u00a0MiRNA base-pairs with the mRNA, mediating mRNA decay or detachment of ribosomes. In addition to potent inhibitory functions in the cytoplasm, in 2008, research demonstrated that the\u00a0introduction of miR-373 and its precursor (pre-miR-373) induced the expression of cold-shock domain-containing protein C2 (CSDC2) and E-cadherin \\[[@CR2]\\]. This is attributed to the sequence complementarity of miR-373 and promoters of those genes. In 2004, another member of small non-coding RNA, small interfering RNA (siRNA) was observed to inhibit the\u00a0transcription of elongation factor 1alpha (EF1A) though promoter interaction \\[[@CR3]\\]. Following these, research interest in promoter-targeting siRNA has increased substantially \\[[@CR4]\\]. With the introduction of newly developed techniques like microarray and RNA-seq, numerous mature miRNAs were found enriched in nucleus, which demonstrates that nuclear miRNAs are more prevalent than what we had"
-"Numerous progresses have been achieved in the last several decades on discrete semiconductor decices, such as memories and light emitting diodes. Nowadays, both the performance and reliability of these devices have already become sufficient for use in practical applications. Future work may involve the research of devices that possess wider functionality and compatibility in a variety of data storage and processing. Notably, the demand of high-speed inter-chip and intra-chip link has dictated the developments of communication. The conventional electronic devices gradually approach their limit due to the increasing difficulties in controlling the carriers at shrinking sizes[@b1][@b2]. Among several candidates for next-generation memory cells, resistive random access memory (RRAM) based on a simple two-terminal electrical switch has the potential to serve as a replacement for conventional memory structures due to its good switching properties, low power consumption and especially, three-dimensional multilayer stacking to achieve high density memory[@b3][@b4][@b5][@b6][@b7][@b8]. The typical current-voltage (I-V) characteristics of the RRAM cells exhibit an extreme change in resistance between high resistance state (HRS) and low resistance state (LRS). One of the underlying mechanisms responsible for the RRAMs arises from the formation of conducting filament networks under the application of a positive voltage across the cell. Upon application"
-"1. Introduction {#sec1}\n===============\n\nBenign metastasizing leiomyoma (BML) is an entity in which benign-appearing uterine smooth muscle tumors are associated with similar-appearing tumors at distant sites \\[[@B1]\\]. The lung is the most common site of involvement and usually shows multiple, occasionally solitary, well-circumscribed nodules, ranging in diameter from a few millimeters to several centimeters \\[[@B2]\\]. The finding of multiple pulmonary nodules raises a broad differential diagnosis, including primary or secondary neoplasms, vasculitis, collagen vascular disease, and granulomatous diseases. BML does not frequently come to the attention of the emergency physician because it is rare and usually asymptomatic. However, BML may exhibit a range of clinical presentations, some emergent, depending on the site of involvement, number, and size of the smooth muscle tumors (leiomyomas). We report a patient with benign metastasizing leiomyoma who presented in the emergency department with pleuritic chest pain.\n\n2. Case Report {#sec2}\n==============\n\nA 51-year-old woman, gravida 2 para 2, presented to the emergency department with a 2-day history of left-sided pleuritic chest pain. Two weeks prior, she underwent subtotal hysterectomy and bilateral salpingo-oophorectomy for a leiomyomatous uterus which was approximately the size of a 12-week gravid uterus. Ten years prior, she underwent a hysteroscopic myomectomy for"
-"All relevant data are within the paper and its Supporting Information files.\n\nIntroduction {#sec005}\n============\n\n*Plasmodium falciparum* malaria infection is still one of the main causes of under-five child morbidity and mortality in Sub-Saharan Africa \\[[@pone.0121643.ref001]\\]. In 2010, the World Health Organisation (WHO) estimated that there were approximately 216 million episodes of malaria worldwide with 174 million cases occurring in sub Saharan Africa, which resulted in over 660,000 deaths mainly in children under-five \\[[@pone.0121643.ref002]\\]. Several factors are thought to be responsible for this high mortality rate \\[[@pone.0121643.ref003]\\], with the host immune response to the infection playing a crucial role \\[[@pone.0121643.ref004]\\].The immune response mechanisms are both antibody and cell mediated \\[[@pone.0121643.ref005]\\].\n\nPassive transfer studies from adults who are immune to malaria have shown that naturally acquired antibodies to *P*. *falciparum* are protective against malaria infection \\[[@pone.0121643.ref006],[@pone.0121643.ref007]\\]. In children, whilst immunity against the severe clinical symptoms may be achieved quite early in life \\[[@pone.0121643.ref008]\\], immunity to parasite multiplication and growth develops slowly and is dependent on repeated exposure to malaria infections over several years \\[[@pone.0121643.ref009]\\]. Exposure to *P*. *falciparum* antigens in children is therefore essential for the acquisition of an effective antibody immune response and substantial disruption of this exposure may delay"
-"Introduction\n============\n\nA selective vulnerability of basal forebrain cholinergic neurons (BFCNs) contributes to cognitive decline in Alzheimer's disease patients ([@aww271-B2]; [@aww271-B59]). BFCNs depend on the neurotrophin nerve growth factor (NGF) ([@aww271-B33]) for their maintenance and survival ([@aww271-B43]). For this reason, the clinical application of NGF for Alzheimer's disease is being pursued. However, due to the poor biodistribution of NGF to the brain after systemic delivery ([@aww271-B50]) and to its potent pro-nociceptive activity after systemic ([@aww271-B49]) and intrathecal ([@aww271-B37]) administration, current clinical trials are based on the neurosurgical injection close to the nucleus basalis of Meynert (NBM) of NGF-secreting cells or of vectors carrying the *NGF* gene ([@aww271-B57]; [@aww271-B40]; [@aww271-B22]). These trials report a positive effect on BFCNs and on cognition, but the outcome on Alzheimer's disease hallmarks such as amyloid pathology were not described in patients ([@aww271-B57]; [@aww271-B40]; [@aww271-B22]; [@aww271-B23]; [@aww271-B28]). In preclinical testing, after 3 months local infusion of NGF in non-human primate brains, amyloid-\u03b2 deposition was found to be identical as in age-matched controls ([@aww271-B56]).\n\nTo reduce the pain-inducing side effects of NGF, we developed painless NGF (hNGFp), a double mutant form of NGF (hNGFP61S/R100E) inspired by the human genetic disease hereditary sensory and autonomic neuropathy type V"
-"INTRODUCTION {#s0}\n============\n\nTo respond to environmental cues and changes, a molecular system that can receive external signals and transduce them to intracellular responses is fundamental for every living organism ([@B1]). In eukaryotes, G-protein-coupled receptors (GPCRs) and their associated heterotrimeric G-protein complexes are important and universal signal transduction components that transduce extracellular signals to intracellular signals. A characteristic feature of GPCRs is their topology, with seven transmembrane (TM)-spanning helices flanked by an extracellular N terminus and an intracellular C terminus. Upon binding of a ligand to a GPCR, conformational changes lead to activation and dissociation of the heterotrimeric G-protein complex. G-protein subunits \u03b1, \u03b2, and \u03b3 regulate key effector enzymes such as adenylate cyclase (AC), phospholipase C (PLC), and phosphoinositide 3-kinase, resulting in the production of secondary messengers, such as cAMP, Ca^2+^, and inositol trisphosphate ([@B2]). GPCRs are encoded by an evolutionarily ancient gene family that was already present in the last eukaryotic common ancestor (LECA) ([@B1]). In mammalians, this is the largest superfamily with genes encoding a very diverse group of transmembrane (TM) proteins. Humans, for example, have over 800 GPCRs ([@B3]). They function in a wide variety of processes not only as sensory receptors for taste, smell, or"
-"Introduction\n============\n\nPeripheral artery disease (PAD) affects approximately 5--10 million people in the USA[@b1-ijwh-4-625]--[@b4-ijwh-4-625] and is a significant cause of lower extremity functional impairment, ulceration, and limb loss. Even without these clinical consequences, PAD is an independent predictor of increased cardiovascular (CV) and all-cause mortality.[@b5-ijwh-4-625]--[@b16-ijwh-4-625] In addition, the economic burden of PAD is higher than one might expect, and comparable to that of coronary artery disease and ischemic stroke.[@b17-ijwh-4-625],[@b18-ijwh-4-625]\n\nThe prevalence and clinical consequences of PAD are similar in magnitude for women and men. Despite this, PAD remains underappreciated in women, and women have been underrepresented in contemporary PAD revascularization studies.[@b19-ijwh-4-625],[@b20-ijwh-4-625] As a result, sex-specific differences in the risk factors, management, and outcomes of PAD remain unclear, creating a critical need for clinical research to evaluate sex differences in PAD. In recognition of this growing problem, the American Heart Association recently released a \"call to action\" to raise awareness of the burden of PAD in women. [@b20-ijwh-4-625] This review will seek to highlight sex differences in the risk factors, presentation, diagnosis, and management of PAD.\n\nPrevalence of PAD\n=================\n\nPAD can be symptomatic or asymptomatic, and can be diagnosed based on several different methods: the ankle brachial index (ABI), duplex"
-"INTRODUCTION {#sec1-1}\n============\n\nThe installation and preparation of a permanent vascular pathway for hemodialysis is an important challenge for surgeons. This challenge is mainly due to the increased number of dialysis patients, such as the elderly and diabetic patients, especially those who are considered and candidates for kidney transplantation, as well as patients requiring long-term dialysis.\\[[@ref1][@ref2]\\]\n\nThe guidelines to improve the outcomes of kidney disease have offered and provided standards for optimal access and maintenance of the route for dialysis.\\[[@ref3]\\] The autologous arteriovenous fistula turns as a selective vascular access in patients requiring long-term dialysis. The use of this type of access results in a long-term patency and also a few potential complications.\\[[@ref4][@ref5]\\] However, these benefits may be accompanied by a high failure rate (up to about 30%).\\[[@ref6][@ref7]\\]\n\nThe arterial/venous grafts are more favorable, compared to the autologous arteriovenous fistulas, because they have more short-term outcomes and fewer deficits; moreover, they can be used immediately for hemodialysis if needed.\\[[@ref8]\\] However, this tool is also associated with low patency, leading to increased morbidity and high hospital costs.\\[[@ref9]\\]\n\nThe application of autogenous arteriovenous fistulas has been increasingly considered today as a temporary access using tunneled catheters. However, the employment of this method"
-"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,"
-"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"
-"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\n============\n\nSeveral factors can lead to weaning failure from mechanical ventilation (MV). Among these, cardiac dysfunction is one of the main causes. NT-proBNP has been proposed as a biomarker of cardiovascular function during weaning from MV. Unfortunately it does not provide for a continuous monitoring of cardiac function. Pulse wave analysis may serve as a continuous bedside monitoring tool of cardiovascular performance. Cardiac cycle efficiency (CCE) is an indirect index of left ventricular performance obtained by the pulse contour method MostCare (Vygon, Padova, Italy). The aim of this study was to evaluate the correlation between NT-proBNP and CCE and the potential usefulness of such variables during the weaning process from MV.\n\nMethods\n=======\n\nTwenty-two long-term (\\>48 hours) mechanically ventilated patients capable of performing a weaning trial of spontaneous breathing (SBT) were enrolled in the study. Inclusion criteria were: age \\>18 years and equipment with a standard arterial catheter line. Exclusion criteria were: neuromuscular disease, tracheotomy, renal failure, and traumatic brain injury. During the weaning process, NTproBNP plasma levels, CCE, and standard hemodynamic and ventilatory data were collected 30 minutes before extubation (T1), 2 hours (T2) and 12 hours later (T3). After removal of tracheal tube, patients with a history"
-"1. Introduction {#sec1-sensors-20-03144}\n===============\n\nResearch into advanced medical and prosthetic devices has generated significant attention in recent years due to the increasing demand for reliable bionic hands capable of manifesting the patient's intentions to perform various tasks. In general, gesture recognition techniques have emerged as a key enabling feature for improving both the accuracy and functionality of bionic hands, allowing the patient control over delicate operations in dangerous situations, or to help patients with movement disorders and disabilities, as well as in the rehabilitation training process.\n\nThe use of bionic hands is not only limited to medical use, but has also found innumerable applications in industrial settings; artificial bionic hands can perform certain tasks in hazardous or restricted environments while maintaining the user's level of dexterity and natural response time. Under such circumstances, vision-based gesture recognition using image detection \\[[@B1-sensors-20-03144],[@B2-sensors-20-03144],[@B3-sensors-20-03144],[@B4-sensors-20-03144],[@B5-sensors-20-03144],[@B6-sensors-20-03144],[@B7-sensors-20-03144]\\] could be sufficient to provide the correct hand motion.\n\nFurthermore, several technologies, such as electrical impedance tomography (EIT), were used for improving motion detection. Zhang et al. \\[[@B8-sensors-20-03144]\\] proposed a hand gesture recognition system based on EIT. The EIT system measures the internal electrical impedance and estimates the interior structure by using the surface electrodes and high-frequency alternating current (AC)."
-"1. Introduction {#s0005}\n===============\n\nSignalling by the Wnt family of secreted glycolipoproteins is considered to be one of the most fundamental developmental signalling pathways and occurs in all animals that share a primary body axis ([@b0070]). Due to its crucial roles in embryonic development and tissue homeostasis it is subject to a multi-layered system of regulation ([@b0040; @b0125; @b0110]). A multitude of Wnt antagonists are secreted which function by blocking receptor access ([@b0160; @b0115; @b0155]), sequestering Wnt ligands ([@b0175; @b0100; @b0105]) or degrading Wnt ([@b0200; @b0075; @b0205]). In contrast, R-spondins (Rspo1-4) are the sole secreted potentiators of Wnt signalling ([@b0080]) and have emerged as crucial regulators of stem cell maintenance *in vivo* and *in vitro* ([@b0150; @b0050]). These stem cell growth factors are found in regenerating tissue such as nail mesoderm ([@b0010]), hair follicle ([@b0015]) and most prominently in the intestinal epithelium ([@b0085]). Structurally they consist of two cysteine rich repeats (similar to those found in Furin and henceforth referred to as Fu1 and Fu2, respectively), which are necessary and sufficient for Wnt activation, as well as a C-terminal Thrombospondin-related domain (TSR) and a positively charged, flexible tail.\n\nAt the level of molecular mechanism Rspo proteins potentiate Wnt signalling by"
-"Polycomb repressive complex 2 (PRC2) represses gene transcription by trimethylating histone H3 on lysine 27 (H3K27me3). The core PRC2 complex is comprised of embryonic ectoderm development (EED), Suppressor of Zeste12 homolog (SUZ12), retinoblastoma-associated protein 48 (RbAp48), and a catalytic subunit, either Enhancer of Zeste Homolog 1 or 2 (EZH1 or EZH2).^[@bib1],\\ [@bib2]^ EZH1 and EZH2 are mutually exclusive in the same PRC2 complex and are partially redundant at certain developmental and disease stages.^[@bib3],\\ [@bib4]^ EED is a core component of PRC2 complex that interacts with EZH1 or EZH2 through a WD40 domain. In addition, EED recognizes H3K27me3 through an aromatic cage structure to recruit PRC2 to established H3K27me3 and thereby enforce maintenance of this repressive epigenetic mark.^[@bib5],\\ [@bib6]^\n\nPRC2 has essential roles of regulating cell fate commitment, organogenesis, homeostasis and disease-related tissue remodeling.^[@bib1]^ In early developing mouse embryos, homozygous *Eed* null mutation abolished global H3K27 methylation and caused defects in primitive streak formation and fetal lethality at E9.5.^[@bib7],\\ [@bib8]^ EZH2 also controls the fate of multiple types of tissue progenitors.^[@bib9]^ Depletion of EZH2 in epidermal precursor cells promoted premature epidermal differentiation and barrier acquisition.^[@bib10],\\ [@bib11]^ EZH2 also had developmental-stage-specific roles in regulating cardiomyocyte differentiation and proliferation.^[@bib12],\\ [@bib13]^ In adult vasculature,"
-"The cardiovascular disease is one of the major healthcare problems of the world population, and understanding its determinants is essential for designing effective interventions.\n\nReactive oxygen species (ROS) are toxic, highly reactive, and unstable compounds formed during a variety of physiological and pathological biochemical reactions. ROS are produced in all viable cells, and strong evidence suggests an important role of ROS in the development and progression of cardiovascular disease. Nevertheless, the precise mechanisms contributing to the cardiovascular system injury due to increased oxidative stress are still under investigation. Recent experimental studies suggest that ROS plays a causational role in the development of systolic dysfunction following myocardial infarction (MI), the brain ischemia-reperfusion injury in the course of stroke and in cardiometabolic disorders. Endothelium plays a crucial role in regulation of vascular tone, and endothelial dysfunction (ED) is an important risk factor of cardiovascular disease. The mechanisms involved in decreased vasodilative activity of endothelial cells include decreased bioavailability of nitric oxide, oxidative stress, and disorders in the metabolism of prostanoids. The decreased bioavailability of nitric oxide (NO), as well as increased oxidative stress, plays a crucial role in contributing to the decrease of endothelial vasodilative properties. According to several experimental studies, increased"
-"INTRODUCTION\n============\n\nRetinoblastoma is the most common primary intraocular malignancy of infancy and childhood with an incidence of 1 in every 20,000 live births.[@b1-jovr-04-169] During the 20th century, retinoblastoma was uniformly fatal. Early diagnosis and recent advances in the management of retinoblastoma particularly the use of chemotherapy have improved the prognosis of this fatal disease. Although this neoplasm has one of the highest cure rates among malignant tumors, it is almost invariably fatal if left untreated.[@b1-jovr-04-169]\n\nTreatment modalities currently available for retinoblastoma can be classified as follows: (1) focal therapy including cryotherapy, conventional laser photocoagulation, transpupillary thermotherapy, photodynamic therapy (in vitro study), and plaque radiotherapy;[@b2-jovr-04-169] (2) external beam radiotherapy;[@b3-jovr-04-169] (3) systemic chemotherapy[@b3-jovr-04-169] and (4) enucleation. With the advent of chemotherapy, radical methods of management such as enucleation and external beam radiation have been relegated to second and third lines of treatment. Chemotherapy is currently the most important treatment modality for globe salvage in retinoblastoma patients.\n\nGENERAL CONSIDERATIONS\n======================\n\nThe goal of chemotherapy, in addition to globe salvage, is avoiding external beam radiation and its complications such as temporal bone atrophy, sicca syndrome, cataracts, radiation retinopathy, neovascular glaucoma and more importantly, the risk of secondary non-retinoblastoma tumors in the field of"
-"Background {#Sec1}\n==========\n\nChildhood psychiatric disorders are of concern because of the associated negative impact on general wellbeing across the lifespan, for example, lower educational achievements \\[[@CR1]--[@CR5]\\]. The findings in several studies suggest that the adverse impact of childhood onset psychiatric disorders on educational attainment is largely accounted by problems of inattention and conduct. Most psychiatric disorders present symptom patterns that cause severe impairment on the emotional, cognitive and social level, resulting into the child being unable to carry out his/her educational potential. Esch et al. \\[[@CR4]\\] and Kumpulainen et al. \\[[@CR2]\\] studied the relationship between psychiatric symptoms and performance level at school among 8-year-old children. Children facing psychiatric difficulties were more likely to receive extra tutoring or special education. The probability of getting special education was highest for attention deficit disorders, anxiety, and oppositional/conduct disorders. Children from low socio-economic status families had more psychiatric symptoms and performed less successfully at school than children from more advantaged environments. This suggests that children with psychiatric symptoms or disorders are more likely to have lower performance levels at primary school.\n\nA few studies have shown that psychiatric disorders in children and adolescents can negatively impact academic performance. Medical drug treatment with antipsychotics"
-"The global incidence of dengue virus (DENV) infection has increased drastically in recent decades. It is estimated that about 400 million people worldwide are infected with DENV annually, resulting in \\~100 million cases of dengue fever and 21,000 deaths[@b1][@b2]. DENV are mainly detected in the tropical and sub-tropical regions around the world, with high incidence reported from the Americas, Eastern Mediterranean, Southeast Asia and the Western Pacific regions. DENV is one of the most important arthropod-borne virus that targets humans. It is transmitted to humans by the bite of infected *Aedes aegypti* or, less frequently, *Aedes albopictus* mosquitoes[@b3].\n\nDENV belongs to the Flaviviridae family, along with other major human pathogens such as West Nile virus, Japanese encephalitis virus and yellow fever virus. There are four DENV serotypes (DENV1--4)[@b4][@b5]. Patients infected with any one of the four serotypes can display a spectrum of symptoms, ranging from being asymptomatic to showing mild dengue fever, to the severe dengue haemorrhagic fever or dengue shock syndrome[@b6]. An initial primary infection by a DENV serotype induces life-long protection against the homologous serotype[@b7]. However, in a secondary infection by a different DENV serotype, the formation of non-neutralizing complex of DENV with cross-reactive antibodies from the previous"
-"Daly L., Dolan R., Power D., N\u00ed Bhuachalla \u00c9., Sim W., Fallon M., Cushen S., Simmons C., McMillan D. C., Laird B. J., and Ryan A. (2020) The relationship between the BMI\u2010adjusted weight loss grading system and quality of life in patients with incurable cancer, Journal of Cachexia, Sarcopenia and Muscle, 11: 160--168. 10.1002/jcsm.12499.\n\nIntroduction {#jcsm12499-sec-0005}\n============\n\nWeight loss (WL) has long been recognized as an important and prognostic clinical feature in patients with cancer. Involuntary WL is estimated to affect between 30% and 70% of patients and has been associated with reduced quality of life (QoL) and physical function, poorer tolerance to anti\u2010cancer therapy, and shortened survival in patients with cancer.[1](#jcsm12499-bib-0001){ref-type=\"ref\"}, [2](#jcsm12499-bib-0002){ref-type=\"ref\"}, [3](#jcsm12499-bib-0003){ref-type=\"ref\"}, [4](#jcsm12499-bib-0004){ref-type=\"ref\"} WL is a cardinal feature of cancer cachexia, a condition characterized by the loss of muscle with or without the loss of fat mass, leading to progressive functional impairment.[5](#jcsm12499-bib-0005){ref-type=\"ref\"} However, current definitions and thresholds for defining clinically important WL are unclear, particularly in the face of a global obesity epidemic. The use of minimum reported degrees of WL (e.g. \\>5% or 10% over 3--6 months) is arbitrary and heterogenous and not based on specific values that relate to adverse clinical outcome. It has been suggested"
-"Upon T cell activation, naive CD4^+^ T cells can differentiate into distinct cell lineages, including the classical Th1 and Th2 cells ([@bib1], [@bib2]), as well as the recently defined Th cells producing IL-17 (Th17 cells) ([@bib3]) and inducible Treg (iTreg) cells ([@bib4]). These cells play important roles in adaptive immunity ([@bib5]). Th1 cells mainly produce IFN-\u03b3 and are involved in immunity against intracellular pathogens. Th2 cells produce IL-4, IL-5, and IL-13, are involved in immunity against helminths and other extracellular parasites, and enhance antibody responses. Th17 cells produce IL-17a, IL-17f, IL-21, and IL-22, and are critical for immunity against extracellular bacteria and fungi. Th1, Th2, and Th17 cells are also involved in the induction or maintenance of autoimmune and immunopathologic diseases. Thus, Th1 and Th17 cells are linked to many organ-specific autoimmune diseases, and Th2 cells play critical roles in asthma and other allergic diseases. iTreg cells, functionally similar to naturally occurring Treg cells ([@bib6]), can regulate immune responses. Among naturally occurring Treg cells, a subset expressing CD103 has been reported to contain the highest suppressive activity and to be present in the mucosal tissues, such as in the gut, as well as at sites of inflammation ([@bib7], [@bib8]). Interestingly,"
-"INTRODUCTION\n============\n\nA number of animal behavior studies have reported individual differences in behavioral characteristics, other than those associated with variables such as sex or age \\[[@b1-ajas-31-8-1098]\\]. The behavioral responses expressed when an animal faces a specific situation are influenced by its temperament \\[[@b1-ajas-31-8-1098]\\]. Temperament is regarded as a type of behavioral tendency that appears in a relatively stable manner across various situations and over time \\[[@b2-ajas-31-8-1098]\\].\n\nHorses have been genetically improved for various purposes, such as sports, leisure, and horseracing, and are categorized by morphological body confirmation or breed. The major traits for which horses have been improved include body size, racing speed, as well as strength, and some behavioral traits have also been enhanced. Temperament is regarded as an important factor to determine the usability of horses. For example, a survey of the members of the Pony Club in Australia, a youth organization that provides programs for horses and riding, reported that the temperament of horses (e.g., quietness, reliability, and stability) were more important traits for horses at the Pony Club than their body type, ridability or purchase price \\[[@b3-ajas-31-8-1098]\\]. In addition, eleven Warmblood Horse Associations in Europe have established criteria for the temperament of horses and use"
-"Introduction {#Sec1}\n============\n\nQuantitative comparison of the behavior of animals is a key element of neuroscience. As important as this is, even the most comprehensive ethograms fail to capture the inherent variability in the behaviors of individuals, whether they consist of simple or complex sets of actions^[@CR1]--[@CR4]^. This is further compounded by the error-prone nature of subjective assessment during human observations. A pertinent issue for behavioral studies, therefore, is the development of appropriate methods for the quantitative comparison of behaviors between two animals or a single individual under two or more conditions.\n\nResearchers typically quantify parameters (such as the average speed or average height climbed) based on expert knowledge of the ethology of that species or the kinematics of a behavior. These measures are useful, yet they can be inadequate as descriptors of behavior for a variety of reasons. One notable reason is that they are gross approximations of the behavioral action being measured. Averaging of observational data may not be representative of the kinematics and can be confounded by what has been described elsewhere as \"the failure of averaging^[@CR2]^\". Furthermore, there can be considerable variability in the execution of even those behaviors that are considered \"stereotypical\" or instinctive. As"
-"Introduction\n============\n\nPeroxisome proliferator-activated receptors (PPARs) heterodimerized with the retinoid X-receptor (RXR), one of the nuclear receptors, have been known to be involved in lipid and carbohydrate metabolism after binding to peroxisome proliferators response element (PPRE) ([@B12]). Currently, three genes (PPAR-\u03b1, PPAR-\u03b3, and PPAR-\u03b4) in the PPAR family are known. PPAR-\u03b1 is most abundantly expressed in the liver and has the effect of diminishing circulating triglycerides and increasing high dense lipoprotein (HDL) cholesterol. PPAR-\u03b3 is present in high concentrations in adipose tissue and improves insulin sensitivity. These effects are well documented, but the function of PPAR-\u03b4 has not been fully investigated ([@B3]).\n\nMany studies have reported that low-grade chronic systemic inflammatory response to nutrient excess is related to obesity, insulin resistance, type 2 diabetes mellitus, and non-alcoholic fatty liver disease (NAFLD), which refers to a wide spectrum of liver disease ranging from simple fatty liver (steatosis), to nonalcoholic steatohepatitis (NASH), and cirrhosis ([@B27]; [@B24]; [@B26]). It is reported that hepatic steatosis, inflammation, and apoptosis are induced by neutrophil infiltration and the production of pro-inflammatory cytokines associated with excessive free fatty acid released from adipocytes ([@B14]).\n\nRecent studies showed that a PPAR-\u03b4 agonist could prevent lipopolysaccharide (LPS)-induced expression and secretion of"
-"The task of identifying and obtaining foods which contribute to the overall human health, satisfy nutritional and energy needs and at the same time not inducing food poisoning, has been around as long as humans have. Human diet, which provides essential nutrients for the organism health, is influenced by different factors, including cultural habits, socio-economic status, and weather/climate. For example, spice consumption in the warm regions is tightly connected to the need for keeping the food resistant to bacteria for a longer period of time[@b1].\n\nIt is a well known fact that certain foods can influence the effect of a drug in an organism[@b2][@b3][@b4][@b5]. The food-induced changes in the bioavailability (the degree and rate at which a drug is absorbed into someone\\'s system) of the drug modify the clinical effect of the drug. Generally, food - drug interactions can result in significant reduction of the drug bioavailability, either by direct interaction between a substance from the food and a chemical component of a drug, or by the physiological response of food intake (e.g. gastric acid secretion). This can often result in treatment failure. Additionally, food - drug interactions can result in an increase in drug bioavailability, either by increased drug"
-"Introduction {#s1}\n============\n\nAssessment of eligibility for antiretroviral therapy (ART) in low and middle-income countries (LMIC) is dependent on CD4 T-lymphocyte enumeration and, if unavailable, WHO clinical staging. [@pone.0088928-Kagaayi1], [@pone.0088928-Jaffar1]. Additionally, CD4 testing is frequently used to monitor patients on ART. In most clinical settings, CD4 enumeration has typically used flow cytometry which has excellent precision, accuracy, and reproducibility. However, flow cytometry requires fresh venous blood and subsequent processing is often at a central facility distant from the sample collection point. Consequently, there is a significant time lapse from sample procurement to return of results, with delays in decisions on ART eligibility and initiation. These delays are a barrier to care and can result in losses to follow-up with negative patient and programmatic outcomes [@pone.0088928-Lawn1]--[@pone.0088928-Stringer1].\n\nPoint-of-care (POC) CD4 T-lymphocyte enumeration is a promising technology that could mitigate many of the barriers and delays associated with flow cytometry and improve access to care. POC CD4 testing could allow timely return of CD4 results to providers and patients, obviating the need for repeated patient visits and rapidly linking patients into care. Several evaluations of POC CD4 technology have been reported, but results have not been entirely consistent, and study settings have been"
-"**Core tip:** Studies have demonstrated a potential role for fecal biomarkers such as fecal calprotectin and fecal lactoferrin (FL) in monitoring Crohn's disease (CD) and ulcerative colitis (UC). However, their correlation with disease burden (endoscopic scores/disease activity and disease extent) has not been extensively investigated. In our study FL separated disease severity categories based on endoscopic scores in both UC and CD patients. FL showed a close correlation with the diseased mucosal surface and with disease extent and was more closely correlated to endoscopy when determined before endoscopy. FL can accurately and timely represent intestinal inflammation in inflammatory bowel diseases.\n\nINTRODUCTION\n============\n\nInflammatory bowel disease (IBD), both Crohn's disease (CD) and ulcerative colitis (UC), are on the rise worldwide, including Asia\\[[@B1]-[@B3]\\]. In the United States, 3.1 million people are reported to be affected\\[[@B4]\\]. The annual burden of IBD is extensive, with over 2.3 million physician visits, 180000 hospital admissions, and a cost of \\$6.3 billion in healthcare services\\[[@B5]-[@B7]\\]. One third of the annual cost of healthcare for IBD patients is classified as outpatient services, with the major components being endoscopy and pathology\\[[@B7]\\].\n\nIBD activity has traditionally been monitored by the severity of clinical symptoms, using clinical scoring systems such as"
-"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"
-"Introduction {#s1}\n============\n\nLactic acid bacteria are applied for food preservation, but more importantly for yogurt and probiotics production. *Lactobacillus plantarum* plays a key role as cholesterol-lowering milk additive, which likely increases the immune responses, exert antimutagenic and anticarcinogenic activities and protect against gastrointestinal diseases, as summarized in numerous scientific review articles, e.g., (Nagpal et al., [@B25]; Kola\u010dek et al., [@B21]). Several tools were introduced to monitor physiologic key parameters in *L. plantarum* cultivations like multi-parameter flow cytometry (Arnold et al., [@B3]; Schenk et al., [@B32]; Bensch et al., [@B4]; Tropcheva et al., [@B34]), quantitative real-time PCR, e.g., (Clementschitsch et al., [@B9]; Davis, [@B10]; Sohier et al., [@B33]; Pega et al., [@B28]; Emerson et al., [@B11]), and viable cell counting for viability analysis (Savini et al., [@B31]; Perdana et al., [@B29]; Glu\u0161ac et al., [@B14]). Although all these systems provide information on the metabolic state and physiology of the cell, they require manual *off-line* sample pre-treatment. The necessity of sample pre-treatment might be the reason for the lack of correlation between results of flow cytometry and colony forming units of *Lactobacillus* sp. (L\u00e9onard et al., [@B24]). The electrooptical analysis of the anisotropy of polarizability (AP), in contrast, represents a fully"
-"Saliva is an important component for speech, digestion of food, and protection from microorganisms. In addition, biomarkers for viral, bacterial, and fungal parasitic infections and for both systemic and nonsystematic diseases have been found in saliva ([@R1])([@R2])([@R3]). These markers can be various molecular species ranging from proteins and antibodies to DNA and viral RNA.\n\nRecently, human RNA obtained from cell-free saliva was shown to be a biomarker for oral cancer ([@R4])([@R5]). By means of expression-based microarray analysis and reverse transcription-quantitative PCR (RT-qPCR), [1](#FN1){ref-type=\"fn\"} we were the first to show that cell-free saliva from healthy individuals contains more than 3000 species of mRNA ([@R6]). We also found 17 mRNAs that were present in higher amounts in patients with oral cancer than in healthy persons ([@R4]). We developed a prediction model based on salivary mRNA concentrations of 4 of these genes and showed that they have 91% sensitivity and specificity for oral cancer detection.\n\nLittle is known about the molecular nature and properties of human salivary RNA ([@R6])([@R7]). Saliva is known to contain ribonucleases from various sources, and this fact may explain the lack of analysis of human salivary RNA ([@R8])([@R9])([@R10])([@R11]). It is not clear how RNA and ribonucleases can coexist in"
-"Introduction\n============\n\nTreatment of acute myeloid leukaemia (AML) is challenging and clinical trials involving novel approaches are considered the best therapeutic strategy in many patients with AML [@R1]. One potential approach, which has shown promising results in *in vitro* and mouse models, is pharmacological activation of a serine/threonine phosphatase-negative regulator, protein phosphatase 2A (PP2A) [@R2].\n\nPP2A is a multimeric enzyme composed of a catalytic subunit (C), a structural subunit (A) and a variable regulatory subunit (B), of which there are at least three different families (B55, B56, B\u2033), each with several isoforms [@R3]. The association of a particular B subunit with the core AC dimer introduces substrate specificity and subcellular targeting of PP2A activity [@R4]--[@R6]. PP2A activity is further regulated by post-translational modifications and by endogenous inhibitory proteins such as the SET and CIP2A (cancerous inhibitor of PP2A) oncogenes [@R7],[@R8]. PP2A is involved in numerous cellular processes, including cell cycle regulation, DNA damage response, apoptosis and migration. The tumour-suppressing activities of PP2A depend on its ability to inactivate multiple components of growth and survival signalling pathways required for tumourigenesis, such as the Ras/ERK, PI3K/Akt, JNK, JAK/STAT and Wnt/\u03b2-catenin pathways. PP2A also regulates c-Myc, p53 and apoptosis-related proteins such as Bcl-2,"
-"Intraductal papillary mucinous tumor (IPMT) of the pancreas is a recently recognized pancreatic cystic neoplasm, characterized by diffuse dilatation of the main pancreatic duct (MPD) or branch ducts and the oozing of a variable amount of mucin from the ampulla of Vater ([@B1], [@B2]). IPMTs have been classified as adenoma, borderline, and carcinoma, the last-mentioned category including both *in-situ* and invasive varieties ([@B3]).\n\nBecause of the potential of IPMTs for malignant growth, radical surgical resection is mandatory. It has also been reported, however, that these tumors progress slowly and have a good prognosis after resection; thus, some investigators have claimed that compared with malignant IPMTs, those that are benign do not require immediate surgery or very aggressive surgical procedures ([@B4]-[@B6]). In addition, the surgical strategy employed may be affected by the grade of malignancy ([@B7]). In view of the above, if a course of treatment is to be planned, differentiation between malignant and benign IPMTs is essential.\n\nSeveral recent reports have described the superiority of magnetic resonance cholangiopancreatography (MRCP) to endoscopic retrograde cholangiopancreatography (ERCP) and CT in the evaluation of IPMTs ([@B8]-[@B11]). However, only one article has assessed the usefulness of MRCP in differentiating malignant from benign IPMT ([@B12]). We"
-"Introduction {#Sec1}\n============\n\nFrontotemporal dementia (FTD) is a progressive presenile dementia with degeneration of the frontal and anterior temporal lobes of the brain \\[[@CR1]\\]. The clinical phenotype of FTD patients is heterogeneous and includes cognitive, behavioral and language impairments with a variable co-occurrence of amyotrophic lateral sclerosis (ALS) \\[[@CR2]\\]. Formation of insoluble protein deposits, largely composed of ubiquitinated, hyperphosphorylated TAR DNA-binding protein 43 (TDP-43), defines one of the major pathological subtypes of frontotemporal lobar degeneration (FTLD-TDP) as well as ALS patients, introducing a clinico-pathological continuum of TDP-43 proteinopathies \\[[@CR3]--[@CR5]\\]. TDP-43 is a multifunctional RNA-binding protein involved in different RNA-related processes including transcription and splicing regulation \\[[@CR6], [@CR7]\\].\n\nOver the past ten years, considerable progress has been made in unraveling the genetic basis of the FTD-ALS continuum. Today, more than 10 genes are linked to FTD-ALS disorders at variable frequencies \\[[@CR8], [@CR9]\\]. A major part of the mutation spectrum described for FTLD-TDP patients is covered by loss-of-function mutations in progranulin (*GRN*) that codes for a multifunctional growth factor with neurotrophic properties in the central nervous system (CNS) \\[[@CR10]\\] and a hexanucleotide repeat expansion mutation in *C9orf72* \\[[@CR11]\\]. Less frequently*,* mutations in TANK-binding kinase 1 (*TBK1*), TAR DNA-binding protein 43 (*TARDBP*), valosin-containing"
-"Introduction {#h0.0}\n============\n\nHuman cytomegalovirus (HCMV) infects a wide spectrum of cell types by utilizing different forms of glycoprotein gH/gL to enter different cell types by distinct routes of entry (reviewed in reference [@B1]). Entry into human fibroblasts requires at least two glycoproteins, gB and gH/gL, and involves fusion with the plasma membrane ([@B2]--[@B4]). HCMV entry into epithelial and endothelial cells requires gB and a pentameric form of gH/gL denoted gH/gL/UL128-131 and involves macropinocytosis or endocytosis and low-pH-dependent fusion with endosomes ([@B3], [@B5], [@B6]). Another glycoprotein, gO, is associated with HCMV gH/gL and is important for incorporation of gH/gL into virions but not for cell surface expression in fibroblasts ([@B7]--[@B9]). We described interference experiments in which different forms of gH/gL were expressed in cells, apparently saturating or altering intracellular traffic of virus receptors and leading to inhibition of virus entry ([@B9], [@B10]). These studies supported a working model suggesting that HCMV gH/gL binds receptors important for entry into fibroblasts and that gH/gL/UL128-131 binds receptors in epithelial cells. Importantly, another major HCMV glycoprotein, gB, did not cause interference in any cell type.\n\nStudies of the better-characterized herpes simplex virus (HSV) and Epstein-Barr virus (EBV) gB and gH/gL homologues have supported models"
-"Colorectal cancer (CRC) is one of the most common malignant diseases worldwide. As prognosis of CRC has improved over the last years ([@bib37]), research on quality of life of CRC survivors has become increasingly important. This research has mainly focused on the negative experiences of cancer survivors like long-term symptoms and restrictions in quality of life ([@bib17]). But studies have shown that a high percentage of cancer survivors also report positive changes in the context of their disease ([@bib10]; [@bib28]; [@bib27]). Two constructs of positive consequences of cancer have been distinguished: post-traumatic growth (PTG) and benefit finding (BF). PTG refers to benefits associated with changes in life perspective, interpersonal relationship, and self-perception. The changes result from the struggle of an extreme event like a cancer diagnosis and treatment and cannot be caused by minor stressors ([@bib31]; [@bib30]) . In contrast, BF is defined as the process in which the patient re-assigns positive value to the illness based on the benefits he or she identifies ([@bib8]; [@bib13]). While BF is hypothesised to start immediately after diagnosis, PTG refers to an active change in one\\'s capacity to deal with adverse events and, thus, may develop even years after the cancer diagnosis ([@bib7])."
-"1. Introduction {#sec1}\n===============\n\nHIV is a retrovirus, characterized by inserting its genomic DNA into the human genome, followed by the phenotypes of acute, chronic, or latent infection based on the interactions of the viral DNA with a host DNA. Once an HIV DNA is inserted into a host genome, no known immune mechanism so far eliminates the viral DNA from the host genome. Several cellular mechanisms, however, govern the HIV DNA expression after the integration, which regulate retroviral replication and thereby control the disease phenotypes or symptoms of an acute, chronic, or latent infection, including the cellular mechanisms that silence the replication of ancient human endogenous retroviruses (HERVs) \\[[@B1]--[@B10]\\]. Development of highly active antiretroviral therapy (HAART) or combination antiretroviral therapy (cART) has changed the natural course of HIV infection. HAART effectively controls the HIV entry, reverse transcription, integration, package, and even release, except for a direct control of the HIV DNA expression \\[[@B10]\\].\n\nCD4 T-cell is the target cell of HIV infection. The status of CD4 T-cells, specifically memory CD4 T-cells after HAART, determines the patient anti-HIV immunity, clinical status, and prognosis. HIV DNA expression in memory CD4 T-cells directly governs the activities of an HIV reservoir or the"
-"Introduction {#S0001}\n============\n\nEnteroviruses (EVs), of the *Picornaviridae* family, are a genus of pathogenic viruses that cause diverse human disorders. The major members of the EV genus include poliovirus (PV), echovirus, coxsackievirus, enterovirus, and rhinovirus \\[[1](#CIT0001)\\]. These medically important viruses pose a significant health burden as evidenced by recent global epidemics across Asia and North America \\[[2](#CIT0002),[3](#CIT0003)\\]. EVs are associated with broad human pathologies, ranging from the common cold to neurological disorder (i.e., encephalitis, aseptic meningitis, and flaccid paralysis) \\[[4](#CIT0004)\\], cardiovascular damage (i.e., viral myocarditis and dilated cardiomyopathy) \\[[5](#CIT0005)\\], and metabolic disease (i.e., type 1 diabetes) \\[[6](#CIT0006)\\]. With the exception of the successful PV vaccination beginning in the 1950s, non-polio EVs continue to be a global health issue.\n\nEVs are a family of small, non-enveloped viruses containing a positive, single-stranded RNA genome of \\~7.5 kb that encodes a single open reading frame flanked by 5\u02b9 and 3\u02b9 untranslated regions (UTRs) \\[[1](#CIT0001)\\]. The life cycle of an EV begins with viral attachment to one or multiple designated cellular receptors. Following internalization, viral RNA is released into the cytoplasm, where it serves as a template for the translation of the viral polyprotein and for the replication of the viral genome. The 5\u02b9UTR"
-"Introduction {#s1}\n============\n\nMalnutrition is a serious condition, characterised by multifactorial causality (Volkert, [@r38]), thought to affect 1.3 million (or 1 in 10) older adults in the UK (Malnutrition Task Force, [@r21]; Malnutrition Task Force, [@r23]) with 93% of malnutrition occurring in community settings (Elia and Russell, [@r11]). The prevalence of malnutrition for community-living older adults in Europe and North America varies between 1% and 15% (Favaro-Moreira *et al*., [@r13]). With a predicted increase in life expectancy within the UK and worldwide (Office for National Statistics, [@r27]), this global phenomenon of population ageing will result in an increase in the numbers of older people at risk of malnutrition. It is well documented that malnutrition in older adults is associated with poor clinical outcomes and increased health and social care use (Agarwal *et al.*, [@r1]). The costs associated with malnutrition within England are substantial, estimated at \u00a319.6 billion per year (\u00a323.5 billion in the UK), equivalent to around 15% of total health and social care (Elia, [@r10]). Despite these statistics, there is little academic work exploring interventions to either prevent or address malnutrition in older people.\n\nMeals-on-wheels (MOW) have played an important part in supporting older people to remain food secure"
-"Introduction {#s1}\n============\n\nMycophenolate mofetil (MMF), a prodrug of mycophenolic acid (MPA), is the predominant antimetabolite immunosuppressant used as a cotherapy with tacrolimus (TAC) or cyclosporine (CsA) to prevent graft rejection after solid organ transplantation ([@B25]; [@B26]). MMF is extensively absorbed and rapidly hydrolyzed to the active component MPA after oral administration. The majority of MPA is metabolized to the pharmacologically inactive 7-O-mycophenolic acid glucuronide (MPAG), whereas a lower fraction is metabolized to the active acyl-glucuronide mycophenolic acid (AcMPAG) ([@B6]; [@B32]). MPA and MPAG are reported to be 97 and 82% bound to serum albumin (ALB), respectively at clinically relevant concentrations ([@B6]). MPAG also undergoes enterohepatic circulation (EHC) through biliary excretion, followed by intestinal deglucuronidation and reabsorption as MPA in the colon. This process contributes to approximately 40% (range: 10--60%) of the area under the concentration--time curve (AUC) of MPA and causes multiple peaks in the concentration--time profile ([@B54]). Most absorbed MMF is eliminated through the kidney as MPAG ([@B54]).\n\nMPA has a narrow therapeutic window and it is recommended to maintain a 12-h dosing interval exposure (AUC~0--12h~) between 30 and 60 mg\u00b7h/L during the early posttransplantation period ([@B52]; [@B58]; [@B34]; [@B37]). Under-exposure is associated with an increased risk for"
-"Introduction {#s1}\n============\n\nA thin body ideal is predominant in different cultures, especially in western countries, whilst body image dissatisfaction (BID) in young women is common, causing in some cases disordered eating attitudes and behaviors ([@B1]). While the prevalence of these disorders is rising, especially among girls ([@B2]), their onset is gradually dropping ([@B3]). In this way, school-age children demonstrate discontentment with their body shape ([@B4], [@B5]), something that is often reinforced by the bidirectional dynamic between society and media, in which a thin ideal that rarely fits with reality, is being promoted ([@B6]--[@B13]).\n\nBody image is a multidimensional construct, which involves perceptions, behaviors, cognitions, and emotions related to individual's body, that are also connected to the degree of one's own body image satisfaction and perceptual accuracy ([@B5], [@B14]--[@B16]). Furthermore, when trying to understand how body dissatisfaction occurs and evolves through the developmental spectrum, it is worth taking into consideration that body image is strongly related to the holistic experience of embodiment (awareness that my body belongs to me), which reflects the attunement between the inner states (emotions, cognitions etc.) and the body ([@B17]--[@B20]) and has been found to be present even in early childhood ([@B17], [@B21]). Embodiment can also"
-"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"
-"Introduction {#s1}\n============\n\nThe incidence of type 1 diabetes is constantly rising in children and adolescents since the mid-1950's [@pone.0091268-Aanstoot1], [@pone.0091268-1]. Allotransplantation of pancreatic islets is currently an option for the treatment of diabetic type-I patients suffering from repetitive and severe hypoglycemic episodes. However, the possibility of receiving an islet transplant is limited mainly due the shortage of organ and the need for life-long immunosuppression. The utilization of islets from other species (xenograft) and administration in encapsulated form represent attractive strategies to overcome both problems.\n\nClinical trials of allogeneic human or xenogeneic pig encapsulated islets have been reported in only a few cases [@pone.0091268-Basta1], [@pone.0091268-Elliott1]. After intra-peritoneal transplantation all patients showed a modest reduction in insulin requirement and a significant diminution of hypoglycemic episodes without any detectable immune response against the islets. Nevertheless, sustained insulin-independence was not achieved after encapsulated allogeneic islet transplantation. In addition, blood porcine C peptide levels remained low or undetectable suggesting graft failure. Certain investigators are of the opinion that this poor outcome is related to the high sensitivity of pancreatic islets to hypoxia [@pone.0091268-Vaithilingam1]. Indeed, islets are highly vascularized structures depending on an arterial oxygen supply of 40 mmHg [@pone.0091268-Carlsson1]. The peritoneum, although it allows"
-"Social distancing, self-isolation, handwashing, provision of hand sanitisers in public buildings, frequent disinfection of high-touch surfaces and the use of face masks have been recommended as effective mitigation measures against the spread of COVID-19 by the SARS-CoV-2 virus. Their effectiveness has been demonstrated by the flattening curves for new cases identified, hospital admissions and deaths across time. However, such gains have come at great expense, with sacrifices including freezing people\\'s movement and closing down academic institutions, schools and businesses, all of which has negatively impacted national and international economies so severely that they have already touched a record low in many countries. A long-term lockdown is therefore unlikely to be affordable. Some countries, such as Denmark and Germany, have already started to ease restrictions, while others, including the United States and the United Kingdom, have followed suit.\n\nThe rate of reproduction (*R*) of the coronavirus is a simple means of understanding the spread of COVID-19 against response measures in a particular country, city or region. The spread of new infections will multiply if the value of *R* increases over one, and will fall and eventually disappear as the value of *R* goes below one. A diverse range of *R* was"
-"Introduction\n============\n\nMaternal vitamin D deficiency is a common public-health problem.[@b1] [@b2] Individuals with deeply pigmented skin and those with minimal skin exposure to sun are considered to be particularly at risk of vitamin D deficiency.[@b3] During intrauterine development, the fetus accumulates about 30\u2005g of calcium from the maternal circulation, and during lactation, a further 280--400\u2005mg/day calcium is secreted into the milk.[@b4] This results in an increased demand for calcium in the mother, so it is important that adequate vitamin D be available to ensure efficient intestinal absorption of calcium.\n\nVitamin D deficiency in pregnancy has been shown to lead to significant pregnancy complications. Maternal complications include decreased weight gain,[@b5] hypertension in pregnancy and pre-eclampsia.[@b1] In the newborn, maternal vitamin D deficiency has been linked to hypocalcaemia, low birth weight,[@b6] poor weight gain, impaired development and rickets.[@b7] Although no health benefits have been associated with vitamin D supplementation during pregnancy,[@b8] current evidence suggests that deficiency may be an independent risk factor for pregnancy and birth complications.[@b1]\n\nA recent revision of Perinatal Guidelines of South Australia[@b9] recommends the measurement of serum vitamin D in all at-risk women during their first antenatal visit. At-risk women are defined as all women"
-"The data from the Enqu\u00eate Multisectorielle Continue (EMC) are co-owned by the Institut National de la Statistique et de la D\u00e9mographie of Burkina Faso and the World Bank. EMC data are available at the World Bank website (via this <http://microdata.worldbank.org/index.php/catalog/2538/get_microdata>) to all interested researchers after accepting the terms. The authors of the present manuscript had no special access privileges to the data.\n\nIntroduction {#sec001}\n============\n\nDietary diversity is essential for meeting dietary nutrient requirements \\[[@pone.0195685.ref001], [@pone.0195685.ref002]\\], and as such, is an important determinant of dietary adequacy, nutritional status and many associated health outcomes \\[[@pone.0195685.ref002]--[@pone.0195685.ref008]\\]. In low-income rural areas of Sub-Saharan Africa (SSA), where the majority of the population still relies on rain-fed, small-scale agricultural production as a principal source of livelihood\\[[@pone.0195685.ref009], [@pone.0195685.ref010]\\], poor diet quality remains an intractable challenge\\[[@pone.0195685.ref011]\\]. Smallholder farming households in these settings are especially vulnerable to seasonal changes in dietary diversity because of fluctuations in food availability and accessibility. Though staple grains and pulses are commonly available at affordable prices during the harvest and immediate post-harvest periods, stocks of these foods deplete during the lean season and can be scarce through to the next harvest \\[[@pone.0195685.ref012]\\]. Indeed, seasonal variations in food availability can have important nutritional consequences"
-"INTRODUCTION {#omx049s1}\n============\n\nTuberculosis (TB) of thyroid is a rare disease even in an endemic country like India \\[[@omx049C1]\\]. To establish a diagnosis of thyroid TB is challenging since it can mimic a carcinoma, suppurative abscess or a haemorrhage in a thyroid cyst. In this paper, we present the case of thyroid TB that developed while the patient was on anti-tubercular therapy (ATT). The diagnosis was made on fine needle aspiration (FNA) of thyroid gland.\n\nCASE REPORT {#omx049s2}\n===========\n\nA 46-year-old gentleman presented with complaints of painless, progressive neck swelling for 2 months and altered sensorium for 1 week. Eight months ago, he was diagnosed to have miliary TB and was started on empirical ATT in a local health care centre. Three months later, he presented with clinical features suggestive of sub-acute meningitis and was diagnosed to have tubercular meningitis based on positive cerebrospinal fluid (CSF) TB PCR. While on the ATT, he developed gradually progressive neck swelling and acute worsening of sensorium. He had no other co-morbid illness and he was not on any immunosuppressive therapy.\n\nAt presentation in the accident and emergency department, his pulse rate was 88 beats per minute, blood pressure 130/80 mm Hg and his"
-"ANNOUNCEMENT {#s1}\n============\n\nDissimilatory sulfate reduction is an important anaerobic carbon mineralization process in peatlands and mitigates the production of the greenhouse gas methane ([@B1]). Members of the genus *Desulfosporosinus* are present in wetlands worldwide but typically at very low relative abundances ([@B2]). Despite its low abundance and near-zero growth, \"*Candidatus* Desulfosporosinus infrequens\" SbF1 was a major driver of sulfate reduction in experimental microcosms established with acidic soil from the Schl\u00f6ppnerbrunnen II fen (Bavaria, Germany) ([@B2][@B3][@B4]). Here, we report the draft genome sequence of *Desulfosporosinus* sp. strain Sb-LF, which was isolated from the same peatland.\n\nStrain Sb-LF was enriched and isolated as described previously under sulfate-reducing conditions, with [l]{.smallcaps}-lactate as the carbon source ([@B5], [@B6]). Briefly, 10\u2009ml of culture was grown to stationary phase on freshwater minimal medium ([@B6]) amended with sulfate (5\u2009mM) and [l]{.smallcaps}-lactate (10\u2009mM) and harvested by centrifugation. Genomic DNA was isolated using the DNeasy PowerSoil kit (Qiagen), and sequencing libraries were prepared using the Nextera XT kit (Illumina) and sequenced on the Illumina HiSeq 2000 platform, yielding 55 million 120-bp paired-end reads. The reads were inspected with FastQC (<http://www.bioinformatics.babraham.ac.uk/projects/fastqc/>) and quality trimmed at a Phred quality score of 10 using the BBDuk function of"
-"Introduction\n============\n\nThe phyto-mediated synthesis is a rapid, suitable and most acceptable biosynthetic method for synthesis of metal nanoparticles. Now a days, various plant parts like bark, leaf, fruit, stem and seed extracts have been successfully used for the synthesis of metal nanoparticles ([@B21]). Among different metal nanoparticles, silver (Ag) nanoparticles have been used enormously due to their potential anti-bacterial ([@B22],[@B23]), anti-fungal and anti-proliferative activity ([@B17]; [@B27]). Due to the excellent antimicrobial properties, the silver (Ag) nanoparticles have been extensively used in food packaging, food and seed preservation, biofertilizers, cosmetics and medicines ([@B19]; [@B10]). Besides these applications, the silver nanoparticles were found to be implemented widely in the field of high sensitive bio-molecular detection, diagnostics, catalysis and micro-electronics ([@B24]).\n\nA number of standard approaches by means of physical and chemical methods have been used for the synthesis of silver nanoparticles (AgNPs) viz. reduction in solutions, chemical and photochemical reactions in reverse micelles, thermal decomposition of silver compounds, radiation assisted, electro chemical, sono-chemical, microwave-assisted process, and most recently using green chemistry technology ([@B45]). The green synthesis approach provides most advantages over the chemical and physical method as it is cost effective, eco- friendly and easy to scaled up for large-scale synthesis"
-"Background:\n===========\n\nThe single-leg hop for distance (SLHOP) is a commonly used functional performance measure to determine return-to-play readiness. However, it is unknown if functional performance at return-to-play can predict future patient outcomes. Therefore, the purpose of this study was to determine if SLHOP performance and symmetry at return-to-play following a lower extremity injury would predict lower extremity patient-reported outcomes six months post-injury.\n\nMethods:\n========\n\nTwo-hundred thirty-six adolescent athletes (15.7\u00b11.4 years, 171.1\u00b17.6 cm, 70.3\u00b115.3 kg) were recruited for this study. If an individual sustained a non-surgical lower extremity injury during their sports season and missed three days of sports participation they were eligible for follow-up functional and patient outcome assessment Thirty-two adolescent athletes were eligible and completed the follow-up testing (15.0\u00b11.1 years, 166.5\u00b14.9 cm, 67.3\u00b110.4 kg; 14 American football, 8 volleyball, 4 girls' basketball, 6 boys' basketball athletes). The SLHOP was completed by affixing a tape measure to the ground and instructing the participant to hop on one leg as far as possible. Each participant performed three trials per leg at return-to-play (alternating legs). To be counted as a successful trial the participant maintained postural stability for 2 seconds after the landing and the contralateral leg was not allowed to"
-"Background\n==========\n\nGlutamate signaling is important for excitatory synaptic transmission in the central nervous system (CNS) and play a critical role in synaptic plasticity, a cellular mechanism for learning and memory \\[[@B1],[@B2]\\]. In addition, glutamate receptors are expressed in non-neuronal cells throughout the body, including bone, skin, lung, liver, heart and kidney, and play distinct physiological roles in these tissues \\[[@B3],[@B4]\\]. Interestingly, glutamate signaling is also involved in diseases such as cancer and neurological disorders \\[[@B5]-[@B7]\\]. In cancer cells, glutamate signaling pathways are dysregulated and glutamate is released from cancer cells, stimulating cell growth \\[[@B8],[@B9]\\]. In pancreatic cancer, glutamate stimulates cell invasion and migration \\[[@B10]\\].\n\nGlutamate receptors are divided into two major groups: ionotropic and metabotropic receptors \\[[@B11],[@B12]\\]. The former group is further classified into three members based on their agonists: N-methyl-D-aspartic acid (NMDA), \u03b1-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) and kainate receptors. Of these, the NMDA receptor forms a heterotetramer between the NR1 and NR2 subunits, including NR2A, NR2B, NR2C and NR2D, or NR3 subunits, such as NR3A and NR3B \\[[@B13]\\]. The NR1 subunit is necessary for calcium conductivity through the channel and the NR2 and NR3 subunits determine electrophysiological and pharmacological properties of the receptors. The different expression and distribution patterns of"
-"INTRODUCTION {#s1}\n============\n\nRobust tumor growth results in hypoxia, which promotes the stabilization of the oxygen-sensitive transcription factor hypoxia-inducible factor-1alpha (HIF-1\u03b1) that induces the expression of multiple genes implicated in angiogenesis, metabolism, and cell survival \\[[@R1], [@R2]\\]. Of the prominent gene products, vascular endothelial growth factor (VEGF) strongly stimulates the formation of new blood vessels (angiogenesis) and vascular networks that supply both nutrients and oxygen to tumor cells, resulting in tumor growth and invasion as well as metastasis \\[[@R3], [@R4]\\]. Thus, antiangiogenic treatment that targets the VEGF/VEGF receptor (VEGFR) pathway is a potential strategy to inhibit tumor vessel growth, thus abrogating tumor progression and metastasis.\n\nSeveral studies have focused on the development of humanized monoclonal antibodies and small molecules that inhibit tumor angiogenesis by targeting the tumor-associated endothelial cells \\[[@R5]--[@R7]\\]. Angiogenesis inhibitors including neutralizing VEGF antibodies and receptor-tyrosine kinase inhibitors, such as bevacizumab, ramucirumab, sunitinib, and axitinib, have been developed and used clinically to treat several solid tumors including colorectal cancer and renal cell carcinoma \\[[@R8]\\]. Recently, they reduce tumor blood vessel abnormalities (that are, vascular junction destabilization, pericyte loss, and vascular permeability and leakage) and improve delivery of anticancer drugs to tumor, thereby potentiating efficacy of their antitumor activity"
-"Introduction {#sec1-1}\n============\n\nAt present, more than 11.4 million men and women are living as cancer survivors;^[@ref1]^ a substantial increase from just a few decades ago. This surge in survivorship is primarily due to early detection and advances in treatment options.^[@ref2]^ However, such treatments often result in long-term physical and psychological sequelae that impact the cancer survivor's quality of life.^[@ref3]^ One such treatment option, chemotherapy, works by interrupting the cell cycle and preventing cell proliferation.^[@ref4]^ While effective at stopping cancer growth, the negative side of systemic chemotherapeutic agents is that normal cells, as well as malignant cells, are disrupted. This leads to many side effects and often long-term morbidities,^[@ref4]^ impacting functional ability and quality of life. The most common neurological side effect of chemotherapy is damage to the peripheral nervous system,^[@ref5]^ which is referred to as chemotherapy-induced peripheral neuropathy (CIPN). The peripheral toxicity involved with CIPN is specific to each chemotherapy drug class, and in most cases, appears to be dose and duration dependent. The chemotherapy agents Docetaxel, Paclitaxel, or Vinorelbine often result in symptoms of CIPN.\n\nThe mechanism behind CIPN is not fully understood, and therefore prophylactic and symptomatic treatments are largely ineffective.^[@ref6]^ While some of these therapies provide"
-"Background & Summary\n====================\n\nComputed tomography (CT) scanning has opened new ways for studying various parts of an organism's biology. This technique has been used in sharks to elucidate the development^[@b1]^, function^[@b2]^ and morphology of their feeding mechanics^[@b6]^. The majority of these studies have focused on small taxonomic subsets to gain detailed anatomical knowledge. However, phylogenetically broad statistical analyses of shark cranial mechanics are still lacking. The lead author of this work is currently undertaking such studies. This contribution provides a descriptor of a large CT dataset of shark anatomy. We used whole specimens from museum collections (a few specimens only comprise the head due to their conservation) to create a dataset of medical CT scans which covers approximately 75% of all extant shark families^[@b9]^.\n\nThe x-ray computed tomography library presented here was created for investigating the ecomorphological diversity of shark feeding systems. The data from the CT scans were used to create a second dataset comprising three-dimensional (3D) models of the lower jaw. These models were used to examine lower jaw disparity in extant sharks species in a separate study by quantifying jaw shape using landmark based geometric morphometrics. The lower jaw was selected because it displays a diversity"
-"See editorial on pages [335--8](http://onlinelibrary.wiley.com/doi/10.1002/cncr.29031/full), this issue.\n\nINTRODUCTION {#cncr29030-sec-0005}\n============\n\nWhen designing a randomized phase 3 (RP3) trial, an appropriate sample size calculation is necessary to ensure adequate study power to demonstrate a statistically significant difference between the experimental and standard arms. The majority of trial designs estimate the required sample size by incorporating 2 variables: the expected outcome for the standard/control arm and the size effect hypothesized for the experimental treatment or, in other words, the magnitude of the benefit the experimental arm is expected to confer relative to the standard arm.[1](#cncr29030-bib-0001){ref-type=\"ref\"} Thus, accurate estimation of the control arm outcome is necessary in order for initial sample size calculations to be precise and reliable.\n\nThe basic concepts of trial design evolve from the initial selection of the null hypothesis and the alternative hypothesis. The consequent treatment effect is intimately related and integral to the calculation of the sample size to achieve adequate statistical power.[2](#cncr29030-bib-0002){ref-type=\"ref\"} Type I (\u03b1) errors and type II (\u03b2) errors are central concepts in this process.[2](#cncr29030-bib-0002){ref-type=\"ref\"} A type I error is the probability of rejecting the null hypothesis when in fact it is true: a false\u2010positive result.[2](#cncr29030-bib-0002){ref-type=\"ref\"} This in general is set at a low value"
-"Highlights {#Sec1}\n==========\n\nIn this review article, we have emphasized the recent developments of YS structured anodes and their applications for enhanced electrochemical performance in LIBs and SIBs.An overview of recent advances in the novel YS structures of spheres, polyhedron and rods with controllable shape and compositions is provided.Enhanced electrochemical performance of LIBs and SIBs based on these novel YS structured anode materials is discussed in detail.\n\nIntroduction {#Sec2}\n============\n\nFossil fuels maintain the backbone for global energy supply. With the fast growth of energy consumption, it is urgent to exploit renewable energy \\[[@CR1]\\]. Until now, solar and wind energy burst out a capability of relieving energy shortage \\[[@CR2]\\]. Diverse energy conversion and storage devices are developed toward efficiently exerting solar and wind energy \\[[@CR3]--[@CR7]\\]. In this respect of energy storage from solar and wind energy to electrical energy, lithium-ion batteries (LIBs) account for a significant status due to its large capacity, long lifespan and high energy density \\[[@CR8], [@CR9]\\]. Furthermore, LIBs play a key role in the development of portable electronic devices and electric vehicles (e.g., laptops and cell phones) \\[[@CR10]--[@CR13]\\]. Generally, the configuration of LIBs consists of an anode, a cathode and electrolyte. During the process of charging"
-"INTRODUCTION {#s1}\n============\n\nFibroblast growth factors (FGF) and their receptors (FGFR) play fundamental roles in many physiologic processes, including embryogenesis and adult tissue homeostasis \\[[@R1]--[@R3]\\]. Aberrant activation of FGFR1 signaling, resulting from FGFR1 amplification or mutation, has been increasingly found to be a driving factor in tumorigenesis for multiple types of cancers \\[[@R4]--[@R9]\\]. In particular, an increasing number of novel FGFR1 fusion genes have been identified by RNA-Seq analysis in different types of cancers \\[[@R10], [@R11]\\]. The only consistent association of FGFR1 abnormalities with cancer, however, involves the constitutive activation of a ligand-independent, chimeric FGFR1 kinase in Stem Cell Leukemia and Lymphoma syndrome (SCLL). This activation results from chromosome translocations that juxtapose the kinase domain of FGFR1 with dimerization domains from a variety of partner genes. These patients develop a myeloproliferative disease that progresses to AML in 80% of patients \\[[@R12]\\], which is classified by the WHO as myeloid and lymphoid malignancies associate with FGFR1 abnormalities \\[[@R13]\\]. Reflecting the stem cell nature of the disease, these patients may coincidentally develop T- or B-cell lymphoma \\[[@R12], [@R14]\\]. The current, standard treatment for SCLL has been adapted from conventional regimens developed for ALL, AML and other leukemias, but survival is still relatively"
-"Introduction {#s1}\n============\n\nOroxylin A (C~16~H~12~O~5~, [Figure S1](#pone.0069555.s001){ref-type=\"supplementary-material\"}) is one of the main bioactive compounds purified from the root of the medicinal herb *Scutellaria* *baicalensis* Georgi that has been widely used in China, Japan, and Korea for treating inflammation and infections in the respiratory and gastrointestinal system \\[[@B1]\\]. Although many biological activities of Oroxylin A, including anti-tumor \\[[@B2],[@B3]\\], anti-bacterial \\[[@B4]\\], and cognitive enhancement \\[[@B5]\\], have been reported, the underlying molecular mechanisms are largely unknown.\n\nOroxylin A is a natural flavonoid, and flavonoids are a class of polyphenolic compounds. Studies from our group and others have showed that some flavonoids have estrogenic activity \\[[@B6]--[@B10]\\] and thus, are named phytoestrogens. Whether Oroxylin A is also a phytoestrogen remains to be determined.\n\nThe effects of estrogen and phytoestrogens are mediated through two well-characterized intracellular receptors, estrogen receptor (ER) \u03b1 and \u03b2 \\[[@B11],[@B12]\\]. ERs are members of the nuclear receptor superfamily and act as a ligand-activated transcription factors to regulate the expression of target genes. They are expressed in various immune cells, including macrophages \\[[@B13],[@B14]\\] that play a critical role in many inflammatory diseases by expressing pro-inflammatory mediators, including tumor necrosis factor (TNF)-\u03b1, Interleukin (IL)-1, interleukin (IL)-6, cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase"
-"Introduction\n============\n\nThe lymphatic system primarily serves to collect and return interstitial fluid to the venous system \\[[@ref1]\\]. Its bodily components (i.e., retroperitoneal, intestinal, and hepatic) ultimately fuse at the cisterna chyli, traversing the mediastinum via the thoracic duct and eventually draining into the left internal jugular or subclavian vein \\[[@ref2]\\]. The anatomic location of the thoracic duct leaves it vulnerable to injury during various thoracic surgical procedures, such as esophagectomy, lung resection, and mediastinal or aortic surgery, all of which typically are invasive in nature. Fortunately, the incidence of clinically significant chylothorax is relatively low, ranging from 1% to 9% \\[[@ref3][@ref4]-[@ref5]\\]. However, chylothorax poses a considerable risk of morbidity and mortality if not appropriately managed at the onset because chylous leakage contains higher nutrient concentrations than non-chylous lymphatic leaks, and the seepage is usually excessive.\n\nConservative and surgical management of postoperative chylothorax\n=================================================================\n\nThe optimal clinical management of postoperative chylothorax has yet to be established. At present, therapeutic strategies generally include the following: (1) conservative management, using total parenteral nutrition or medium-chain triglyceride diets; (2) somatostatin and octreotide administration; and (3) surgical intervention involving talc pleurodesis, pleurectomy, or thoracic duct ligation \\[[@ref6]\\]. Surgical ligation of the thoracic duct is"
-"Introduction\n============\n\nGrade IV astrocytoma, or glioblastoma (GBM) is one of the most aggressive forms of cancer. GBM patients typically exhibit a median survival after diagnosis of 12-15 months [@B1], [@B2]. These tumors frequently exhibit molecular alterations in several oncogenes and tumor suppressor genes affecting some of the most relevant signaling pathways involved in the control of tumorigenesis, including through tyrosine kinase receptors (RTKs). Enhanced RTK signaling is thought to contribute to the high invasiveness and resistance to most anticancer therapies exhibited by GBMs [@B1], [@B2]. The standard treatment for these tumors is based on surgical resection, which frequently is not complete due to the proximity of the tumor mass to vital brain regions, followed by radiotherapy and concomitant chemotherapy with the alkylating agent temozolomide (TMZ) [@B1]-[@B3]. Unfortunately, almost all patients with GBM relapse after a few months. The identification within these tumors of a restricted cell population with characteristics of stem cells \\[termed Glioma stem-like cells or Glioma Initiating Cells (GICs)\\] exhibiting a high resistance to present anti-glioma therapies led to postulate the currently-accepted theory that GICs are directly involved in GBM relapse. Therefore one of the strategies to improve the survival of patients with this disease should be"
-"1. Introduction {#sec1-materials-12-02064}\n===============\n\nAluminum alloys have the advantages of low weight, high strength, ease of processing, low-temperature resistance, corrosion resistance, and low maintenance. They are widely used in machinery manufacturing, shipbuilding, aerospace, and chemical industries. In recent years, with the continuous promotion and application of fabricated buildings in the field of civil engineering, aluminum alloys have gradually become one of the most extensively used building materials for the main stressed members in construction engineering. Concerning the large-span aluminum alloy reticulated shell structures used in construction, Guo et al. \\[[@B1-materials-12-02064],[@B2-materials-12-02064]\\] used theoretical analysis, experimental research, and numerical simulation methods to study the influence of semi-rigid joints on the mechanical properties of single-layer reticulated shells. Under the action of major earthquakes, the metal-stressed members of the main structure in the actual construction project are prone to low-cycle fatigue damage, and the failure mechanism is the plastic deformation of the material under low-cycle fatigue loading \\[[@B3-materials-12-02064],[@B4-materials-12-02064]\\].\n\nAt present, scholars have carried out fatigue performance tests under low-cycle fatigue loading on different types of aluminum alloys, both at home and abroad. Shaha et al. and Huang et al. \\[[@B5-materials-12-02064],[@B6-materials-12-02064]\\] conducted low-cycle fatigue tests on Al-Si casting alloys with Ti, V, and Zr, and"
-"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*"
-"Introduction\n============\n\nStroke remains one of the leading causes of disability and death worldwide,[@b1-vhrm-15-011] despite a decrease in stroke mortality in the last decades. The substantial long-term risk for recurrent stroke might justify prolonged management strategies for stroke survivors.[@b2-vhrm-15-011]\n\nAfter a coronary event, participation in a cardiac rehabilitation program reduces total and cardiovascular mortality, as well as hospital readmissions.[@b3-vhrm-15-011] Successful programs involve a multifactorial risk-reduction regimen including exercise. In contrast, stroke survivors have limited lifestyle support.[@b4-vhrm-15-011] Since stroke and coronary heart disease share many risk factors, a multifactorial intervention after stroke may potentially have beneficial effects on mortality.[@b5-vhrm-15-011]\n\nIn the CAST study (Cognition After Stroke), 227 patients with first-ever stroke or transient ischemic attack (TIA) were randomized to a multifactorial intervention program aimed to preserve cognition. At 1 year poststroke, there were no statistically significant differences between the groups on cognition, but the intervention was associated with a reduction in anxiety and depression.[@b6-vhrm-15-011] More patients in the intervention group reached the targets for blood pressure and lipid values.[@b7-vhrm-15-011]\n\nLong-term follow-up of intervention studies poststroke are important. The aim of this follow-up and post hoc analysis was to evaluate the effect on survival after 7 years of the 1-year multifactorial risk"
-"Sasaki M, Miyahisa I, Itono S, et\u00a0al. Discovery and characterization of a small\u2010molecule enteropeptidase inhibitor, SCO\u2010792. Pharmacol Res Perspect. 2019;e00517 10.1002/prp2.517\n\nYus uke Mo rito h and Mas ano ri Watanabe are co ntributo rs from SCOHIA P\n\nBCAA\n\n:   branched\u2010chain amino acids\n\nFRET\n\n:   Fluorescence resonance energy transfer\n\nHTS\n\n:   High\u2010throughput screening\n\n1. INTRODUCTION {#prp2517-sec-0001}\n===============\n\nProteins are pivotal macronutrients for various cellular activities, as well as whole\u2010body metabolism. Amino acids show many functions within the body. For example, amino acids serve as the only source of nitrogen in mammals.[1](#prp2517-bib-0001){ref-type=\"ref\"} Amino acid\u2010derived nitrogen is a critical element in the synthesis of the precursors (purine and/or pyrimidine) of major energy molecules, such as adenosine triphosphate, adenosine diphosphate, and/or nucleic acids.[1](#prp2517-bib-0001){ref-type=\"ref\"} In addition, nitrogen is incorporated into compounds that can regulate major biochemical signaling pathways, such as nitric oxide.[1](#prp2517-bib-0001){ref-type=\"ref\"} Furthermore, amino acid deamination in the body\\'s proteins generates a carbon skeleton rich in oxygen and hydrogen suitable for subsequent biochemical transformation.[1](#prp2517-bib-0001){ref-type=\"ref\"} This carbon skeleton can be used by the liver to generate glucose through gluconeogenesis and other macromolecules, such as lipids.[1](#prp2517-bib-0001){ref-type=\"ref\"} The carbon skeleton derived from amino acids is also relevant in producing intermediaries fueling the Kreb\\'s cycle that are"
-"Introduction\n============\n\nThe overall incidence of abortion is about 10-15% of pregnancies ([@B1], [@B2]). Although many abortions are a result of fetal chromosomal disorders, a large number of abortions occur in the absence of any genetic abnormalities. Nevertheless, previous studies could not recommend a definite factor for predicting the probability of a spontaneous abortion ([@B3]). Progressions in science and technology have generated some available methods for delaying preterm delivery and abortion; therefore, discovering an easy, non-invasive, practical, and non-expensive predictive factor can help us perform the preventive methods in healthy pregnant women, without any risk factors.\n\nPrevious studies have evaluated various factors for predicting miscarriage, each introducing a different factor; pregnancy-associated plasma protein A (PAPP-A) ([@B4], [@B5]); macrophage inhibitory cytokine ([@B6]); progesterone ([@B7], [@B8]); and hyperglycosylated human chorionic gonadotropin (HCG) ([@B9]).\n\nHowever, their use is clinically limited because advanced technology is needed for performing methods based on these factors ([@B10]). Although measuring serum HCG is useful for indicating pregnancy and for predicting miscarriage, frequent blood sampling, which is necessary for predicting miscarriage, is not convenient for pregnant women.\n\nTherefore, finding a non-invasive, easy formula that does not require multiple blood sampling and is independent of knowing the exact time of"
-"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"
-"Introduction {#S1}\n============\n\nThe evolutionary emergence of lymphocytes with diversified antigen receptors allows the immune system to recognize and respond to a myriad of unknown antigens. However, despite the enormous number of B cells and T cells in the naive compartment, the frequency of B cells or T cells with any particular specificity is miniscule, necessitating efficient mechanisms to acquire and present antigens to the responding lymphocytes ([@B1]). Moreover, B and T cells of the same specificity must find one another and interact in a cognate way in order to differentiate into effector cells ([@B2]). In order to accomplish these goals, the immune system has evolved a system of secondary lymphoid organs ([@B3]).\n\nSecondary lymphoid organs, such as spleen, lymph nodes, Peyer's patches, and other mucosa-associated lymphoid tissues, recruit naive B and T cells from the blood and sample antigens from local non-lymphoid organs and mucosal surfaces, thereby allowing naive lymphocytes to efficiently peruse antigens from all the tissues of an entire organism without having to migrate through those tissues themselves ([@B4]). Moreover, secondary lymphoid organs are highly organized and contain architectural domains that facilitate sequential cellular interactions between antigen-presenting cells and lymphocytes and efficiently promote B and T cell"
-"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"
-"Background {#Sec1}\n==========\n\nA large and growing body of evidence indicates that postprandial hyperglycemia is a contributing factor for the development of several health related disorders \\[[@CR1], [@CR2]\\]. Firstly, postprandial hyperglycemia has been shown to begin prior to type 2 diabetes occurring \\[[@CR3]--[@CR5]\\] and its control is essential for achieving recommended glycosylated hemoglobin levels (representing mean glycemia over a prolonged period of time) since control of fasting hyperglycemia only is necessary but usually insufficient \\[[@CR4]\\]. The human and economic cost of diabetes could be significantly reduced through prevention, and the control of postprandial glycemia is a good area to target for this purpose. Secondly, several studies suggest that low glycemic index diets, inducing lower postprandial glycemic responses, improve lipid profiles and body weight gain patterns \\[[@CR6]--[@CR9]\\]. These diets decrease total fat mass \\[[@CR7], [@CR8]\\], total cholesterol and LDL cholesterol, thus improving plasma lipid profiles in healthy subjects \\[[@CR6], [@CR7], [@CR9]\\]. Thirdly, a causal relationship has been demonstrated between postprandial hyperglycemia and oxidative stress \\[[@CR10]\\], carotid intima-media thickness and endothelial dysfunction \\[[@CR11]\\], and increased the risk of cardiovascular diseases occurring \\[[@CR12], [@CR13]\\]. Moreover, results from the Baltimore Longitudinal Study on aging showed that impaired glucose tolerance (IGT), by itself, increases the"
-"1. Introduction {#sec1}\n===============\n\nEye-hand coordination requires skillful and integrated use of the eyes, arms, hands, and fingers in goal-directed precision movements \\[[@B1]\\]. The more complicated the stimulus presented and the more decisions to be made, the slower will be the reaction time of persons of any age \\[[@B2]\\]. Studies have shown that reaction time slows with advancing age, and the slowing-down becomes more pronounced as the task difficulty increases \\[[@B2], [@B3]\\]. Other investigators have suggested that increases in task complexity would lead to increases in the demand on central processing resources. Since older adults have fewer available resources for processing information in the brain, their performance could be affected more than that of younger adults when task complexity increases \\[[@B3]\\]. Thus, age-dependent-task complexity effect is probably due to age-induced changes in the cognitive processing resources of the central nervous system.\n\nTai Chi, a mind-body exercise, has a long history and is now practiced by millions of older adults both in the East and the West. Performing its 108 forms amounts to complex motor skill training \\[[@B4]\\] and requires a great deal of eye-hand coordination and balance control. Previous findings in our laboratory have shown that experienced Tai Chi practitioners"
-"Introduction\n============\n\nSleep is essential for normal life and very important for health. Sleep disorders negatively influence the health of individuals sometimes causing gastrointestinal disorders, fatigue, and tension as well as negatively influence socio-economic potential through loss of productivity and can decrease concentration, which may lead to accidents and injuries \\[[@B1],[@B2]\\]. As modern society changes, becomes more complicated, and grows, the prevalence of sleep disorders is increasing, and sleep disorders area rising social issue that may lead to economic losses not only for the individuals but also for the entire society. In South Korea, a telephone survey of 5,000 people 20--69 years of age found that 22.8% reported having a sleep disorder \\[[@B3]\\]. In addition, another study surveying normal adults reported that 31% suffered from sleep difficulties including difficulties falling asleep, waking up frequently, or waking up too early \\[[@B4]\\]. Moreover, among relevant studies conducted outside of South Korea, a majority of normal adults also reported suffering from a sleep disorder. For example, 10%--30% of normal adults in one previous study were found to be suffering from a sleep disorder \\[[@B5]-[@B7]\\].\n\nConsidering that firefighters in South Korea are national government officers who not only handle fire control/prevention but also perform"
-"1. Introduction {#sec1-sensors-17-01101}\n===============\n\nBreast cancer is one of the most common malignant tumors women face. It has the highest incidence and mortality of all diseases affecting women and even holds a rising trend. The early detection of suspicious lesions is very important for effective treatment of breast cancer. Ultrasound, mammography and magnetic resonance imaging (MRI) are general methods for the clinical detection of lesions, among which ultrasound (US) has been widely used due to its non-invasion, non-ionization radiation and non-injury \\[[@B1-sensors-17-01101],[@B2-sensors-17-01101]\\]. However, the shortcomings of US breast images, such as low contrast, serious speckles, and low spatial resolution, make it difficult for doctors to read and analyze these suspicious lesions. Furthermore, with an increasing number of patients, doctors feel heavily burdened, resulting in a higher rate of misdiagnosis.\n\nIn recent years, to improve the usability of US computer-aided diagnosis (CAD) has been preferred to achieve more reliable and accurate diagnostic conclusions and to reduce the unnecessary MRI and biopsies. In addition, CAD techniques used to investigate suspicious lesions in US breast images can also help reduce the workload of doctors \\[[@B3-sensors-17-01101],[@B4-sensors-17-01101],[@B5-sensors-17-01101],[@B6-sensors-17-01101]\\]. Generally, a CAD system mainly contains three steps: image segmentation, feature extraction and object classification. Image segmentation is"
-"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"
-"Dear Editor in Chief\n====================\n\n*Mycobacterium tuberculosis* usually manifests as a pulmonary disease and extra pulmonary tuberculosis is less common ([@B1]). Among the patients with extra pulmonary disease, ocular manifestations are rarely reported and the affected individuals usually have concomitant pulmonary findings ([@B1],[@B2]). Although ocular tuberculosis is potentially a curable disease, due to absence of enough data, uniform diagnostic and therapeutic protocols are not yet established ([@B3]). On the other hand, the wide range of possible diagnosis for inflammatory eye diseases may lead to a diagnostic delay ([@B2]--[@B4]).\n\nRegarding these facts, we describe a challenging patient who was referred to our ophthalmology clinic with pain and redness in both eyes from two weeks earlier. The patient reported poor appetite and significant weight loss without any other accompanying symptoms from eight months earlier for which he was evaluated in several occasions. He had undergone brain, thoracic and abdominal computed tomography (CT) scan without any abnormal findings. Upper and lower gastrointestinal endoscopy in two different occasions were both normal. Previous laboratory studies revealed a chronic normochromic normocytic anemia (Hemoglobin: 10.7 gr/dl, Mean-Corpuscular-Volume: 90.8 fl) and increased erythrocyte sedimentation rate (ESR: 115 millimeter/hour). Lymphocyte and platelet counts were both normal. Evaluations for hematological"
-"Introduction\n============\n\nThe branch-site test of positive selection (BSPS)[@b1-ebo-suppl.2-2015-011],[@b2-ebo-suppl.2-2015-011] is a standard approach to detect sites that evolve under episodic positive selection, ie, in a subset of branches in a phylogeny. It is based on a codon model of sequence evolution[@b3-ebo-suppl.2-2015-011] with an explicit parameter *\u03c9* defined as the nonsynonymous to synonymous substitution rate ratio (dN/dS), which is commonly interpreted as evidence for positive selection when greater than one. Given a multiple sequence alignment (MSA), a gene tree relating these sequences, and a partition of the branches into the so called \"foreground\" and \"background,\" the parameters of two models are estimated by maximum likelihood (ML). The null model corresponds to the hypothesis that no sites evolve under positive selection in the foreground. It has three free parameters: two specifying proportions of site classes and an *\u03c9* constrained to values below one (refer the study by Zhang et al.[@b2-ebo-suppl.2-2015-011] for the detailed mathematical description). The alternative model has an additional free parameter *\u03c9* constrained to values above one and corresponds to the alternative hypothesis that some sites evolve under positive selection in the foreground branches. Given the model likelihoods corresponding to the ML parameter estimates, a likelihood ratio test (LRT) determines"
-"Single solid-state nanopore technologies show great promise for bio-macromolecule detection or DNA sequencing[@b1]. For example, an important field of research is dedicated to developing nanopores that can uncover the changes in DNA that often play a role in cancer and other diseases and are hard to detect with current methods of sequencing. To carry out this program, different nanopore fields are currently being developed based on protein and synthetic nanopores[@b2]. Protein nanopores are certainly better suited for recognizing nucleotides (but suffer from liability), whereas synthetic nanopores can be manufactured on a large scale and be integrated into electronic devices. Synthetic nanopores still need to be better understood, however, before they can be perfected to the point of presenting the same advanced properties as protein ones[@b3][@b4][@b5]. The development of new generation high-performance nanofiltration membranes for important industrial applications, such as sea water desalination[@b6][@b7][@b8] is also being given a strong impetus from careful studies of transport through single nanopores.\n\nMost studies focus on nanopores of the following types: (i) graphene[@b9][@b10], (ii) silicon nitride[@b11][@b12][@b13], (iii) polymeric track-etched[@b14][@b15] and (iv) carbon[@b16][@b17] or boron-nitride[@b18]. For all of them macromolecule detection is based on voltage clamp experiments where the recorded electrical signal is induced by ionic"
-"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"
-"Background {#Sec1}\n==========\n\nBesides several non-pathogenic species, the genus *Corynebacterium* comprises more than 50 medically relevant ones. Some of them have a high pathogenic potential for human and animal hosts \\[[@CR1], [@CR2]\\]. An important pathogen is *Corynebacterium diphtheriae*, with humans as their almost exclusive reservoir and only very rare case reports of isolates from infected animals, such as e.g. horses or pigs \\[[@CR3], [@CR4]\\]. Additional important pathogenic species include zoonotic *C. ulcerans* and *C. pseudotuberculosis*. Despite the omnipresence of vaccination programs against toxoids in most developed countries, diseases with toxigenic corynebacteria occur consistently, due to various reasons: For example vaccination gaps and/or global travel activity from and to endemic countries occur \\[[@CR5]\\]. Also other factors, for example quality and availability of vaccines may be problematic, especially in low-income countries \\[[@CR6]\\]. In addition to classic *C. diphtheriae* mediated diseases, infections with toxigenic *C. ulcerans* outnumber those of toxigenic *C. diphtheriae* since several years in central Europe. *C. ulcerans* is increasingly recognized as emerging pathogen with inland animal contact as the most important risk factor \\[[@CR7], [@CR8]\\] in contrast to most often abroad acquired infections by toxigenic *C. diphtheriae*. *C. diphtheriae*, as well as *C. ulcerans* and *C. pseudotuberculosis* are all able"
-"Introduction\n============\n\nFor more than 350 million years, insects live and survive in almost every ecosystem on the planet, what have resulted in the development of protection and defense mechanisms against adverse situation. This feature has stimulated research into new agents with pharmacological and biotechnology potential in the class of arthropods.\n\nRecently, we have identified and isolated proteins of pharmacological and biotechnological interest in the hemolymph of caterpillars from family Saturnidae (*Lonomia obliqua*). Two proteins have been further characterizes: one with antiapoptotic activity and other with an antiviral action.\n\nObjectives\n==========\n\nThe main objective of this project is to build, characterize and compare the transcripts generated by the construction of a cDNA library of the integument of caterpillars *Megalopyge albicolis*(Megalopygidae family).\n\nMethods\n=======\n\nThe mRNA was isolated using the Dynabeads mRNA Direct kit (Invitrogen) and quantified with the RiboGreen RNA Reagent (Invitrogen). Subsequently, a cDNA library was produced and sequenced with a 454 GS-Junior machine (Roche). These procedures were repeated for two different tissue samples, originated from two different animals.\n\nResults and discussion\n======================\n\nAs a result, we obtained 38,2456 reads for the first tissue cDNA sequencing and 138,177 for the other one, with an average size of 240,66 and"
-"For many years, anterior cruciate ligament (ACL) injury has been the primary focus when considering impaired knee stability.[@bib1] However, numerous articles have reported an anterolateral capsular injury (Segond fracture) associated with ACL tears.[@bib2], [@bib3], [@bib4], [@bib5], [@bib6] Despite this well-known association, little has been published on the anatomy of this region, and the importance of the anterolateral structures to rotational stability has been downplayed. Historically, some authors believed that anterolateral rotational instability caused by an ACL tear could be treated by extra-articular surgery rather than ACL reconstruction. Numerous techniques were developed that focused exclusively on extra-articular reconstruction to control the instability.[@bib7], [@bib8], [@bib9], [@bib10], [@bib11], [@bib12]\n\nThe current standard of care is to reconstruct the ACL with autograft tissue and disregard any anterolateral injuries. However, the recent \"rediscovery\" and description of the anterolateral ligament (ALL) by Claes et\u00a0al.[@bib13] in 2013 brought new attention to treatment of the anterolateral corner of the knee.[@bib7] In an effort to decrease failure rates in patients with ligamentous laxity, prior failed ACL surgery, or grade 3 pivot-shift findings, numerous surgeons have described combining ACL reconstruction with extra-articular surgery. They have reported improved knee stability and patient-reported outcomes (PROs).[@bib14], [@bib15], [@bib16], [@bib17], [@bib18], [@bib19], [@bib20],"
-"Background {#Sec1}\n==========\n\nPharmaceutical expenditures have been growing rapidly in most European countries exceeding the growth in overall health spending \\[[@CR1]\\]. This is a source of concern to governments and several strategies for reducing or slowing down public expenditure on pharmaceutical products have been discussed and implemented. Essentially, cost containment measures for pharmaceuticals aim to control prices of medicines, or influence demand by implementing financial or professional measures \\[[@CR2]\\],\\[[@CR3]\\].\n\nReference pricing in drug reimbursement is a widely used cost containment method. It was first formally adopted in Germany in 1989 followed by many of the European Union countries, as well as New Zealand, Australia and Canada among others \\[[@CR4]\\],\\[[@CR5]\\]. In reference-based pricing, pharmaceuticals are classified into clusters based on generic groups, related drug groups or groups according to similar therapeutic effects. The payer then sets a reference price for each cluster based on e.g. either the lowest or the average price of drugs in that group. The reference price defines the maximum reimbursement for all products in the group. Drugs priced at or below the reference price are subsidized while drugs above the reference price require the patient to pay the excess in part or in total. Rather than to"
-"Background\n==========\n\nFew studies, if any, of hepatitis B (HBV), hepatitis C (HCV) and HIV co-infections in pregnant women in Zambia have been undertaken. HBV, HCV and HIV share at least one common route of infection: blood to blood contact through various transmission modalities.\n\nObjective\n=========\n\nIn this study, the researcher attempted to evaluate the prevalence of HBV and HCV co-infections among HIV positive pregnant women.\n\nMethod\n======\n\nNinety-seven HIV positive pregnant women (not yet on HAART) admitted to mostly labor ward were clinically examined and had their case files reviewed. They were also on PMTCT program for HIV. HBV surface antigens and anti-HCV antibodies were checked using ELISA. Information concerning their HIV status was obtained from the case files and antenatal cards.\n\nResults\n=======\n\n\u2022 HCV antibody seroprevalence was 4.1%(4/97), while the prevalence of HBV was found to be 9.3%(9/97).86.6%(84/97) of the cases had only HIV infection\n\n\u2022 Those with HBV/HCV co-infection tended to be older (age range 26--37 years), and all were black women three quarters of whom had poor socio-economic status\n\n\u2022 38.5% of those with co-infection reported having had a sexually transmitted infection (STI)\n\n\u2022 Only 9.3% of all the cases had done their CD4 counts."
-"1. Introduction {#sec1-materials-13-01786}\n===============\n\nIndustrial pipelines are widely used for many applications and are the lifelines of cities worldwide. To avoid unexpected leaks or ruptures, identification of pipeline damage is of major importance \\[[@B1-materials-13-01786],[@B2-materials-13-01786]\\]. Among potential pipeline leakage locations, pipe elbows are important but difficult to detect due to their characteristics of easy accumulation, strong impact, and complex structure \\[[@B3-materials-13-01786]\\].\n\nSensing technologies are important for locating defects. Traditional ultrasonic detection technology scans all points on the surface of interest and detects defects by ultrasonic propagation time and wave velocity. This method requires a high time cost and must have access to all surfaces of interest \\[[@B4-materials-13-01786]\\]. In recent years, a new member of the ultrasonic family, ultrasonic guided wave detection technology, has been developed and, in addition to the advantages of general ultrasonic detection, can carry out long-distance transmission along the detected structure \\[[@B5-materials-13-01786]\\]. Structural defects can be realized with one detection point, so the efficiency is high \\[[@B6-materials-13-01786]\\]. In addition, the ultrasonic sound field guided wave spreads throughout the whole wall thickness of the detected component, and, thus, the internal and external defects of the structure can be detected simultaneously \\[[@B7-materials-13-01786]\\]. Ultrasonic guided wave tomography, which is an important"
-"The online version of this article contains supplemental material.\n\nIntroduction\n============\n\nCytoskeletal--cell membrane attachments are critical for establishing the proper relationships between cells during tissue morphogenesis and for maintaining the integrity of tissues during differentiation. In vertebrates, intermediate filaments (IFs)[\\*](#fn1){ref-type=\"fn\"} provide the tensile strength required for tissue integrity ([@bib13]). In complex epithelia and other tissues such as heart that experience mechanical stress, the association of IFs with intercellular adhesive junctions known as desmosomes generates a stress-resistant scaffolding that integrates all of the cells within the tissue ([@bib26]; [@bib46]). Perturbation of either the IF cytoskeleton or its desmosome anchor compromises tissue integrity ([@bib16]; [@bib46]); however, the respective contributions and molecular mechanisms by which these integrated components serve their mechanical roles have not been fully elucidated. Specifically, the question of whether IFs strengthen desmosomal cadherin-mediated adhesion, much in the way actin has been proposed to strengthen classical cadherin-mediated adhesion, has not been directly addressed.\n\nDiseases targeting IFs as well as proteins that tether IFs to desmosomes demonstrate the importance of the desmosome--IF scaffolding. On one hand, point mutations that interfere with the assembly of IFs into networks lead to epidermolysis bullosa simplex, which is characterized by cell fragility and cytolysis in response"
-"INTRODUCTION\n============\n\nChemerin, also known as retinoic acid receptor responder protein 2 or tazarotene-induced gene 2, plays a regulatory role not only in the immune system but also in energy metabolism. Chemerin is a secreted protein whose gene expression is observed in several tissues, especially in adipose tissue and the liver ([@b14-ajas-28-8-1084]), which are essential organs for energy metabolism. Recent studies in mice and humans indicate that chemerin regulates glucose and lipid metabolism ([@b6-ajas-28-8-1084]; [@b15-ajas-28-8-1084]) and is involved in metabolic disorders such as obesity, insulin resistance in skeletal muscle tissue, and non-alcoholic fatty liver disease ([@b4-ajas-28-8-1084]; [@b16-ajas-28-8-1084]). In our previous studies, chemerin was up-regulated during bovine adipocyte differentiation, and chemerin analog regulated insulin secretion related to glucose metabolism and the release of triglycerides in sheep *in vivo* ([@b13-ajas-28-8-1084]; [@b18-ajas-28-8-1084]; [@b19-ajas-28-8-1084]). In addition, in fully differentiated adipocytes, the treatment of tumor necrosis factor (TNF)-\u03b1 and adiponectin up-regulated both chemerin and chemokine-like receptor 1 (CMKLR1) gene expression levels, although leptin did not show such effects ([@b19-ajas-28-8-1084]). These results suggest that the expression of chemerin in bovine adipocytes might be regulated by chemerin itself and other adipokines, which indicates the possible role of chemerin in modulating the adipokine secretions in adipose tissues.\n\nJapanese"
-"The amygdala is critical for the acquisition of conditioned responses (CRs) to stimuli (CSs) that predict aversive[@b1] or rewarding outcomes[@b2][@b3]. As the amygdala\\'s main recipient of sensory inputs from the thalamus and cortex[@b1], the lateral nucleus (LA) is ideally positioned to store associations between CSs and unconditioned stimuli (USs). Consistent with this, many LA neurons acquire robust responses to positively or negatively valenced CSs as a result of conditioning[@b4][@b5][@b6][@b7][@b8][@b9][@b10]. Moreover, *ex vivo* studies have shown that conditioning alters the efficacy of thalamic and cortical synapses thought to convey CS information to LA neurons[@b11][@b12][@b13][@b14][@b15]. Together, these and other findings led to the view that the changes in CS responsiveness displayed by LA neurons following appetitive or aversive conditioning constitute potentiated sensory responses that drive approach or defensive CRs via different downstream neuronal populations targeted by LA.\n\nOne of the main recipients of LA inputs is the basolateral nucleus (BL) of the amygdala[@b16][@b17]. BL is a good candidate for mediating LA influences over different CRs. Indeed, different subsets of BL neurons could drive a variety of aversive and appetitive CRs via their divergent projections to the central medial amygdala[@b17][@b18][@b19], bed nucleus of the stria terminalis[@b20], nucleus accumbens[@b21][@b22] or the dorsolateral striatum[@b22][@b23]. Consistent"
-"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"
-"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\nAn estimated number of 1.68 million men and 3.23 million women are affected by dry eye disease in the United States.[@b1-opth-7-253],[@b2-opth-7-253] A study of the impact of dry eye disease has determined that the disease has a detrimental effect on the daily visual functioning of patients who report problems with all types of visual tasking.[@b3-opth-7-253] The tendency towards decreased blink rate during visual function tasks, such as computer use, reading, video gaming, and watching TV can exacerbate the signs and symptoms of dry eye, further limiting a patient's visual function.[@b4-opth-7-253]--[@b6-opth-7-253] Furthermore, visual function has been shown to deteriorate throughout the day.[@b7-opth-7-253]--[@b9-opth-7-253] Compromised and fluctuating visual function has also been shown to negatively affect the patients' quality of life.[@b3-opth-7-253]\n\nTear film characteristics, components, and dynamics have been studied for many years to better define changes in tear film stability and, most recently, how those changes can affect visual function. Traditionally, tear film stability has been measured by tear film breakup time, a standard diagnostic test for dry eye, while limited attention has been given to the role of blink patterns. This is in part due to the difficulty of analyzing their widely variable and dynamic nature.\n\nIn 1977, we"
-"1. Introduction {#sec1}\n===============\n\nXeroderma pigmentosum (XP) is a rare autosomal recessive genetic disorder first described by Hebra and Kaposi in 1874 \\[[@B1]\\]. It presents variable prevalence, with estimates of 1/1,000,000 in North America \\[[@B2]\\], 1/22,000 in Japan \\[[@B3], [@B4]\\], and 1/10,000 in Tunisia \\[[@B5]\\].\n\nThe disease causes the patient to be susceptible to UV damage. It occurs due to a protein-enzymatic deficiency responsible for the repair of damaged DNA induced primarily by ultraviolet (UV) radiation \\[[@B6], [@B7]\\]. This primary defect leads to an increased susceptibility to UV radiation- (UVR-) induced skin pigmentation, skin cancers, ocular surface disease, and, in some patients, sunburn and neurological degeneration \\[[@B8]\\], with the development of cutaneous and systemic neoplasms \\[[@B9], [@B10]\\]. Eight different genes are affected, which were classified as complementary groups (XP-A, B, C, D, E, F, G, and XPV) \\[[@B10], [@B11]\\]. The prevalence of these groups differs across the world, and groups A, C, D, and V are most common in the United States and Europe \\[[@B7], [@B10]\\]. Complementary groups from A to G show deficiency in the repair of the DNA formation/transcription phase, and the complementary group XPV (or variant) occurs because of a defect in the postreplication repair, due to"
-"Introduction\n============\n\nMainstays of cancer treatment include chemotherapy and radiotherapy that are used in various regimens as first-line treatments for most malignancies. A major mechanism of tumor inhibition by chemotherapy is undoubtedly through direct toxicity to tumor cells. A range of chemical agents are used with varied mechanisms of action including their alkylating properties and their nucleoside analog properties. The use of chemotherapeutics exploits the preferential toxicity against rapidly dividing cells, such as tumor cells. Similarly, radiation can induce DNA damage in tumor cells leading to the selective elimination of malignant cells.\n\nHowever, in addition to these mechanisms, chemotherapy and radiation can have a wide range of effects on tumors including modifications to the tumor microenvironment. This can lead to the induction of inflammatory cytokines and upregulation of death receptors such as Fas, which can increase antigen availability and presentation, increase the expression of major histocompatibility molecules, normalize vessels, induce danger signals and increase T cell localization.[@R1]\n\nThe tumor microenvironment is composed of cancer cells in association with a variety of other cells that comprise the stroma. Stromal cells include fibroblasts and endothelial cells in addition to a variety of leukocytes, some of which can be immunosuppressive. Such immunosuppressive leukocytes"
-"Wang S, Li M, Zhang L, Xie M. Multimodal imaging evaluation of a primary cardiac lymphoma in an immunocompetent patient. Echocardiography. 2018;35:2121--2123. 10.1111/echo.14150 30315591\n\nDrs Shuyuan Wang and Meng Li contributed equally to this work.\n\nA 55\u2010year\u2010old man presented in our department with palpitations and occasional chest distress for 1 month. Biochemical examinations were all within normal limits and test for HIV was negative. On the day of hospitalization, an electrocardiogram showed a Q wave in the II, III, and aVF leads. Transthoracic echocardiography (TTE) demonstrated pericardial effusion with a multi\u2010segmental infiltrated ill\u2010defined hypoechoic mass that extensively affected the mitral and papillary muscle level of the left ventricular (LV) anterior wall (Figure [1](#echo14150-fig-0001){ref-type=\"fig\"}A, [Movie S1](#echo14150-sup-0001){ref-type=\"supplementary-material\"}), the middle to upper part of the right ventricular (RV) free wall, the RV outflow tract, and the initial segment of the main pulmonary artery (Figure [1](#echo14150-fig-0001){ref-type=\"fig\"}B). The thickness of the infiltrated wall ranged from 2.8 to 3.4 cm. The mitral and tricuspid valves were not affected, but the main pulmonary artery was narrowed where the peak systolic velocity measured 1.7 m/s. The myocardial contrast echocardiography (MCE) study revealed rich perfusion in the thickened RV wall myocardium similar to other myocardial segments (Figure [1](#echo14150-fig-0001){ref-type=\"fig\"}C, [Movie"
-"Introduction {#s001}\n============\n\nLymphedema is a leading cause of disability worldwide, yet it remains underdiagnosed, under-researched, and underfunded in most health systems.^[@B1]^ It is a connective tissue disease that occurs in the subcutaneous tissues when normal lymphatic clearance is disturbed.^[@B6]^ The etiology of lymphedema can be wide ranging, and pathogenesis of the resulting connective tissue disease may also vary.^[@B7]^ Despite these variations, when lymph flow is impeded for any reason, an accumulation of protein-rich fluid in the loose connective tissue follows. This excess fluid is eventually replaced by fibrotic induration and fat deposition. Regardless of the cause, long-term reduction in lymphatic activity will always lead to chronic inflammation, skin pathologies, and an increased risk of bacterial and fungal infections.^[@B11],[@B12]^ Untreated lymphedema is progressive and beyond the earliest stages management becomes increasingly difficult and resource intensive.^[@B4],[@B13]^\n\nLymphedema can affect anyone. Male, female, young or old, rich or poor, in every country there will be people living with, or at risk of developing lymphedema. Global prevalence estimates are as many as 250 million people worldwide.^[@B14]^ The major single cause is lymphatic filariasis (LF), a parasitic disease affecting 17 million people in developing tropical countries where it is closely associated with poverty.^[@B15]^ At"
-"Background\n==========\n\nHeterotrimeric G proteins, important for signal transduction in hepatocytes, attach through lipid modifications to the cytoplasmic face of plasma membranes, particularly lipid rafts, where they interact with G protein coupled-receptors (GPCR) to initiate signal transduction \\[[@B1],[@B2]\\]. G~s\u03b1~, G~i\u03b11,2~, G~i\u03b13~and G~\u03b2~have been identified on rat liver basolateral (BLM) and canalicular (CM) membranes \\[[@B3],[@B4]\\]. Although current concepts of signal transduction envision interaction of the cytoplasmic tails of activated receptors with intracellular signal transduction cascades at the plasma membrane, insulin and epidermal growth factor (EGF) receptors and some GPCRs are internalized in endocytic vesicles \\[[@B2],[@B5]-[@B8]\\]. GPCRs such as the \u03b2~2~adrenergic receptor are endocytosed with \u03b2-arrestins which regulate receptor desensitization and recycling \\[[@B2]\\].\n\nFurther, the internalized receptors with \u03b2-arrestins contribute to the assembly of internalized signalling complexes and MAPK activation \\[[@B2]\\]. In rat liver activated insulin and EGF receptors continue to generate signals from endosomes \\[[@B5],[@B7]\\] and critical elements of mitogen-activated protein kinase (MAPK) signalling pathways are found on endosomes \\[[@B6],[@B9]\\]. Little is known, however, regarding whether heterotrimeric G proteins involved in cAMP signalling pathways and effectors like adenylate cyclase (AC) are located on endocytic vesicles. The observations that in vitro GTP-\u03b3S stimulates acidification of rat liver endosomes \\[[@B10]\\], that liver endosomes"
-"INTRODUCTION\n============\n\nNon-LTR retrotransposons (NLRs) \\[retrotransposons lacking long terminal repeats (LTRs)\\], are a class of transposable elements that are mobilized by reverse transcription of an RNA intermediate ([@b1]). Multiple copies of NLRs inhabit variable fractions of the genome of most eukaryotes. Whereas most copies are defective, some are functional and their retrotransposition can result in several types of genetic effects including mutations associated with diseases in humans and mice ([@b2]). The *Drosophila* NLR *I factor* and the mammalian NLR L1 ([@b3]) provide well-known examples of the impact of NLR mobilization.\n\nMost NLRs contain two open reading frames, ORF1 and ORF2, which are translated from a bicistronic messenger RNA that presumably also serves as a template for retrotransposition ([@b4]--[@b6]). The sequence of the ORF2 product (ORF2p) is relatively well conserved among NLRs. ORF2p is involved in reverse transcription and integration, and its endonuclease and reverse-transcriptase activities have been demonstrated *in vitro* for different elements ([@b7]--[@b12]). The sequence of the ORF1 product (ORF1p) is, in contrast, poorly conserved in evolution. ORF1p of human and mouse L1 are expressed in some carcinoma cells and can be isolated as a 40 kDa full-size protein (p40) which forms, in association with L1 RNA, high molecular"
-"Introduction {#sec1-1}\n============\n\nHabit is a way of acting through fixed repetition. The word habit is such that when the letter \"H\" is removed, \"A BIT\" remains; when the letter \"A\" is removed, \"BIT\" remains; when the letter \"B\" is removed, \"IT\" still remains. This implies the persistence of act and interference with regular pattern of facial growth. The presence of oral habit in 3-6 year old children is an important finding in the clinical examination. An oral habit is no longer considered as normal for children near the end of this age group.\\[[@ref1]\\] In pre-school children, digit and dummy sucking is a predominant habit,\\[[@ref2]--[@ref4]\\] and girls are found to have a higher level of sucking habit than boys do.\\[[@ref5]--[@ref7]\\] Here is a case report of a unique sucking habit leading to malocclusion.\n\nCase Report {#sec1-2}\n===========\n\nA 3-year-old girl was presented to the Department of Pedodontics, HKE\\'s S Nijalingappa Institute of Dental sciences, Gulbarga, by her parents, with complaints of unusual forearm sucking habit \\[[Figure 1](#F1){ref-type=\"fig\"}\\]. The mother was worried about her child\\'s unusual pattern of sucking habit. Dental history revealed that the child was visiting the dentist for the first time. Interrogation revealed that the child started the"
-"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."
-"Background\n==========\n\nInfection of the central nervous system (CNS) by human immunodeficiency virus type 1 (HIV-1) causes neurotoxicity and inflammatory disorders such as encephalitis and associated neurocognitive deficits \\[[@B1]\\]. Since the introduction of highly active antiretroviral therapy (HAART) as the standard of care for seropositive patients, the incidence of severe neurological complications caused by HIV-1 such as dementia has greatly diminished, but a more subtle form of CNS dysfunction known as minor cognitive and motor disorder has emerged \\[[@B2]\\]. Although a discordance between cerebrospinal fluid (CSF) and plasma viral load is often observed, sustained virus replication in the CNS despite suppressive antiretroviral therapy correlates with acute or subacute neurological alterations \\[[@B3]-[@B5]\\]. Moreover, the viral strains present in the CNS may, over time, genetically differ from virus isolates circulating in peripheral blood \\[[@B6]\\]. Unsuppressed virus replication in the brain favors the emergence of drug-resistant viruses and the appearance of viral variants with reduced dependence for CD4, the primary cellular receptor for HIV-1 \\[[@B7]\\]. Nevertheless, some studies have shown that the level of CNS penetration in patients receiving HAART does not significantly influence clinical efficacy \\[[@B1],[@B8]\\], although this issue remains controversial \\[[@B9]\\].\n\nEntry of HIV-1 into the CNS occurs very early after"
-"Introduction {#s1}\n============\n\nTraumatic Spinal Cord Injury (SCI) results in partial or complete alterations of motor, sensation, and autonomic functions. Despite the advances in biomedical research for acute SCI, there is no effective treatment for axonal regeneration and functional restoration at chronic stages.\n\nAfter SCI, efficient cord regeneration is mainly limited by a local inhibitory environment due in part to a biochemical barrier formed by molecules like myelin-associated proteins ([@B1], [@B2]) as well as proteins constitutive of the extracellular matrix, markedly chondroitin sulfates ([@B3], [@B4]). In addition, a physical barrier (fibrogial scar) formed by microglia, oligodendrocytes, meningeal cells, and reactive astrocytes also inhibits axonal regrowth ([@B5], [@B6]).\n\nSome strategies for promoting axonal regeneration and functional restoration in spinal cord injury models are relevant to the present study, especially those based on bone marrow stromal cell (BMSC) transplantation ([@B7]), fresh and pre-degenerated peripheral nerve (PPN) transplantation ([@B8]), and chondroitinase ABC ([@B9], [@B10]), all of which promote partial neuroprotective and regenerative effects after early SCI.\n\nIf used independently, the benefits of the above-mentioned strategies seem insufficient to be translated to patients, but several experimental studies have shown that combined therapies may produce a greater benefit ([@B11]--[@B14]). In fact, recently, we reported on"
-"Macroautophagy (hereafter referred to as autophagy) is an intracellular turnover pathway that is used to remove long-lived and aggregated proteins, organelles, and parasites from the cell[@b1]. With this pathway, damaged or senescent cytoplasmic contents are sequestered in double-membrane vesicles called autophagosomes. Biogenesis and maturation of autophagosomes begins with the phagophore, an autophagosome precursor[@b2], whose membrane lipids can be derived from multiple sources, including the endoplasmic reticulum (ER)[@b3], clathrin-coated vesicles from the plasma membrane[@b4], the outer membrane of mitochondria[@b5], and the trans-Golgi network[@b6]. The autophagosome then fuses with early or late endosomes or with lysosomes for degradation of sequestered contents.\n\nAutophagy plays a critical role in neuronal survival[@b7]. For example, blocking autophagy in neurons in the mouse central nervous system leads to protein aggregation and neurodegeneration[@b8][@b9]. Autophagosomes have been observed in many neurodegenerative disorders[@b10]. Small molecules that stimulate autophagy ameliorate pathogenic changes in a number of neurodegenerative disorders[@b1][@b11][@b12]. Despite the mounting evidence demonstrating the importance of autophagy in neurons, the molecular players that regulate neuronal autophagy are not fully understood.\n\nIn a search for novel regulators of autophagy in neurons, we investigated whether sphingosine kinase 1 (SK1), which regulates autophagy in cancer cells[@b13], is necessary for autophagy in neurons. There are"
-"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"
-"Introduction\n============\n\nTelomeres, the nucleoprotein structures at the ends of chromosomes, consist of 5\u2032-TTAGGG-3\u2032 repeats bound by a dedicated set of proteins forming the shelterin complex ([@b54]). Three members of the six protein complex directly bind telomeric DNA and were the only direct telomere-specific binding proteins known so far: TRF1 and TRF2 bind double-stranded DNA (dsDNA; [@b79]; [@b9]; [@b11]), whereas POT1 binds single-stranded 5\u2032-TTAGGG-3\u2032 repeats ([@b7]). This complex constitutively associates with telomeres and shields the ends of linear chromosomes from being recognized as a double-stranded break, thus protecting telomeres from end-to-end fusions ([@b54]). While this solves the end-protection problem ([@b24]), maintaining telomere integrity itself is of outstanding importance and major factors may have remained elusive.\n\nTelomere length homeostasis, a crucial process in stem cell biology, aging and cancer, depends on the equilibrium between telomere lengthening (in most cases due to telomerase activity) and shortening reactions (generally due to replication and controlled processing) ([@b34]). Telomerase is capable of adding telomeric repeats to chromosome ends *de novo.* The enzyme works as a ribonucleoprotein complex, which consists of a catalytic subunit with reverse-transcriptase activity (called TERT), and an RNA serving as the elongation matrix for telomeres (called TR or TERC) ([@b29]). While these"
-"In the surgical treatment of hip disorders, a major cause of failure is either insufficient correction or a failure to fully recognize the underlying deformities causing pain and joint damage.^[@R1][@R2][@R3]^ One type of femoral deformity that is still frequently overlooked are rotational deformities of the femur, that is, excessive anteversion or femoral retroversion. These rotational deformities may occur alone or may coexist with acetabular dysplasia^[@R4][@R5][@R6]^ or various types of hip impingement.^[@R2],[@R5],[@R7][@R8][@R9]^ Rotational deformities may also be associated with cerebral palsy^[@R10]^ and labral tears^[@R11]^ and are not unusual after the fixation of femoral shaft fractures.^[@R12][@R13][@R14]^\n\nExcessive femoral anteversion can cause instability, damage of the articular cartilage and acetabular labrum, and eventually osteoarthritis.^[@R15][@R16][@R17]^ Furthermore, it can cause a decrease in the length of the abductor lever arm,^[@R18]^ posterior extra-articular impingement,^[@R9]^ and ischiofemoral impingement.^[@R19]^ Finally, excessive femoral anteversion may cause increased hip and knee adduction moments, an intoeing gait and patellofemoral maltracking, with resultant knee pain and arthritis.^[@R20][@R21][@R22]^\n\nFemoral retroversion, on the other hand, causes damage due to impingement between the femoral neck and acetabulum, which may result in damage to the labrum and articular cartilage, ultimately resulting in osteoarthritis of the hip.^[@R16],[@R23]^ Other potential retroversion problems include an increased risk of slipped"
-"Introduction {#s1}\n============\n\nWith industrialization, volatile organic compounds (VOCs), as the significant precursors of photochemical smog and secondary organic aerosol (SOA), have raised stringent environmental threat for many industrial processes. Generally, VOCs originate from a wide range of manmade sources (e.g., industrial processes, vehicle emissions, solvent manufacturing, gasoline evaporation, fuel coatings manufacturing) and in a gaseous state at atmospheric pressure of 133.322 Pa (Okada et al., [@B26]). VOCs were promulgated to be composed of more than 500 compounds with different properties and most of them were demonstrated to be with high toxicity (Lewis et al., [@B20]). Being as an important photochemical oxidant of atmospheric environment, some of VOCs act as nerve agent could cause neurological disturbance and cell cancerization, bringing a great threat to human health (Atkinson, [@B2]). Therefore, the VOCs pollutants removal has already been one of the most urgent research areas.\n\nIn previous studies, several VOCs abatement technologies were developed, including oxidation (Johnsen et al., [@B15]; Zhang et al., [@B39]), biological treatment (Chen et al., [@B6]; Cheng et al., [@B8]), condensation (Khan and Ghoshal, [@B16]), absorption (Darracq et al., [@B9]; Hariz et al., [@B13]) and adsorption (Zhang et al., [@B38]). However, constrain was found in each technology during"
-"Current state of the art MR cholangiographic examination, which relies upon the T2-weighted sequences, is highly accurate in identifying biliary diseases ([@B1]-[@B3]). However, the T2-weighted MR cholangiography (MRC) has diagnostic limitations which include poor visualization of the intrahepatic biliary tree compared with the extrahepatic biliary tree ([@B4], [@B5]), variation in the degree of T2-weighting that might obscure the biliary structures ([@B6]), and limited spatial resolution.\n\nDuring the past few years, T1-weighted MRC using hepatocyte-directed contrast agents has created interest in the field of MRC because of its potential to provide functional information and to improve the visualization of the non-dilated biliary system ([@B7]-[@B13]). Initially, mangafodipir trisodium (Mn-DPDP), which is mainly being excreted into biliary system, has been used for this purpose ([@B8], [@B9], [@B11]-[@B13]). However, dynamic MR imaging of the liver cannot be performed because this agent needs to be administered slowly. Recently, contrast agents that are excreted through both the renal and biliary pathways, such as gadobenate dimeglumine (Gd-BOPTA) have become available ([@B14]-[@B17]). Using a bolus injection technique, these agents can be used for dynamic imaging as an extracellular space agent in the early phase as well as a biliary contrast agent in the delayed phase. However, because the"
-"A reader raised concerns about potential data duplication in several figures. Specifically, the reader identified regions of overlap among the following figure panels:\n\n-   Panels E25, E50, and D50 shown in Figure 4\n\n-   Panels C and D25 panels in Figure 4\n\n-   Panel C in Figure 4 (Migration) and Panel C in Figure 5 (Invasion)\n\nThe authors acknowledged that there was an error in the preparation of these figures. However, they no longer have the data underlying the results shown in the panels in Figure 4, and they were unable to replicate these results using the same experimental conditions.\n\nDue to the concerns about the integrity of the results, and the absence of data reproducing the findings, the authors have concerns about the validity and robustness of the results reported and have requested the retraction of this article.\n\nThe authors apologize to the readers and editors of *PLOS ONE*."
-"Background\n==========\n\nZinc-alpha2-glycoprotein (AZGP1) is a secreted soluble protein which is synthesized in adipocytes and a variety of other cell types \\[[@B1]\\]. Although the definite role of AZGP1 remains unclear, it has been implicated in several biological processes. Besides its potential role in regulation of cell cycling and cancer progression \\[[@B1]-[@B3]\\], AZGP1 has been characterized as a functional modifier of lipid metabolism \\[[@B4],[@B5]\\]. *In vitro*, AZGP1 stimulated lipolysis in adipocytes via activation of \u03b13-adrenoceptors \\[[@B6]\\]. Injections into rats triggered expression of lipolytic enzymes, resulting in increased lipid mobilization and loss of body fat \\[[@B7]\\]. In mice with cancer cachexia the expression of AZGP1 was up-regulated suggesting that AZGP1 might act as a cancer cachexia factor \\[[@B5]\\]. Genetic deletion of AZGP1 resulted in increased body weight and reduced lipolytic capacity \\[[@B8]\\].\n\nIn 2008 an ELISA was developed which allowed measurement of AZGP1 levels in patient serum \\[[@B9]\\]. Several studies have since been conducted determining serum AZGP1 in different patient populations. While Stejskal et al. did not find significantly altered levels of AZGP1 in patients with metabolic syndrome \\[[@B9]\\], Yeung et al. showed a positive correlation between serum AZGP1 and BMI, insulin resistance and serum triglycerides \\[[@B10]\\]. Other conditions associated with increased"
-"###### Strengths and Limitations of the study\n\n-   To our knowledge, this is the first systematic review protocol that has\u00a0attempted to evaluate the burden of tuberculin skin test and interferon-gamma release assay-confirmed latent tuberculosis infection\u00a0(LTBI) in Africa.\n\n-   This study could potentially inform policy and practice to reduce the reservoir of latently infected persons from which new tuberculosis\u00a0(TB) cases arise.\n\n-   The chosen time period is short; however, it portrays an important era in Africa as significant gains have been made in the screening and treatment of TB, which could have theoretically huge impact on the burden of LTBI on the continent.\n\nIntroduction {#s1}\n============\n\nTuberculosis\u00a0(TB) is the second leading cause of mortality from an infectious disease globally after the HIV\u00a0infection.[@R1] In 2013, WHO estimated 9\u2009million new TB cases and 1.5\u2009million TB deaths globally, of which 80% of the cases and 70% of deaths were reported in low-income and middle-income countries.[@R2] Latent tuberculosis infection (LTBI) is defined as a state in which individuals harbour live *Mycobacterium tuberculosis* without evidence of manifestation of clinical or other symptoms of active disease.[@R3] Projections from mathematical models in 2000 estimate that over 30% of the population globally"
-"INTRODUCTION {#SEC1}\n============\n\nAs the world population is rapidly aging, the prevalence of aging-related diseases and the demand for expensive, long term health care is also rising ([@B1]--[@B4]). To offset the burden of this shift, scientific knowledge and innovation will become increasingly crucial, and anti-aging and disease prevention strategies will become national and international priorities. Aging research as a field will boom. Nevertheless, it faces several challenges, and the growth will need direction.\n\nOne of the challenges is the current lack of a freely available, comprehensive collection of aging-related biological pathways and encyclopedia of aging knowledge. Biological pathways are one of the most powerful visualization tools in biology ([@B5]). They provide an intuitive, systems view of the interactions between the multitude of individual elements in any given process. They can be interactive for user-directed exploration and amenable to computational methods, and they are indispensable in making sense of large-scale data sets, where a multitude of individual changes may reflect a small number of more biologically important (and more statistically powerful) changes at the pathway level ([@B6]). Pathway collections are a key feature of many biological data repositories in the public domain ([@B7]).\n\nAging processes are particularly suited for representation by"
-"1. Introduction {#sec1}\n===============\n\nGranulocyte-colony stimulating factors (G-CSF) are commonly used in patients with chemotherapy-induced neutropenia. Recently G-CSF has been used in clinical trials to research neovascularization and/or to reduce the damaged size of infarct. Common uses of the granulocyte-colony stimulating factors in the clinical practice raise the concern about side effects of these agents. Studies showed that nearly 5% of patients undergoing peripheral blood stem cell mobilization with G-CSF developed venous thromboembolic events (VTEs) \\[[@B1]\\]. In addition an early dose escalation study for G-CSF revealed that 5/39 patients had chest pain and 1/39 patient had abnormal ST segment depression \\[[@B2]\\]. We also presented a case about an acute myocardial infarction with non-ST segment elevation during filgrastim administration.\n\n2. Case Report {#sec2}\n==============\n\nA 73-year-old man had squamous cell carcinoma of larynx with lung metastasis treated with the chemotherapy including the docetaxel, cisplatin, and fluorouracil regimen. The patient was admitted to the hospital for pneumonia after the 3rd course of chemotherapy. Piperacillin tazobactam of 4\u22172.25\u2009gr per day was given. On the 4th day of the treatment of antibiotic, patients become neutropenic without fever, and then filgrastim 5\u2009mcg/kg/day was administered. Patient had a chest discomfort on the second day"
-"Neuromyelitis optica spectrum disorders (NMOSD) and multiple sclerosis (MS) are distinct autoimmune CNS diseases with sometimes overlapping clinical phenotypes.^[@R1]^ Since treatment options for these 2 CNS diseases differ considerably,^[@R1]^ the distinction between NMOSD and MS is of high clinical relevance. Recently, new international consensus diagnostic criteria were proposed for NMOSD emphasizing the role of MRI and aquaporin-4 immunoglobulin G antibody testing.^[@R2]^ Notwithstanding this success, the distinction of NMOSD vs MS can still be challenging in current clinical practice. Ultra-high field MRI at 7 tesla (T) has improved the detection and morphologic characterization of brain lesions by visualizing a central intralesional vein and a T2\\*-weighted (T2\\*w) hypointense rim around many MS lesions.^[@R3],[@R4]^ Contrarily, these imaging features are only rarely depictable in NMOSD lesions.^[@R3],[@R4]^ At 3T, susceptibility-induced MRI phase signal changes were reported to be specific for MS in contrast to other neurologic disorders such as migraine, antiphospholipid syndrome, and Parkinson disease.^[@R5]^ Inspired by these findings, we rescanned previously reported patients with NMOSD at 7T^[@R3]^ and included additional NMOSD cases to describe MRI phase signal changes in NMOSD vs MS lesions in a cross-sectional study.\n\nMETHODS {#s1}\n=======\n\nStudy participants. {#s1-1}\n-------------------\n\nTen patients with NMOSD underwent ultra-high field MRI at 7T."
-"1. Introduction {#sec1-animals-10-01072}\n===============\n\nThe genus *Neofelis* comprises one species of clouded leopard found in continental South-east Asia (*Neofelis nebulosa*) and one species living on the islands of Borneo and Sumatra (*N. diardi*)---the Sunda clouded leopard. The island species is more endangered than the mainland one, with an estimated 750 individuals in Sabah, Borneo, and is classified as endangered, under the International Union for Conservation of Nature Red List \\[[@B1-animals-10-01072],[@B2-animals-10-01072]\\]. It also is the least studied species of large cats in terms of ecology, behavior, and reproduction. In general, clouded leopards reach sexual maturity between the ages of 20 and 30 months. The breeding season observed in Khao Kheow Open Zoo, Thailand is between November to March, with gestation period ranging from 85 to 121 days. Lifespan in captivity ranged from 13 to 15 years \\[[@B3-animals-10-01072],[@B4-animals-10-01072],[@B5-animals-10-01072]\\].\n\nThe population under human care has fewer than 20 individuals with no breeding success (Dr. Bongot Huaso Mulia, Taman Safari Indonesia, personal communication, 23 March 2020). Captive breeding of clouded leopards is challenging due to male--female aggression, which sometimes leads to the death of individuals \\[[@B6-animals-10-01072]\\]. The development of assisted reproductive techniques is therefore essential to propagate the population and ensure a good genetic"
-"INTRODUCTION {#s1}\n============\n\nPancreatic cancer (PC) is one of the most aggressive and lethal malignancies, causing the deaths of an estimated 330,400 men and women worldwide in 2012 \\[[@R1]\\]. Total deaths due to PC are projected to increase dramatically, making it second leading cause of cancer-related deaths in the United States by 2030 \\[[@R2]\\]. Gemcitabine, the current standard first-line treatment, offers marginal symptom control and prolongation of life. Clinical trials aiming to improve the efficacy of gemcitabine have provided little improvement in survival outcomes \\[[@R3]\\]. New therapeutic strategies, including therapeutic antibodies or/and small molecule inhibitors, have been successful for a number of malignancies, but results obtained on PC treatments have so far been extremely frustrating \\[[@R4]\\]. A number of molecular mechanisms responsible for transformation and progression of PC have been identified, providing a set of potential pharmacological targets \\[[@R5]\\]. Among these is loss of adhesion between tumor cells caused by downregulation of CDH1 (also called E-cadherin) in response to genetic or epigenetic changes \\[[@R6]--[@R8]\\].\n\nHistone acetylation is a dynamic epigenetic mechanism regulated by the histone acetyltransferases (HAT) and histone deacetylases (HDACs). HDAC3 (histone deacetylases 3), a member of class I HDACs, is overexpressed in the majority of carcinomas \\[[@R9], [@R10]\\],"
-"INTRODUCTION {#s1}\n============\n\nInhibitors of thymidylate synthase (TS), a key enzyme in the *de novo* thymidine synthesis pathway, play a role in the treatment of a number of malignancies including non-small cell lung cancer (NSCLC). Examples of commonly used TS inhibitors in cancer therapy include 5-fluorouracil (5-FU), pemetrexed and capecitabine. Successful inhibition of TS results in a transient compensatory \"flare\" in activity of the thymidine salvage pathway \\[[@R1]--[@R4]\\], which also sources thymidine to the dividing cell. As a result, this drug-induced compensatory \"flare\" in thymidine salvage pathway activity is an indicator of successful TS inhibition. This drug-induced change in tumor metabolism can be made visible through ^18^F-thymidine (FLT)-positron emission tomography (PET)\\[[@R2], [@R5]--[@R7]\\], an analog of thymidine. FLT, first described by Shields in 1998 \\[[@R8]\\], is an investigational imaging biomarker of the thymidine salvage pathway currently in use for human clinical trials primarily as a validated surrogate marker of tumor proliferation \\[[@R9]--[@R12]\\]. Here we consider FLT-PET imaging as a means of detecting successful TS targeting by pemetrexed, a TS inhibitor currently in use for NSCLC therapy.\n\nIn our recent publication \\[[@R7]\\], we characterized the kinetics of the pemetrexed-induced thymidine salvage pathway \"flare\" in a xenograft mouse model of human NSCLC and"
-"Plain language summary\n======================\n\nThis study examined whether the 24-hour pattern of motor activity, ie, information that can be collected easily from wrist-worn activity monitors (such as Fitbit or other activity trackers), can be used to identify whether the effects of a promising new treatment for depression are both rapid and durable. The therapeutic drug ketamine produces rapid (within minutes to hours) antidepressant effects in up to 70% of patients with depression, including those with treatment-resistant depression, the more severe form of the disease. However, in patients who respond to ketamine, the duration of clinical benefit varies, typically ranging from a day to a week. Researchers are eager to identify easily obtained biomarkers, such as information obtained from activity trackers, that could predict which subjects are likely to respond to ketamine, as well as which responders are likely to have a continued antidepressant effect vs those who will quickly relapse. This study used easily worn activity watches to collect activity data from subjects with depression. We found differences between baseline patterns of 24-hour activity and initial response to ketamine (ie, response vs nonresponse) and differences between baseline patterns and continuing response to ketamine. The findings show that prior to treatment,"
-"INTRODUCTION\n============\n\nHepatitis B virus (HBV) infection is a major cause of liver cirrhosis and hepatocellular carcinoma (HCC) worldwide. Globally, 350 million patients are chronically infected with HBV.^[@R1]^ In regions highly endemic for HBV infection, the infection is usually acquired via mother-to-infant transmission. In China, the hepatitis B surface antigen (HBsAg) carrier rate in pregnant women ranges from 6.0% to 7.8%.^[@R2]--[@R6]^ This prevalence is of particular concern as mother-to-infant transmission remains the predominant mode of HBV infection. The risk of perinatal transmission of HBV is associated with the HBV DNA levels and HBeAg status of mother, thus, it is important to investigate the influence of pregnancy on the viral replication and antigens expression in pregnant women infected with HBV. Little, however, is known whether pregnancy influences viremia levels in women with chronic HBV infection.\n\nHepatitis B virus is a noncytopathic virus and the associated hepatic inflammation is mediated by the host\\'s immune responses. During pregnancy, several alterations in the maternal immune system allow mothers to tolerate the foetus,^[@R7]^ such as maternal alloreactive T-lymphocyte depletion, alloreactive Th1 cell blocking, increasing of the regulatory T-cells, and increasing apoptosis of activated maternal lymphocytes.^[@R8],[@R9]^ The maternal immunosuppressive status may result in increased viremia levels"
-"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"
-"Introduction {#s1}\n============\n\nFalciparum malaria is one of the commonest potentially fatal infections in sub-Saharan Africa. Most deaths from malaria occur in young children living in areas of intense *Plasmodium falciparum* transmission. African children bear 90% of the brunt of mortality from falciparum malaria, with high case fatality rates in children with cerebral malaria even with good treatment [@pone.0025626-Newton1]. Falciparum malaria is a major cause of morbidity and mortality in Malawi particularly in children under the age of five. More than 40% of in-hospital deaths in Malawian children are attributed to malaria, and cerebral malaria is a common manifestation of severe and complicated malaria [@pone.0025626-Ettling1]. Children in Blantyre district, where transmission is stable and intense, suffer on average 2.8 symptomatic malaria episodes per year while adults, though still susceptible to infection, are less likely to have symptomatic disease [@pone.0025626-Sulo1].\n\n*In vivo* von Willebrand Factor (VWF) biosynthesis is limited to endothelial cells and megakaryocytes. VWF is produced and released by vascular endothelial cells, and is frequently used as an indicator of endothelial cell activation in vascular disorders such as thrombotic thrombocytopenic purpura (TTP) and sepsis [@pone.0025626-vanMourik1]--[@pone.0025626-Zeigler1]. Published work has demonstrated that VWF plays a critical role in primary haemostasis by mediating"
-"Introduction {#s1}\n============\n\nExperiences are an area of strong academic and practical interest (Kim, [@B54]; Tung and Ritchie, [@B118]; Volo, [@B125]; Kirillova et al., [@B58]). Tourists\\' seek memorable tourism experiences (MTEs) (Scott et al., [@B105]), which have the propensity to generate destination loyalty (Chen and Rahman, [@B18]; Zhang H. et al., [@B137]), increase satisfaction (Kim, [@B53]) and promote emotional engagement (Michalk\u00f3 et al., [@B80]). However, the creation of memorable experiences requires an understanding of the mental processes which occur at different stages of a tourist experience, including the antecedent and consequent conditions (Knobloch et al., [@B60]).\n\nPrevious studies of MTEs have focused on concepts such as motivation (Gnoth and Matteucci, [@B37]; Prayag et al., [@B96]; Yoo et al., [@B136]; Passafaro, [@B91]), expectations and satisfaction (Tynan and McKechnie, [@B120]; Kim, [@B53]), well-being and quality of life (Uysal et al., [@B121]), as well as emotions and memories (Chandralal and Valenzuela, [@B16]; Moyle et al., [@B86]). Psychological antecedents of MTEs include hedonism, involvement, knowledge, refreshment, meaningfulness, and novelty (Chandralal and Valenzuela, [@B17]; Kim, [@B52]). Recent studies indicate the importance of novelty in elicitation of emotions and a connection to memorability (Ma et al., [@B70]; Mitas and Bastiaansen, [@B83]). Although the importance of novelty"
-"Background {#Sec1}\n==========\n\nOne of the hallmarks of higher social Hymenopterans (social bees, wasps, and ants) is the reproduction division of labor among nest members \\[[@CR1]\\]. Queens are the reproductive caste that is morphologically adapted for dispersal and reproduction while workers are the non-reproductive caste specialized in foraging, nest maintenance and brood tending. A haplodiploid sex determination system is common to all hymenopterans, in which males arise parthenogenetically from unfertilized eggs (arrhenotoky) and are haploid, whereas females arise from fertilized eggs and are diploid \\[[@CR2], [@CR3]\\]. Such unique system results in an asymmetrical genetic relatedness among the colony members where workers are more genetically related to the queen's daughters (their sisters) (*r*\u00a0=\u00a00.75) compared to their own daughters and sons (*r*\u00a0=\u00a00.50) in a monogynous colony headed by a singly mated queen \\[[@CR4]\\]. According to Hamilton's kin-selection theory, this unusual asymmetry in relatedness appears to favor evolution of a sterile worker caste as workers gain indirect fitness (i.e., propagation of their own genes) by behaving altruistically and assisting in raising the queen's instead of their own offspring.\n\nReproductive constraints impair the worker reproduction either through behavioral mechanisms (e.g., worker policing) or by suppressing the development of the reproductive"
-"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\nEnjoying a satisfying aging, particularly with regard to cognitive health, is desirable by people globally. Not all individuals enjoy healthy cognitive functioning, and even those who do usually show structural changes in their brain with aging. The mismatch between the relative preservation of cognitive abilities in the presence of structural changes in the brain is conceived as if the brain had some sort of \"cognitive reserve,\" a heavily used term defined as the individual differences in cognitive task performances which provides resilience to age-related brain damage or pathology ([@B3], [@B4]), giving rise to disparity between the degree of brain damage or pathology and the clinical manifestation of cognitive performance. Cognitive reserve is usually estimated using different intercorrelated factors---education ([@B5]), occupation ([@B6]), and second language learning ([@B7]--[@B9]). These factors have been studied in literature over the years as proxies of cognitive reserve.\n\nIn the context of lifelong bilingualism, cognitive reserve can be conceptualized as a cognitive resilience resulting from the use of, and exposure to, two or more languages. In such a context, it is believed that practiced bilingualism provides cognitive resilience to the cognitive control mechanisms allowing to counter, partially or totally the impact of age-related changes"
-"Introduction {#Sec1}\n============\n\nKir2.x channels are inward rectifier K^+^ channels that play an important role in maintaining stable resting membrane potentials, controlling excitability, and shaping the initial depolarization and final repolarization of ventricular myocytes \\[[@CR13], [@CR19], [@CR21], [@CR27]\\]. Gain and loss of function of Kir2.x channels, which mediate cardiac inwardly rectifying currents (*I* ~K1~), can cause reentry and arrhythmia, respectively \\[[@CR19]\\]. Reentry is facilitated by shortening of the action potential duration (APD), which abbreviates refractoriness. On the other hand, excessive APD prolongation may cause torsades de pointes arrhythmia and sudden cardiac death \\[[@CR25]\\].\n\nWe previously demonstrated that extracellular spermine inhibits the outward current through Kir2.1 channels expressed in oocytes and the outward *I* ~K1~ of myocytes, but the effect was much greater in oocytes than in cardiac myocytes \\[[@CR3]\\]. However, why the effects of extracellular spermine are quantitatively different in oocytes and guinea pig myocytes is unclear \\[[@CR3]\\]. It may be simply attributable to the fact that the effects of spermine on Kir channels in different cell types vary. Alternatively, the actions of extracellular spermine may be more diverse in complex cell types such as cardiac myocytes. For example, extracellular spermine can activate the calcium-sensing receptor, CaR \\[[@CR34]\\]. This receptor"
-"Introduction\n============\n\nThyroid hormones have a significant role in regulation of metabolism and increasing the concentration of these hormones in hyperthyroid patients increases the meta-bolism and generates the reactive oxygen species (ROS). These molecules can cause oxidative stress resulting reduced global efficacy of the antioxidant defense system.^[@B1]^ In other words, increased thyroid hormone concentrations affect the oxidant/antioxidant equilibrium and may injure the cells,^[@B2]^ which in the long time, lead to oxidative damage of many organs including the cardiovascular, respiratory and nervous system.^[@B3]^ Treatment with anti-thyroid drugs like propylthiouracil (PTU) cannot restore the balance of the disturbed oxidative and antioxidative activities.^[@B4],[@B5]^ Thus, controlling the concentration of thyroid hormones and using antioxidants such as vitamins and minerals in hyperthyroid patients for diminishing the related side effects seem vital. The disturbed antioxidant system indicates the possible usefulness of supplementation with antioxidants to preventing the oxidative stress damage in hyperthyroid patients. The beneficial effects of anti-oxidants on oxidative stress induced by hyperthyroidism was shown in several animal models.^[@B6]-[@B8]^ On the other hand, use of herbal medicine for treatment of hyperthyroidism is well known in recent years due to their safety, high efficacy and lower cost.\n\n*Satureja khuzestanica* Jamzad (SKJ; Marzeh Khuzestani in Persian, family"
-"***Background.***\u2003*Clostridium difficile* infection (CDI) causes 3 million cases of diarrhea and colitis in the US annually. Although standard antibiotic is effective in suppressing *C. difficile*, it does not prevent relapse. Indeed, 15 to 30% of patients experience recurrence within 3 months following antibiotic treatment. Recovery of the gut microbiota has been proposed as an important key factor in preventing recurrent *C. difficile*. However, the stability and responsiveness of gut microbiota following *C. difficile* treatment and their relationship to recurrence is poorly understood. We have previously showed that *Lachnospiraceae*, *Ruminococcaceae* and butyrogenic bacteria are depleted in patients with CDI. We hypothesize that persistent depletion of these organisms is associated with recurrent CDI.\n\n***Methods.***\u2003Culture-independent high-density Roche/454 pyrosequencing was used to characterize distal gut microbiota of 30 adults following CDI sampled longitudinally for up to 1 year, and compared to fecal microbiota from 14 healthy controls.\n\n***Results.***\u2003We analyzed \u223c2 million partial V1-V3 16S rRNA sequences from \u223c500 longitudinal fecal samples, identifying a total of 5,904 bacterial phylotypes. Phylogenetics-based analysis revealed that the gut microbiome undergoes a slow but steady recovery in microbial diversity and species richness over a period of a few months following *C. difficile* therapy. However, in patients"
-"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"
-"Introduction\n============\n\nIn 1966, Worth and Wollin described a condition of hyperostosis corticalis generalisata which was dominantly inherited \\[[@B1]\\]. It is radiologically similar to the autosomal recessive condition called van Buchem syndrome, and some authors refer to the two conditions as endosteal hyperostosis \\[[@B2]\\]. Facial dysmorphism and diaphyseal radiographic changes are present by adolescence and consist of an elongation of the mandible and an increased gonial angle. The forehead becomes flattened and there is a slowly enlarging osseous prominence of the hard palate (torus palatinus). The early radiographic changes include thickening of the endosteum of the long bones and the skull. A progressive increase in the density of the posterior elements of the spine has been noted in some patients \\[[@B3]-[@B5]\\].\n\nMore than 13 kindreds with endosteal hyperostosis have been reported. Four families out of 13 had autosomal dominant inheritance, including male-to-male transmission. Only two patients have been reported in the literature with a history of fractures \\[[@B6]\\].\n\nWe present a father and daughter with endosteal hyperostosis. They were unusual in that both had fractures, odontoid hyperplasia (subclinical basilar invagination), and a simultaneous process of anterior longitudinal spinal sclerosis along the thoracic vertebrae, associated with progressive sclerosis of the posterior"
-"Abbreviations used: CFSE, carboxyfluorescein diacetate succinimidyl ester; dox, doxycycline; HPRT, hypoxanthine phosphoribosyltransferase; Ii, invariant chain; MCC, moth cytochrome c; tet, tetracycline; TIM, tetracycline-inducible invariant chain with MCC.\n\nR. Obst and H.-M. van Santen contributed equally to this work.\n\nH.-M. van Santen\\'s present address is Centro Biolog\u00eda Molecular Severo Ochoa, Consejo Superior de Investigaciones Cient\u00edficas, Universidad Aut\u00f3noma de Madrid, Madrid 28049, Spain.\n\nThe exact way in which CD4^+^ T cell responses depend on the orchestrated activity of antigen presentation, costimulation, cytokines, and lymphocyte trafficking remains incompletely understood. In particular, the role that antigen plays in the expansion of antigen-specific T cells during an immune response in vivo has only recently been addressed. On the encounter of antigen-presenting DCs in the T lymphocyte zones of secondary lymphoid organs, T cells proliferate after a latency period of \u223c24 h. They divide rapidly and, in parallel, express genes that enable them to become completely differentiated effector cells over the following days ([@bib1]--[@bib5]). Understanding how external signals guide the T cells\\' internal processes in vivo is critical both for better eliciting protective immune responses and for interfering with pathological ones.\n\nIn the case of CD8^+^ T cells, it seems that a relatively brief engagement of"
-"1. Background {#sec32578}\n=============\n\nLike other systems in the society, the health system is growing very fast and technology appliance is getting inevitable more and more. A crossing through many hospitals show many technological devises if are used effectively, safely, and correctly can significantly improve patient care status ([@A10305R1]). This issue leads to more attention to the healthcare technology in the beginning of the recent century.\n\nNursing practice has been altered considerably informatics and health care technology application ([@A10305R2]). Technology ranges from simple using of a digital thermometer to complex electronically equipment and hospital information systems. Informatics and health care technology have revolutionized health care delivery and created a level of complexity never experienced previously by health care providers ([@A10305R3]).\n\nIntroduction of technology into the health care means that there is no specialist nurse who does not use at least one form of health care technology in her/his profession daily. Therefore, it is important for nurses to improve their knowledge and skills about technology, which has the deep affects on technology application and its capabilities ([@A10305R4]-[@A10305R7]).\n\nThe more technology application in health care means that nurses and other health care providers need more information about technology, and there is a"
-"Introduction\n============\n\nAlport syndrome (ATS; OMIM \\#301050, \\#104200, \\#203780) is an inherited glomerular disease caused by mutations in one of the novel chains (\u03b13, \u03b14, and \u03b15) of type IV collagen, which is the major protein component of the glomerular basement membrane (GBM) \\[[@b1-kjp-2018-06772]\\]. ATS is characterized by persistent microscopic hematuria starting from infancy, eventually leading to either progressive nephritis or end-stage renal disease (ESRD). Extrarenal symptoms, including cochlear dysfunction and ocular anomalies, are also present in proportion to the severity of renal manifestations \\[[@b1-kjp-2018-06772]\\].\n\nThere are 3 known genetic forms of ATS: X-linked ATS, autosomal recessive ATS, and autosomal dominant ATS. About 80% of patients with ATS have X-linked ATS, caused by mutations in the type IV collagen gene \u03b15 chain gene, *COL4A5* \\[[@b1-kjp-2018-06772],[@b2-kjp-2018-06772]\\]. In about 15% of cases, autosomal recessive ATS results from either compound heterozygous or homozygous mutations in *COL4A3* or *COL4A4*. Approximately 5% of ATS cases exhibit autosomal dominant inheritance caused by heterozygous mutations in either *COL4A3* or *COL4A4* \\[[@b1-kjp-2018-06772],[@b2-kjp-2018-06772]\\].\n\nThe clinical manifestations of X-linked ATS differ between males and females \\[[@b1-kjp-2018-06772]\\]. The classic presentation, including hematuria and sensorineural hearing loss, is fully seen in male patients with X-linked ATS. The majority of these cases show"
-"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"
-"Background {#Sec1}\n==========\n\nSystemic inflammation is one of the main causes of adverse events after a major surgery. The lungs are one of the most susceptible organs to systemic inflammation during and after a major surgery, including liver transplant \\[[@CR1]\\], cardiac surgery \\[[@CR2]\\], spine surgery \\[[@CR3]\\], and thoracic surgery \\[[@CR4]\\]. Pulmonary complications after a major surgery include pleural effusion, atelectasis, pulmonary edema, respiratory distress syndrome, and pneumonia \\[[@CR1]\\].\n\nPositive inotropes and vasopressors such as adrenaline and volume resuscitation are often used to prevent blood pressure decline caused by systemic inflammation during and after a major surgery. Previous studies demonstrated that \u03b2-adrenergic agonists increase alveolar liquid clearance (ALC) \\[[@CR5], [@CR6]\\]. On the other hand, systemic administration of \u03b2-adrenergic agonist increases cardiac output and aggravates pulmonary edema on oleic acid-induced lung injury \\[[@CR7]\\]. Furthermore, drugs that have \u03b1-adrenergic property may impair lung edema due to increased pulmonary vascular resistance \\[[@CR8]\\]. From these observations, administration of adrenaline, a potent \u03b1- and \u03b2-adrenergic agonist, for systemic inflammation and shock status may affect lung injury; however, the effect of continuous administration of adrenaline on injured lungs during shock status have not yet been elucidated.\n\nWe had shown that repeated hepatic inflow obstruction and reperfusion concomitant"
-"Introduction {#s1}\n============\n\nCancer-associated fibroblasts (CAFs) are a heterogenous and plastic population of activated fibroblasts, which represent a significant proportion of the tumor microenvironment. For instance, CAFs can account up to 70 and 90% of breast and pancreatic cancer tumor mass, respectively ([@B1], [@B2]). The role of CAFs in tumorigenesis is widely established and they have been shown to contribute to tumor growth, metastasis and resistance to therapy ([@B3]). Moreover, CAFs play an important role in the regulation of cancer metabolism, primarily through the secretion of metabolites and the generation of a stiffer and fibrotic ECM, which in turn affects cancer cell metabolism.\n\nCells interact with the ECM through plasma membrane receptors. Integrins are transmembrane receptors that regulate cell adhesion, migration, and mechanotransduction through mediating cell-ECM interaction ([@B4], [@B5]). Integrins can trigger different intracellular signaling pathways promoting cell growth, survival, and proliferation ([@B6]). Furthermore, ligand bound-integrin trafficking has recently been shown to directly or indirectly affect nutrient signaling ([@B7], [@B8]). Mechanistic target of Rapamycin (mTOR) signaling pathway is the key regulator of anabolic and catabolic processes of the cells. During nutrient availability, mTOR induces anabolic processes such as protein, nucleotide, and lipid biosynthesis and inhibits cellular autophagy and lysosomal biogenesis"
-"Introduction {#sec1}\n============\n\nPolyunsaturated fatty acids in cellular membranes are major targets for oxidative damage induced by xenobiotics and inflammatory stimuli. The initial oxidation products are fatty acid hydroperoxides, which can be converted to a number of reactive lipid electrophiles. Some of these electrophiles are readily diffusible and can modify proteins and DNA, thereby propagating damage initiated by oxidation.^[@ref1],[@ref2]^ This may be an important contributor to diseases associated with environmental exposures or chronic inflammation such as Parkinson's disease, atherosclerosis, diabetes, and cancer.^[@ref3],[@ref4]^\n\nLipid peroxidation generates a plethora of electrophilic products, varying in length and reactivity; two of considerable interest are 4-hydroxy-2-nonenal (HNE) and 4-oxo-2-nonenal (ONE) (Figure [1](#fig1){ref-type=\"fig\"}). HNE and ONE react rapidly with the side chains of Cys, His, and Lys residues in proteins via Michael addition. HNE and ONE can also form Schiff bases through reaction with Lys residues, while ONE alone is capable of 4-ketoamide formation.^[@ref1],[@ref5]^ ONE is \\>150-fold more reactive than HNE and displays a broader range of reaction products due to differences in its stereoelectronic properties.^[@ref6],[@ref7]^ Comprehensive proteomic analyses indicate that HNE and ONE react with many proteins in cells (\\>1,000) but that they display significant differences in protein targets and sites of reactivity;^[@ref8]\u2212[@ref10]^ few studies"
-"Background {#Sec1}\n==========\n\nVon Hippel-Lindau (VHL) disease is an autosomal dominant hereditary cancer syndrome attributed to germline mutation of the *VHL* gene, located on chromosome 3p25 \\[[@CR1],[@CR2]\\]. The clinical phenotype is characterized by the development of vascular tumors, including hemangioblastomas of the central nervous system and retina, clear cell renal cell carcinomas (ccRCCs) and pheochromocytomas. In the kidney, loss of the remaining wild-type *VHL* allele, consistent with a 'two-hit' model of tumor suppressor inactivation \\[[@CR3]\\], results in multiple pre-neoplastic cysts and ccRCC tumors. In sporadic ccRCC, somatic mutation or hypermethylation of *VHL* occurs in the majority \\[[@CR4]--[@CR6]\\] and 3p loss of heterozygosity (LOH) in over 90% of cases \\[[@CR6]--[@CR8]\\]. Furthermore, recent work from our group has demonstrated that 3p LOH and *VHL* mutation or methylation are early truncal (ubiquitous) events in 10 of 10 cases of sporadic ccRCC subjected to multi-region sequencing (M-seq) \\[[@CR9]\\]. Biallelic inactivation of the tumor suppressor gene *VHL* is therefore established as an early event in both germline mutant *VHL*-associated and sporadic ccRCC \\[[@CR6],[@CR8]--[@CR11]\\].\n\nNext-generation DNA sequencing has identified an additional set of tumor suppressor genes that are recurrently mutated in sporadic ccRCC \\[[@CR6],[@CR7],[@CR11]--[@CR14]\\]. Several of these (*PBRM1*, *SETD2* and *BAP1*) are also located on chromosome"
-"Introduction {#s0005}\n============\n\nInnate immune response is the first line of defense during the earliest hours of exposure to a novel pathogen. Its mechanisms are nonspecific and rely on a group of proteins and phagocytic cells that quickly activate to help destroy invaders. Alongside these pathways, a novel innate immune strategy has begun to reveal connections between cholesterol metabolism and immune response against viral infections. [@bib1], [@bib2], [@bib3].\n\nThe most widely studied effector of this branch of innate immunity is an oxysterol, 25-hydroxycholesterol (25HC) [@bib1], [@bib2]. Oxysterols contain 27 carbon atoms per molecule and are derived from cholesterol by both enzymatic and nonenzymatic oxidation [@bib4], [@bib5], [@bib6]. Several among the various cholesterol oxidation products of enzymatic origin contribute to physiological functions: they are intermediates of pregnenolone and steroid hormone synthesis [@bib7] and target nuclear receptors (e.g., the liver X receptor \\[LXR\\] and the estrogen receptor \u03b1 \\[ER \u03b1\\]), cellular membrane receptors (e.g., C-X-C motif chemokine receptor 2 \\[CXCR2\\]) and transport proteins (e.g., insulin induced gene protein \\[INSIG\\], Niemann-Pick protein 1 \\[NPC1\\], oxysterol binding protein \\[OSBP\\] and its related proteins \\[ORPs\\]) [@bib8], [@bib9], [@bib10], [@bib11], [@bib12], [@bib13]. In contrast, the oxysterols derived from cholesterol autoxidation, a not-regulated and therefore potentially harmful"
-"Introduction {#Sec1}\n============\n\nThe infraorbital nerve (ION) derives from the trigeminal nerve exiting the maxilla via the infraorbital foramen (IOF) and provides midface sensation^[@CR1]^. Regional nerve block of the ION can be used for regional anesthesia during surgeries involving the midface region or when treating neuralgia of the infraorbital nerve with a complaint of unusual facial pain. However, sometimes the ION is duplicated, and the presence of the accessory infraorbital nerve (AION) often results in anesthesia failure^[@CR2],[@CR3]^. Thus, clinicians should consider the presence of this accessory branch passing through accessory infraorbital foramen (AIOF) in order to accomplish satisfactory anesthesia of the midfacial region and also to avoid iatrogenic injury to the duplicated ION.\n\nWhile the ION has been investigated extensively in the prior literature, there are few reports on the topography of the AIOF, resulting in insufficient information on this foramen in the literature^[@CR4]--[@CR6]^. Previous studies determining the location of the AIOF used the nasomaxillary suture and anterior nasal spine as reference landmarks^[@CR7],[@CR8]^. However, palpitating such deep bony landmarks externally is very difficult, and so they are rarely used in clinical situations, which makes it necessary to identify identifiable external landmarks as references for easily predicting the location of the"
-"Introduction\n============\n\nEmbolization of vascular tumours of the head, the neck and the central nervous system (CNS) has become an important adjunct to treatment of these pathologies. The technique of selective embolization has extensively been used to occlude vessels, either as an alternative to traditional therapy or when traditional therapy fails. Recently, embolization techniques have been employed more commonly and with higher precision and facility. As a result, this alternative technique has quickly evolved into the first-line therapy for many complex clinical conditions, surgical repairs of which are considered to bear high risk of various degrees. The introduction of this procedure has improved morbidity and mortality rates of patients with tumours of the head, the neck and the central nervous system, while also facilitating their removal \\[[@B1],[@B2]\\]. The technological advances in microcatheters and new, safer embolic agents have permitted a wider range of applications of this form of treatment. In spite of this, the number of publications on the application of selective embolization of thyroid arteries (SETA) in the treatment of thyroid disorders is rather limited. The published reports are limited to the applications of SETA in treatment of thyrotoxicosis -- particularly in Graves\\' disease \\[[@B3]-[@B5]\\] -- and thyroid cancer"
-"Introduction {#s1}\n============\n\nTumor suppressor p53 plays a central role in tumor prevention ([@bib18]; [@bib19]; [@bib43]). Trp53 is the most frequently mutated gene in human tumors; it is mutated in over 50% of all tumors. Majority of Trp53 mutations are missense mutations that are localized in the p53 DNA binding domain (DBD), including several mutational hotspots in tumors (e.g., R175, R248, and R273) ([@bib13]; [@bib10]; [@bib31]). Many tumor-associated mutant p53 (mutp53) proteins not only lose the tumor suppressive function of wild-type p53 (wtp53), but also gain new oncogenic activities independently of wtp53, which is defined as mutp53 gain-of-function (GOF) ([@bib10]; [@bib31]). So far, many mutp53 GOFs have been identified, including promoting tumor growth, metastasis, chemoresistance and metabolic changes ([@bib17]; [@bib34]; [@bib29]; [@bib2]; [@bib9]; [@bib7]; [@bib45]).\n\nUnder the non-stressed condition, wtp53 protein levels are kept low in normal cells and tissues mainly through the proteasomal degradation mediated by E3 ubiquitin ligase MDM2, the most critical negative regulator for wtp53 ([@bib3]; [@bib14]). At the same time, as a direct transcriptional target of p53, MDM2 is up-regulated by p53 under both non-stressed and stressed conditions. Thus, p53 and MDM2 forms a negative feedback loop to tightly regulate p53 protein levels in cells. However,"
-"All relevant data are within the paper and its Supporting Information files.\n\nIntroduction {#sec001}\n============\n\nGross primary production (GPP), the rate at which atmospheric carbon dioxide is fixed by photosynthesis, is the largest carbon flux from the atmosphere to the terrestrial biosphere \\[[@pone.0184466.ref001], [@pone.0184466.ref002]\\]. Spatiotemporal variation in GPP directly influences atmospheric CO~2~ concentrations and the global climate, making continuous monitoring of GPP an essential component of international policy aimed at climate change mitigation \\[[@pone.0184466.ref003]--[@pone.0184466.ref006]\\]. A photosynthesis algorithm (PSN) incorporating satellite observations from the Moderate Resolution Imaging Spectrometer (MODIS) provided the first remote-sensing based global GPP data product at 1-km resolution (MOD17) \\[[@pone.0184466.ref007]\\]. The MOD17 data product is a widely-used tool for monitoring spatiotemporal trends in global GPP, but uncertainty likely increases at the regional scale due to reliance on coarse resolution climate and land cover data inputs to the PSN algorithm \\[[@pone.0184466.ref008]--[@pone.0184466.ref010]\\]. Understanding the uncertainty in remote-sensing based GPP estimates is important to consider when applying these estimates at different spatial scales \\[[@pone.0184466.ref011]--[@pone.0184466.ref013]\\]. Yet quantifying the uncertainty in MOD17 GPP estimates remains challenging because the uncertainties in land cover and climate input data are not themselves well quantified \\[[@pone.0184466.ref014]\\]. Here we examine how local, high-resolution land cover and climate data"
-"Macrophage migration inhibitory factor (MIF) is a pluripotential proinflammatory cytokine with a possible role in the pathogenesis of rheumatoid arthritis (RA). MIF is expressed in RA synovium, and directly activates RA synoviocyte gene expression and proliferation, as well as exerting anti-apoptotic effects via inhibition of p53. MIF activates ERK and p38 mitogen-activated protein (MAP) kinase, but evidence for direct activation of NF-\u03baB by MIF is lacking.\n\nAnti-MIF monoclonal antibodies prevent IL-1 activation of fibroblast-like synoviocytes *in vitro*, implicating MIF in the activation of cells by IL-1. The mechanism of this action of MIF has not been adduced. We studied the activation of signal transduction pathways by IL-1 in cells deficient in MIF. Dermal fibroblasts were cultured from MIF^-/-^and WT mice, and were exposed to IL-1. MAP kinase and NF-\u03baB activation were studied by Western blotting, electrophoretic mobility shift assay (EMSA), and reporter gene assays.\n\nIL-1 rapidly induced phosphorylation of p38, JNK, and ERK MAP kinases in WT cells. In contrast, MIF^-/-^cell p38, JNK, and ERK activation in response to IL-1 was reduced. Consistent with this observation, MIF^-/-^cells were hyporesponsive to IL-1-induced AP-1 DNA binding as measured by EMSA (*P*= 0.03). IL-1-induced activation of an AP-1 luciferase reporter gene system was"
-"INTRODUCTION\n============\n\nThe effect of granulocyte colony-stimulating factor (G-CSF) on the course of neurological diseases has drawn considerable attention over the past decade. G-CSF mobilizes hematopoietic (CD34+) stem cells and-with repeated administration-recruits immature CD34+/CD133+ stem cells that are capable of differentiating into neuronal progenitors.[@B1],[@B2] G-CSF receptor expression may play an autocrine protective role in various cells of the nervous system,[@B3] and G-CSF may protect against ischemic neuronal damage by inhibiting apoptosis and inflammation, mobilizing stem cells, or enhancing neuronal differentiation.[@B3],[@B4]\n\nRecent studies have suggested a role for G-CSF in the treatment of amyotrophic lateral sclerosis (ALS).[@B5],[@B6],[@B7],[@B8],[@B9] In a mouse model of ALS, G-CSF significantly improved motor performance and motoneuron survival, and reduced denervation atrophy.[@B10] A study involving subjects with ALS found significantly reduced G-CSF receptor expression in motoneurons and increased G-CSF expression in reactive astrocytes.[@B8] The authors suggested that reduced G-CSF receptor expression on motor neurons might account for the pathophysiology of ALS. Simultaneously the levels of monocyte chemoattractant protein-1 (MCP-1) were increased, suggesting that reduced-CSF receptors can exacerbate the ALS course.\n\nMost studies of G-CSF efficacy in subjects with ALS have been limited in several ways. A nonrandomized study involving 13 subjects with ALS demonstrated a significantly lower monthly"
-"The authors confirm that all data underlying the findings are fully available without restriction. All rawdata and historic data are supplied as electronic supplements.\n\nIntroduction {#s1}\n============\n\nPresent day atmospheric carbon dioxide (CO~2~) concentrations are now over 30% higher than the maximum observed in the previous 2 million years [@pone.0109092-Hnisch1]. Approximately 28% of this additional CO~2~ is absorbed by the world\\'s oceans [@pone.0109092-Tyrrell1], [@pone.0109092-Khatiwala1], leading to lower seawater pH (Ocean Acidification; OA) with reduced carbonate ion concentrations (CO~3~ ^2\u2212^) and a reduced saturation state (\u03a9) of calcium carbonate minerals (CaCO~3~). Surface seawater pH has decreased by 0.1 units since pre-industrial times and is predicted to fall by a further 0.3**--**0.5 units in the next 100 years [@pone.0109092-Caldeira1]. Large-scale spatial and temporal variations (seasonal, inter-annual) in surface seawater CO~2~ concentrations are known to be caused by biogeochemical and air-sea exchange processes. Knowledge of this variability is critical to understand the current state of the carbon cycle and to predict how the ocean will react to future increases in atmospheric CO~2~ concentration. A recent review indicated that the partial pressure of CO~2~ (*p*CO~2~) in coral reef waters is increasing more rapidly than in the atmosphere, most likely due to other anthropogenic impacts"
-"Introduction {#sec1}\n============\n\nFor the cryopreservation of mammalian cells, the standard protocol is freezing in a solution containing 5--10 wt % of the cryoprotective agent (CPA) dimethyl sulfoxide (DMSO), which was introduced in 1959^[@ref1]^ and remains the gold standard. DMSO is able to enter cells and, at least partly, reduce injury by moderating the increase in solute concentration during freezing.^[@ref2]\u2212[@ref4]^ While freezing in DMSO works for most cell lines (and indeed is a key underpinning technology), there remains many where it is not satisfactory. For example, DMSO causes differentiation of human leukemic cell lines,^[@ref5]^ as well as certain cells such as leukocytes and RAW 264.7 (murine macrophage) cells, which are highly sensitive to DMSO, with concentrations even below 1% significantly affecting ROS production.^[@ref6]^ In addition to these specific instances, there is a concern with using DMSO for all cell lines due to its cytotoxicity at high concentrations and/or at room temperature.^[@ref7],[@ref8]^ Emerging cell-based therapies such as CAR-T (chimeric antigen receptor T-cell) are now approved for some cancers including acute lymphoblastic leukemia. One potential side effect of these therapies is from the DMSO transfusion, which in the case of Tisagenlecleucel is 7.5 wt %, leading to nausea/vomiting.^[@ref9]^ Removal of DMSO prior"
-"Introduction {#s0005}\n============\n\nHepatocyte-like cells (HLCs), differentiated from pluripotent stem cells (PSCs), offer promise as *in vitro* models of human liver development, function, and toxicity [@b0005; @b0010]. Most protocols have attempted mimicry of embryogenesis through the addition of soluble factors to the media. Activin A [@b0015; @b0020; @b0025; @b0030; @b0035; @b0040; @b0045; @b0050; @b0055; @b0060; @b0065], alone or together with Wingless-related integration site (Wnt) 3A [@b0035; @b0040; @b0045; @b0070; @b0075], promotes definitive endoderm (DE)-like differentiation. Fibroblast growth factor (FGF) and bone morphogenetic protein (BMP) family members encourage hepatic differentiation [@b0025; @b0030; @b0040; @b0045; @b0055; @b0060; @b0065]; and hepatocyte growth factor (HGF), the synthetic glucocorticoid, dexamethasone (DEX), and oncostatin M (OSM) support increased maturity [@b0015; @b0020; @b0030; @b0040; @b0045; @b0050; @b0055; @b0060; @b0065; @b0070; @b0080]. However, fully mature hepatocytes have not been produced, which raises two unanswered questions: are cells aberrant because human liver development has not been followed with adequate specificity; or, if the lineage is correct, are HLCs actually 'stuck' in a fetal-like state? Assessment of the latter is problematic for two largely unaddressed reasons. HLC maturity is over-estimated if compared to sub-optimal adult hepatocytes. Thawed cells taken into culture are challenging to maintain [@b0085]; in a well-controlled example,"
-"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.,"
-"1. Introduction {#sec1}\n===============\n\nWith the discovery of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in late 2019 ([@bib76]) and very recently with the subsequent pandemic of COVID-19 ([@bib35]), society and economies worldwide are experiencing an unprecedented exogenous shock ([@bib23]). Although the occurrence of a pandemic caused by a new virus is unsurprising for virologists, the infection control measures such as social distancing ([@bib28]) taken to slow the spread of COVID-19 exert tremendous pressure on large parts of a nation's economy. Most actors central to shaping the economy would admit to the current pandemic being a metaphorical black swan event, that is, a surprising, unpredictable event of great significance and severe consequences that dramatically changes the political and economic environment ([@bib74]). While such events could be interpreted as opportunities, the unprecedented lockdown of large parts of society arising from the COVID-19 crisis marks the current situation out as an acute crisis. SARS-CoV-2 triggered a twofold crisis: The COVID-19 pandemic has placed an unprecedented burden on many health systems worldwide, and the infection control measures have caused an economic crisis by bringing a vast amount of economic activity to an abrupt halt. Moreover, while many other past crises have hit"
-"1. Introduction\n===============\n\nTuberculous pleural effusion (TPE) is one of the most common forms of extrapulmonary tuberculosis.^\\[[@R1]\\]^ On a global scale, tuberculosis (TB) remains one of the most frequent causes of pleural effusion.^\\[[@R2]\\]^ TPE occurs in approximately 5% of patients with *Mycobacterium tuberculosis* infection.^\\[[@R3]\\]^ In the same way, pleural effusion can also be caused by some parasitic infections, such as paragonimiasis, infections by amoeba, and *Echinococcus granulosus*. With increasing travel and migration, the rates of parasitic pleural diseases are also increasing.^\\[[@R4]\\]^ Parasitic pleural effusion (PPE) and TPE present with similar clinical manifestations, but the prognosis and therapy for each are quite different. Therefore, rapid differentiation of the 2 types is important. However, the differential diagnosis of PPE and TPE remains a challenge.\n\nThe gold standard for diagnosing TPE includes the Ziehl Neelsen (ZN) acid-fast bacilli stain and a laboratory culture of *Mycobacterium tuberculosis*. However, *Mycobacterium tuberculosis* is rarely observed on direct examination by acid fast bacilli (AFB) staining in pleural fluid. Less than 30% of cultured pleural fluid samples are positive for *Mycobacterium*.^\\[[@R2]\\]^ Furthermore, laboratory culture of *Mycobacterium tuberculosis* requires 8 weeks to yield a positive result.^\\[[@R5]\\]^ The other method considered for diagnosing TPE is a pleural biopsy, which is"
-"Introduction\n============\n\nIdiopathic inflammatory myopathies (IIM) are a heterogeneous group of muscle disorders characterized by symmetrical proximal muscle weakness, decreased muscle endurance, and inflammatory infiltrates in skeletal muscle tissue \\[[@B1],[@B2]\\]. Polymyositis (PM) and dermatomyositis (DM) are two common subsets of IIM. Although the pathological mechanism of IIM remains unclear, recent studies suggest that an interplay between adaptive immune, innate immune, and nonimmune mechanisms may be responsible for the damage and dysfunction that occur in myopathic muscle tissue \\[[@B3]\\]. Multiple players - such as adaptive immune cells \\[[@B4]\\], cytokines and chemokines \\[[@B5]-[@B7]\\] - may be involved in the pathogenesis of IIM.\n\nTumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a recently identified pro-inflammatory cytokine belonging to the TNF superfamily \\[[@B8]\\]. TWEAK has emerged as a multifunctional cytokine that regulates multiple cellular responses, including pro-inflammatory activity; angiogenesis; and cell proliferation, differentiation, migration and apoptosis \\[[@B9]\\]. The only known signaling receptor for TWEAK is fibroblast growth factor-inducible 14 (Fn14), which was first recognized by differential display technique \\[[@B10]\\]. TWEAK exerts pleiotropic functions through binding to Fn14 and activating downstream signaling pathways. Fn14 is a type I transmembrane protein and is highly inducible by various growth factors, including epidermal growth factor (EGF), platelet-derived"
-"INTRODUCTION\n============\n\nAccurately reconstructing the true rates and magnitudes of past climate change depends on a dense temporal sampling of inorganic and organic proxy records (for example, \u03b4^18^O, \u03b4^13^C, Mg/Ca, and TEX~86~). Marine sediments are thought to provide a nearly continuous history of oceanic conditions on time scales of 10^2^ to 10^3^ years due to the steady accumulation of the sediment and associated preservation of the proxy material (for example, microfossil tests and organic matter) ([@R1]--[@R4]). Moreover, high-resolution age models can be constructed from abundant volcanic ashes, reversals of Earth's magnetic polarity, and biostratigraphic data, which enhance the fidelity of the paleoclimate time series (in the absence of major sea-level falls and carbonate dissolution) ([@R1], [@R3], [@R5], [@R6]). Terrestrial paleoclimate records of the Plio-Pleistocene and Holocene exploit similar depositional behavior in lacustrine systems and annual to sub-annual accumulation of snow layers in ice sheets and limestone precipitation in speleothems ([@R7]--[@R9]). These terrestrial records also contain a suite of independent geochronometers that produce highly resolved age models ([@R7]--[@R9]). By integrating marine and terrestrial proxies, researchers have comprehensively tested paleoclimate models and identified the key atmospheric and oceanic processes operating during past climate change events ([@R10], [@R11]). Furthermore, the rates and magnitudes"
-"Introduction {#Sec1}\n============\n\nThe demand for energy storage devices (batteries) for both stationary and mobile applications has increased rapidly during the past years and it is expected to continue to grow in the future. The most commonly used electrochemical energy storage devices are intercalation based Li-ion batteries, which exhibit very high efficiency and reversibility^[@CR1],[@CR2]^. Nonetheless, other Li-storage schemes are being presently pursued especially conversion or alloying modification approaches since they hold the promise for achieving very high capacity storage systems. Unfortunately, many of these systems have been found to lack both good reversibility and efficiency^[@CR3],[@CR4]^.\n\nRecently, a new class of oxide systems, also known as high entropy oxides (HEO), was formulated and reported with first demonstrations for transition-metal-based HEO (TM-HEO)^[@CR5]--[@CR7]^, rare-earth-based HEO (RE-HEO)^[@CR8]^ and mixed HEO (TM-RE-HEO)^[@CR9]^. HEO are based on a new, quite revolutionary concept of entropy stabilization, that is, to stabilize a certain crystal structure that can differ from the typical crystal structures of the constituent elements, thereby increasing the configurational entropy of the resulting compounds. This concept was first reported for metallic high entropy alloys (HEA). In recent years, the study of HEA has grown into an independent field of materials research, as evidenced by numerous publications^[@CR10]^."
-"Introduction\n============\n\nAt present, venous thromboembolism (VTE) is a major problem for international public health policies \\[[@B1]\\]. It is the first cause of death in hospitalized patients, and the third cause of death of cardiovascular origin. In fact, it is the most important clinical problem in many patient subgroups: it is the first cause for readmission after hip arthroplasty and the first cause of death during pregnancy, after gall-bladder surgery and hernia repair \\[[@B2]\\]. The Federal Agency for Health Research and Quality (AHRQ) in the U.S. (United States) considers that the appropriate use of thromboprophylaxis (TP) is the most important procedure today for an institution to improve the quality of its practices \\[[@B1]\\].\n\nOne of the dominant characteristics of this disease is that for every symptomatic pulmonary embolism diagnosed, there are 2.5 cases of VTE that we are not able to identify. Moreover, 40 to 60% of the deaths from VTE occurs in patients whom lacked a previous diagnosis of deep vein thrombosis (DVT), and 20% of the patients have a sudden death secondary to massive embolism as their first and only symptom \\[[@B3]\\]. To put these numbers in perspective, the total number of deaths from this condition in hospitalized"
-"CASE REPORT\n===========\n\nA 35-year-old man visited our hospital presenting with a palpable mass on his left lateral chest wall, which was movable, rubbery, and non-tender. A gun biopsy assisted by ultrasonography was performed, but failed to confirm a specific diagnosis; therefore, we performed a local excision. The mass was 3\u00d72\u00d71 cm, non-adhesive, round, and pink; the cut sections evidenced well-demarcated, gray-white gelatinous masses. A microscopic examination revealed a tumor in the subcutaneous tissues without invasion to the adjacent structures ([Fig. 1](#F1){ref-type=\"fig\"}). The specimen exhibited a mixture of myxoid, hyaline, and inflammatory zones ([Fig. 2](#F2){ref-type=\"fig\"}). Scattered and enlarged tumor cells, each with a large eosinophilic nucleus resembling a virocyte, were observed, consistent with a diagnosis of myxoinflammatory fibroblastic sarcoma (MIFS) ([Fig. 3A, B](#F3){ref-type=\"fig\"}). An immunohistochemical study revealed that the tumor cells had a strong positivity for vimentin and focal positivity for CD34 and CD68, confirming the diagnosis of MIFS.\n\nA microscopic histological analysis of the specimen revealed that the mass was abutting to the resection margin in a series of multifocal areas. Thus, an additional wide excision was advised for an adequate tumor-free margin. On combined positron emission tomography and computed tomography, fluoro-2-deoxy-D-glucose uptake was increased at the left chest"
-"Introduction {#sec1-1}\n============\n\nThis study was conducted to identify the effectiveness of core indicators' monitoring in a blood storage unit of a National Accreditation Board for Hospitals and Healthcare Providers (NABH) accredited tertiary care hospital. Four core indicators were observed and monitored monthly, which were:\n\nPercentage (%) of blood component usage,Percentage (%) of transfusion reactions,Percentage (%) of wastage of blood and blood components, andAverage turnaround time for issue of blood and blood components.\\[[@ref1]\\]\n\nThe information was gathered in a structured manner and then, adverse events associated with the transfusion were reported. The root causes were analyzed and specified corrective and preventive actions were taken.\n\nMaterials and Methods {#sec1-2}\n=====================\n\nA total of four parameters were observed in all the wards, intensive care units, and operation theaters of a NABH accredited tertiary care neurosciences institute for a period of 2 years that included 2011 and 2012. The study parameters included whole blood and blood component usage, transfusion reactions, wastage of blood and blood products, and the average turnaround time for issue of blood and blood components. These were documented monthly by the concerned clinical staff that included the nursing staff and doctors of clinical departments in a specific *proforma* \\[[Annexure 1](#F1){ref-type=\"fig\"}\\]."
-"Introduction {#s1}\n============\n\nNanomaterials, designed on the nano-scale (1--100\u2005nm), have specific functional physical and chemical properties. They are used for various products, adding or improving a function[@r1]^)^. However, there is growing concern regarding their possible adverse health effects[@r2]^)^ through exposure during handling in the workplace.\n\nThe concentrations of nanomaterial aerosol particles and their size distributions are essential when considering the particle dynamics in the workplace air, the exposure control plan, and the risk assessment. Different real time aerosol sizers measuring particle concentration and size distribution are currently commercially available. They have great advantages, since they are easy to use and the data can be checked on site. Therefore, their use is recommended for an initial screening of nanomaterial exposure[@r3], [@r4]^)^.\n\nHowever, there are some difficulties in measuring the size distribution of nanomaterial aerosol particles, because nano-sized particles generally form agglomerates caused by interparticle forces, such as liquid bridges, van der Waals, and electrostatic forces, so that the agglomerates exhibit a wide range of sizes (nanometer to micrometer). Therefore, to monitor the concentrations and size distributions of nanomaterial aerosol particles a combination of an optical particle counter (OPC), which measures submicrometer- to micrometer-sized particles, and a scanning mobility particle sizer"
-"1. Introduction {#sec1-nanomaterials-08-00025}\n===============\n\nAmong iron's many critical roles in metabolic processes, the most essential function is in the synthesis of hemoglobin to meet the need for oxygen transport. Iron replacement medications formulated as parenteral nano-sized colloids of carbohydrate-coated ferric oxyhydroxide are an effective treatment for iron deficiency anemia in chronic kidney disease patients receiving hemodialysis and responding to erythropoiesis stimulating agents. As of May 2017, innovator iron-carbohydrate complex drug products on the U.S. market include INFed (iron dextran), Dexferrum (iron dextran), Ferrlecit (sodium ferric gluconate (SFG) complex), Venofer (iron sucrose), Feraheme (ferumoxytol), and Ferinject (ferric carboxymaltose). These iron colloidal nanoparticle products differ in the composition of their carbohydrate shells, iron core sizes and hydrodynamic radii. Nevertheless, in humans these drugs are distributed and cleared from the bloodstream through a similar process that involves phagocytosis in the reticuloendothelial system (RES) \\[[@B1-nanomaterials-08-00025]\\]. In addition, these drug products may have different clearance rates as a result of their varied compositions. The mechanism of action of these iron colloidal drugs involves uptake by cellular lysosomes in which iron ions are released from the colloidal nanoparticles and become part of the intracellular labile iron pool for use in biological processes \\[[@B2-nanomaterials-08-00025]\\].\n\nThe availability of"
-"Key Points\u00a0for Decision Makers {#FPar11}\n==============================\n\nImmunization delivery costs are a necessary component of high-quality cost-effectiveness models, and are also used to inform resource mobilization for immunization programs.Our study provides estimates produced via meta-regression analyses that can help improve resource mobilization and planning in situations where empirical cost data are unavailable or of low quality.\n\nBackground {#Sec1}\n==========\n\nRoutine immunization is critical to achieving 14 of the 17 Sustainable Development Goals (SDGs) adopted by countries in 2015 to \"ensure prosperity for all\" \\[[@CR1]\\]. To monitor progress towards these goals, to plan for the financial sustainability of immunization programs, and to improve program coverage and equity, decision-makers need to know how much immunization programs cost beyond the cost of the vaccine. Non-vaccine immunization delivery unit cost estimates are essential for resource mobilization and planning for routine health systems, which have required the development of new financing mechanisms to support the increasing costs of country immunization programs \\[[@CR2]\\]. Moreover, delivery cost estimates can help to identify and evaluate strategies to improve efficiency in vaccine service delivery \\[[@CR3]\\]. Cost estimates can significantly influence the cost-effectiveness estimates used to allocate resources at the country level, particularly as service delivery can be the main"
-"Background {#Sec1}\n==========\n\nThere is a growing body of evidence demonstrating changes in the architecture in subchondral bone underlying OA cartilage lesions, which may contribute to the pathogenesis of both structural and symptomatic features of OA \\[[@CR1]\\]. The principal role of the subchondral bone is mechanical with the cortical and trabecular bone compartments continually responding to loads applied to them by remodeling, via the osteocyte network and Wnt signaling \\[[@CR2]--[@CR4]\\]. The resulting changes in the mechanical properties of the subchondral plate determine, in part, the load exposure of the cartilage at the joint surface leading to a dynamic interplay between loading and bone structure \\[[@CR5]\\].\n\nOA is a disease involving cartilage damage, changes in underlying subchondral bone, osteophyte formation, and inflammation of the joint with unknown factors that initiate these changes \\[[@CR6]\\]. Our current knowledge of the factors that may be involved in the progression of OA includes weight bearing with aging, increased loading from obesity, and previous injuries \\[[@CR7], [@CR8]\\]. The search for other factors that may be involved in cartilage degradation accompanied by alterations in underlying bone has introduced new directions for investigations focused on signaling pathways such as Wnt-frizzled pathways and associated protein regulators. The Wnt-\u03b2-catenin pathway"
-"1.. Introduction\n================\n\nUltrasound transducers are core modules of medical imaging systems. Traditional ultrasound transducers are all based on rigid substrates \\[[@b1-sensors-15-02538]--[@b4-sensors-15-02538]\\], while two-dimension arrays do not conform to the human body shape and line-arrays are difficult to operate. At the same time, transducers cannot be used for implant ultrasound imaging \\[[@b5-sensors-15-02538],[@b6-sensors-15-02538]\\]. A variety of flexible ultrasound transducers have been reported recently. Mastronardi *et al.* proposed a flexible ultrasound transducer made of AlN \\[[@b7-sensors-15-02538]\\], and Zhou *et al.* mentioned that they took advantage of the properties of ZnO nanowires to make a flexible ultrasound transducer \\[[@b8-sensors-15-02538]\\]. However, these materials do not have as good performance as lead zirconate titanate (PZT, Pb(Zr~1\u2212x~Ti~x~)O~3~). Bernstein *et al.* fabricated monomorph sonar transducers using sol-gel PZT films up to 12 \u03bcm in thickness and successfully generated high-resolution images at a range of two meters underwater using 8 \u00d7 8 and 6 \u00d7 6 arrays \\[[@b9-sensors-15-02538]\\]. Another piezoelectric micro-fabricated ultrasound transducer (pMUT) structure driven by a sol-gel-deposited PZT layer up to 4 \u03bcm thick was built, tested, and simulated by Muralt *et al.* \\[[@b10-sensors-15-02538]\\]. However, the piezoelectricity of the sol-gel PZT film is not as good as that of PZT ceramic, so the performance of the"
-"Background\n==========\n\nThe genus *Mycobacterium*includes species found in a wide range of ecological niches. *M. tuberculosis*, *M. leprae*, and *M. avium*subsp. *paratuberculosis*, are pathogenic species causing clinical disease in humans or animals. Other species as *M. smegmatis*and *M. phlei*are saprophytes. In addition, an intermediate position is occupied by species opportunistic pathogens such as *M. fortuitum*, a rapidly growing mycobacteria that is ubiquitous in soil and water. This mycobacteria is known to cause cutaneous infection, typically in association with trauma or clinical procedures \\[[@B1],[@B2]\\]. Due to its capacity to growth and to survive intracellularly, *M. fortuitum*has been previously used as a model for studying the intracellular killing of mycobacteria \\[[@B3],[@B4]\\].\n\nMost bacteria, when exposed to toxic oxygen metabolites, exhibit an adaptive response and express several genes involved in detoxification of oxygen reactive species, such as superoxide dismutases (SOD), catalases and peroxidases \\[[@B5],[@B6]\\]. This type of adaptative response has been implicated in the intracellular survival of pathogenic mycobacteria, promoting their maintenance in the host \\[[@B7]-[@B9]\\].\n\nThe major pathogen, *M. tuberculosis*, produces an iron co-factored SOD encoded by the gene *sod*A \\[[@B10]\\] and a copper and zinc SOD encoded by the gene *sod*C \\[[@B11]\\] whose involvement in protection against oxidative stress of *M."
-"1. Introduction {#sec1}\n===============\n\nFor topical application of active agents various novel carrier systems were explored till date in the form of microparticles, nanoparticles, liposomes and cochleates, and so forth. Food and Drug Administration (FDA) has approved wide range of products like Retin-A, Carac cream, MicroPeel Plus, and oil control lotion due to improved efficacy and safety compared to the conventional topical drug delivery systems. Typically, such products form a highly concentrated layer of active ingredients on the skin which results in skin irritation and toxicity \\[[@B1]--[@B4]\\].\n\nAt present, the need of an exclusive delivery system has been required for the topically active sunscreen agents. Microsponge is sponge-like porous polymeric system in the range of 10--25\u2009*\u03bc*m with extended release of drug. It offers increased payload of drug and stability with reduced irritation, mutagenicity, allergenicity, and side effects for the topical applications. Due to these undue advantages, in the current era of topical products, microsponge has got wide acceptance. Microsponge for topical route has been reported for the controlled release of benzyl peroxide, mupirocin, retinoid, and 5-fluorouracil which reported minimal penetration through dermis, less drug accumulation, and irritation without sacrificing the efficacy of drug \\[[@B5]--[@B7]\\].\n\nThe ultraviolet (UV) rays responsible"
-"Introduction {#S0001}\n============\n\nBreathlessness, fatigue, and cough/sputum are the most common symptoms in COPD \\[[1](#CIT0001),[2](#CIT0002),\\] and are also prevalent in lung cancer (LC) \\[[3](#CIT0003)\\]. Patients with head- and neck cancer (HNC) suffer from fatigue and cough and to some degree also dyspnea \\[[4](#CIT0004),[5](#CIT0005),\\]. Smoking is a known risk factor for both LC and HNC, thus making COPD a common comorbidity in both diseases \\[[6](#CIT0006),[7](#CIT0007),\\].\n\nStudies have shown a negative correlation between a number of comorbidities, including COPD, and survival of both HNC and LC \\[[8](#CIT0008),[9](#CIT0009),\\]. A recent study from Norway comprising 174 patients newly diagnosed with LC found that the prevalence of concomitant COPD or emphysema was 69% \\[[10](#CIT0010)\\]. Among the 212 patients with either LC or HNC examined for inclusion in the present study, the prevalence of COPD was 54% (69% of those with LC and 25% with HNC) \\[[11](#CIT0011)\\].\n\nCOPD is widely underdiagnosed and under-treated and it is estimated that there are between 3- and 400.000 patients with COPD in Denmark, of which approximately 100.000 receive medical treatment \\[[12](#CIT0012)\\]. Smoking cessation is the most powerful intervention for changing disease progression and prognosis, however, symptomatic patients will normally require treatment with bronchodilators. Pharmacotherapy for COPD is used to reduce"
-"Background {#Sec1}\n==========\n\nDiabetes mellitus currently afflicts 171 million people worldwide and its prevalence continues to rise \\[[@CR1], [@CR2]\\]. The adverse cardiovascular consequences of diabetes mellitus are recognized by the accelerated rate of atherosclerosis, predisposing patients to coronary artery disease, myocardial infarction, and death \\[[@CR3], [@CR4]\\].\n\nAngiotensin-converting enzyme inhibitors (ACE) has been repeatedly shown to decrease cardiovascular mortality in the diabetic population \\[[@CR5]\\]. Angiotensin-receptor blockers (ARB) were developed for patients intolerant of ACE inhibitors and have similarly shown to reduce major cardiovascular disease outcomes \\[[@CR6]\\]. Telmisartan, in particular, has been shown to be equivalent to ACE inhibitors in providing cardiovascular protection in high-risk heart failure patients, particularly the diabetic population \\[[@CR7], [@CR8]\\]. It has been postulated that telmisartan may attenuate the myocardial injury in DM patients sustaining an MI. The anti-apoptotic, anti-fibrotic and angiogenic effects of telmisartan with the modulatory role on peroxisome proliferator-activated receptor gamma (PPAR\u03b3) may contribute to the microvasculature of the peri-infarct region to salvage the injured myocardium, reduce the remodeling of the myocardium and improve cardiac function \\[[@CR9]\\].\n\nThe distinction between reversible and irreversible myocardial injury within the region at risk is imperative since the selection of an appropriate therapy can alter the overall mortality and"
-"1. Introduction {#sec1}\n===============\n\nSarcomas are malignant tumors of mesenchymal origin, including bones, muscles, fat, nerves, and blood vessels. According to the Surveillance Epidemiology and End Results (SEER) database, prevalence of sarcoma accounts for nearly 21% of all pediatric solid malignant tumors and less than 1% of all adult solid malignant tumors \\[[@B1]\\]. It was estimated that approximately 11,400 Americans would be diagnosed with soft tissue sarcomas and 3,000 with bone sarcoma in 2013 \\[[@B2]\\]. Based on the survival data obtained from the National Cancer Data Base of the American College of Surgeons, the relative 5-year survival rate is approximately 66% for patients with bone and soft tissue sarcomas, 53.9% for osteosarcomas (*n* = 8,104), 75.2% for chondrosarcoma (*n* = 6,476), and 50.6% for Ewing\\'s sarcomas (*n* = 3,225) \\[[@B3]\\]. According to the classification by the World Health Organization, the group of bone and soft tissue sarcomas includes more than 100 histological subtypes \\[[@B4]\\]. The prognosis of patients with bone and soft tissue sarcomas is associated with histological diagnoses \\[[@B5]\\]. Standard treatment modalities include surgical resection, chemotherapy, and often radiotherapy \\[[@B6]--[@B8]\\]. Despite these multimodality therapies, survival rates have not been improved over recent 20 years \\[[@B9]\\]. Therefore, new effective treatment"
-"All relevant raw data are in the Supporting Information files.\n\nIntroduction {#sec001}\n============\n\nIn order to manage or conserve migratory birds and other wildlife, it is essential to consider the complete annual cycle by making spatial connections between key breeding, migration and wintering sites \\[[@pone.0135938.ref001]\\]. While such migratory connections are poorly known for most of the world's migratory birds, recent development of increasingly sophisticated and light weight tracking devices are moving the field forward at a rapid rate \\[[@pone.0135938.ref002]\\]. In particular, light-sensitive geologgers have been miniaturized to now be used effectively in studies of small (\\~15g) passerines but require recapture, and can have significant error especially during the equinox \\[[@pone.0135938.ref003], [@pone.0135938.ref004]\\]. Within this scenario, the use of intrinsic markers and particularly the analysis of stable isotopes in feathers has emerged as a powerful contribution to the ecologist's toolbox by providing a relatively cheap method to describe migratory patterns and population connectivity \\[[@pone.0135938.ref005]\\]. Feathers are metabolically inert following formation and their isotopic composition thus reflects isotopic values derived from foodwebs at areas of growth. Isotopic values in foodwebs, in turn, can vary spatially in a predictable fashion creating isoscapes that can be a useful means of inferring origins of birds later"
-"1. Introduction {#sec1-ijms-19-03626}\n===============\n\nBenzo\\[*\u03b1*\\]pyrene (B\\[*\u03b1*\\]P) is a prototypical polycyclic aromatic hydrocarbon (PAH) that is formed by incomplete combustion of organic materials. It is found in large amounts in diet, air pollution, cigarette smoke and some occupational atmospheres \\[[@B1-ijms-19-03626]\\]. Human exposure to this widespread environmental contaminant has been correlated to various pathological situations such as cancer development, and inflammation contributing to cardiovascular and pulmonary diseases \\[[@B2-ijms-19-03626],[@B3-ijms-19-03626]\\]. Therefore, B\\[*\u03b1*\\]P has been classified as a priority toxicant by the United States Environmental Protection Agency, the World Health Organization and the European Union. Most of the B\\[*\u03b1*\\]P-related toxic effects have been linked to the activation of the aryl hydrocarbon receptor (AhR) and its subsequent binding to specific xenobiotic responsive elements within the promoter of responsive genes \\[[@B4-ijms-19-03626]\\]. For example, the activation of the AhR-related signaling pathway by B\\[*\u03b1*\\]P results in the up-regulation of xenobiotic metabolizing enzymes such as cytochromes P-450 (CYPs) 1A1, 1A2 and 1B1; this in turn bioactivates B\\[*\u03b1*\\]P into epoxide derivatives that largely account in a major way for carcinogenic effects in several organs such as lung, liver and lymphoid tissue \\[[@B5-ijms-19-03626]\\].\n\nAmong cell types targeted by B\\[*\u03b1*\\]P, lymphocytes, in particular T cells which express AhR and possess a CYP1-metabolizing system"
-"INTRODUCTION\n============\n\nBone is an important organ to perform exercise by support the body and has various functions such as a store for calcium and other minerals which is essential for sustaining life, and hematopoietic action creating new blood \\[[@b1-jenb-18-1-69]\\]. In addition, bone is a highly active tissue in the body, which is sensitive to external mechanical stimuli as well as internal metabolic changes. So it occurs changes in bone mineral density (BMD) and bone metabolism. These changes in bone metabolism are influenced by the environmental factor such as gene \\[[@b2-jenb-18-1-69]\\] and nutrition \\[[@b3-jenb-18-1-69]\\], and the exercise do the most important role to increase and maintain bone mass in particular \\[[@b4-jenb-18-1-69]\\]. That is, the inactivity environment such as space flight \\[[@b5-jenb-18-1-69]\\] or weightlessness \\[[@b6-jenb-18-1-69]\\] stimulates to reduce bone mass, but it is known that regular exercise is suitable to maintain or increase bone mass \\[[@b7-jenb-18-1-69]\\]. Nuti *et al*. \\[[@b8-jenb-18-1-69]\\] also prove that even the period of growth and the adolescence, elderly group has a different form of exercise, exercise is effective on enhancing BMD. However, most of the research is usually focused on \\'phenomena\\' that reveal a degree of changes in BMD as the effects of exercise, but it is"
-"![Credit to Stanford School of Medicine.](autopsy-03-01001-g01){#g01}\n\nRonald F. Dorfman (1923-2012), an Emeritus Professor of Pathology at the Stanford University School of Medicine, had significant input in advancing the study of diseases of hematopoietic cells and the lymph nodes, which included identifying a disease that has been named after him. Dr. Dorfman was one of the founders of the field of Hematopathology, and, with Dr. Costan Berard, founded the Society of Hematopathology in 1981, serving as its president from 1982 through 1984, and published a classification of non-Hodgkin lymphomas in 1974,[@B001] which was a variant of the Rappaport classification.[@B002]\n\nDr. Dorfman was born in Johannesburg, South Africa, on March 14, 1923 and studied medicine at the University of the Witwatersrand. From 1944 to 1946 his medical studies were suspended due to his military service during World War II. In 1948, he received his medical degree and completed medical and surgical internships and residencies at the Johannesburg General Hospital. After that, he went to England, to obtain his MD in Internal Medicine at the Royal Postgraduate Medical School and Hammersmith Hospital. At one point, he concluded that clinical medicine was not his passion and switched to pathology, initially in London and subsequently"
-"Introduction {#s1}\n============\n\nAdolescence is a sensitive period in which person faces some biological changes associated with puberty, increased pressure for social integrity, challenges of new roles, future adulthood related stressors, conflicts with peers and so other problems that can produce stress.\\[[@R1]\\] Forty to 70 percent of adolescents experience one or more stressful events during the teenage period.\\[[@R2]\\] According to Lazarus and Folkman, stress is defined as a relationship between the person and the environment that is appraised by the person as relevant to his or her well-being and in which the person's resources are taxed or exceeded.\\[[@R3]\\]\n\nAn individual will only perceive a situation as stressful if it is an issue for this person and if this person feels that it threatens or surpasses his/her internal or external resources.\\[[@R4]\\] Depending on how an individual perceives the situation, he/she will choose certain coping strategies (CS) over others. These strategies may facilitate adaptation at a later stage.\\[[@R3]\\]\\[[@R4]\\]\n\nAdolescents more readily tend to engage in experiences or encounter situations that are stressful and associated with developing emotional and behavioral problems. Teenagers are also at the stage of developing their personal styles of coping. The CS can be reviewed, modified if needed and"
-"Introduction {#Sec1}\n============\n\nAffecting about 50 million people worldwide, epilepsy has in recent years been recognized as a serious public health concern^[@CR1]^. More than 30% of patients with epilepsy continue to experience seizures despite adequate treatment with antiepileptic therapy^[@CR2]^. Approximately 25% of all cases of refractory focal epilepsy are categorized as frontal lobe epilepsy (FLE). Abnormal neuronal connections are increasingly postulated as a crucial factor in the pathogenesis of epilepsy^[@CR3]^.\n\nFollowing temporal lobe epilepsy (TLE), FLE has long been considered the second most prevalent type of the focal epilepsies^[@CR4]^. In FLE, seizures originate in the frontal lobe, but the clinical symptoms of these seizures are variable and dependent on the brain regions involved or the functional networks impacted^[@CR5]^, although most are recognized as multi-cognitive defects and motor-related abnormality networks^[@CR6]^. Additionally, the interictal discharges arising from a unilateral focus in frontal lobe are more likely to spread to both hemispheres and result in secondary bilateral synchrony^[@CR7]^. These phenomena implicate abnormality in multiple functional systems in FLE patients.\n\nThe clinical outcome of FLE is also widely variable. It is reported that, of all patients whose long-term seizure-free outcome has been reported, those with isolated FLE represent approximately 11%^[@CR8]^. There is also considerable"
-"Introduction\n============\n\nGeranylgeranoic acid (GGA), a 20-carbon polyprenoic acid (all-*trans* 3,7,11,15-tetramethyl-2,4,6,10,14-hexadecapentaenoic acid) consisting of 4 isoprene units and its derivatives were historically developed as synthetic \"acyclic retinoids\" by screening for their ability to bind to cellular retinoic acid-binding protein^([@B1])^ as well as to nuclear retinoid receptors,^([@B2])^ which exert transcriptional activation of certain hepatocyte-specific genes in hepatoma cells.^([@B3])^ 4,5-Didehydro GGA, one of the most potent acyclic retinoids, has been reported to prevent chemically induced and spontaneous hepatocarcinogenesis in animals.^([@B4],[@B5])^ Further, the efficacy of 4,5-didehydro GGA in preventing second primary hepatoma was proven in a placebo-controlled double-blinded and randomized phase II clinical trial using postoperative hepatoma patients, with few side effects observed.^([@B6])^ Later, it was revealed that the oral administration of the polyprenoic acid for 12 months significantly increased the 5-year survival rate in these patients after a radical therapy for primary hepatoma.^([@B7])^\n\nAlthough GGA, an acyclic retinoid, shares characteristics of natural cyclic retinoids *in vitro*, GGA also apparently differs from natural retinoids such as all-*trans* and 9-*cis* retinoic acids in the following respects: 1) GGA up-regulated albumin mRNA expression in human hepatoma-derived cell lines, HuH-7 and PLC/PRF-5, whereas all-*trans* retinoic acid down-regulated it;^([@B3])^ 2) GGA was much less toxic than natural"
-"Background {#Sec1}\n==========\n\nAccording to the World Health Organization, tuberculosis is a global public health problem and about one-third of the world's population is infected \\[[@CR1]\\]. In Morocco, 26,000 to 27,000 new cases of all forms of tuberculosis are detected annually and extra pulmonary tuberculosis accounts for 46% of tuberculosis cases, dominated by lymph node tuberculosis \\[[@CR2]\\]. In rare cases, tuberculosis and cancer can be detected at the same time, creating a real therapeutic challenge. Not only in Morocco, Africa, but all over the world and especially in Eastern Europe and the greater part of Asia, surgical and medical oncologists as well as pathologists should be aware of the possibility and associated treatment sequence.\n\nCase presentation {#Sec2}\n=================\n\nWe hereby present the rare case of a 29-year-old white woman married for 5\u2009years gravida 1 para 1 without significant personal or family history who found during breast self-examination a left breast mass. Then she went to a high medical center where she received breast ultrasound and a mammogram that revealed the presence of a left breast cancer classified 5 in the Breast Imaging Reporting And Data System of the American College Of Radiology, that is to say highly suggestive of"
-"###### Strengths and limitations of this study\n\n-   Administrative data permitted the undertaking of a large long-term evaluation of a policy, which otherwise would have been very costly and indeed, perhaps infeasible.\n\n-   Data were available for over 70% of the practices in Scotland, which could be used to classify those who did and did not experience a change in prescription fees.\n\n-   The data were only available at the general practice, not the individual level.\n\n-   The time series for both admissions and prescriptions were highly variable, preventing the drawing of specific conclusions from the evaluation.\n\nIntroduction {#s1}\n============\n\nWhen the National Health Service (NHS) was founded in the UK in 1948, all the services provided were free. However, as early as 1950 expenditure was higher than expected, so a charge (1 shilling) for prescribed items (including medicines, medical devices, dressings, borderline substances, etc) was introduced in 1952.[@R1] This prescription fee has increased over time and now in England the charge is \u00a38.80 per item.[@R2] In 1968 a list of medical conditions for which no prescription fee would be charged was introduced; these were easily recognisable, lifelong, life-threatening conditions that required regular, prescribed medication.[@R1] Over time further exemptions were"
-"1. Case report {#sec0005}\n==============\n\nA 23-year-old African American woman developed an abscess in the right anterior chest wall just lateral to the sternum 1 month after a normal vaginal delivery under epidural anesthesia. She was admitted elsewhere and underwent incision and drainage of the abscess. A culture from the abscess grew MRSA sensitive to vancomycin (MIC less than 1), trimethoprim-sulfamethaxazole, clindamycin, tetracycline, and linezolid. She received intravenous vancomycin (MIC less than 1) for 10 days with apparent resolution. The abscess recurred in the same location 7 and 15 months after the initial episode. These recurrences were managed with incision and drainage, and oral trimethoprim-sulfmethoxazole. Cultures of the drainage consistently grew MRSA with the same susceptibility pattern. The patient reported that the wound healed with treatment each time.\n\nNineteen months after the initial episode, the abscess recurred and she was seen in our emergency department. Computerized tomography of the chest showed right upper and middle lobe parenchymal abnormalities suggestive of granulomatous infection, paraspinal abscess formation, periosteal thickening and osseous changes involving the 3rd to 6th vertebral bodies and right 3rd rib. She noted a mild cough. She denied back pain and neurological symptoms. Incision and drainage was performed and she"
-"All relevant data are within the paper and its Supporting Information files.\n\nIntroduction {#sec001}\n============\n\nUDP-glycosyltransferase (UGT) catalyzes the transfer of glycosyl groups (including glucuronic acid, glucose, glycoside, and galactose) to exogenous or endogenous chemicals \\[[@pone.0205266.ref001]\\]. Vertebrate UGT genes are classified into 5 groups: 1, 2, 3, 5, and 8 \\[[@pone.0205266.ref002]--[@pone.0205266.ref004]\\]. In each UGT subfamily, genes were amplified by tandem duplication, with some of them specifically amplified (or even absent) of in lineages. For instance, UGT5 family genes are only in teleost fishes \\[[@pone.0205266.ref003]\\], while the UGT3 family is absent in chicken, turkey, and zebra finch \\[[@pone.0205266.ref004]\\], suggesting that avian species have 3 UGT families (UGT1, UGT2, and UGT8). Among these UGT enzymes, UGT1, UGT2, and UGT5 family enzymes were reported to catalyze the exogenous chemicals in zebrafish \\[[@pone.0205266.ref005]\\]. UGT1 and UGT2 family enzymes are known to be related to xenobiotic metabolism in mammals as well\\[[@pone.0205266.ref006]\\]. Therefore, UGT1 and UGT2 enzyes would be considered to be related to xenobiotic metabolism also in avian species.\n\nUGT1 enzymes use UDP-glucronic acid (UDPGA) to engage in glucronic-acid transfer \\[[@pone.0205266.ref001], [@pone.0205266.ref006]\\]. Functional differences in UGT1As derive from a variable first exon among the 5 exons that constitute these genes (exon2-5 are conserved), with a"
-"Introduction {#Sec1}\n============\n\nAsthma and obstructive sleep apnea (OSA) may coexist^[@CR1]^ to result in an overlap syndrome^[@CR2]^ where a bidirectional relationship may deleteriously affect each other^[@CR3]^. At least 5% of the general population suffer from asthma^[@CR4],\\ [@CR5]^; Center for Disease Control and Prevention estimates the prevalence of asthma at 7.7% (6.3% in males and 9% in females)^[@CR6]^. On the other hand, OSA is an under-diagnosed condition^[@CR7]^. In a general population survey, of the 451 individuals who were invited to participate in sleep study, only 3.6% had OSA diagnosis but 24% had mild, 12.5% moderate, and 2.9% had severe OSA^[@CR8]^. In a larger population sample of 2121 individuals, 84% men and 61% women had mild, and 50% men and 23% women were found to have moderate OSA^[@CR9]^. More recently, Senaratna *et al*.^[@CR10]^ after reviewing 24 relevant studies have estimated the prevalence of OSA ranging between 9% to 38%. These authors also found this disease more common in men^[@CR11]^.\n\nAsthma is a common respiratory disorder with complex interactions between airflow obstruction, hyper-responsiveness, reversible expiratory flow limitation and inflammation^[@CR11]^, whereas OSA is characterized by snoring and interruptions in breathing during sleep with symptoms such as brief paroxysmal nocturnal dyspnea, choking during sleep, and"
-"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"
-"Published: August 13, 2019\n\nIntroduction {#sec1}\n============\n\nAging is characterized by a decline in metabolic and physiological functions of all organs within the body. A hallmark feature of aging is the progressive loss of skeletal muscle mass and function that can progress to sarcopenia, which is associated with significant morbidity and mortality and substantial healthcare costs ([@bib38], [@bib60]). Exercise is considered a frontline modality to combat age-related muscle decline ([@bib13]). However, nutritional strategies may also offer an effective countermeasure to age-associated morbidities and promote healthy muscle aging ([@bib6]).\n\nNicotinamide adenine dinucleotide (NAD^+^) homeostasis is critical to cell and organismal function. In addition to its classical role in redox metabolism, NAD^+^ is a substrate for enzymes such as sirtuins, poly-ADPribose polymerases (PARPs), and cyclic ADPribose synthetases that regulate key cellular processes of energy metabolism, DNA damage repair, and calcium signaling ([@bib71]). Improving NAD^+^ availability via the supplementation of the NAD^+^ precursor nicotinamide riboside (NR) ([@bib5], [@bib63]) has emerged as a potential strategy to augment tissue-specific NAD^+^ homeostasis and improve physiological function ([@bib22]). A range of physiological stresses associated with the depletion of NAD^+^ and/or nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) have been ameliorated with NR supplementation in mice, including prevention of"
-"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"
-"INTRODUCTION\n============\n\nChilling processes of livestock carcasses is one of the most important factors that affect product quality and is employed to ensure food safety, extend shelf-life, and reduce shrinkage ([@b27-ajas-25-8-1197-19]). Conventional carcass chilling is a lengthy, energy-expensive process ([@b13-ajas-25-8-1197-19]) and introduces extra microbial hazards and increases evaporative weight loss ([@b14-ajas-25-8-1197-19]). RC can increase production efficiency by decreasing the required chilling time and lowering evaporative loss ([@b13-ajas-25-8-1197-19]). However, RC may decrease tenderness and increase the variation in tenderness, both of which influence consumer's satisfaction for beef palatability ([@b22-ajas-25-8-1197-19]; [@b27-ajas-25-8-1197-19]; [@b33-ajas-25-8-1197-19]). Many studies also reported that RC has detrimental effect on beef color, resulting in darker meat color ([@b13-ajas-25-8-1197-19]; [@b2-ajas-25-8-1197-19]) and reducing purchase desire of consumers.\n\nAlthough China has become the third-largest beef producer in the world, some techniques such as electrical stimulation are not used broadly and the tenderness of beef product need to be increased urgently, so the processing technology of beef in China appeals for further improvement. The effects of RC and ES on beef quality of Chinese Yellow crossbred bulls have been reported ([@b16-ajas-25-8-1197-19]), however, the effects on meat color have not been reported and mechanisms of tenderizing were not investigated extensively.\n\nIt is generally accepted that"
-"Introduction {#section1-2050313X19882843}\n============\n\nLupus erythematosus is an autoimmune disease that can be skin limited or systemic. Discoid lupus erythematosus (DLE) is the most common variant of cutaneous lupus. While it has a lower chance (5%--10% life time) compared to other subtypes to progress to systemic forms, it has significant morbidity because of its tendency to involve cosmetically important areas such as the face and scalp and resulting disfiguring scarring alopecia.^[@bibr1-2050313X19882843]^ Similar to other subtypes of lupus, DLE is most commonly seen in women and in the third to fourth decade of life.^[@bibr2-2050313X19882843]^ DLE typically presents as erythematous to violaceous papules or plaques that eventually develop scales, follicular plugging, central hypopigmentation and scarring in photo-distributed areas.^[@bibr3-2050313X19882843]^ A localized form of the condition occurs in 80% of the patients with lesions developing solely on the face, ears, and/or scalp and 20% of patients present a disseminated form of the disease defined by the presence of lesions beyond the head and neck area.^[@bibr2-2050313X19882843]^ Rarely, discoid and other forms of cutaneous lupus may present in linear fashion following the lines of embryologic migration (lines of Blaschko).^[@bibr4-2050313X19882843]^ We report, the first to our knowledge, case of linear lupus with *en coup de saber* presentation clinically"
-"Introduction {#Sec1}\n============\n\nHigh mass loading and fast charge transport are at the heart of electrochemical energy storage^[@CR1]--[@CR3]^. The former is crucial for high energy per device, and the latter for high power^[@CR4]^. Low-cost, high-capacitance, and environment-benign pseudocapacitive MnO~2~ are loaded on electrically conductive supports and used as supercapacitor electrodes with a theoretical limit of 1367\u2009F\u2009g^\u22121^ (based on a potential window of 0.8\u2009V)^[@CR5]--[@CR9]^. Toward commercialization, the mass loading of the total active materials must be at least 5\u2009mg\u2009cm^\u22122[@CR10]^. However, high mass loadings often lead to thick and dense layers of insulating MnO~2~ (10^\u22125^\\~10^\u22126^\u2009S\u2009cm^\u22121^) on the supports^[@CR11]--[@CR14]^. Consequently, the internal resistance increases and the ion diffusion is perturbed, resulting in sluggish charge transport---both electron conduction and ion diffusion^[@CR5],[@CR11],[@CR15]^. Here we innovate the design of porous carbon fiber (PCF) as a lightweight, flexible, binder-free, and conductive-additive-free support for MnO~2~. Using the disparate concept of block copolymer microphase-separation to generate uniform mesopores in PCFs, we have bridged the two mutually exclusive characteristics, *i.e*., high mass loadings and ultrafast electron/ion transport.\n\nAn ideal support for MnO~2~ and other transition metal oxides (RuO~2~, NiO, WO~3~, and Fe~2~O~3~, etc.) needs the characteristics of (1) lightweight, (2) large surface areas"
-"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"
-"1. Introduction {#sec1-cancers-12-00229}\n===============\n\nRASSF1A, which is a well described tumour suppressor, is one of the most commonly deregulated genes in human cancers \\[[@B1-cancers-12-00229]\\]. RASSF1A is a scaffold protein member of the C-terminal RASSF family \\[[@B2-cancers-12-00229]\\] and is encoded by the *RASSF1* gene \\[[@B2-cancers-12-00229],[@B3-cancers-12-00229]\\]. This gene expresses eight isoforms due to alternative splicing, and RASSF1A along with RASSF1C are the most abundantly expressed isoforms. RASSF1A is a signalling hub that plays an important role in signal transduction, where it seems to mediate a complex network that includes the ERK, Hippo, apoptotic and p53 subnetworks \\[[@B3-cancers-12-00229]\\]. RASSF1A is also a downstream effector of KRAS mediating the antiproliferative signal that is triggered by the activation of this proto-oncogene \\[[@B4-cancers-12-00229]\\]. The RASSF1A signalling network (SN) can mediate the regulation of different biological functions, such as apoptosis, cell cycle arrest, regulation of the microtubule network, migration, and autophagy \\[[@B3-cancers-12-00229],[@B5-cancers-12-00229],[@B6-cancers-12-00229]\\]. Unsurprisingly, the deregulation of RASSF1A function results in the development of different pathologies, including cancer and cardiovascular diseases \\[[@B7-cancers-12-00229]\\]. However, we still have a very patchy picture of the RASSF1A SN (particularly its upstream regulators) and how this tumour suppressor inputs different signals to effector pathways.\n\nThe study of RASSF1A at the molecular level and"
-"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"
-"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"
-"The ethics requirements of the committees that approved this study, and the partnership agreement made with school administrators, require that the data be kept by the authors. Therefore, all data are available from the corresponding author, Dr. Javier G. Ogembo (<javier.ogembo@umassmed.edu>), University of Massachusetts Medical School, for researchers who meet the criteria for access.\n\nIntroduction {#sec001}\n============\n\n> *\"If you want the truth*, *ask a child...\"*\n>\n> ---Portion of Danish proverb (Sandheden skal man h\u00f8re fra b\u00f8rn)\n\nRegistration of a child's birth is one of the more fundamental, far reaching, and troublesome, steps for securing the health and happiness of a society \\[[@pone.0149925.ref001]\\]. Registration is noted as a vital, basic human right. It allows children to be counted and acknowledged by a government, and is the first line of protection for shielding children from underage labor, marriage, prostitution, trafficking, and military conscription \\[[@pone.0149925.ref002], [@pone.0149925.ref003], [@pone.0149925.ref004]\\]. Registration, *and increasingly having a physical birth certificate*, is also vital to ensure that children receive access to healthcare or vaccination \\[[@pone.0149925.ref005], [@pone.0149925.ref006], [@pone.0149925.ref007]\\], and is required for many children to enter schooling, travel, gain employment; and therefore is directly tied to their own, and their communities,' health and future development.\n\nAt the same"
-"Introduction {#s1}\n============\n\nSelf-incompatibility (SI) is a widespread genetic system in many flowering plants which serves to prevent self-fertilization and maintain genetic diversity. It is based on self/non-self pollen--pistil recognition interactions followed by inhibition of self-pollen hydration, germination, or pollen tube growth.\n\nIn the Brassicaceae, SI is sporophytically controlled by a multiallelic locus termed the *S* locus ([@CIT0002]). Male and female determinants have been identified as SP11/SCR (*S*-locus protein 11/*S*-locus cysteine-rich) ([@CIT0038]; [@CIT0049]) and SRK (*S* receptor kinase) ([@CIT0047]), respectively. When a compatible pollen grain lands on the stigma, it swells and a pollen tube is allowed to grow, whereas when self-pollen attaches to the stigma, SP11/SCR binds specifically to the extracellular domain of SRK of the same *S*-haplotype ([@CIT0050]), which triggers an SI signalling pathway to reject self-pollen. Another stigmatically expressed gene located at the *S* locus, *S* locus glycoprotein (*SLG*) ([@CIT0028]; [@CIT0048]), has been shown to enhance the recognition process between self-pollen and stigma ([@CIT0047]); however, this function of *SLG* remains controversial ([@CIT0040]). A recent study suggested that the plants in the Brassicaceae genus Levenworthia use paralogous *SRK* and *SP11/SCR* genes, *Lal2* (*Leavenworthia alabamica SRK-related 2*) and *SCRl* (*SCR-like*), for self/non-self recognition in SI, but the function of"
-"1. Introduction {#sec1-nutrients-12-00978}\n===============\n\nSkeletal muscle atrophy and loss of strength is frequently observed and correlated with poor outcomes in patients with cancer \\[[@B1-nutrients-12-00978]\\]. We previously reported that low volume of skeletal muscle at diagnosis is associated with worse survival in patients with hematological malignancies \\[[@B2-nutrients-12-00978],[@B3-nutrients-12-00978]\\]. Recently, metabolomics analysis has been used to understand how amino acid profiles are affected by glucose metabolism \\[[@B4-nutrients-12-00978]\\], aging \\[[@B5-nutrients-12-00978]\\], and cancer \\[[@B6-nutrients-12-00978]\\]. Toyoshima et al. \\[[@B7-nutrients-12-00978]\\] have reported an association between plasma amino acid profiles and age-related sarcopenia, and demonstrated that sarcopenia was correlated with lower tryptophan (Trp) and histidine (His) and higher glutamine (Gln) and proline (Pro) concentrations. Furthermore, plasma Trp and His concentrations are often reduced in patients with particular types of cancer \\[[@B8-nutrients-12-00978]\\]. These findings suggest that Trp may be a key essential amino acid associated with cancer-related sarcopenia; hence, analysis of serum Trp levels may help improve our understanding of the mechanisms underlying sarcopenia in patients with cancer.\n\nTrp is involved in two important metabolic pathways, namely, kynurenine and serotonin synthesis pathways \\[[@B9-nutrients-12-00978]\\]. Most of Trp degradation occurs through the kynurenine pathway. Indoleamine 2,3-dioxygenase (IDO) is involved in the first and rate-limiting step of Trp metabolism, which produces kynurenine"
-"INTRODUCTION\n============\n\nTo understand cellular responses to endogenous genotoxic stress, it is important to have insight into the DNA repair process known as base excision repair (BER). BER is involved in repairing base lesions and single-strand breaks that occur thousands of times during the average mammalian cell cycle ([@B1; @B2; @B3]) and is generally considered to involve two subpathways defined by the size of the repair patch and the enzymes involved ([@B4; @B5; @B6; @B7]). These subpathways are termed single-nucleotide (SN) BER and long-patch (LP) BER. As these names imply, in SN BER one nucleotide in the damaged strand is excised and replaced ([@B8; @B9; @B10; @B11]), whereas LP BER excises and replaces several nucleotides in the damaged strand ([@B6],[@B9]). LP BER appears to be a backup subpathway in cases where the SN BER system stalls or where the DNA lesion is refractory to the enzymatic steps of the SN BER subpathway ([@B6],[@B9],[@B12; @B13; @B14]).\n\nComponents of the BER system are constitutively expressed in mammalian cells, but also exhibit widely divergent tissue-specific expression levels plus up- or down-regulation after genotoxic stress and cytokine exposure ([@B15; @B16; @B17; @B18; @B19; @B20]). This dynamic regulatory picture suggests the potential for cell type"
-"I. Introduction\n===============\n\nThe number of cases of carcinoma of the lips and oral cavity worldwide was about 300,000 in 2012, or 2.1% of all carcinomas that year[@B1][@B2]. Among them, squamous cell carcinoma was most common among males aged over 60 years who drank and smoked[@B3][@B4][@B5]. In recent years, however, the incidence has been increasing in women 40 years and below who do not have these same cancer risk factors[@B6][@B7][@B8].\n\nOral squamous cell carcinoma (OSCC) is treated with surgery, radiotherapy, and chemotherapy, often in combination. For patients in early TNM stages I and II, the effect of a single surgical treatment or radiotherapy was not statistically significant[@B9]. However, for patients in a more advanced TNM stage (III or IV), the combination of surgical and radiotherapy showed the best therapeutic effect[@B10].\n\nThe TNM staging, especially for lymph node metastasis, is the scoring system most widely used among prognostic factors for patient survival[@B11][@B12]. Several biomarkers have been studied as serologic markers, but their specificity is low and clinical applications are difficult[@B13]. It is essential that clinicians discover effective and clinically efficient biomarkers as prognostic factors for OSCC.\n\nIn studies conducted over the last few decades, platelet activation has been considered an important"
-"Introduction {#S1}\n============\n\nDysregulation of fibrous connective tissues in fibroproliferative diseases is a leading cause of morbidity and mortality in developed countries with about 45% of deaths attributed to such disorders \\[[@R1]\\]. Alterations in vascular remodeling and angiogenesis are associated with fibrotic processes in different organs \\[[@R2]--[@R5]\\], and systemic sclerosis is correlated with progressive disappearance of blood vessels in the skin \\[[@R6]\\]. Recently, it has been reported that high levels of vascular endothelial growth factor A (VEGF) aggravates fibrosis in experimental animal models and stimulates collagen production by cultured fibro-blasts isolated from the skin of systemic sclerosis patients \\[[@R7]\\]. Understanding how such VEGF activities can be reconciled with the disappearance of skin blood vessels during progression of fibrosis in vivo, is problematic without deeper insights into molecular mechanisms responsible for regulating interactions between endothelial and fibroblastic cells, inflammatory cells and macrophages in physiological connective tissue homeostasis.\n\nFor several reasons, studies of the receptor ANTXR1 \\[[@R8]--[@R11]\\], also known as TEM8 \\[[@R12]\\]; are likely to provide such insights. In vitro data suggest that TEM8 has a role in adhesion, spreading and migration of cells through its interaction with extracellular matrix (ECM) components \\[[@R13]--[@R16]\\]. Expression in different cell types and the existence of"
-"Introduction\n============\n\nElderly people make up an increasingly growing proportion of patients in ophthalmologists' practices. On average, every third patient over the age of 65 is suffering from sight problems.[@b1-cia-11-407] The global number of older people (aged \u226560 years) increased from 9.2% in 1990 to 11.7% in 2013 and will continue to grow as a proportion of the world population, reaching 21.1% by 2050. Globally, this number is expected to more than double from 841 million people in 2013 to more than two billion in 2050. Presently, about two-thirds of the world's older people live in developing countries.[@b2-cia-11-407] Extended life expectancy results mainly from the promotion of a healthy life style, a reduced number of smokers, and greater involvement of patients in disease prevention, namely their participation in screening tests.[@b3-cia-11-407] Advances in medicine including access to high-tech diagnostic procedures, therapies, and surgical equipments also cannot be overestimated. Currently, the beginning of the old age is defined by the World Health Organization as 60 years of age.\n\nGeneral health\n==============\n\nWhen performing surgery on the eyes in elderly patients, consideration must be given to the patients' general health status. If the person is in overall good health, eye surgery may not"
-"INTRODUCTION\n============\n\nNeuroendocrine tumors (NETs) are rare neoplasms that mainly occur in the gastrointestinal system. The liver is the most common site of NET metastases, but it is a rare site of primary NETs \\[[@B1][@B2]\\]. Diagnosis of primary hepatic NET (PHNET) is based on 2 prerequisites: the liver mass must be immunohistochemically compatible with NET, and the liver should be the primary site of tumor development with strict exclusion of hepatic metastases from other locations. Differentiating between PHNET and liver metastasis from gastroenteropancreatic NETs is essential for accurate diagnosis of PHNETs. We aim to heighten our understanding of PHNET by retrospectively reviewing our surgical experiences with PHNET patients.\n\nMETHODS\n=======\n\nDuring 10 years from January 1997 to December 2015, more than 15,000 patients underwent liver resection for various diseases in our institution. Of them, 35 patients were diagnosed with NET pathologically. To select PHNET study cases, we excluded 18 patients diagnosed with metastatic NET from other sites as well as 4 patients additionally diagnosed with NET from other gastroenteropancreatic sites 3 to 12 months later during postoperative follow-up up to 12 months. Ultimately, 13 patients were diagnosed with PHNET.\n\nWe reviewed the clinicopathological characteristics and prognosis in these 13 patients"
-"1. Introduction {#sec1}\n===============\n\nConsequences of sleep deprivation and fragmentation are being increasingly recognized. We are a sleep deprived society with evidence showing that we sleep on an average 6.8 hours as opposed to 9 hours a century ago. Around 30% of adults report sleeping less than 6 hours per night \\[[@B15]--[@B17]\\]. The 24/7 economy and its subsequent impact on sleep patterns may be testing the bodies limits to maintain metabolic and hormonal equilibrium. Prevalence of both diabetes and obesity has increased to acquire pandemic proportions. Though other factors such as diet and reduced physical activity have contributed to the obesity epidemic the impact of sleep dysregulation on causing metabolic derangements is being increasingly recognized. Considering only a small percentage of people can maintain a healthy weight over a long period on diet and exercise alone, the impact of sleep on weight has opened a new venue for potential intervention.\n\nUnderstanding this topic is important as both sleep and metabolic dysregulation are common and growing problems. There are many unresolved issues including cause and effect, pathogenesis and potential implications to therapy.\n\n2. Metabolism in Normal Sleep {#sec2}\n=============================\n\nHuman sleep comprises of nonrapid eye movement sleep (NREM) and REM sleep."
-"1. Introduction {#sec1-ijms-21-05932}\n===============\n\nA series of coronaviruses crossed the species barrier, with the severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003 and the Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, and they caused major outbreaks of lethal pneumonia. Now, a new coronavirus emerged in December 2019 in Hubei province and was named the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. The disease caused by this virus, called COVID-19 has spread worldwide causing as early as August 2020 more than 18 million cases and more than 700,000 deaths \\[[@B1-ijms-21-05932]\\].\n\nSARS-CoV-2 is an enveloped virus with a positive RNA genome belonging to the beta genus of the Coronaviridae family \\[[@B2-ijms-21-05932]\\].\n\nThe clinical features of COVID-19 range from asymptomatic or mild disease to critically life-threatening ill patients conditions. The most prevalent symptoms are fever, shortness of breath, dyspnea, cough and fatigue \\[[@B3-ijms-21-05932]\\] and are commonly associated with diarrhea, headache, anosmia, lymphopenia or liver injury. An increasing number of less common manifestations are being described like acute kidney injury, vasculitis or myocarditis \\[[@B4-ijms-21-05932]\\]. The most common comorbidities in critically ill patients are age, hypertension, diabetes, obesity, cardiovascular disease and respiratory system disease \\[[@B3-ijms-21-05932]\\].\n\nViral and host interaction plays a key role"
-"On February 20, 2015, a northeastern university's student health center was notified of five veterinary medicine students with gastrointestinal symptoms. An investigation was conducted to establish the existence of an outbreak, determine the etiology, evaluate risk factors, and recommend control measures.\n\nAll five students had attended a training session at the university's bovine obstetrics laboratory on February 13, which included the handling of two euthanized calves. Patient symptoms, date of onset, and history of calf exposure suggested cryptosporidiosis. Infection with *Cryptosporidium*, a protozoa that causes watery diarrhea and is transmitted by infectious oocysts via the fecal-oral route ([@b1-773]), is common among calves ([@b2-773]). Symptoms in humans typically begin 7 days (range = 2--10 days) after infection and include intermittent abdominal cramps, nausea, vomiting, fever, and weight loss, lasting approximately 1--2 weeks ([@b3-773]).\n\nTwo calves used in the training sessions had been euthanized and frozen at \u22121.4\u00b0F (\u221217.0\u00b0C) on February 11. Approximately 28 hours later, the calves were thawed and detergent-washed by laboratory staff in accordance with standard protocols. Necropsies were performed on both animals on February 23, and revealed *Cryptosporidium* oocysts on an acid-fast stain of an intestine smear from one of the calves.\n\nInterviews revealed that 22 students had"
-"Background {#Sec1}\n==========\n\nCarbamazepine (CBZ) is an effective drug used for epilepsy, trigeminal neuralgia and many psychiatric disorders \\[[@CR1]\\]. Although considered as a well tolerated anti-epileptic drug, several adverse drug reactions to CBZ may occur including hypersensitivity syndrome, hematotoxicity and hepatotoxicity \\[[@CR2], [@CR3]\\]. Severe CBZ-induced hepatotoxicity is exceptional. Elevation in hepatic enzymes is reported in almost 22% of CBZ-treated patients \\[[@CR4]\\]. Adverse effects to CBZ have been attributed to reactive metabolites of the drug \\[[@CR3], [@CR5]\\]. In fact, in the liver, CBZ is oxidized to its major metabolite, the 10,11-epoxy-carbamazepine (CBZ-E) \\[[@CR6], [@CR7]\\] and to additional metabolites CBZ-arene oxide and CBZ iminoquinone by the cytochrome P450 enzymes \\[[@CR3]\\]. Glutathione S-transferases (GST) are enzymes involved in phase II reactions and playing a key role in detoxifying drugs and xenobiotics. The implication of the metabolites of CBZ has been suggested to induce adverse-drug reactions, cytotoxicity, and also genotoxicity \\[[@CR3], [@CR5]\\].\n\nBoth Glutathione S-transferase class mu (GSTM1) and class th\u00eata (GSTT1) are involved in reactions of gluco-conjugation of the main metabolite and also in the detoxification of toxic metabolites of CBZ \\[[@CR3], [@CR7]--[@CR9]\\]. Null alleles of the GSTM1 and GSTT1 resulting on a deletion of the entire genes, lack any functional enzyme activity"
-"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"
-"1. Introduction {#s0005}\n===============\n\nA tooth size- arch length discrepancy is a common form of malocclusion in most orthodontic patients and the amount of such discrepancy; especially in mandibular arch is a vital factor for the extraction decision ([@b0165], [@b0090], [@b0170]). Given that treatment strategies have been changed lately to more conservative approaches, there is great awareness in non-extraction alternatives for space gaining, particularly in borderline cases. Among these are; interproximal reduction, distalization, and arch expansion. While the severity of crowding and the soft-tissue profile are the important determinants of the appropriate approach; stability, timing of treatment and different treatment approaches must also be considered ([@b0180], [@b0025], [@b0060], [@b0170]).\n\nRelative to maxillary deficiency, transverse mandibular deficiency has received little awareness from researchers. Even though expansion can be done successfully in the maxillary arch, in mandibular arch, the expansion procedure has been thought to be less effective. This could be attributed to the anatomical limitations in the mandible, since, the maxilla has a midpalatal suture but the mandible has not. Therefore, the effect of mandibular expansion was believed to be localized to the alveolar process and mostly generate tipping of the buccal segment ([@b0050], [@b0020], [@b0025], [@b0085], [@b0095], [@b0140], [@b0145]).\n\nIndeed,"
-"Background\n==========\n\nLung disorders in children are quite common\\[[@B1],[@B2]\\] and usually of an obstructive nature, generally confined to the intra-thoracic, intrapulmonary airways\\[[@B3]\\]. Reliable information on pulmonary function would aid the diagnostic process and patients\\' follow up. Studies on respiratory function tests concerning school children and adolescents have already been published \\[[@B4],[@B5]\\]; and specific criteria for acceptance of maximal expiratory flow volume (MEFV) curves have also been proposed \\[[@B5]\\]. In recent times attention to this issue in pre-school children has increased \\[[@B3],[@B6]\\]; different methods and means of measurement have been suggested, particularly spirometry \\[[@B5],[@B7],[@B8]\\], whole body plethysmography \\[[@B9]\\], interrupter techniques \\[[@B10],[@B11]\\]. With regard to spirometry, important studies assessing the feasibility and repeatability of the tests in preschool children have been conducted and have moreover demonstrated that many children are able to perform the required manoeuvres \\[[@B5],[@B7],[@B8],[@B12]-[@B15]\\]. The latest guidelines on standardization of spirometry \\[[@B16]\\] emphasized that, with appropriate coaching, children as young as 5 years of age are often able to perform acceptable spirometry.\n\nInfants and preschool children normally have large airways in relation to their lung volume \\[[@B15]\\], thus they empty their lungs more rapidly than older children and adults do. Therefore the forced expiratory volume in one second (FEV1)"
-"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"
-"Background {#Sec1}\n==========\n\nThe low cardiac output syndrome (LCOS) is an acute circulatory disorder that may occur in 2% to 10% of patients after cardiac surgery \\[[@CR1]--[@CR4]\\]. When pre-operative left ventricular ejection fraction (LVEF) is altered, the prevalence of LCOS increases up to 20% \\[[@CR2]\\]. In patients with coronary artery disease, the LCOS further impairs their ability to satisfy the myocardial demand in oxygen after coronary artery bypass graft (CABG) and is associated with a very high mortality rate \\[[@CR5]\\]. The therapeutic management of LCOS involves dobutamine, an adrenoceptor agonist, which, having stronger beta- than alpha-adrenergic effects and resulting in a decreased afterload, is considered the inotrope of choice \\[[@CR6]\\]. However, dobutamine also has a strong chronotropic effect that may compromise the expected hemodynamic improvement for two main reasons. First, the tachycardia decreases left ventricular filling time and may reduce stroke volume (SV) despite the improvement in ejection force \\[[@CR7]\\]. Thus, as the increase in heart rate (HR) is dose-dependent, dobutamine global effect on cardiac output (CO) is often limited by the inherent tachycardia \\[[@CR8], [@CR9]\\]. Second, tachycardia is responsible for an increase in myocardial oxygen consumption that may aggravate myocardial oxygen imbalance \\[[@CR10]\\]. These phenomena may also explain, in"
-"INTRODUCTION\n============\n\nGastric cancer is the fourth most common form of cancer worldwide, and almost a million new cases are diagnosed annually \\[[@B1]\\]. Although the mortality rate due to gastric cancer decreased slightly from 774,000 in 1990 to 700,000 in 2012, it is the third-most common cause of cancer-related deaths, followed by lung cancer and hepatoma \\[[@B2]\\]. In Korea, gastric cancer has been the most commonly diagnosed cancer since 1999, when the Korea Central Cancer Registry first reported the incidence of gastric cancer \\[[@B3]\\].\n\nMalnutrition is a condition that results from consuming a diet that has not enough or excess nutrients, resulting in health problems. Specifically, malnutrition is often used to refer to a state of under-nourishment, where there is insufficient intake of calories, proteins, carbohydrates, vitamins, and minerals \\[[@B4]\\]. Cancer patients tend to lose weight and suffer from malnutrition because of poor oral intake and alterations in metabolic pathway(s). The prevalence of malnutrition in cancer patients is reported to be around 10%--85%, which varies according to the type, location, grade, and stage of the tumor \\[[@B5]\\]. Underweight people typically find it difficult to sustain normal health. Being underweight is a condition generally defined as either having a body mass"
-"Background\n==========\n\nThe advances in oral health research have not reached all population groups around the world and this leads to inequalities in periodontal health and other chronic diseases \\[[@B1]\\]. Periodontal diseases are highly prevalent, particularly amongst socially disadvantaged populations, impact on quality of life and are costly to treat \\[[@B2]\\]. These diseases are also associated with major chronic conditions including coronary heart disease and diabetes mellitus \\[[@B3],[@B4]\\].\n\nIn many parts of the developing world, clinical care and chair-side prevention are both unaffordable and inappropriate for the control of periodontal diseases. The burden of disease on populations around the world could be prevented with simple and cost-effective public health interventions. There must be more focus on translating knowledge into action to improve public health \\[[@B1]\\]. The 'common risk factor approach', advocated by the World Health Organization (WHO), concentrates on several common causative or risk factors such as smoking and hygiene that have impact on oral diseases e.g. periodontitis and a number of important other health problems \\[[@B5],[@B6]\\].\n\nOral health promotion in the form of organized activities can be used in the community level using different vehicles such as media to transfer health messages \\[[@B7]\\]. In middle and low-income countries electronic"
-"The Potential of Healthcare Data\n================================\n\nOn June 21, 2016, the Chinese State Council promulgated its Guiding Opinions on Promoting and Regulating the Development of the Application of Healthcare Big Data. The report identified healthcare data to be a strategic national resource and that its development would significantly impact healthcare and medical treatment. It also raised the importance of gathering and utilizing healthcare data to a national level.\n\nHealthcare data comes from many sources, giving rise to various fields (ie, medical and health informatics, translational bioinformatics, sensor informatics, and imaging informatics), and within each field, new analytic tools to understand health and disease \\[[@ref1]\\]. In particular, the analysis of data contained within electronic health records (EHRs) is a promising avenue of research for clinicians and data scientists. EHRs contain large volumes of data regarding patient care, both structured and unstructured, making them highly valuable resources for knowledge discovery \\[[@ref2]\\].\n\nFor decades, clinical research has relied on randomized controlled trials (RCTs) as the authoritative methodology---conclusions from RCTs are deemed inherently more reliable compared to those of observational studies. While medical societies rely on RCTs to develop clinical practice guidelines, they have some well-known and notable drawbacks \\[[@ref3]\\]. They are costly, labor-intensive,"
-"Cytotoxic lymphocytes, encompassing cytotoxic T cells and natural killer (NK) cells, play a pivotal role in immune defense. By directed release of perforin-containing lytic granules, cytotoxic lymphocytes can eradicate pathogen-infected, tumorigenic, and otherwise stressed cells. By the virtue of cytokine and chemokine secretion, they can also influence other cells of the immune system. In addition, cytotoxic lymphocytes can kill activated immune cells to limit excessive immune reactions and maintain homeostasis. In recent years, much progress has been made with respect to the mechanisms by which cytotoxic lymphocytes develop, differentiate, and exert their effector functions. In this Research Topic, we collected several exciting articles that highlight the mechanisms controlling the development and effector function of cytotoxic lymphocytes, as well as the role these cells play in several disease conditions.\n\nWe open the Research Topic with a review providing an up-to-date view on the development and differentiation of NK cells, and their relationships to other innate lymphoid cells. The authors describe in detail NK cell developmental progression through distinct stages before reaching the mature phenotype, and discuss possible reasons behind functional and phenotypic plasticity among NK cells from different tissues ([@B1]). With respect to differentiation, NK cells receive cues from several other"
-"Background {#Sec1}\n==========\n\nDomestication of the pig took place more than 9000\u00a0years ago. Since then, natural and artificial selection have led to the formation of many different breeds and strains. Currently, the pig is one of the most important livestock animals with more than 250 breeds worldwide. While most breeds (e.g. Large Black, Schw\u00e4bisch-H\u00e4llisch and Cerdo Iberico) serve mainly for commercial niche (high price) markets, for large-scale commercial pork production, only a few breeds (e.g. Large White, Landrace, Pietrain, Duroc and Hampshire) are used \\[[@CR1],[@CR2]\\]. These major breeds are of enormous economic interest and thus, it is not surprising that much effort has been put into Quantitative Trait Locus (QTL) mapping in pigs during the last two decades (reviewed by \\[[@CR1],[@CR3]\\]). Today, there are almost 10 000 QTL listed in the Pig QTL database (pigQTLdb, \\[[@CR4]\\]; SS_10.2 downloaded on 04.02.2014). Among other reasons, insufficient resolution due to marker availability has limited traditional QTL analyses (many QTL cover more than 20\u00a0cM), which has delayed identification of causal genes or variants \\[[@CR5]\\]. However, recently, the availability of cost-effective genome-wide SNP genotyping has made it possible to map QTL more accurately and this has increased opportunities to identify candidate genes and/or"
-"The insect olfactory system is unique among animal olfactory systems. Unlike mammalian, fish, and nematode olfactory receptors (ORs), insect ORs are not GPCRs. Relative to other ORs, insect ORs have an inverted topology, with an intracellular N-terminus and extracellular C-terminus[@b1][@b2]. This inverted orientation allows them to form a heteromeric complex via intracellular domains[@b1], which functions as an odorant-gated ion channel[@b3][@b4]. Each heteromeric complex is comprised of a unique odorant-detecting OR, and the ubiquitously expressed Orco. The Orco sequence is highly conserved among insect species[@b5], and is necessary to target the complex to olfactory neuron dendrites[@b1][@b6]. Moreover, its presence is required for ion channel function[@b3][@b4].\n\nWhile significant progress has been made in understanding the insect olfactory system, relatively little is known about how the ORs function at the molecular level. One study was able to show that residues between transmembrane 3 and the second extracellular loop are involved in odorant recognition[@b7], while another demonstrated that a V91A mutation in the predicted second transmembrane region could confer resistance to DEET in DmOR59b[@b8]. A third study showed that the second extracellular loop likely forms \u03b2-turns which may be critical for olfactory function in all insects[@b9], while a fourth study demonstrated that a single"
-"Introduction {#Sec1}\n============\n\nApproximately 17.5 million people die each year from cardiovascular disease. An estimated 30% of all deaths worldwide are due to heart attacks and strokes. Coronary artery disease (CAD) accounts for the greatest proportion of cardiovascular diseases. Overall, CAD is the leading cause of death worldwide and is predicted to remain so for the next 20\u00a0years \\[[@CR1]--[@CR3]\\]. In Europe between 14% and 20% of women and 16--25% of men die from CAD \\[[@CR4]\\]. Furthermore, CAD is a\u00a0leading cause of morbidity and poor quality of life. Thus, CAD is a\u00a0major public health problem which exerts heavy economic costs. Overall, CAD is estimated to have cost the European Union \u20ac45\u00a0billion in 2003 and this estimate even might be an underestimate \\[[@CR5]\\]. Nevertheless, improved management of the disease consisting of life style interventions, revascularization or optimal drug therapy have resulted in a\u00a0decrease in CAD mortality since 1995 by 34% \\[[@CR6], [@CR7]\\]; however, most data regarding CAD are from patients with acute coronary symptoms or in the case of patients with stable CAD come from randomized trials of drugs used in the prevention of cardiovascular events (e.\u2009g. EUROPA \\[[@CR8]\\]). In order to generalize the findings from"
-"Introduction {#sec001}\n============\n\nThere is considerable evidence from cross-sectional studies of older people that depression and poorer cognitive performance often coexist. Higher scores on self-rating measures of depressive symptoms such as the Center for Epidemiologic Studies Depression Scale (CES-D), the Hospital Anxiety and Depression Scale, the Beck Depression Inventory or the Geriatric Mental State Schedule have been associated with lower scores on measures of fluid-type cognitive ability (Scherr *et al.* [@ref044]; La Rue *et al.* [@ref031]; Rabbitt *et al.* [@ref042]; Gale *et al.* [@ref020]) and on cognitive screening tests such as the Mini-Mental State Examination (MMSE) (Kay *et al.* [@ref027]; Fuhrer *et al.* [@ref016]; Auperin *et al.* [@ref004]; Mangione *et al.* [@ref032]). Fluid-type cognitive ability tests involve the carrying out of active mental work and not just recalling knowledge. The association between depression and poorer cognition is not confined to older people. Christensen *et al.* ([@ref009]) carried out a meta-analysis of studies that compared the cognitive performance of people with depression (either clinically diagnosed or with high scores on self-rating measures) with non-depressed controls and found that the presence of depression was associated with deficits on a wide range of standard cognitive tests, involving speed, attention, tracking and conceptual tasks."
-"Background\n==========\n\nHow to interpret the nature of biological processes, which, when perturbed, cause certain phenotypes, such as human disease, is a major challenge. The completion of sequencing of many model organisms has made \\'reverse genetic approaches\\' \\[[@B1]\\] efficient and comprehensive ways to identify causal genes for a given phenotype under investigation. For instance, genome-wide knockout strains are now available for *Saccharomyces cerevisiae*\\[[@B2],[@B3]\\], and diverse high throughput RNA interference knockdown experiments have been performed, or are under development, for higher organisms, including *C. elegans*\\[[@B4]\\], *D. melanogaster*\\[[@B5]\\] and mammals \\[[@B6],[@B7]\\].\n\nCompared to the direct genotype-phenotype correlation observed in the above experiments, what is less obvious is how genetic perturbation leads to the change of phenotypes in the complex of biological systems. That is, we might perceive the cell or organism as a dynamic system composed of interacting functional modules that are defined as discrete entities whose functions are separable from those of other modules \\[[@B8]\\]. For example, protein complexes and pathways are two types of functional modules. Using this concept as a basis for hypothesis, it is tempting to conclude that it is the perturbation of individual genes that leads to the perturbation of certain functional modules and that this, in"
-"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"
-"Background {#Sec1}\n==========\n\nBiopsies of the prostate have been used to diagnose prostate cancer since the beginning of the last century \\[[@CR1]\\]. The field of prostate diagnostics, especially biopsy techniques develops rapidly \\[[@CR2]\\]. Transrectal ultrasonography (TRUS) guided prostate biopsy, which isperformed with a core biopsy needle passing through the rectum, was first applied for the biopsy of prostate in 1968 \\[[@CR3]\\]. Since the introduction of the systematic 12-core transrectal prostate biopsy guided by TRUS, it has become awidely accepted, routinely performed technique for prostate cancer detection \\[[@CR4]\\]. The transperineal prostate biopsy, which is performed with the core biopsy needle passing through the skin of the perineum, is far less common compared with transrectal biopsy \\[[@CR5]\\].\n\nSeveral studies have demonstrated that the transrectal technique is a faster and convenient approach for prostate biopsy. Though the minor complications rate of hematuria, rectal bleeding, hematospermia, vasovagal episodes, infection was reported to be similar in these two techniques \\[[@CR6]\\], transrectal prostate biopsy had more major complicationse.g. sepsis, bleeding or other complications requiring admission compared with the transperineal biopsy \\[[@CR7], [@CR8]\\]. More importantly, an increasing risk of septic shock was reported in the transrectal biopsy, which might be life-threatening \\[[@CR9], [@CR10]\\].\n\nRecently, transperineal prostate biopsy"
-"INTRODUCTION\n============\n\nBreast reconstruction rates continue to rise in the United States of America with implant-based reconstruction rising at a higher rate than autologous modalities.^[@R1]^ Although direct-to-implant reconstruction is gaining popularity, a 2-stage tissue expander-to-implant procedure remains, by far, the most common technique.^[@R2]^ As the 2-stage technique has evolved since its inception in the early 1980s,^[@R3],[@R4]^ it became preferable to place the expander and therefore, the final implant in the subpectoral plane rather than in the prepectoral plane.^[@R5]^ The subpectoral technique was thought to offer increased tissue coverage of the expander/implant, camouflage for capsular contracture, and a more natural upper pole slope compared with subcutaneous reconstructions.^[@R6],[@R7]^ With the introduction of acellular dermal matrices in the past decade, the pendulum is swinging back to placement of breast prostheses in the prepectoral plane. Acellular dermal matrix coverage and implant placement in the prepectoral plane completely avoids disruption of the pectoralis major muscle, which is often painful, results in animation deformities, and results in a lateralized appearance of the reconstructed breasts.^[@R8]--[@R11]^\n\nDespite multiple refinements, the overall technology behind saline tissue expanders remains quite similar to the concept introduced by Dr. Radovan almost 40 years ago.^[@R12]^ Traditional saline expanders typically involve the use of"
-"INTRODUCTION\n============\n\nGiven our dramatic impact on ecosystems ([@b53-jmbe-17-23]) and the consequences of such impacts on human welfare, ecology has emerged as a key scientific field for building an informed citizenry ([@b28-jmbe-17-23]). However, significant gaps exist in our knowledge about the interrelationships between organisms and the environment. In particular, the lack of awareness of microbial life often represents an important gap in our world view of nature ([@b3-jmbe-17-23], [@b42-jmbe-17-23]). Microbes are, by definition, invisible to the naked eye, and this hampers an appreciation of their enormous diversity and key ecological roles. Along these lines, D'Arcy Thompson, in his classic book *On Growth and Form,* recognized how the microbial world might hide from our regular human intuition:\n\n> Man is ruled by gravitation, and rests on mother earth. \\[...\\] where the bacillus lives, \\[...\\] the predominant factors are no longer those of our scale: we have come to the edge of a world of which we have no experience, and where all our preconceptions must be recast. ([@b51-jmbe-17-23])\n\nAs a consequence of this microbial ignorance, there are some under-recognized facts about the importance of microbes that are fundamental to understanding the functioning of Earth as an ecological system. These are: i)"
-"1. Introduction {#sec1-sensors-18-00490}\n===============\n\nAs the only part that keeps the contact between the vehicle chassis and the road, tires are a key factor for electronic control systems as well as for comfort and fuel consumption, among others. Despite the fact that current tires perform well in a huge variety of situations, they are just passive elements that do not contribute actively to driver or vehicle control systems to improve the driving experience and traffic safety. All these reasons encourage researches and companies to invest time and efforts in the development of an intelligent tire that works as a source of information for drivers and active control systems such as the Traction Control System (TCS) or the Electronic Stability Program (ESP) to intervene before a crash occurs.\n\nUp to now, the Tire Pressure Monitoring System (TPMS), which was introduced in the market in 2002 \\[[@B1-sensors-18-00490]\\] and provides information about tire inflation pressure, is the only system installed in tires that gives the drivers some kind of information about tire working conditions while driving. Nevertheless, real-time monitoring of other parameters like forces at the tire-road interface, wear and tire-road friction, which also depend on uncontrollable environmental factors, is the main obstacle"
-"INTRODUCTION {#sec1-1}\n============\n\nTooth wear is a collective term used to describe the surface loss of dental hard tissues from causes other than dental caries.\\[[@ref1]\\] It is a complex, multifactorial, irreversible phenomenon which involves an interplay of mechanical, chemical, and biological factors.\\[[@ref2]\\] Although the process is considered physiological, which is cumulative with age, excessive wear not proportionate to the age may affect the normal function or esthetics, hence may be deemed pathological.\\[[@ref1][@ref3]\\]\n\nTooth wear as found in the dental literature includes abrasion, erosion, attrition, and abfraction.\\[[@ref4]\\] Abrasion is the pathological wear of dental hard tissue by abnormal mechanical processes which usually occurs by the friction of exogenous material forced over tooth surfaces.\\[[@ref5]\\]\n\nThe pattern of abrasion is highly variable depending on the type of agent causing it. The most common of them include faulty toothbrushing that usually leads to wedge-shaped defects in the cervical regions, followed by the use of abrasive dentifrices that can cause lesions on labial surfaces of teeth.\\[[@ref6][@ref7]\\] Toothpicks and floss can cause abrasion on the proximal surfaces of exposed roots.\\[[@ref8]\\] Occupational abrasion as seen in hairdressers and cobblers due to opening of bobby pins with teeth, holding nails between teeth, etc., can present as notching of"
-"INTRODUCTION\n============\n\nThe cognitive trait of hypnotizability ([@B16]) -- the ability to accept hypnotic suggestions -- has been classically attributed to peculiar characteristics of the supervisory attentional system ([@B30]; [@B33]) allowing a more flexible attentional control in the subjects scoring high (*highs*) at hypnotizability scales. In fact, a few neuropsychological ([@B42]; [@B48]) and genetic studies ([@B25]; [@B34]; [@B35]; [@B41]) have suggested greater abilities of focused attention in *highs* with respect to low hypnotizable individuals (*lows*), based on higher dopaminergic activity.\n\nIn the general population, attention seems to be more efficiently controlled in subjects with the Met/Met or Val/Met variant of the single nucleotide polymorphism (SNP) rs4680 at the catechol-*O*-methiltransferase (COMT) gene than in the homozygous Val/Val individuals ([@B38]). In fact, the Met/Met variant shows 40% less enzymatic activity than the Val/Val and, thus, is associated with higher dopamine levels in the prefrontal ([@B36]) and anterior cingulate cortex ([@B3]).\n\nThe three association studies conducted so far on the relation between the COMT Val^158^Met polymorphism and hypnotizability have provided inconsistent results. Two of them ([@B25]; [@B34]) applied analysis of variance on the hypnotizability scores in subjects stratified by the COMT genotype. In this approach, a sample of subjects not selected for hypnotizability"
-"1.. Introduction {#s1}\n================\n\nUltrasound (US) assessment of gestational age up to 24 weeks provides the most accurate prediction of the expected date of delivery (EDD) and is more reliable than the last menstrual period (LMP) \\[[@RSIF20110376C1],[@RSIF20110376C2]\\]. Although accurate gestational age assessment is not a problem unique to resource-poor settings \\[[@RSIF20110376C3]--[@RSIF20110376C5]\\], there is lower availability of US dating for women in these settings \\[[@RSIF20110376C6]--[@RSIF20110376C8]\\]. Owing to the sheer numbers of births and economics in developing countries, the LMP remains to be the most widespread predictor of gestational age \\[[@RSIF20110376C9],[@RSIF20110376C10]\\]. In some cultures, particularly where literacy levels are low, LMP can be very unreliable \\[[@RSIF20110376C7]\\]. In such settings, methods to date such pregnancies have relied on inexpensive tools including validated scored assessments of superficial and neurological newborn criteria, for example the Dubowitz \\[[@RSIF20110376C4],[@RSIF20110376C11]--[@RSIF20110376C13]\\] and Ballard or modified Ballard \\[[@RSIF20110376C4],[@RSIF20110376C14]--[@RSIF20110376C18]\\] score. Training and ongoing quality control of testers are needed to maintain the accuracy of these methods. The symphysis-pubis fundal height (SFH) measurement is also widely available, routinely practised in nearly all antenatal settings in the world and simple to perform. While Neilson\\'s \\[[@RSIF20110376C19]\\] Cochrane review concludes that there is not enough evidence to evaluate the use of SFH during antenatal care"
-"**PURPOSE:** Gustilo type IIIC open tibia fractures are characterized by an ischemic limb requiring immediate arterial repair. Despite recent advances in microvascular reconstruction, these patients are at high risk of complications and the decision between primary amputation and limb salvage can be challenging for plastic surgeons. The purpose of this study is to evaluate our experience with Gustilo type IIIC patients who have underwent reconstruction with a free tissue transfer.\n\n**METHODS:** We retrospectively reviewed an institutional database of all patients who underwent free tissue transfers. Patients with Gustilo type III open tibia fractures that underwent reconstruction with free flap coverage were included in this study. The following information was collected: patient demographics and comorbidities, operative details including flap type and anastomosis details, extent of arterial injury as determined by preoperative angiography and/or intraoperative findings, perioperative complications, and flap outcome (e.g., partial or total failure, take-backs, and salvage rates). To elucidate the difference in outcomes based on the extent arterial injury, we specifically compared the outcomes of Gustilo type IIIC patients and Gustilo type IIIB patients with 1 patent vessel.\n\n**RESULTS:** Thirty-two patients with Gustilo type IIIC injuries underwent reconstruction with free tissue transfers. The average patient age was 32.6\u2009\u00b1"
-"Background\n==========\n\nAge, atrial fibrillation, and stroke\n------------------------------------\n\nStroke accounts for significant morbidity and mortality globally every year, including in Australia (where this study is being conducted) \\[[@B1]\\]. Advancing age is a key non-modifiable risk factor for stroke, and this is important to recognize given that 80% of stroke sufferers are over 60 years old and that 80% of stroke-related deaths occur in those over 75 years old \\[[@B1]\\]. As the population ages the incidence of stroke rises, doubling the disability burden by the year 2031 \\[[@B2]\\].\n\nAtrial Fibrillation (AF), commonly dubbed the 'a*rrhythmia of the millennium*', is the commonest irregular heart rhythm encountered in clinical practice, and is reportedly most prevalent in the elderly population \\[[@B3],[@B4]\\]. It is infamous for its propensity to form stroke-causing thrombi in the heart chambers (atria) that can embolize to other parts of the body; these thrombo-emboli can subsequently occlude the blood vessels and disrupt the circulatory supply through to the brain, causing ischemia, i.e., stroke \\[[@B5]\\].\n\nPatients with AF have at least a 5 to 6-fold increased risk of stroke \\[[@B6]\\], and in the elderly the proportion of stroke attributable to AF is at least one-third \\[[@B7]-[@B9]\\]. Independently, 'old' age and chronic AF"
-"Background\n==========\n\nInvasive pulmonary aspergillosis is a severe and often lethal infection. It mainly occurs in patients with malignancy who experience deep and prolonged neutropenia, but there are other established risk factors (e.g. high-dose long-term corticosteroid therapy or advanced forms of AIDS) \\[[@B1]\\]. Invasive pulmonary aspergillosis has recently been described in critically ill patients without malignancy \\[[@B2]-[@B4]\\], and Aspergilluss is increasingly considered as an emerging pathogen in non-hematological patients. Among the non-hematological patients diagnosed with invasive pulmonary aspergillosis in the critical care setting were patients with Child C liver cirrhosis \\[[@B3]\\]. This condition has thus be considered as a possible risk factor for invasive pulmonary aspergillosis, all the more so that acute liver failure is known to promote fungal infection \\[[@B5]\\]. In support of this contention and to raise the awareness of clinicians managing patients with decompensated cirrhosis, we report invasive pulmonary aspergillosis in three such patients.\n\nCase presentations\n==================\n\nThe three cases were diagnosed over a 18 months period, in two different hospitals.\n\nCase 1\n------\n\nA 54-year-old man was admitted for ascites and acute renal failure revealing Child-Pugh stage C13 alcoholic cirrhosis. A liver biopsy showed severe acute alcoholic hepatitis and treatment with prednisolone 1 mg/kg a day"
-"Introduction\n============\n\nThe number of nuclear plants in the world, either in or out of service, is growing and many of them are built with obsolete technology and are becoming older and older [@ref1]. Therefore some release of radionuclides into the environment can be expected in the future.\n\nFor this reason, the average (informed) citizen and big organizations could both be interested in innovative and simple methods to check the radiological safety of the local environment and of commodities, starting from foods. Traditional methods require special expertise with expensive and heavy devices and for this reason they are not very popular and only specialized organizations can afford them. On the other hand, if detecting radioactivity were as simple and cheap as measuring atmospheric pressure or body temperature, it could raise a great interest especially in our networked society and particularly during a radiological emergency.\n\nIn recent years, an astounding availability of portable and wearable [@ref2] sensors has flooded the consumer market, as an effect of the explosion of the smartphone market.\n\nAlmost anyone can currently monitor georeferenced environmental parameters and can find out and share their measurements in real time [@ref3].\n\nThe parameters that can be more easily measured by"
-"1. Introduction {#sec1-nanomaterials-08-00943}\n===============\n\nEgg white protein (EWP) is an important ingredient in food processing, because of its abundant nutritive value and various functional properties. The main components of EWP are ovalbumin (OVA, 54%), ovotransferrin (OT, 12%), ovomucoid (OM, 11%) and lysozyme (LY, 3.4%) \\[[@B1-nanomaterials-08-00943]\\]. These proteins mainly show a globular structure. However, its industrial application is limited by its poor thermal stability and emulsifying properties. It was reported that heat-induced nanoparticles formed from globular proteins could increase their emulsifying capacity and binding ability to hydrophobic bioactive compounds \\[[@B2-nanomaterials-08-00943],[@B3-nanomaterials-08-00943],[@B4-nanomaterials-08-00943]\\]. Although half of the amino acid residues in OVA are hydrophobic, EWP presents good water-solubility, since most hydrophobic amino acid residues are embedded into protein molecules under natural conditions. Heating promotes EWP unfolding, in which hydrophobic amino acids are exposed, conferring an increase in protein surface hydrophobicity \\[[@B5-nanomaterials-08-00943]\\]. However, considering the thermolability of EWP, and in particular the OT (denaturation temperature *TD* = 62 \u00b0C, p*I* = 6.1) \\[[@B6-nanomaterials-08-00943]\\], the aggregation of which occurs easily under neutral conditions, the application of thermal modification technology in improving the functional properties of EWP is limited. Attempts in fabrication of EWP nanoparticles by heat treatment under extremely acidic \\[[@B7-nanomaterials-08-00943]\\] or alkaline conditions \\[[@B8-nanomaterials-08-00943]\\] have"
-"1. Introduction {#sec1}\n===============\n\nHypertension is a major risk factor for cardiovascular disease, chronic kidney disease, cerebrovascular disease, ischemic heart disease, stroke, and coronary heart disease. Approximately 30% of adults in the United States are not aware of their hypertension and in two-thirds of patients, hypertension is not being controlled \\[[@B1]\\]. According to the Korean National Health and Nutrition Examination Survey, the prevalence of hypertension among adults aged over 30 years was approximately 30% in Korea. The prevalence of hypertension has not been constant over time; the prevalence was 29% in 1998, decreased slightly to 24% in 2007, and then increased again to 28% in 2011 \\[[@B2]\\]. Despite the improvement in the treatment rate of hypertension, some older patients still have untreated and uncontrolled hypertension. Although the prevalence of hypertension has remained relatively stable over the last several decades, the number of older people with hypertension has been steadily increasing due to a rapidly aging society. In particular, isolated systolic hypertension, one of four subtypes of hypertension, is becoming more prevalent \\[[@B3]\\].\n\nHistorically, traditional herbal medicines (THMs) have been the conventional treatment method in the Korean medical system for treating various diseases. Traditional Korean medicine, which was discovered around 5,000"
-"1. Introduction {#sec1-sensors-19-00798}\n===============\n\nThe wearable device has been widely studied in recent years. In the related researches, it is essential to monitor the cardiac and physical activities in users with congestive heart issues at home. The electrocardiogram (ECG) is an important signal in monitoring the cardiac activity. A Holter ECG device is frequently applied to record long-term ECG signals and helps to find arrhythmic heartbeats within twenty-four hours \\[[@B1-sensors-19-00798]\\]. Another apparatus is called an Event Recorder that is able to record one-minute ECG signals when a user feels uncomfortable on the chest region \\[[@B2-sensors-19-00798]\\]. Currently, the commercial Holter ECG apparatus or Event Recorder only record the ECG signals, and is lacking in the real time analysis of the ECG signals. Moreover, the user has been encouraged to neither do any severe exercises nor take a shower, because these two kinds of devices do not have a high ingress protection rating.\n\nAn ECG patch is a wearable device, which not only records ECG signal, but also shows some cardiac information on the smart phone in real time \\[[@B3-sensors-19-00798]\\]. However, its function for the arrhythmic beat detection is not better than the ECG Holter analysis. The problem is that the ECG"
-"INTRODUCTION\n============\n\nBaseline whole-body ^18^F-fluoride PET/CT is ideal for staging and restaging prostate cancer and has been shown to be an independent prognostic imaging biomarker of patients undergoing radium-223 dichloride (^223^RaCl~2~) therapy^(^[@r1]^)^. However, although treatment with ^223^RaCl~2~ improves survival in prostate cancer patients^(^[@r2]^-^[@r4]^)^, not all patients respond to this therapy. It would be beneficial to identify nonresponders early in the course of treatment, thereby reducing morbidity and unnecessary costs.\n\nAfter successful treatment of osteoblastic bone metastases, an osteoblastic reaction (flare) can occur, which increases bone uptake even in responsive cases. That can be confused with the osteoblastic reaction and inflammation that occur in response to tumor-associated growth factors during progression. This phenomenon has been well described in conventional bone scintigraphy, and that method is therefore not recommended for use as the sole means of determining the response to treatment^(^[@r5]^,^[@r6]^)^.\n\nAlthough interim studies performed with ^18^F-FDG PET/CT can change the management of patients with a variety of cancer types^(^[@r7]^-^[@r10]^)^, the exact role of ^18^F-fluoride PET/CT in evaluating the early response to therapy (interim study) is not well established. The importance of ^18^F-fluoride PET/CT has extended beyond the diagnosis of metastases to the evaluation of optimal strategies for use in patients submitted"
-"Introduction {#Sec1}\n============\n\nThe detection of uranium trace concentrations is of great importance due to its extensive use in nuclear power plants. According to estimations by the International Atomic Energy Agency (IAEA), the total generated nuclear power will rise in coming decades^[@CR1]^,pp. 21. Simultaneously, nuclear power plant dismantling will require fast on-site monitoring of uranium in nearby water and soils. A variety of spectroscopic techniques such as atomic absorption spectroscopy (AAS), inductively coupled plasma optical emission spectroscopy (ICP-OES), mass spectroscopy (ICP-MS)^[@CR2]^, and X-ray fluorescence spectroscopy (XFR)^[@CR3]^ can be used to detect uranium content in water samples at lab-scale. However, all these classic techniques are not portable and thus, involve large sample campaigns, making fast on-site monitoring difficult. In addition they are complicated and of high cost.\n\nTo address fast and simple on-site analysis, we have recently proposed a portable electrochemical sensor for trace uranium detection in water^[@CR4]^. These sensors are made of track-etched poly(vinylidene fluoride) (PVDF) membranes functionalised with poly(bis\\[2-(methacryloyloxy)ethyl\\] phosphate) (PB2MP) enabling efficient uranyl preconcentration thanks to their nanoporous structure. The limit of detection (LOD) was estimated to be 17 ppb (3*\u03c3*/slope) with a quantification limit (LOQ) of 51 ppb. In aqueous solutions, the most thermodynamically stable form of"
-"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"
-"Background\n==========\n\nHeart failure (HF) is the most common hospital discharge diagnosis in elderly patients \\[[@B1]\\]. Between the age of 70 and 80 years the incidence of HF is 10 to 20%. HF is associated with high mortality and morbidity, readmission rates and costs \\[[@B1]\\]. The readmission rates vary between 25% and 50% within 6 months after the first hospitalisation for HF, with a higher readmission rate within the first month after discharge\\[[@B2],[@B3]\\]. The costs related to HF contribute to 1-2% of all healthcare expenditures and are mainly the result of hospital stay \\[[@B4]-[@B6]\\]. Because of an increasing shortage of resources, HF is a major public health problem and therefore, a more effective and efficient organisation of care for HF patients needs to be reconsidered. A first step in organising treatment and care for patients with chronic HF more efficiently, was the implementation of specialised outpatient HF clinics. In the recent European Society of Cardiology (ESC) guidelines, HF management programmes are strongly recommended for all patients with HF \\[[@B1]\\] and HF clinics are considered as \\'usual care\\' in several European countries \\[[@B7]\\]. A widely used way to implement HF management is the use of specific disease management (DM) programs.\n\nDM"
-"The catalytic enantioselective nucleophilic allylation of aldehydes and imines is a useful route to homoallylic alcohols and amine derivatives.\\[[@b1]\\] Recently, we described the enantioselective rhodium-catalyzed nucleophilic allylation\\[[@b2]\\] of cyclic imines\\[[@b3],[@b4]\\] using the chiral dienes **L1**/*ent*-**L1**\\[[@b5]\\] which, to our knowledge, are the first examples of rhodium-catalyzed enantioselective additions of allylboron reagents to \u03c0-electrophiles.\\[[@b6]\\] These reactions enable the formation of products with up to two stereocenters with high diastereo- and enantioselectivities.\\[[@b2]\\] Herein, we report the discovery of an isomerization of allylrhodium intermediates, resulting in more complex allylrhodium species that would otherwise be difficult to access. This isomerization allows the formation of products containing up to three new stereochemical elements (two stereocenters and an alkene of defined geometry) with high diastereo- and enantiocontrol.\n\nPreviously, we demonstrated that the cyclic aldimine **1\u2009a** reacted with the prenyltrifluoroborate **2\u2009a** (Scheme\u2005[1](#fig01){ref-type=\"fig\"}\u2009a)2a or its isomer **2\u2009b** (Scheme\u2005[1](#fig01){ref-type=\"fig\"}\u2009b)2b to give the same reverse prenylation product **3\u2009a**, thus suggesting the involvement of a common allylrhodium intermediate. In further experiments, the racemic allylation of the saccharin-derived cyclic ketimine **4\u2009a** with the prenyltrifluoroborate **2\u2009a** was attempted (Scheme\u2005[2](#fig02){ref-type=\"fig\"}). Surprisingly, a 70\u2009% yield of a mixture of products was obtained, in which"
-"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"
-"\"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"
-"Introduction\n============\n\nBased on the thermodynamic law, obesity results from a state of positive energy balance in which energy intake exceeds energy expenditure over a prolonged period of time. In the past decades, there has been a dramatic increase in the prevalence of obesity.^[@bib1]^ The reasons for such epidemic are unknown and are the subject of an ongoing debate.^[@bib2],\\ [@bib3]^ In the search for hidden causative factors, it was noted that the obesity epidemic has been paralleled by a concomitant shortening in self-reported sleep and by an increase in the prevalence of obstructive sleep apnea (OSA).^[@bib2]^ Thus, we and others have hypothesized that these pervasive contemporaneous epidemics, sleep deprivation and obesity, may be linked together in causal, reverberating circuits.^[@bib2]^\n\nMost of the information available for the effects of sleep deprivation on food intake is derived from acute studies conducted in healthy lean male volunteers. Experimentally induced acute sleep deprivation increases appetite in healthy lean humans.^[@bib4]^ In rodents, sleep deprivation changes the hypothalamic expression of several neuropeptides, including the orexogenic neuropeptide Y and the anorexogenic proopiomelanocortin.^[@bib5]^ Less is known about food intake in chronically sleep-deprived human subjects, especially in those with obesity. The information about long-term association between sleep duration and"
-"Introduction\n============\n\nLiver cancer is a prevalent gastrointestinal tract cancer in China, with a total of 355,595 newly diagnosed cases and 322,417 deaths reported in 2011.[@b1-ott-9-1945] The most common histological type of liver cancer is hepatocellular carcinoma (HCC). Even with the implementation of new treatment strategies including liver transplantation, surgical resection, chemotherapy, and molecular targeting therapy, the prognosis for HCC patients remains poor.[@b2-ott-9-1945] To facilitate better management of HCC patients, it is crucial to identify specific biomarkers for prognosis prediction.\n\nHippo pathway is composed of a network of molecules that regulate HCC cell proliferation, apoptosis, migration, and differentiation.[@b3-ott-9-1945] The core of the mammalian Hippo pathway is a kinase cassette comprising mammalian STE20-like protein kinase 1/2 (MST1/2), salvador family WW domain containing protein 1 (SAV1), large tumor suppressor kinase 1/2 (LATS1/2), and MOB kinase activator 1 (MOB1). Upon activation of the Hippo pathway, MST1/2-SAV1 phosphorylates and activates LATS1/2. The subsequent binding of LATS1/2 with MOB1 will then phosphorylate the Yes-associated protein (YAP) and tafazzin (TAZ), leading to their cytoplasmic retention. In this way, excessive cell proliferation and tumorigenesis will be inhibited.[@b4-ott-9-1945],[@b5-ott-9-1945] When components of the core kinase cassette are dysregulated, hypophosphorylated YAP will be translocated into the nucleus and will directly"
-"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"
-"1. Introduction {#sec1-toxins-09-00277}\n===============\n\nThe genus *Bordetella* comprises nine species. Among them, *B. pertussis*, *B. parapertussis* and *B. bronchiseptica* are so closely related, despite differences in host range, that they are often considered as subspecies of the same species and are called \"classical species\" \\[[@B1-toxins-09-00277]\\]. *B. pertussis* is the agent of whooping cough, a severe respiratory disease in humans which can be dramatic for newborns and elderly subjects. *B. parapertussis* is the agent of respiratory disease in sheep and in humans; however, the clinical symptoms induced in humans last less than those induced by *B. pertussis* although clinically similar \\[[@B2-toxins-09-00277],[@B3-toxins-09-00277]\\]. *B. bronchiseptica* is a respiratory pathogen for several mammal species and sometimes for immuno-suppressed patients \\[[@B1-toxins-09-00277]\\]. *B. pertussis* and *B. parapertussis* appear to have independently emerged from a *B. bronchiseptica* ancestor through rearrangement and loss of genetic material \\[[@B4-toxins-09-00277],[@B5-toxins-09-00277]\\]. Those three species are closely related and produce similar as well as specific virulence factors. The three species produce (i) similar adhesins such as filamentous hemagglutinin (FHA) and pertactin (PRN), but different fimbrial proteins (FIM); (ii) similar toxins such as adenylate cyclase-hemolysin (AC-Hly) toxin, tracheal cytotoxin and dermonecrotic toxin, but *B. pertussis* is the only species producing pertussis toxin (PT); (iii)"
-"Introduction\n============\n\nThe incidence of atrial fibrillation (AF) increases dramatically in the older population ([@B46]). Aging results in a series of structural and physiological changes of the human atria, which may act as substrates to trigger AF ([@B40]; [@B39]). Advanced age causes aging-related atrial cardiomyopathy and facilitates the development of AF in patients without cardiovascular diseases ([@B18]). Moreover, aging significantly contributes to the high risk of ischemic stroke and heart failure in AF patients ([@B25]). Therefore, aging has a close relationship with AF.\n\nA growing number of studies have documented the evidence for the effects of aging on atrial structural remodeling, atrial electrophysiological remodeling, oxidative stress, and inflammation within the atria ([@B32]). However, few studies were reported to systematically study miRNA and mRNA expression profiles in aged human atria, which should provide new insights into the miRNA-mRNA regulatory networks during the progression of atrial aging (AA) ([@B4]; [@B3]).\n\nMicroRNA (miRNA) belongs to a class of small non-coding RNAs with 20--22 nucleotides in length. These small molecules exist in virtually all organisms and are evolutionarily conserved. By binding to their target mRNAs, miRNAs induce translational repression, mRNA deadenylation and mRNA decay at the post-transcriptional level ([@B35]). Many important biological processes are"
-"All relevant data are within the manuscript and its Supporting Information files.\n\nIntroduction {#sec001}\n============\n\nGlanders is an infectious zoonotic disease of equids, caused by the gram-negative bacterium *Burkholderia* (*B*.) *mallei*. Although the disease has been eradicated in most European and North American countries in the last century, there are still outbreaks throughout the South American and Asian continents \\[[@pone.0214963.ref001]--[@pone.0214963.ref005]\\]. The disease is mainly chronic in horses and latently-infected animals pose a high risk of reintroduction of the infection into glanders-free countries \\[[@pone.0214963.ref006]\\]. Therefore, trade restrictions with animals and products from endemic regions or outbreak areas are mandatory.\n\nBacterial isolation and identification of *B*. *mallei* from cutaneous lesions and nasal exudates are considered to be the \"gold\" (perfect reference) standard for diagnosis of glanders. As approximately 90% of early infections occur in a non-clinical or latent form, clinical and bacteriological diagnosis are difficult \\[[@pone.0214963.ref007]\\].\n\nCurrently, mallein (allergic hypersensitivity test) and complement fixation test (CFT) are used for indirect diagnosis \\[[@pone.0214963.ref008]\\]. The CFT is the World Organisation for Animal Health (OIE) prescribed serodiagnostic method for international trade purposes and is also recommended for surveillance investigations \\[[@pone.0214963.ref007]\\]. This test is known to have high sensitivity, but it gives a considerable number of"
-"Introduction {#Sec1}\n============\n\nConsumption of the so-called Mediterranean diet has been associated with a decreased risk of chronic diseases, in particular cardiovascular disease (CVD), when compared to other dietary regimes \\[[@CR1], [@CR2]\\]. These effects may be attributed, in part, to the olive oil (OO) component of the diet \\[[@CR3]\\]. Research comparing refined OO to extra virgin OO (EVOO) has highlighted the biological activity of the (poly)phenol components contained within the water-soluble fraction of EVOO \\[[@CR4], [@CR5]\\]. In addition to the fruit (from which OO is derived), the leaves of the olive plant (*Olea europaea*) also contain phenolic compounds at a much higher concentration than those of the olive fruit and oil (1450\u00a0mg total phenolics/100\u00a0g fresh leaf \\[[@CR6]\\] vs. 110\u00a0mg/100\u00a0g fruit \\[[@CR7]\\] and 23\u00a0mg/100\u00a0ml EVOO \\[[@CR8]\\]). The most abundant phenolic compounds present in the leaves are verbascoside, apigenin-7-glucoside, luteolin-7-glucoside, hydroxytyrosol (HT), tyrosol and the secoiridoid oleuropein, with secoiridoids being uniquely present in plants of the *Oleaceae* family \\[[@CR9]\\].\n\nData emanating from a number of studies suggest that olive leaf extract (OLE) may influence CVD risk via its potential to induce anti-atherosclerotic, hypotensive, antioxidant, anti-inflammatory and hypocholesterolaemic effects (for review see \\[[@CR10]\\]). The majority of these"
-"Composition-structure-properties correlations are important topics with great significance in materials science research fields[@b1][@b2][@b3][@b4][@b5]. Crystallographic method describes simple crystalline materials' structure by means of \"atomic positions plus space lattice\", and usually knowledge of a few atoms within the unitcell is sufficient to deduce their partial properties[@b6][@b7]. For complex metallic alloys (CMAs) like some intermetallics, quasicrystals and amorphous alloys, the problem becomes complicated because their structural information is often submerged in a long list of atomic coordinates. In this case, the structural characteristics of CMAs cannot be reflected through the crystallographic method, not to mention their structure-related properties[@b8][@b9][@b10]. Since the atomic clusters are advocated as primary units to represent materials' structural features, to solve the above problem, various cluster-based models have been developed during the past decades[@b11][@b12][@b13][@b14][@b15][@b16][@b17]. Among these cluster-based models, Dong's \"cluster-plus-glue-atom\" model[@b15] can be used to describe the atomic structure of nearly all materials. Denoted by a uniform cluster formula of \\[cluster\\](glue atoms)~x~[@b18][@b19][@b20][@b21], this cluster-plus-glue-atom model regards the atomic structure of any materials, no matter whether crystalline or non-crystalline, to be composed of the clusters part and the glue atoms part[@b22][@b23][@b24][@b25][@b26][@b27][@b28]. Accordingly, all atoms in a given structure belong to three kinds of the central atoms, the shell atoms and"
-"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"
-"Introduction {#Sec1}\n============\n\nDepression is a complex and heterogeneous neuropsychiatric disorder with a high prevalence and incidence^[@CR1]^. Despite decades of research, the neurobiological mechanisms underlying its pathogenesis are still poorly understood. Several hypotheses have been put forward, implicating dysregulation of monoamines, stress hormones, neuroplasticity and neuroinflammation^[@CR2],[@CR3]^. However, none of them has emerged as a lead mechanism and probably all are involved, most likely in an intricate fashion, in triggering or maintaining this disease. Imaging studies have nevertheless revealed that structural modifications, such as hippocampal atrophy^[@CR4],[@CR5]^, could occur in recurrent major depression, demonstrating the role of neuroplasticity in this pathology. This was further confirmed in rodent models, reporting impaired neurogenesis (see^[@CR6]^ for a review), neuron dendrite shrinkage and glial cell loss^[@CR7],[@CR8]^, as well as in postmortem brains, with a decrease in brain-derived neurotrophic factor (BDNF) expression in depressed subjects^[@CR9]--[@CR11]^.\n\nSeveral types of therapies, including psychotherapy, electroconvulsive therapy, deep brain stimulation and pharmacotherapy have shown some efficacy for treating depression. Treatment with available antidepressant molecules still has serious limitations because of their delay of action and lack of efficacy in about one third of patients^[@CR12]^. One of the most prescribed antidepressants, the selective serotonin reuptake inhibitor (SSRI) fluoxetine, targets the presynaptic serotonin"
-"1. Introduction {#sec1}\n===============\n\nCurrently, it is estimated that between 12,000 and 20,000 new cases of MDS are diagnosed each year in the United States. Although MDS can affect all ages, the highest prevalence occurs in those over 60 years of age \\[[@B1], [@B2]\\]. Much of the population has indolent forms of MDS, making it one of the most prevalent hematologic malignancies of older adults.\n\nMDS represents a heterogeneous group of hematopoietic disorders which are derived from an abnormal multipotent progenitor cell and are characterized by hyperproliferative bone marrow, cellular dysplasia, and ineffective hematopoiesis \\[[@B3]\\]. Morbidity and mortality result from anemia, bleeding, and infection, along with transformation to acute myelogenous leukemia (AML) in approximately one-third of patients \\[[@B4], [@B5]\\]. The basis of therapy is supportive care, including red blood cell or platelet transfusions and treatment of infections. Stem-cell transplantation remains the only chance for cure, but it is associated with significant treatment-related morbidity and mortality and is generally restricted to patients \\<60 years of age \\[[@B6]\\]. Similar limitations exist for the use of high dose chemotherapy. Given the limitations of existing therapies, there is a clear need for additional therapeutic options for patients with MDS.\n\nCancer cells are characterized by"
-"INTRODUCTION {#sec1-1}\n============\n\nHerbs and their extracts are inexpensive and rich resources of active compounds that can be utilized as novel cytotoxic agents as well as can be used for the treatment of dermatological disorders associated with melanin hyperpigmentation. *In vivo* antitumor activity is an emerging research area in cancer biology. Research in the development of antitumor drugs, worldwide, has been focused on screening therapeutically effective and safe, synthetic and herbal molecules. There are numerous natural or synthetic drugs which were studied for their antitumor potentials, but none of them have uniqueness to meet all the desired requisites, that is, freedom from cumulative or irreversible toxicity, effective long-term protection, prolong stability and ease of administration.\\[[@ref1]\\]\n\n*Ipomoea pes-caprae* (*Convolvulaceae*) also known as do-patti-lata, railroad vine, goat\\'s foot and morning glory, is a valuable medicinal plant, distributed in the tropics and subtropics. Traditionally, leaf juice of *I. pes-caprae* used as a first aid for treatment of jellyfish stings.\\[[@ref2]\\] In some part of India, it is used in ritual baths to alleviate evil spirits. The plant is astringent, acrid, refrigerant, mucilaginous, somatic, laxative, diuretic and tonic and used in the treatment of skin diseases, boils, swelling, wounds, ulcer, carbuncle, dropsy, menorrhagia, hemorrhoids, colic,"
-"Background\n==========\n\nHuman immunodeficiency virus (HIV) reached all 31 provinces in China by 1998; the first indigenous Chinese acquired immunodeficiency syndrome (AIDS) case was detected in 1989 \\[[@B1]\\]. An assessment by the Chinese Ministry of Health, the Joint United Nations Program on HIV/AIDS and the World Health Organization suggested that approximately 740,000 were HIV infections in China at the end of 2009 \\[[@B2]\\], while the cumulative number of HIV infections actually diagnosed by the end of 2009 was 326,000 in China \\[[@B2]\\]. It was reported that 44.1% of HIV infections were not aware of their infection \\[[@B2]\\]. There were 13715 newly-diagnosed HIV infections in 2009 in China, 55.7% of which occurred through sexual transmission, and it was estimated that there were actually 48000 new HIV infections in China in 2009, 74.7% occurring through sexual transmission \\[[@B2]\\]. Heilongjiang Province, in northeast China, is still an area of low HIV/AIDS incidence and prevalence, but HIV infection has been rapidly spreading to the general population \\[[@B3]\\]. The incidence rate increased from 0.16 per 100,000 in 2004 to 0.33 per 100,000 in 2006, to 0.91 per 100,000 in 2009 in Heilongjiang Province. 66.5% people who were newly diagnosed and reported in 2009 acquired their"
-"Introduction {#Sec1}\n============\n\nAdvances in pneumatic tourniquet technology over the last 35\u00a0years have significantly improved the safety, efficacy, and reliability of tourniquet instruments and cuffs. However, tourniquet-related nerve injury is a potentially harmful complication of tourniquet use. Nerve injuries from tourniquet use range from a mild transient loss of function to permanent, irreversible damage \\[[@CR1]\\]. Ochoa et al. \\[[@CR2]--[@CR4]\\] showed that in most cases, nerve damage is limited to the part of the nerve that is underneath and near the edges of the cuff and that the underlying cause of tourniquet paralysis is compressive neurapraxia rather than ischemic neuropathy or muscle damage. Compression of the large myelinated fibers underneath the tourniquet cuff results in displacement of the node of Ranvier from its usual position under the Schwann-cell junction. Studies of the distribution of pressures beneath tourniquet cuffs have shown that high tourniquet inflation pressures in narrow uncontoured tourniquet cuffs result in high pressure gradients near the cuff edges. In turn, this results in higher compressive pressures and higher pressure gradients along the underlying nerves and soft tissues \\[[@CR5], [@CR6]\\]. Consequently, higher levels of tourniquet inflation pressure and higher pressure gradients beneath tourniquet cuffs are associated with a higher risk"
-"Introduction {#S0001}\n============\n\nOvarian cancer ranks at the top of the list of the most lethal gynecological malignancies.^[1](#CIT0001)^ Therefore, it is of utmost importance to identify molecular biomarkers predicting prognosis and response to chemotherapy, and potential new targets for molecular inhibition.\n\nCurrently, taxanes combined with cisplatin or its analogs (the TP regimen) are the standard first-line treatment of ovarian cancer patients.^[2](#CIT0002),[3](#CIT0003)^ It replaced platinum-cyclophosphamide (the PC regimen) and other protocols based on DNA damaging agents. Nevertheless, in patients with advanced disease, the overall survival rates are still poor.\n\nPlatinum compounds induce DNA damage by the formation of DNA adducts and interstrand crosslinks (ICL). These lesions inhibit DNA replication, transcription and induce cell cycle arrest and apoptosis.^[4](#CIT0004)^ Homologous recombination (HR) during the S phase of the cell cycle is one of the mechanisms removing DNA adducts.^[5](#CIT0005)--[8](#CIT0008)^ HR-mediated DNA repair requires activation of Fanconi anemia (FA) pathway. Abnormalities of genes involved in the FA pathway, resulting in the homologous recombination deficiency (HRD) have been described to be essential for cell sensitivity to DNA damaging agents (for reviews, see refs.^[9](#CIT0009)--[11](#CIT0011)^) and PARP inhibitors.^[12](#CIT0012)-[14](#CIT0014)^ On the other hand, taxanes impair the cell tubular system through polymerization and stabilization of \u03b2-tubulin in G2 and M"
-"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\n============\n\nIntercostal (IC) muscles are diverse and widely spread throughout the rib cage. These muscles are morphologically and functionally skeletal muscles, and it helps in upward and outward movement of the ribs which results in increase in antero-posterior diameter of the thoracic cavity (De Troyer et al., 2005\\[[@R5]\\]). The IC muscles help both in inspiration and forced expiration. Even though these muscles engage in respiration, their activities are fewer during active contraction among normal healthy adults (Hirai et al., 1996\\[[@R10]\\]). Neglect of skeletal muscle from a low level of physical activity is also a factor that may have detraining effect on muscle mass. This will have an impact on the oxidative capacity of the skeletal muscles and it will reduce the proportion of muscle fibers from type I to type II (Gosker et al., 2000\\[[@R9]\\]). Hence, it can be hypothesized intercostal muscles which aids in the mechanical aspects of breathing may undergo atrophy when there is a poor physical activity. Therefore, this could have an impact on chest wall mobility and expansion in turn to ventilation on normal healthy adults.\n\nVarious research studies demonstrated that IC stretching improved expired tidal volume, decreased the level of dyspnea level and increased"
-"Background {#Sec1}\n==========\n\nCaseous lymphadenitis (CLA) is a chronic, debilitating infection caused by the Gram-positive bacterium *Corynebacterium pseudotuberculosis*. CLA affects mainly small ruminants, such as sheep and goats, and is the leading cause of economic loss associated with the reduction of wool, meat and milk production, and also results in carcass and skin condemnation in the majority of sheep and goat production areas \\[[@CR1]\\]. CLA infection is typically initiated by inoculation via oral, respiratory, and membrane wounds \\[[@CR2]\\]. Once inside, the bacteria are phagocytosed by macrophages, which are then drained to local lymph nodes. Once internalized, the bacteria evade the cellular immune response mechanisms, being able to survive and rapidly multiply within the macrophage phagosome. Bacterium proliferation results in the death of the host cell and the subsequent release of bacteria into the extracellular environment, which can then spread through the lymphatic system to regional lymph nodes and internal organs \\[[@CR3]\\]. Clinical signs of the disease include the formation of caseous abscesses either in superficial or internal lymph nodes. While antibiotic therapy is not usually helpful, management of the disease combines the identification and removal of infected animals along with vaccination of healthy animals \\[[@CR2]\\].\n\nIn recent years, novel mechanisms"
-"Background {#Sec1}\n==========\n\nIn the global scale, lung cancer is one of all common carcinoma, which always keeps the leading position, and is the first cancer in the morbidity and mortality of carcinoma. According to the GLOBOCAN 2008 data, there are 23\u00a0% of total cancer-related mortalities and 17\u00a0% of newly diagnosed cancer cases for primary lung cancer \\[[@CR1]\\]. Over the past 30\u00a0years in China, the mortality rate of lung cancer has increased by 465\u00a0% \\[[@CR2]\\], it is responsible for more deaths than prostate, colon, and breast tumors combined \\[[@CR3]\\]. Although there are great advances recently in the cancer treatments, the prognosis of patients with lung cancer is poor even after curative surgery and chemotherapy, the rate of 5-year survival is less than 15\u00a0% \\[[@CR4]\\]. The main reasons for the low survival rate of the patients could involve the lack of sensitive and specific biomarkers for prognosis of lung cancer. Therefore, it is necessary to identify the biomarkers for the prognosis of lung cancer that lead to enhancing more effective individual therapies, reduce the mortality, and increase 5-year survival rate.\n\nClassically, lung cancer is pathologically classified into non-small cell lung cancer (NSCLC) and small cell lung"
-"1. INTRODUCTION {#sec1}\n===============\n\nThis paper is a continuation of the previously published article \\[[@r1]\\]. Analogously to the preceding review, the PubMed, Cochrane and other databases were searched for relevant articles reporting trials as well as reviews and meta-analyses. More articles came to the attention through other means *e.g*. reference lists. It is evident for a reviewer of scientific literature that the quality of argumentation in some areas of medical and biological research deteriorated since last decades. Another tendency is that substances without proven effects and questionable treatments have been advertized, corresponding products being marketed in the guise of evidence-based medications. Scientific publications are required to register drugs and treatments to obtain permissions for the practical use; accordingly, such publications appeared, sometimes being evidently biased. Patients can be influenced not only by the advertizing but also by unobjective professional publications. In Russia, the marketing of placebos under the guise of evidence-based medications is quite usual \\[[@r1]\\]. Several examples are discussed in this review, where drugs and dietary supplements with unproven effects and unclear action mechanisms are directly or indirectly presented as evidence-based medications. It was not the aim of this article to provide a comprehensive review of substances under discussion;"
-"1. Introduction {#sec1-sensors-18-02070}\n===============\n\nThe CD Rewritable (CD-RW) optical recorder provides functions of reading, writing, erasing, and overwriting information onto the optical disc. CD-RW recorders have become standard computer accessories due to their low cost and high data storage capacity. Phase-change recording media are mainly used for CD-RW recorders due to their attractive characteristics including high speed, high density, low power consumption, long life cycle and scalability \\[[@B1-sensors-18-02070],[@B2-sensors-18-02070],[@B3-sensors-18-02070]\\]. Various write pulse generator circuits associated with the infrared diode generating the write pulse train (WPT) for both the CD-RW and DVD \u00b1 RW have been proposed. The WPT circuitry is controlled by a digital signal processor (DSP) in the recording servo control system. The control scheme implemented in the DSP fine-tunes the WPT, leading to well-formed pits and lands recorded on the disc. This is called the write strategy \\[[@B4-sensors-18-02070],[@B5-sensors-18-02070]\\].\n\nA good write strategy results in good recording performance, allowing the data recorded onto the optical disc to exactly follow the industry specifications \\[[@B6-sensors-18-02070],[@B7-sensors-18-02070]\\]. The write strategy is implemented using a set of control parameters called write strategy parameters \\[[@B6-sensors-18-02070],[@B7-sensors-18-02070]\\]. The write strategy parameters specify the laser power, pulse widths and delays of WPT generated from the infrared diode for the"
-"The DNA damage response (DDR) is a cellular defense mechanism that integrates genotoxic event detection to the activation of checkpoint pathways to arrest cells in different phases of the cell cycle to facilitate DNA repair or induce apoptosis and eliminate damaged cells.^[@bib1]^ The product of the *TP53* gene plays an important role in DDR, where it works as a tumor suppressor mainly involved in the transcriptional regulation of a large number of growth-arrest- and apoptosis-related genes,^[@bib2]^ and inactivation of the p53 pathway is a pivotal aspect of tumor formation in the majority of human cancers.^[@bib3]^ Many factors influence the ability of p53 to determine cell fate decision. Indeed, upon genotoxic damage, p53 is rapidly subjected to a series of posttranslational modifications thought to regulate its stability and biological functions.^[@bib4]^ In addition, there is a complex interplay between p53 modifications and its interaction with specific transcriptional co-factors that cooperate with p53 to induce transcriptional activation of specific targets involved in determining cellular fate.^[@bib5]^\n\nChe-1/AATF/Traube (Che-1) is a RNA polymerase II-binding protein involved in the regulation of gene transcription and cell proliferation.^[@bib6],\\ [@bib7],\\ [@bib8]^ It has been shown that this protein exhibits strong antiapoptotic activity,^[@bib9],\\ [@bib10],\\ [@bib11]^ and it is rapidly degraded"
-"Introduction\n============\n\nViruses are the most abundant biological entities on the planet ([@ref-9]), an order of magnitude more abundant than bacteria ([@ref-23]). Most ocean viruses prey upon bacteria ([@ref-23]), and as a result, play a critical role in ecosystem dynamics. When these viruses (bacteriophage, or phage) lyse bacterial cells, carbon is converted to its dissolved form, slowing the export of carbon to the deep ocean ([@ref-79]). Marine viruses thus ultimately influence biogeochemical cycling and can affect the rate of atmospheric warming ([@ref-90]; [@ref-18]). Besides being abundant and fundamental contributors to the Earth's biogeochemical cycles, marine viruses are also extremely diverse. Although recent work examining viral protein clusters in metagenomes suggests the global virome may be smaller than previously thought, marine viruses still constitute one of the largest reservoirs of genetic diversity on the planet ([@ref-67]; [@ref-34]). Moreover, viruses can change the genetic makeup of bacteria through horizontal gene transfer ([@ref-41]; [@ref-49]; [@ref-33]) and affect bacterial community composition through lysis of specific host cells ([@ref-52]). For all of these reasons, understanding the diversity of marine viruses has been a research focus for more than 20 years, since [@ref-4] documented high viral abundance in the oceans.\n\nStudying viral diversity is challenging because"
-"Sir,\n\nMinitracheostomy kits are commercially available and are used for the tracheal toileting in intensive care units. Commercially available kits are expensive; despite the expense they are not perfect. We have used the indigenously prepared kit several times in place of minitracheotomy kits and found it useful. Following this experience, we have also kept the same kit for carrying out emergency cricothyroidotomy is a potentially life-saving procedure in the \"cannot intubate cannot ventilate (CICV)\" scenario.\\[[@ref1][@ref2][@ref3][@ref4]\\] Although, surgical cricothyroidotomy remains the technique recommended in many \"CICV\" algorithms, the insertion of a tracheostomy as a cannula over a trocar, or using the Seldinger\\'s method, may have advantages as they are more familiar to the anesthetist.\\[[@ref5]\\]\n\nIntra-aortic balloon catheter pump (IABP) is used in cardiac centers to treat intractable low cardiac output syndrome. A typical IABP catheter kit contains intra-aortic balloon catheter, Seldinger needle, guide wires, sheaths with the dilators. Of these, a few optional items are rarely used. They are: The non-reinforced sheath and dilator wire reinforced sheath and dilator \\[1 and 2, [Figure 1](#F1){ref-type=\"fig\"}\\], and extra set of the guide wire (0.036 inch, 100 cm long). The sheath provided in the IABP kit is nowadays not used by most clinicians, because"
-"INTRODUCTION\n============\n\nMultiple myeloma (MM) is the result of a proliferation of a neoplastic clone of plasma cells in the bone marrow and encompasses 13% of all haematologic malignancies \\[[@sfy065-B1]\\], showing an annual incidence of \u223c60 cases per million population \\[[@sfy065-B2]\\]. Clinical manifestations are heterogeneous, ranging from skeletal disease (70%), anaemia (40%), impaired humoural immunity (80%) and, as we will focus on this review, renal impairment (20--40%) \\[[@sfy065-B3], [@sfy065-B4]\\].\n\nSince late last century, when immunofluorescence and electronic microscopy clarified the physiopathology of myeloma kidney, several therapeutic strategies have been tested to reduce the impact of myeloma paraproteins on kidney function, especially with extracorporeal techniques to remove free light chains (FLCs) \\[e.g. plasmapheresis (PLEX) or high cut-off (HCO) dialysis\\]. There were also some efforts to characterize FLCs' structure and physico-chemical properties in order to investigate potential inhibitors of FLCs' intratubular aggregation.\n\nHerein, our purpose is to review all the relatively new therapeutic strategies from a nephrologist's perspective, focusing on the use of extracorporeal techniques to reduce the levels of FLCs in serum, especially with HCO dialysis membranes. We also summarize the knowledge acquired over the last two decades regarding the implication of FLCs in the renal pathology of MM.\n\nPATHOGENESIS: THE"
-"1. Introduction {#sec1}\n===============\n\nParkinson\\'s disease (PD) is a progressive neurodegenerative disease characterized by motor symptoms, including bradykinesia, tremor, and muscle rigidity \\[[@B1]\\]. The neuropathological hallmark of PD is intracellular protein inclusions of misfolded *\u03b1*-synuclein, termed Lewy bodies (LB) \\[[@B2]\\]. Lewy pathology is present in the central nervous system (CNS), but can also be found throughout the peripheral autonomic nervous system (PNS) \\[[@B3]\\] and has been detected in the enteric nervous system up to 20 years prior to diagnosis \\[[@B4]\\]. Symptoms of autonomic dysfunction including constipation, decreased saliva production, urinary dysfunction, orthostatic hypotension (OH), and sweating abnormalities are common in PD patients \\[[@B5], [@B6]\\].\n\nResearch in skin abnormalities in PD patients is gaining increasing interest, especially since Lewy pathology (aggregated alpha-synuclein) can be detected in autonomic nerve fibers in most patients using simple punch biopsies \\[[@B7]\\]. Also, a significant loss of autonomic nerve fibers, including fibers with vasomotor function, is seen in many patients \\[[@B8]\\], and it has been reported that PD patients have altered skin blood flow regulation resulting in cold limbs \\[[@B9]\\]. However, our understanding of autonomic skin dysfunction in PD is still very limited.\n\nA recent study used infrared thermography and demonstrated that PD patients display abnormal"
-"With improving access to facility-based neonatal care (FBNC), an increasing number of preterm neonates are surviving in India and new challenges are emerging about their ongoing care.\\[[@ref1]\\] Such a major challenge is ensuring the survival of preterm neonates with intact and optimal neurosensory abilities. Retinopathy of prematurity (ROP) is one of the important conditions which endangers intact survival, and which needs to be detected in a timely manner and treated promptly, if severe. ROP is also amenable to primary prevention by improving adherence to evidence-based clinical care practices in hospitalized sick preterm neonates.\\[[@ref2][@ref3]\\] Improved access to FBNC does not, however, ensure adherence to best practices, and thus a quality-improvement and assurance system needs to be put in place to prevent the consequences of suboptimal clinical care. The recent expansion of neonatal care services in many low- and middle-income countries, coupled with suboptimal care is leading to an increasing number of infants with stage 4 and 5 ROP being seen by ophthalmologists, including India.\\[[@ref4][@ref5]\\]\n\nROP is not only among the commonest causes of acquired blindness in children but is also an excellent indicator of the quality of care provided to preterm neonates in a healthcare facility. Risk factors for ROP include"
-"Although the observation that patients with alcohol abuse and dependence (collectively termed alcohol use disorders \\[AUDs\\]) frequently suffer from co-occurring mood and anxiety disorders predates the founding of the National Institute on Alcohol Abuse and Alcoholism (NIAAA) 40 years ago, our improved understanding of the nature of the associations among these common psychiatric disorders largely parallels the growth of NIAAA's research portfolio in this area. Four decades ago, the psychiatric diagnostic systems in place (i.e., the Feighner \\[[@b21-arh-33-1_2-109]\\] and the Research Diagnostic Criteria \\[RDC\\] \\[[@b54-arh-33-1_2-109]\\]) used a simple approach to describe the complex nature of co-occurring disorders. As a first step, these systems attempted to classify comorbid conditions based solely on the chronological timing of their occurrence. Thus, a person who was diagnosed with alcohol dependence before the onset of his or her psychiatric disorder was labeled as a \"primary\" alcoholic, whereas a patient whose alcoholism followed the onset of another diagnosable psychiatric illness was labeled as a \"secondary\" alcoholic. Indeed, the definitions of the alcohol dependence syndrome also were evolving during this period, further complicating the diagnostic picture ([@b23-arh-33-1_2-109]).\n\nWith the advent of the *Diagnostic and Statistical Manual of Mental Disorders, Third Edition* (DSM--III) ([@b7-arh-33-1_2-109]) and the incorporation of"
-"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"
-"1. Introduction {#sec1}\n===============\n\nAging is a major risk factor for Parkinson\\'s disease (PD), meaning that the number of patients living with PD is steadily increasing as people live longer \\[[@B1]\\]. In addition, individuals with PD experience not only motor symptoms but also various nonmotor symptoms, such as cognitive dysfunction, psychiatric symptoms, sleep disturbance, urinary problems, sexual dysfunction, and dysautonomia, all of which affect their quality of life (QOL). These symptoms can fluctuate throughout the day and from day-to-day, thus requiring frequent reassessment. At an advanced disease stage, patients may require device-aided therapy, such as a levodopa-carbidopa intestinal gel or deep brain stimulation, due to motor complications such as the \"wearing off\" phenomenon and dyskinesia.\n\nDue to the fluctuating symptoms and multiple therapeutic choices, it is preferable for patients with PD to consult a neurologist specializing in PD treatment. In fact, reports suggest that, in patients with PD, care under a neurologist might be associated with a better prognosis \\[[@B2]\\]. However, access to PD specialists may be limited for some individuals as a result of declining mobility with the disease progression, as well as uneven distribution of these specialists between urban and rural areas and the limited number of neurologists"
-"A large proportion of viral pathogens that have recently emerged in humans have originated in various animals. After initial interspecies transmission, these viruses have evolved and disseminated into the human population through various distinct mechanisms. However, understanding of the initial steps of the emergence of some viruses and associated diseases remains poor. Microbiologic studies of these high-risk populations are thus necessary to obtain new insights into the early events of this emergence process ([@R1]--[@R4]).\n\nNonhuman primates represent a potential source of microbes for humans ([@R1],[@R5]--[@R12]), e.g., simian immunodeficiency virus and simian T-lymphotropic virus ([@R12]--[@R15]). Simian foamy viruses (SFVs) are exogenous complex retroviruses, highly prevalent in several animal species in which they cause persistent infections ([@R16]--[@R26]). Phylogenetic analyses have demonstrated a species-specific distribution of such retroviruses. This species specificity indicates a long-term coevolution of SFVs with their natural hosts ([@R27]), which could explain their possible lack of pathogenicity observed in vivo and the persistence of the infection ([@R23],[@R24],[@R28]--[@R31]). Among nonhuman primate populations, SFV seroprevalence can reach 75%--100% in adults, and SFVs appear to be present at high concentrations in the saliva of infected animals ([@R16]--[@R18],[@R22],[@R29],[@R31]).\n\nIn humans, SFV infection has been reported in 1%--4% of persons occupationally exposed to nonhuman primates"
-"1. Introduction {#sec1-molecules-25-02440}\n===============\n\nMycotoxins are one of the most important contaminants in cereals. They are toxic secondary metabolites usually produced, in favorable environmental conditions, by *Aspergillus*, *Penicillium*, *Alternaria*, and *Fusarium* fungi. Among these species, *Fusarium* are the most prevalent mycotoxin-producing fungi in Central and Southern Europe. *Fusarium* species are known as producers of several mycotoxins, including regulated ones fumonisins, trichothecenes, and zearalenone. Generally, in Italy, the most widespread mycotoxins for maize and wheat are fumonisins (FBs) and deoxynivalenol (DON), respectively. Besides these toxins, moniliformin (MON) is a not negligible emerging *Fusarium* mycotoxin occurring in cereals; generally, higher levels have been found in maize than in other crops. MON is mainly produced by *F. subglutinans, F. temperatum, F. verticilloides*, and *F. proliferatum*. Moreover, the last two fungal species are also able to produce FBs \\[[@B1-molecules-25-02440]\\]. MON is a highly polar and acidic molecule ([Figure 1](#molecules-25-02440-f001){ref-type=\"fig\"}) and occurs as a water-soluble sodium or potassium salt \\[[@B2-molecules-25-02440]\\].\n\nCardiotoxicity and hepatotoxicity are its major adverse health effects, as indicated by the Panel on Contaminants in the Food Chain (CONTAM) of the European Food Safety Authority (EFSA) \\[[@B3-molecules-25-02440]\\]. The main target of MON seems to be enzymes with thiamine as a cofactor. Since these"
-"Yoshida K, Kita K, Yamashiro S. A 56\u2010year\u2010old female with celiac artery compression syndrome recovering through dietary changes and weight gain. J Gen Fam Med. 2017;18:165--167. <https://doi.org/10.1002/jgf2.50>\n\n1. Introduction {#jgf250-sec-0001}\n===============\n\nCeliac artery compression syndrome is defined as chronic, recurrent abdominal pain related to compression of the celiac artery by the median arcuate ligament.[1](#jgf250-bib-0001){ref-type=\"ref\"}, [2](#jgf250-bib-0002){ref-type=\"ref\"}, [3](#jgf250-bib-0003){ref-type=\"ref\"}\n\nWe experienced the rare case of a middle\u2010aged female who was diagnosed with celiac artery compression syndrome who recovered with no specific treatment other than gaining weight by changing her dietary habits.\n\n2. Case Report {#jgf250-sec-0002}\n==============\n\nA 56\u2010year\u2010old female patient was evaluated for a 3\u2010week history of postprandial epigastric pain. The pain radiated to her back, sometimes with a cold sweat. Those symptoms started 2\u00a0hours after taking food, mostly after dinner, and continued for 2\u20103\u00a0hours. She had no appreciable past medical history and took no medicine. She was a nonsmoker and drank a can of beer most days of the week. She lost 6\u00a0kg over the previous 4\u00a0years although she explained the weight loss was from the stress of her new career and not from the postprandial pain.\n\nOn examination, her height was 146.4\u00a0cm, body weight 42.9\u00a0kg,"
-"Introduction\n============\n\nEsophageal cancer, the sixth leading cause of cancer-related death, has currently ranked the eighth in the malignant tumors worldwide ([@b1-ol-0-0-7009]). There were 455,800 new esophageal cancer cases and 400,200 deaths estimated in 2012. The incidence rates of esophageal cancer vary internationally, the highest rates are found in Eastern Asia and in Eastern and Southern Africa and the lowest rates are found in Western Africa. There are two main histological types of esophageal cancer, including squamous cell carcinoma and adenocarcinoma ([@b2-ol-0-0-7009]). Although, the diagnosis and treatments for esophageal cancer update constantly ([@b3-ol-0-0-7009],[@b4-ol-0-0-7009]), the overall 5-year survival rate is only around 20% ([@b5-ol-0-0-7009]). Therefore, it is important and urgent to elucidate an exactly novel molecular mechanism underlying esophageal cancer formation, which may provide new strategies for the diagnosis and treatments of esophageal cancer in future healthcare.\n\nTG-interacting factor (TGIF) belongs to the three-amino acid loop extension (TALE) subfamily of atypical homeodomain proteins ([@b6-ol-0-0-7009]). Heterozygous loss of TGIF gene causes holoprosencephaly in humans ([@b7-ol-0-0-7009]). It has been reported that TGIF is involved in at least three signaling pathways, including retinoic acid (RA) ([@b6-ol-0-0-7009]), transforming growth factor \u03b2 (TGF-\u03b2) ([@b8-ol-0-0-7009]), and wnt/\u03b2-catenin signaling pathways ([@b9-ol-0-0-7009]). A number of studies have reported that"
-"Cardiovascular disease (CVD) is one of the leading causes of morbidity and mortality globally, accounting for 17.5 million CVD-related deaths annually in the United States and other countries and is projected to rise to almost 23.6 million deaths annually by the year 2030[@b1][@b2]. Although multiple risk factors for progression of CVD, dyslipidemia, which results from one or more abnormalities of blood lipids metabolism, remains a major key factor for this pathology and leads to the development of atherosclerotic plaques[@b3][@b4]. Observational epidemiologic evidence suggests that risk of heart attack in subjects with hyperlipidemia is 3 times higher than those in general population with normal lipid status, whereas a 1% decrease in serum cholesterol is strongly associated with 3% reduction in CVD risk[@b3][@b5]. Moreover, hypertension is also considered to be another important risk factor for CVD, since 60% of strokes and half of ischemic heart disease cases are attributable to elevated blood pressure (BP)[@b6][@b7]. From a public health perspective, nutraceuticals or functional foods composition intervention is considered a first approach in treating and controlling CVD[@b8]. In recent decades, both dietary therapy and pharmacologic interventions were used in CVD patients to improve their lipid profiles or BP. Multiple approaches to diet therapy have"
-"Introduction {#S1}\n============\n\nThe rate of surgical wound infections is strongly influenced by operating room quality, which is determined by the structural features of the facility and its systems and by the management and behavior of healthcare workers \\[[@R01], [@R02]\\]. It has been suggested that the main sources of contamination, especially in clean surgical procedures, are the patient\\'s skin and airborne particles from operating room personnel \\[[@R02], [@R03]\\]. In this regard, a study conducted by the Medical Research Council showed a correlation between microbial air contamination and the incidence of surgical site infections (SSI) in prosthetic joint surgery \\[[@R04]\\]. Hipand knee-replacement operations are common procedures and are performed to improve quality of life in individuals with end-stage joint degeneration. However, SSI can give rise to very severe complications which nullify the efficacy of the procedure. Infection rates after primary total knee arthroplasty reported in the literature range from 0.39% to 2.5%; total hip infection rates are approximately 0.2%-2.2% for primary procedures \\[[@R05]\\]. In addition to the devastating consequences for the patient, such infections have an enormous economic impact on the treating hospital, since they substantially prolong hospitalization and increase costs \\[[@R06]\\]. Approximately 12,000 joint infections occur annually in the United"
-"Data files have been uploaded as Supporting Information.\n\nIntroduction {#sec005}\n============\n\nThe brain's functional architecture of interconnected network-related oscillatory patterns in discrete cortical regions has been well established \\[[@pone.0173448.ref001], [@pone.0173448.ref002]\\]. The signal modalities identifying these networked regions have largely been either resting-state metabolic activity studied with functional magnetic resonance imaging (fMRI) studies \\[[@pone.0173448.ref001]--[@pone.0173448.ref008]\\] or direct cortical electrophysiology from electrodes placed on the surface of the brain, or electrocorticography (ECoG) \\[[@pone.0173448.ref002], [@pone.0173448.ref009]--[@pone.0173448.ref012]\\]. One of the earliest and most robust links between cortical electrophysiological signals and the radiographic blood oxygenation level dependent (BOLD) signal are those physiologic signals within the infraslow frequency band (\\<0.5 Hz) or the slow cortical potential (SCP) \\[[@pone.0173448.ref002]\\]. These resting state SCP networks exhibit a robust functional architecture that persists through all stages of sleep and under anesthesia and represent the physiologic correlate of the BOLD imaging signal \\[[@pone.0173448.ref002], [@pone.0173448.ref013]\\]. While the stability of these networks provides a fundamental understanding of the organization of the brain, understanding how these regions can be perturbed or altered is also critical in defining the brain's ability to adapt while learning and recovering from injury.\n\nDeliberate training and learning appears to strengthen resting state connectivity between brain regions that are mutually engaged"
-"Primary stem cell cultures are complex and heterogeneous systems. In the in vitro culture of human hematopoietic progenitors, soluble factor-mediated feedback inhibition limits the ex vivo expansion of hematopoietic stem and progenitor cells (HSPCs) (Kirouac and Zandstra, [@b8]). Strategies to minimize the impact of emerging mature cell populations have provided some success towards controlling endogenous factor accumulation (Csaszar et al., [@b2]; Madlambayan et al., [@b13]; Sandstrom et al., [@b15]; Yang et al., [@b17]); however, these approaches are typically optimized for a specific set of culture conditions and do not allow for the flexibility to easily accommodate changing culture supplements or input cell compositions. One approach to overcome this limitation would be a cell culture regulation system that allows for in-line or at-line monitoring of soluble signaling factors in the culture media, thereby providing dynamic response to system variations. A major challenge in implementing control strategies for endogenously secreted proteins is their non-linear and dynamic secretion profiles (Csaszar et al., [@b2]) and the low concentration at which they are bioactive. As a result, dynamic regulation of signaling proteins has not yet been integrated into stem cell culture systems.\n\nHerein, we describe the development and demonstration of a real-time control system for"
-"Background {#Sec1}\n==========\n\nAbnormal Wnt/Wingless signaling pathway activation has been reported in many cancers and is supposed to promote proliferation, invasion, and metastasis \\[[@CR1], [@CR2]\\]. Wnt/\u03b2-catenin signaling is active during embryogenesis facilitating new organism formation. Normally, it is down-regulated in differentiated cells, however, the deregulated Wnt signaling is correlated with almost all stages of oncogenesis, from malignant transformation to metastatic dissemination and resistance to treatment \\[[@CR3], [@CR4]\\], it also induces radioresistance in several human cancers including head and neck, breast, nasopharyngeal, esophageal, glioblastoma, and colorectal cancers \\[[@CR5]\\]. Abnormalities of Wnt components such as: mutation in \u03b2-catenin or APC gene, overexpression of Wnt ligands, loss of inhibition of regulatory could induce the activity and stimulates expression of downstream genes, such as: cyclin D1 and c-myc, matrix metalloproteinase-7 (MMP-7), connexin 42, CD44, claudin-1 and so on \\[[@CR6]--[@CR9]\\]. The overexpression of its downstream targets is correlated with the alteration of cell cycle progression, proliferation, invasiveness, Epithelial-mesenchymal transition (EMT), cancer stem cells (CSCs) and contribute to tumorigenesis \\[[@CR6]--[@CR9]\\].\n\nDisabled-2 (Dab2) is a member of the Mammalian/Drosophila disabled gene family, which can stabilizes Axin and serves as an inhibitor of the Wnt pathway \\[[@CR10]--[@CR14]\\]. Lung cancer is now the leading cause of malignant tumor related"
-"1. Introduction {#sec1-insects-10-00106}\n===============\n\nNatural and planted forests encompass \\~300 million hectares and \\~32% of total land area in the US. \\[[@B1-insects-10-00106]\\]. Of these forests, 56% are privately owned and the rest are publicly owned, that is, managed by local, tribal, state, and federal governments \\[[@B1-insects-10-00106]\\]. The western region contains the majority of the country's public forestlands, managed for a mix of uses including timber production, recreation, and conservation, while the eastern US is dominated by private forests, some of which are heavily utilized for timber production \\[[@B2-insects-10-00106]\\]. This leads to vastly different management goals, objectives, and approaches especially under variable political conditions. However, a common goal for these various types of forests across the nation is to maintain their long-term productivity and resilience, as demands and pressure on resources grow with time.\n\nAmerica's extensive and diverse forests, including those in urban areas, provide a basis for multiple uses, including but not limited to timber and fiber extraction; non-timber products; recreation; wildlife habitat; clean water, soil, and air; and carbon sequestration, and are of high economic values to local communities, worth billions of dollars each year \\[[@B3-insects-10-00106],[@B4-insects-10-00106],[@B5-insects-10-00106],[@B6-insects-10-00106]\\]. Further, US forests are rich repositories of local biodiversity with thousands of endemic"
-"1. Introduction {#s1}\n===============\n\nThe atherosclerotic plaque and thrombosis in coronary artery may lead to acute coronary syndrome (ACS) and cause microvascular obstruction (MVO).[@b1] The therapeutic efficacy of percutaneous coronary intervention (PCI) may seriously deteriorated in the presence of MVO or no-reflow.[@b2] A previous report indicated that 57% of patients demonstrated MVO even if PCI was successful.[@b3] In addition, some evidence has indicated that the presence of MVO or no-reflow predicted poor clinical outcomes independent of myocardial infarct size.[@b4] Furthermore, patients who displayed ST-segment elevation myocardial infarction (STEMI) with MVO had a three-fold higher mortality rate than those without MVO after PCI.[@b5] Studies have demonstrated that myocardial injury caused by MVO is characterized by persistent ischemia/hypoxia (IH) of cardiomyocytes after microembolization.[@b6] However, the molecular mechanisms underlying the regulation of MVO remain elusive.\n\nAutophagy contributes to the maintenance of intracellular homeostasis and plays a significant role in cardiac physiology, and its dysregulation could lead to a variety of cardiovascular diseases.[@b7],[@b8] Autophagy of cardiomyocytes can be activated under pathological stress conditions to inhibit apoptosis, and the level of apoptosis is negatively correlated with autophagy levels.[@b9],[@b10] On the other hand, suppression of autophagy can result in cell death and heart dysfunction.[@b11],[@b12] Therefore, targeted"
-"The authors confirm that all data underlying the findings are fully available without restriction. All relevant data are are available from the GenBank database and accession numbers are provided in the Supporting Information file S2.\n\nIntroduction {#s1}\n============\n\nThe genus *Meconopsis* Vig. includes about 50--60 species that are distributed mainly in the Qinghai-Tibetan plateau (QTP) [@pone.0104823-Taylor1]--[@pone.0104823-Yoshida1] and is a symbol of the Himalayan alpine flowers. The only European species, *Meconopsis cambrica* is distributed in the humid and shady deciduous forests of Ireland and from south-west England to Northern Spain. The genus is well known as the 'Himalayan blue poppy' and has fascinated the Western world because of its attractive flowers [@pone.0104823-Taylor1]--[@pone.0104823-Yoshida2]. Species of this genus can also be found in some European gardens, since they were introduced in these regions about two centuries ago. However, the taxonomy and phylogeny of the genus of this famous garden plant species remain largely unresolved [@pone.0104823-Wu1], [@pone.0104823-Egan1], [@pone.0104823-Toshio1].\n\nThe genus *Meconopsis* was founded in 1814 on the basis of the single European species *Papaver cambrica* L. [@pone.0104823-Taylor1]. This species is different from typical *Papaver* species because of the presence of a short style and the complete absence of a sessile stigmatic disc surmounting the"
-"Background {#Sec1}\n==========\n\nOn April 12, 2019, new recommendations from the Global Initiative for Asthma (GINA) were released \\[[@CR1]\\]. Initially, the report was available only in a shortened form (a \"pocket guide\"), yet it heralded a long-awaited breakthrough in asthma management, especially regarding the approach to intermittent and mild asthma treatment.\n\nAccording to GINA experts, changes proposed in the 2019 report are the most fundamental change to asthma therapy in the last 30\u00a0years, which is approximately since the first guidelines were developed.\n\nIn brief, currently experts recommend introducing anti-inflammatory treatment at the very initiation of asthma therapy, i.e., all adults and adolescents with mild asthma should receive low-dose inhaled corticosteroids (ICS) either for symptom-driven use or as a regular daily medication to reduce the risk of serious exacerbations. The withdrawal of the recommendation for on-demand short-acting \u03b22 agonists (SABA) as monotherapy as the first step of asthma treatment and the introduction/addition of symptom-driven ICS treatment on the first/second step of asthma therapy is the major paradigm shift from the previous GINA report.\n\nThe main goal of these changes is to reduce the risk of serious asthma exacerbations and asthma-related deaths in the population of patients with mild asthma. It"
-"1. Introduction {#sec1-diseases-05-00003}\n===============\n\nVisual impairment and blindness are important issues in public health systems around the world. Visual impairment is defined as a corrected visual acuity of 6/18 or worse in the better-seeing eye, and is estimated to affect approximately 285 million individuals worldwide \\[[@B1-diseases-05-00003]\\]. Blindness is believed to affect 39 million of the total visually impaired population, and is defined as a corrected visual acuity of 3/60 or worse in the better-seeing eye \\[[@B2-diseases-05-00003]\\]. The global issue of visual impairment and blindness is felt in New Zealand with close to 125,000 New Zealanders aged 40 or over (6.1% of the population in that age group) facing a form of visual impairment \\[[@B3-diseases-05-00003]\\]. Of this population, 12,000 New Zealanders suffer from blindness and 86% of these cases occur among individuals aged 70 or over. The number of people aged 40 and over suffering from visual impairment is expected to rise to 174,000 by 2020, and those suffering from blindness will rise to 18,300 \\[[@B1-diseases-05-00003],[@B2-diseases-05-00003]\\].\n\nThere are three primary causes of visual impairment, including: cataracts (CAT), age-related macular degeneration (AMD), and glaucoma (GLA) \\[[@B1-diseases-05-00003]\\]. These three ocular diseases induce damage to the eye through mechanisms of oxidative stress \\[[@B3-diseases-05-00003]\\]. The"
-"Introduction {#Sec1}\n============\n\nMature blood cell lineages originate from a pool of self-renewing hematopoietic stem cells (HSCs) and are an attractive source for stem-cell-based therapies like hematopoietic stem cell transplantation (HSCT) that offer a potential cure for various malignant (leukemia, lymphoma, and myeloma) and non-malignant (aplastic anemia) hematologic disorders. Currently, bone marrow (BM), umbilical cord blood (UCB), and peripheral blood from G-CSF (granulocyte-colony stimulating factor) treated donors are the major sources of stem cells for transplantation, and peripheral blood stem cell transplantation (PBSCT) is the most common and widely used procedure in the clinical setting^[@CR1]^. However, issues regarding the yield of transplantable HSCs still prevail, especially in the context of UCB transplantation^[@CR2]^, despite the recent increase in the number of suitable donors and the success of haploidentical HSCT^[@CR3]^. As low HSC numbers at transplantation have been associated with greater incidence of graft failure, delayed hematopoietic recovery, slow immune reconstitution, and early mortality, even in PBSCT recipients^[@CR4]^, protocols that facilitate the *ex vivo* expansion of HSCs represent an important step to overcome these limitations. Further, efficient *ex vivo* expansion of genetically modified HSCs, obtained using novel gene editing techniques, can potentially be applied in patients with inborn genetic diseases (e.g. hemoglobinopathies)^[@CR5]^."
-"INTRODUCTION {#s1}\n============\n\nMicroRNAs (miRNAs) are important regulators of cell signaling pathways crucial for the growth of human cancer cells \\[[@R1]\\]. Cancer-associated miRNAs are located downstream of major oncogenes and tumor suppressor genes that act as transcription factors \\[[@R2]\\]. Alterations in miRNAs can result in cancer genesis and progression. For example, levels of some miRNAs are decreased in human cancers \\[[@R3]\\]. Therefore, understanding the regulatory function of miRNAs during tumor progression will contribute to the development of targeted molecular therapies.\n\nA member of the miRNA-200 family, miRNA-200c (miR-200c), recently was found to have tumor-suppressive properties by inhibiting the epithelial-mesenchymal transition (EMT) process in several cancers. In primary glioblastoma multiforme (GBM) tissues, miR-200c and E-cadherin were found to be downregulated when epidermal growth factor receptor (EGFR) was highly amplified \\[[@R4]\\]. *EGFR* wild-type non-small cell lung cancer (NSCLC) cell lines regained sensitivity to EGFR tyrosine kinase inhibitors when EMT was inhibited by miR-200c overexpression \\[[@R5]\\]. miR-200c also interacts with various cellular signaling molecules and regulates many important signaling pathways, such as STAT3, PI3K/Akt \\[[@R6]\\], and ERK \\[[@R7]\\]. Clinically, analysis of patient data using The Cancer Genome Atlas (TCGA) datasets showed that decreased miR-200 family expression was associated with poor overall survival in"
-"INTRODUCTION\n============\n\nOn March 11^th^, 2020, the World Health Organization declared the outbreak caused by the novel coronavirus (SARS-CoV-2), the coronavirus disease 2019 (covid-19), as pandemic. The disease is responsible for more than 180 thousand deaths worldwide, with approximately 4,000 occurring in Brazil until the end of April 2020 (https://coronavirus.saude.gov.br/). Fatality rates have varied among countries depending on factors that influence both numbers of confirmed cases and registered deaths, as well as the proportion of at-risk individuals in the population (older adults, people with chronic diseases), access to health services, availability of accurate diagnostic tests and resources to deal with severe and critical cases (ICU, mechanical ventilators, trained health care professionals).\n\nA huge number of studies has helped clarify clinical profiles of SARS-CoV-2 infection, showing consistently that the presence of chronic morbidities such as diabetes mellitus (DM) and its associated diseases (obesity, hypertension, and cardiovascular disease) represent major risk factors for the severity and prognosis of the disease, in addition to advanced age. Accumulated evidence has caused a great concern in countries with high prevalence of these morbidities such as Brazil.\n\nThis text shows the picture of diabetes in Brazil, followed by epidemiological data and explanatory hypothesis for the association"
-"Background {#Sec1}\n==========\n\nPositron imaging is widely used to non-destructively visualize the dynamics of positron-emitting radionuclides in vivo. The most common use of positron imaging is cancer screening by positron emission tomography (PET), which exploits the tendency of fluorodeoxyglucose labeled with the positron-emitting radionuclide ^18^F to accumulate in cancer cells. In addition, PET has been used in medical research to analyze the kinetics of drugs labeled with ^11^C, ^13^N, and ^15^O. Meanwhile, in recent years, positron imaging has been used to study plants in research facilities around the world \\[[@CR1]--[@CR8]\\]. A recent review article emphasized the advantages of positron imaging for understanding the function of the xylem and phloem \\[[@CR9]\\].\n\nBecause the major and minor essential elements for plants have a number of positron-emitting radionuclides, positron imaging is a potentially useful tool for understanding the mechanisms of nutrient transport in plants. The radionuclides typically used for positron imaging of plants are limited to ^11^C, ^13^N, ^15^O, and ^18^F, which are processed using well-established purification methods developed for medical research \\[[@CR3], [@CR9]\\]. We have previously studied positron imaging of minor essential and toxic elements, such as ^64^Cu (half-life: 12.7\u00a0h) \\[[@CR10]\\] and ^107^Cd (half-life: 6.5\u00a0h) \\[[@CR11]--[@CR16]\\], using the positron-emitting tracer"
-"Introduction\n============\n\nScotland has seen a halving of mortality from coronary heart disease in the past two decades.[@ref1] However, cardiovascular mortality in this country is still among the highest in Europe and globally.[@ref2] In other countries with high but declining coronary heart disease mortality, several reports suggest that these trends are changing.[@ref3] [@ref4] [@ref5] [@ref6] Slowing or flattening of the decline in coronary heart disease mortality in young adults has now been reported in England and Wales,[@ref5] the United States,[@ref6] France, Australia,[@ref3] and New Zealand.[@ref4]\n\nThe pattern for trends in major cardiovascular risk factors is also changing, with dramatic increases in obesity and diabetes in all industrialised countries,[@ref7] flattening of falls in blood pressure in US women,[@ref8] and persistent smoking in young adults in the United Kingdom and elsewhere.[@ref9] Recent trends in cardiovascular risk factors among Scottish adults present a correspondingly complex picture. Considerable progress was seen between 1997 and 2003, with decreases in physical inactivity, dietary intake of fat and salt, and smoking (which reached government targets set for 2010).[@ref10] However, recent substantial rises in obesity and diabetes among young adults raise concerns about subsequent increases in their coronary heart disease mortality.[@ref11]\n\nBecause most cardiovascular risk factors are powerfully"
-"All relevant data are within the paper and its Supporting Information files.\n\nIntroduction {#sec001}\n============\n\nThe development of urban rail transit systems (URTS) has been proposed as a coping strategy to relieve traffic congestion around the world. A URTS not only has the properties of large capacity with less land occupation, but also has the advantages of energy conservation, environmental protection, high safety and reliability. It is a sustainable transportation mode.\n\nUrban traffic demand is known as the time-varying origin--destination (O-D) demand. For example, during the morning rush hour, passengers gather from places of residence to their work place; during the afternoon rush hour, passengers disperse from their work place to other places. The time-varying demand makes the URTS operation complex.\n\nThe core of the URTS operation is the train schedule. A high-quality schedule must fit the time-varying flow, i.e., it should have a high train frequency when the flows are large in some time intervals. Train schedule design of urban rail network is a rather complex problem with considering the time-varying demand. To simplify the schedule design problem, it is always divided into the schedule design for each single rail line \\[[@pone.0188874.ref001]--[@pone.0188874.ref002]\\]. Niu and Zhou \\[[@pone.0188874.ref001]\\] used the time-varying"
-"Introduction {#s1}\n============\n\nHumans have the ability to detect fine features of textured surfaces and to discriminate between them using *direct, active finger touch* (Katz, [@B12]; Sathian et al., [@B27]; Connor et al., [@B1]; Libouton et al., [@B20]). During this exploration mode, the tactile roughness discrimination is believed to be mediated through two combined mechanisms. Firstly, a spatial code represents texture information spatially, through the distributed activation of populations of adjacent mechanoreceptors. This channel is thought to rely on slowly adapting (SA1) mechanoreceptors (Connor et al., [@B1] and Connor and Johnson, [@B2]) and the density of the mechanoreceptors naturally limits its resolution. Secondly, a temporal code represents the time-dependent variations of the finger-surface interaction due to their relative movement. Depending on the temporal frequency of the stimulation, either rapidly adapting (RA) or Pacinian (PC) systems are thought to encode these vibrations (Muniak et al., [@B24]). Textured surfaces can also be felt *indirectly*, namely by actively exploring a surface through a probe being held in the hand (indirect touch) (Klatzky and Lederman, [@B13]; Yoshioka et al., [@B35]). During this second scanning mode, roughness is necessarily encoded through vibrations transmitted through the probe to receptors in the hand.\n\nYoshioka et al. ([@B35])"
-"Introduction {#s1}\n============\n\nAlzheimer\\'s disease (AD) is a growing concern in the modern world. It is the most common type of dementia affecting mainly the elderly population. With the better living conditions and longer life span, the number of individuals affected with AD is increasing exponentially [@pone.0032616-Abbott1], [@pone.0032616-Rafii1]. Some of the major changes occurring during AD in the brain are the accumulation of amyloid plaques, tau protein hyperphosphorylation, mitochondrial dysfunction, oxidative and inflammatory stress. The current medications do not seem to be too optimistic in halting the disease, and due to the multifactorial nature of the disease a number of factors have to be taken care of while tackling AD. As a result of this multifactorial and heterogeneous nature of the disease, compounds with multiple properties are very good candidates for treating AD [@pone.0032616-Rafii1]--[@pone.0032616-Iqbal1]. Curcumin is such a versatile compound having multitude of properties. Curcumin is the major polyphenolic compound of *Curcuma longa*, a herbaceous tuberous plant endemic to South Asia. Curcumin (M.W 368.37) is chemically diferuloymethane (C~21~H~20~O~6~) and is a mixture of three major curcuminoids- curcumin, demethoxy curcumin and bis-demethoxy curcumin (Structure of curcumin: [Figure: S1-A](#pone.0032616.s001){ref-type=\"supplementary-material\"}). It has a broad spectrum of biological and pharmacological activities which has been"
-"###### What is already known on this topic?\n\n-   Therapeutic hypothermia for 72 hours reduces brain injury on neonatal MRI and improves later neurodevelopmental outcomes after moderate or severe hypoxic-ischaemic encephalopathy (HIE).\n\n-   Despite a lack of evidence, many cooling centres in the UK and in other high-income countries routinely cool babies with mild HIE.\n\n###### What this study adds?\n\n-   Whole-body cooling initiated within 6 hours of birth and continued for 72 hours reduces cerebral metabolite perturbations and white matter brain injury seen on MRI.\n\n-   A small proportion of the non-cooled babies with mild HIE may develop seizures after 6 hours of age and progress to moderate HIE.\n\nIntroduction {#s1}\n============\n\nSeveral major cooling trials in the past decade provide conclusive evidence for the safety and efficacy of cooling therapy in improving survival without disability after moderate or severe hypoxic-ischaemic encephalopathy (HIE) in high-income countries.[@R1] These trials excluded babies with mild HIE, and hence the optimal neuroprotective strategies for these babies remain unclear. Although adverse neurodevelopmental outcomes at 2 years or more are seen in up to 25% of infants with mild HIE, pooled data from clinical trials involving 117 babies fail to show any benefits of therapeutic"
-"Sobhani et al: Serum ferritin levels and irregular use of iron chelators predict liver iron load in patients with major beta thalassemia\n\nExcess iron load, resulting from increased gastrointestinal absorption and repeated red blood cell transfusions, in patients with thalassemia heralds a wide range of complications, including arrhythmia and congestive heart failure ([@R1]). Almost 50% of patients with beta-thalassemia major (TM), a transfusion-dependent form of thalassemia syndromes, are affected by myocardial siderosis before the age of 35 and are at risk of congestive heart failure ([@R2]) as a major cause of morbidity ([@R3]). Also, it is important to point out that in patients with beta TM, transfusion-dependent complications comprise the highest share of economic ([@R4]) and global burden ([@R5]).\n\nTwo main predictors of survival in TM patients are iron load in organs and adherence to chelating drugs ([@R6]). Indeed, persistent serum ferritin above 2500 ng/mL and liver iron concentration (LIC) above 15 mg/g dry weight can significantly predict 10-year survival of patients with TM ([@R7]). Currently there are three available iron-chelating drugs: deferoxamine (DFO) as the first available agent, deferiprone (DFP), and deferasirox (DFX) ([@R6]), which are shown to be equally effective in preventing complications ([@R8],[@R9]).\n\nMagnetic resonance imaging (MRI)"
-"INTRODUCTION\n============\n\nThe Shockley-Queisser efficiency limit for converting light into electricity exists mainly as a result of the spectral loss of photon energy below and above the absorber's bandgap. For instance, any excess energy of an above-bandgap excitation will dissipate as loss in conventional devices. However, if this excess energy can be used to excite secondary carriers, leading to carrier multiplication, it is possible to outperform the standard limit ([@R1]). The realization of this goal hinges on the identification of suitable physical systems, where both the multiplication process occurs and the subsequent carrier extraction efficiency is high. Among the promising candidates, such as quantum dots or carbon nanotubes, graphene has an outstanding potential because of its broadband absorption, ultrahigh carrier mobility, and structural flexibility. Recent ultrafast optical and photoemission measurements have revealed multiple hot-carrier generation per photon excitation in moderately doped graphene due to strong carrier-carrier scattering ([@R2]--[@R6]). In principle, this process minimizes spectral loss because graphene has zero gap and all the absorbed photons release their energy efficiently by generating useful hot carriers, making graphene an excellent platform for light-harvesting. However, effective conversion of these hot carriers into current has not been shown in graphene optoelectronic devices, which have"
-"Background {#sec1}\n==========\n\nSodium plays an important role in regulating different physiological functions in broiler chickens. Along with potassium and chlorine, the other regulators of dietary electrolyte balance (DEB), Na is of utmost importance for tissue protein synthesis, cellular homeostasis and the body's acid--base balance, to ensure optimum performance of broilers \\[[@B1]\\]. DEB may be defined by the following formula: DEB (mEq/kg) = Na^+^ + K^+^ \u2212 Cl^\u2212^ and 250 mEq/kg of DEB is suggested to be optimum for broiler growth and litter quality \\[[@B2]\\]. The intestinal uptake and absorption of different nutrients, particularly glucose and amino acids, are influenced by Na because of its involvement in Na-dependent transport systems and Na-K-ATPase activity \\[[@B3],[@B4]\\]. Low Na can have a negative impact on broiler performance \\[[@B2]\\], whereas mortality rate and wet litter problems are increased by excess Na in diets \\[[@B5]\\]. Although, in 1994, the NRC \\[[@B6]\\] recommended 2.0 and 1.5 g/kg Na in starter and grower chicken diets, uncertainty exists about the optimum level of Na necessary for maximum performance.\n\nExogenous microbial phytase is commonly used in poultry diets to replace inorganic phosphates and reduce the anti-nutrient effect of phytate. The benefit of phytase supplementation on diet costs, bird performance,"
-"A national outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019 in Wuhan, China, rapidly evolving to the coronavirus disease 2019 (COVID-19) pandemic. Neurologic complications of COVID-19 include headache, confusion, hyposmia, and dysgeusia,^[@R1]^ with encephalitis being rarely reported. Coronaviruses can potentially invade the CNS through trans-synaptic propagation via nasal entry, likely causing hyposmia. Alternatively, CNS dysfunction may result from the systemic hyperinflammatory response to the virus. We report 2 patients supporting this hypothesis.\n\nPatient 1 {#s1}\n=========\n\nA 25-year-old healthy man presented with 1-day history of headache, left-sided paresthesias, and ipsilateral paresis progressing within 12 hours to confusion and agitation. His axillary temperature was 38.2\u00b0C. Brain CT and MRI scans were normal. CSF showed lymphocytic pleocytosis and increased proteins. He was started on IV acyclovir, ampicillin, and ceftriaxone, which were discontinued when CSF cultures and PCR ruled bacterial or viral etiologies. PCR of SARS-CoV-2 was negative in CSF but positive in the nasopharyngeal swab. On day 2, he fully recovered except for amnesia of the previous 2 days.\n\nPatient 2 {#s2}\n=========\n\nA healthy 49-year-old man presented with fever, myalgias, and dry cough lasting 1 week. A few hours after admission, he developed difficulty naming objects,"
-"INTRODUCTION {#sec1_1}\n============\n\nWith a maternal mortality ratio (MMR) of approximately 445 per 100,000 livebirths, the state of Rajasthan contributes significantly to India\\'s burden of maternal deaths ([@B1]). The context of Rajashan sets the stage for this high MMR, both in terms of its terrain and the sociocultural environment of women\\'s lives. This paper reviews the context of maternal health in Rajasthan and the development and present status of maternal health services in the state.\n\nWith a land area approximating 10% for India, Rajasthan is the largest state in the country. More than 60% of the state\\'s total land area is desert, characterized by extreme temperature, low rainfall, and sparse habitation (Fig. [1](#F1){ref-type=\"fig\"}). It is also the eighth most populous state of India, with a total population of 56.4 million (Census 2001), three-quarters of which lives in rural areas (Table [1](#T1){ref-type=\"table\"}) ([@B2]). The decadal growth rate continues to be high compared to other states. Over 90% of the population follows the Hindu faith, followed by 9% Muslims ([@B3]). Hindus constitute a larger proportion (95%) in the southern and south-eastern regions. Most working people in Rajasthan are engaged in agriculture and animal husbandry, although the situation in some regions is changing"
-"Background\n==========\n\nAngiomyolipomas (AMLs) are well-characterized triphasic tumors composed of varying amounts of vascular (thick-walled dysplastic or dysmorphic blood vessels), smooth muscle (spindled or epithelioid with clear cytoplasm) and mature adipose elements \\[[@B1]\\]. AML usually occurs in the kidney, but can occasionally involve the liver and retroperitoneum. AML comprise 2.0--6.4% of all renal tumors, however they represent one of the most common benign renal lesions \\[[@B1]\\]. AML can occur as an isolated renal lesion or as part of the tuberous sclerosis complex (TSC). Approximately 50% of patients with TSC develop AML, which tend to be bilateral and multifocal \\[[@B2]\\]. The triphasic nature of AML has led many in the past to consider these lesions as hamartomatous. However, recent detection of clonal genomic alterations \\[[@B3]-[@B5]\\] and rare case reports of malignancy in AMLs \\[[@B1],[@B6]-[@B8]\\] favor their classification as neoplastic lesions. AMLs share morphologic and immunohistological features with perivascular epithelioid cell (PEC), and are considered to be among the growing family of tumors derived from these distinctive cells, also referred to as PEComas, and that includes clear cell (\\\"sugar\\\") tumors of the lung and pancreas, and lymphangioleiomyomatosis \\[[@B9],[@B10]\\]. Although the diagnosis of AML is usually straightforward, some cases showing predominance of any"
-"Introduction {#sec1-1}\n============\n\nBrown tumors are not true tumors and arise in the settings of excess osteoclast activity caused by excretion of parathyroid hormone in association with hyperparathyroidism. Brown tumor affects multiple bones in the body with variable clinical symptoms, which may be misdiagnosed as multiple bone metastases or primary bone tumor. Microscopically, giant cell tumor (GCT) and brown tumor of hyperparathyroidism (BTH) have a similar finding containing giant cells and spindle-shaped cells in fibrous matrix but treatment-wise, both these conditions are totally different.\n\nCase Report {#sec1-2}\n===========\n\nA 42-year-old female patient presented with history of bone pain in the upper region of the left tibia. Magnetic resonance imaging (MRI) showed an expansile lesion in the metadiaphyseal region of the upper one-third region of the left tibia. A biopsy from tibial lesion showed large osteoclastic giant cells in a background of spindle-shaped cells and mononuclear cells. A diagnosis of giant cell tumor (GCT) was made and the patient was treated with curettage and bone grafting followed by local radiotherapy. Subsequently, bone scan was done for metastatic workup of the GCT. (a) 99mTc-methoxyisobutylisonitrile (MIBI) bone scan [Figure 1a](#F1){ref-type=\"fig\"} showed multiple foci of increased uptake in the skull bones, mandible, and axial"
-"Introduction {#Sec1}\n============\n\nAtomoxetine is the first non-stimulant medication approved for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children, adolescents, and adults. It has a potent and selective inhibitory effect on norepinephrine reuptake^[@CR1],[@CR2]^. Guidelines from several organizations, including the American Academy of Pediatrics and the National Institute for Health and Care Excellence in the United Kingdom, recommend atomoxetine for the treatment of ADHD in patients of all ages.\n\nOne *in vitro* study found that the main metabolic pathway of atomoxetine is its oxidation to 4-hydroxyatomoxetine (4-HAT) by CYP2D6. To a minor degree, CYP2C19 is responsible for the biotransformation of atomoxetine to N-desmethylatomoxetine (N-DAT)^[@CR3]^. 4-HAT is equipotent to atomoxetine, but promptly undergoes further glucuronidation to 4-HAT-O-glucuronide and therefore circulates in the plasma at very low concentrations^[@CR4]^. The same study also indicated the effect of the CYP2D6 phenotype on the pharmacokinetics of atomoxetine. CYP2D6 is a highly polymorphic enzyme with more than 113 known variants (<https://www.pharmvar.org/gene/CYP2D6>). Among others, *CYP2D6\\*3*, *\\*4*, *\\*5*, and *\\*6* are defective alleles that lack CYP2D6 enzyme activity. These alleles occur in \\~20% of Caucasians. Approximately 7% of Caucasians are known to be poor metabolizers (PMs) due to presence of two non-functional alleles^[@CR5],[@CR6]^. Oral administration of atomoxetine resulted in"
-"1. Introduction {#sec1-molecules-21-00609}\n===============\n\nThe discovery of selenium by the Swedish chemist J.J. Berzelius in 1817 initiated studies evaluating the influence of the inorganic forms of this element on living organisms. Unexpectedly, in 1957, Schwartz and Folz demonstrated the protective effect of selenium on organisms. Thanks to these studies, selenium was included in a group of trace elements whose deficiencies in the diet may cause numerous diseases. Due to the biological activity of selenium and its importance in human and animal nutrition, this element has an impact on health improvement and the immune system \\[[@B1-molecules-21-00609],[@B2-molecules-21-00609]\\].\n\nSelenium deficiency in the diet may have an adverse effect on health. Dietary selenium deficiency affects 0.5--1 billion people in the world, and currently, in many countries there is an inadequate intake of this element \\[[@B3-molecules-21-00609]\\]. According to the World Health Organization (WHO), the maximum daily intake of selenium should not exceed 70 \u03bcg/day \\[[@B1-molecules-21-00609]\\]. One should strive to adhere to the recommended supply dosage as well as the upper tolerable intake limit of this element. Selenium doses above 400 \u03bcg/day to 700 \u03bcg/day may exert toxic actions. The average content of selenium in the daily diet is far from the recommended content of this"
-"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"
-"Introduction\n============\n\nMethane is the second most abundant greenhouse gas after carbon dioxide (CO~2~), which accounts for 14% of global greenhouse gas emissions (EPA [@b14]). The concentration of methane in the atmosphere has increased \u223c2.5 times than the preindustrial level, rising from 720\u00a0ppb in 1750 to 1803\u00a0ppb in 2011 (Hartmann et\u00a0al. [@b24]). Although the methane concentration in the atmosphere is lower than the CO~2~ concentration (391\u00a0ppm), methane is 25-fold more effective in trapping heat in the atmosphere than CO~2~ on a per-molecule basis (IPCC [@b31]). Methane contributes to \u223c30% of the anthropogenic warming, with the radiative forcing of 0.48\u00a0Wm^\u22122^ in 2011 (Myhre et\u00a0al. [@b57]). After maintaining a relatively stable level for approximately a decade in the 1990s, the atmospheric methane concentration began to grow in 2007 (Hartmann et\u00a0al. [@b24]). The concentration of methane in the atmosphere is determined by the balance of sources and sinks. The anaerobic oxidation of methane (AOM) is an important sink of the atmospheric methane concentration (Conrad [@b6]), which significantly impacts global warming. In marine sediments, the total amount of gas hydrates is up to 150--3000 times the atmospheric methane concentration (500,000--10,000,000\u00a0Tg CH~4~) (Reeburgh [@b71]). Fortunately, most of"
-"Introduction\n============\n\nRecently, using Fiber-Reinforced Composites (FRC) which can be mostly used instead of the fixed metal framework prostheses, has been more advocated due to the enormous demands for the conservative and esthetic restoration. Compared with fixed metal dental prostheses, this type of restoration is lighter and more elegant. In addition, it can be attached to the dental tissues and will cause less harm to the remained teeth \\[[@B1]\\]. Although the durability of these types of prostheses is smaller than the metal frameworks, the cost and the time consumed to prepare such conservative prostheses are lesser \\[[@B1]\\]. FRC\\'s durability has been reported differently in the related studies, so that the overall durability rate of 75 to 94.75 percent has been reported after three to five years \\[[@B2]-[@B4]\\].\n\nFRC is a combination of fiber and resin matrix. Fiber is the reinforcing part, providing stability and stiffness, whereas resin matrix is the protecting part, producing the reinforcement and the ability to work with the material \\[[@B5]-[@B6]\\]. The mechanical characteristics and the effectiveness of the fiber reinforcement in FRC are based on the type of the fiber (Glass, Carbon, Polyethylene, Aramid), quantity of fibers, fiber structure including unidirectional, bidirectional and randomly oriented fiber,"
-"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"
-"All data files are available from the <https://figshare.com/s/5297ddc238766def6afc> and supporting information file.\n\nIntroduction {#sec001}\n============\n\nCloud computing has become a new computing model that provides elastic, on-demand and robust services \\[[@pone.0173666.ref001]\\]. Services in cloud computing may be virtualized with specific servers that host abstracted details \\[[@pone.0173666.ref002]\\]. Many legacy applications are being migrated to the cloud computing platform \\[[@pone.0173666.ref003]--[@pone.0173666.ref004]\\]. In cloud computing, the cloud service environment can be dynamic and unexpected because servers may be active, busy, offline or may have even crashed for various reasons \\[[@pone.0173666.ref005]\\]. It is important to address the variability and provide an effective control scheme to guide service conditions and cloud resources (such as energy and throughput management \\[[@pone.0173666.ref006]--[@pone.0173666.ref007]\\]). Fault tolerance schemes are designed to provide reliable and continuous services in cloud computing despite the failures of some servers \\[[@pone.0173666.ref008]--[@pone.0173666.ref010]\\]. As an essential building block for cloud computing, a failure detector (FD) plays a key role in the engineering of such dependable systems \\[[@pone.0173666.ref011]\\]. Effective failure detection can detect failures in a timely and accurate way. In cloud computing, the FD adapts to the various network conditions. Moreover, it is necessary to satisfy different quality of service (QoS) requirements of multiple cloud applications simultaneously \\[[@pone.0173666.ref012]\\].\n\nThe"
-"1. Introduction {#s0005}\n===============\n\nFungal infections kill more than 1.5 million people every year \\[[@bb0005],[@bb0010]\\]. Despite the high mortality rates, diseases caused by fungi are still underappreciated by decision makers and the general public, representing, therefore, a major problem of public health \\[[@bb0015]\\]. There are only four major classes of antifungal drugs currently in clinical and agricultural use: azoles (inhibitors of ergosterol synthesis, a major plasma membrane component), polyenes (ergosterol-binding compounds), echinocandins (inhibitors of \u03b2-1,3-glucan synthesis), and *pyrimidine analogues* (inhibitors of nucleic acid synthesis). These drug classes are ineffective in a number of cases, which is linked to toxicity, low bioavailability in target tissues and antifungal resistance \\[[@bb0020]\\]. In this scenario, morbidity and mortality rates due to fungal infections remain high, which highlights the need for studies on new antifungal targets and compounds \\[[@bb0015]\\].\n\nFungal membranes and membrane-associated biosynthetic and metabolic pathways are important targets for antifungal compounds and prophylactic strategies \\[[@bb0025], [@bb0030], [@bb0035], [@bb0040], [@bb0045]\\]. Composed of a double layer of lipids, cellular membranes provide a permeability barrier and an interface between the interior and exterior of a cell and between compartments within the cell. Each membrane is composed of hundreds of different lipid species and has its own"
-"1. Introduction {#sec1-nutrients-12-00321}\n===============\n\nHepatitis B virus (HBV) infection is a global disease. Approximately two billion people worldwide have been infected with HBV, more than 350 million people are chronic carriers \\[[@B1-nutrients-12-00321]\\], and more than 780,000 die each year from acute or chronic HBV infection \\[[@B2-nutrients-12-00321]\\]. In North America, the prevalence of asymptomatic hepatitis B in adults is 0.5%; the prevalence of asymptomatic adults in Taiwan is about 15%, indicating that Taiwan is a high-prevalence area of HBV infection. A hepatitis B vaccine program for newborns with hepatitis B surface antigen-positive mothers has existed since July 1984 in Taiwan. In July 1986, hepatitis B vaccination of infants and young children was fully implemented. Thereafter, the hepatitis B carrier rate of six-year-old children significantly decreased from 10.5% in 1989 to 0.8% in 2007, but there are still 2.8 million to 3.3 million chronic hepatitis B carriers (CHB). Chronic hepatitis B carriers are a high-risk group for cirrhosis and hepatocellular carcinoma. About 50% of CHB die from liver cancer or cirrhosis in Taiwan \\[[@B3-nutrients-12-00321]\\].\n\nHepatitis B virus is a deoxyribonucleic acid (DNA) virus with a diameter of 42 nm. The virus is covered with a lipoprotein coat, which contains the hepatitis B"
-"Introduction\n============\n\nObesity is worldwide epidemic with 1.5 billion adults (age\u2009\\>\u200920\u2009years) and 43 million children under the age of 5 overweight, of which approximately 500 million are clinically obese (BMI\u2009\\>\u200930; WHO, [@B59]). Obesity and its comorbidities impose a substantial healthcare burden which are associated with mounting international healthcare costs (Eckel et al., [@B21]; Ashrafian et al., [@B5]). Although several treatment strategies such as lifestyle modification (Wing and Phelan, [@B60]) and medications have been used to combat obesity, their long-term efficacy has yet to be demonstrated. Bariatric surgery, also called weight loss or metabolic surgery, was introduced 50\u2009years ago to provide drastic weight loss in morbidly obese patients (Kremen et al., [@B31]; Ashrafian et al., [@B6]) and is now increasingly used to treat patients with lower adiposity, or occasionally purely for metabolic benefit (Ashrafian et al., [@B4]). Currently the three most common types of bariatric surgery are the Roux-en-Y gastric bypass (RYGB), Adjustable Gastric Band and the Sleeve Gastrectomy. Of these, the RYGB is considered to be the \"gold standard\" procedure due to its established efficacy, metabolic benefits, and safety from side effects. Typically the RYGB operation is performed laparoscopically and consists of the creation"
-"INTRODUCTION\n============\n\nAntibiotics have served as the corner stone of modern medicine. Emergence of antibiotic resistance is a worldwide public health problem and a threat to mankind.^[@B1]^ In India, the burden of infectious disease is highest among the world; and recent reports showed the inappropriate and irrational use of antimicrobial agents against the diseases led to increase in the development of antimicrobial resistance (AMR).^[@B2]^ Besides poor financial conditions, inadequate infrastructure, high burden of disease, and unregulated sales of cheap antibiotics have amplified the crisis of AMR in India.^[@B3],[@B4]^\n\nBacterial infections are a frequent cause of hospitalization, and particularly nosocomial infections are more common in critical care settings.^[@B5]^ Globally the emergence of antibiotic resistance and limited availability of treatment options present an increasing challenge for the management of bacterial infections worldwide. Rate of nosocomial infections range from 5% to 30% among ICU patients. The increased risk of infection is associated with severity of patient illness, length of exposure to invasive devices and procedures, increased patient contact with healthcare personnel, and length of stay in hospital. Over the past 15--20 years, infection control practices and new antimicrobial development have primarily targeted control and treatment of infections caused by gram-positive organisms.^[@B6]--[@B9]^ Recently the"
-"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"
-"The data used in this analysis are available upon request given the data is from a third party---the Haitian Ministry of Health. Additionally, there is too much data from the GHESKIO clinics to publish an anonymized dataset. GHESKIO is the largest provider of HIV services in the Caribbean, and this dataset includes the majority of HIV-infected patients who are in care at GHESKIO. If a researcher would like to have access to the data, they would need to contact Dr. Jean William Pape, the Director of GHESKIO (<jwpape@gheskio.org>). He would then discuss with them specifically what they would want to look at and present it to the Ministry of Health for approval, and the persons requesting data would need to sign a confidentiality agreement before viewing the data.\n\nIntroduction {#sec005}\n============\n\nOver the past decade, the scale-up of HIV services, particularly access to antiretroviral therapy (ART), in resource-poor settings has been enormously successful with over 18 million adults initiating treatment \\[[@pone.0175521.ref001]\\]. While these efforts have saved millions of lives, many patients fail to realize the benefits of ART due to discontinuation of treatment, loss to follow-up (LTF), or death within the first year of treatment \\[[@pone.0175521.ref002]--[@pone.0175521.ref009]\\]. Though the Caribbean is"
-"Introduction {#s1}\n============\n\nAngiogenesis is defined as the formation of new blood vessels from pre-existing vasculature. Angiogenesis is relevant not only to cancer but also to non-neoplastic diseases including macular degeneration, psoriasis, endometriosis, and arthritis [@pone.0015905-Folkman1], [@pone.0015905-Carmeliet1]. The growth and metastasis of tumors are critically dependent on angiogenesis [@pone.0015905-Carmeliet2], [@pone.0015905-Bergers1]. Thus, the inhibition of angiogenesis has become an important therapeutic strategy for cancer [@pone.0015905-Herbst1]. Although the existing anti-angiogenesis therapies have been reported to have less toxicity than conventional chemo or radiotherapy, they are often associated with clinical side effects, and limited tumor regression [@pone.0015905-Thomas1]. Therefore, there has been an increased focus toward development of novel angiogenesis inhibitors and novel approaches to maximize the anti-angiogenic therapies [@pone.0015905-Watanabe1].\n\nHuman apolipoprotein E (apoE) is one of the most frequently studied proteins known to be involved in lipid metabolism and cardiovascular disorders [@pone.0015905-Hill1]. Experimental studies on apoE are focused on its receptor binding region, which is located between residues 130--150 and is critical for its biological activity. This receptor binding region of apoE is known to be responsible for binding apoE to the low-density lipoprotein receptor [@pone.0015905-Mahley1]. Within this receptor binding region, residues 142--147, also known as heparin-binding domain, mediate the attachment of apoE"
-"INTRODUCTION {#sec1-1}\n============\n\nCerebral vasospasm is a serious complication of subarachnoid hemorrhage (SAH); delayed narrowing of the large capacity arteries and cerebral vasospasm are associated with significant morbidity and mortality following a SAH.\\[[@ref6]\\] The anterior choroid artery (AChA) is the most important branch of the supraclinoid segment of the ICA. It supplies the optic tract, uncus, lateral part of the geniculate body, posterior two-thirds of the posterior limbs of the internal capsule, optic radiation, and choroid plexus of the lateral ventricles. The classical features of AChA occlusion include contralateral hemiplegia, hemianesthesia and hemianopsia. Vasospasm of the choroid arteries may be severe when a SAH causes damage to the choroid plexus. This can affect structures that play an important role in immune, endocrine, detoxifying, thermoregulatory, and secretory functions of the brain; such abnormalities are associated with a poor prognosis.\\[[@ref10][@ref23][@ref25][@ref30][@ref31]\\] The response of AChAs, in a rabbit model of SAH, was evaluated in this study.\n\nThe cerebral arteries are innervated by several systems that contribute to the autonomic control of cerebral blood flow. Parasympathetic fibers affect vasodilation and sympathetic fibers cause vasospasm of the cerebral arteries.\\[[@ref16]\\] Cerebrovascular sensory nerves originate mainly from the first division of ipsilateral trigeminal ganglion (TGG), known as"
-"The transition from egg to embryo involves major changes in cell fate and potential, including progression of the cell cycle from meiotic arrest through completion of meiosis to the initiation of mitosis (reviewed in [@bib12]; [@bib20]). This developmental transition involves major molecular changes in the egg including the polyadenylation of some maternal mRNAs (*e.g.*, for *Drosophila*: [@bib5]; [@bib13], [@bib14]) and the degradation of others (*e.g.*, [@bib10]; [@bib17]; [@bib25]), synthesis of new proteins, and phospho-modulation of others ([@bib18]; [@bib23]; [@bib33], [@bib34]). The molecular changes of \"egg activation\" are critical for pronuclear formation and cell cycle modulation, for embryonic patterning and morphogenesis, and for structural and chemical changes to the egg's outer coverings to block polyspermy and support the developing embryo.\n\nRemarkably, most of this transition is driven or conducted entirely by parental (mostly maternal) molecules. In particular, maternally encoded mRNAs drive production of proteins needed for oocyte maturation and maintenance, for reversing this differentiated state after fertilization to permit totipotency, and for initiating early embryonic cell divisions and cell fate decisions. The maternal mRNAs needed for embryonic development must be kept stable until fertilization, and then must be translated at the appropriate time and place (*e.g.*, reviewed in [@bib24]; [@bib40], [@bib39];"
-"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"
-"1. Introduction {#s0005}\n===============\n\nPerioperative blood management is an important consideration in all types of shoulder surgery. With increasing incidence [@b0005], [@b0010] and in some cases, complexity of shoulder surgery, the effects of perioperative blood loss have become more obvious.\n\nThe rate of blood transfusion following shoulder surgery is relatively low [@b0015], [@b0020]. There is significant increased morbidity associated with whole blood transfusion [@b0025], [@b0030]. Excessive bleeding during shoulder surgery may influence length of stay, postoperative pain, swelling, and wound healing. The use of tranexamic acid (TXA) is one method of attempting to reduce blood loss. TXA is synthetic derivative of the amino acid lysine. It is an antifibrinolytic agent that binds reversibly to plasminogen, inhibiting its conversion to plasmin. It therefore stabilises formed clots by preventing fibrin degradation [@b0035], [@b0040], [@b0045].\n\nTXA has been used effectively across different specialties in surgery to reduce blood loss [@b0035], [@b0045]. Recent systematic reviews have demonstrated TXA to be effective in reducing blood loss and transfusion rates in lower limb arthroplasty and spinal surgery [@b0050], [@b0055], [@b0060]. Most recently, clinical trials investigating its use in shoulder arthroplasty have shown favourable results [@b0065], [@b0070], [@b0075], [@b0080], [@b0085], [@b0090]. The overall clinical effectiveness of tranexamic"
-"1. Introduction {#sec1}\n===============\n\nAging is an elevated risk of common diseases, including obesity, hypertension, atherosclerosis, and diabetes \\[[@B1]--[@B3]\\]. Currently, about 800 million people are at least 60 years old, which accounts for about 11% of the world\\'s population, and aging population is estimated to increase to more than 2 billion by 2050 \\[[@B4]\\]. Aging is closely related to damaged adipogenesis in various fat depots in humans \\[[@B5], [@B6]\\]. White adipose tissue (WAT) is considered as an important regulator for multiple physiological processes and highly linked to the development of multiple morbidities \\[[@B7]--[@B9]\\]. Therefore, it is significant and urgent to reveal the relationships of aging and adipose, which is very important for understanding the diseases in the elderly.\n\nPrevious studies have discovered a set of genes that are implicated in the aging process in an adipose depot-dependent manner. For example, age-related increase in*IL-6* (interleukin 6), which was related to stress responses and cellular senescence, was observed in a fat depot-dependent manner \\[[@B5]\\].*Sirt1* (sirtuin 1) and*SOD2* (superoxide dismutase 2), which were correlated with mitochondrial aging, were significantly decreased in aging epididymal adipocytes \\[[@B10]\\]. Furthermore, the expression of*MMP-3* (matrix metallopeptidase 3) was increased in mouse subcutaneous fat cells and human skin fibroblasts"
-"1. Introduction\n===============\n\nBreast cancer is one of the most important female cancers in many countries, and its incidence has increased in recent decades.^\\[[@R1]\\]^ That rise is attributed to the more widespread use of mammography and a consequent earlier detection of the disease. Earlier detection---and therefore earlier treatment---is expected to result in improved survival rates.^\\[[@R2]\\]^ The improvement in survival rates has been related to the concern with quality of life (QOL) among the surviving breast cancer patients.^\\[[@R3]\\]^ With advanced treatment, the role of the patient shifts to that of survivor, and there is a need for continued focus on overall QOL issues.^\\[[@R4]\\]^\n\nGenerally, the evaluating indices of QOL mainly include 2 aspects: information from physician and patient-rated indices. There is some difference between physician and patient-rated indices in survival status of patient with breast cancer. The patient rating is viewed as more useful because it includes subjective information only patients can provide. There is a paradigm shift in evaluating the outcomes of medical care in the past years. The outcome assessment has a more focus on the patients' perception of their health than clinical indexes of disease activity. The term \"patient-reported outcome\" (PRO) has been used to denote the inclusion"
-"INTRODUCTION\n============\n\nAcupuncture has been practiced for thousands of years in Eastern countries to manage pain, and it is now considered as one of the most important strategies in complementary and alternative medicine. Electroacupuncture (EA) is a modified acupuncture technique that utilizes electrical stimulation. Zusanli (ST36) is one of several the acupuncture point that are used for clinical pain control \\[[@B1], [@B2]\\]. Many studies have demonstrated that acupuncture and/or EA stimulation applied to the ST36 acupoint can increase the experimental pain threshold mediated by the release of endogenous opioid peptides \\[[@B3]\\] and/or by activation of the descending pain inhibitory system \\[[@B3]-[@B10]\\].\n\nHowever, there are marked individual variations in the sensitivity to EA, which often cause clinical and experimental difficulties. Previous studies reported that 20\\~40% of rats were insensitive to EA in an acute thermal pain test \\[tail flick latency (TFL) test\\] \\[[@B11]\\]. We previously identified and characterized the genes that cause these differences between the responder rats that were sensitive to EA and the non-responder rats that were insensitive to EA based on the TFL test, using the hypothalamus, a main center of the descending inhibitory system and \u03b2-endorphin secretion \\[[@B12]\\]. Among the genes that were more abundantly expressed in"
-"Introduction {#sec1}\n============\n\nHemangioendothelioma is a vascular neoplasm that was first identified in soft tissues by Weiss and Enzinger.[@bib1], [@bib2], [@bib3] It is very rare found in the bladder.[@bib1], [@bib3]\n\nWe report the second case of hemangioendothelioma in pediatric patient.\n\nCase report {#sec2}\n===========\n\nA 2 years 7 months-old boy presented with painless, intermittent, gross hematuria, and mass in suprapubic region in 6 months duration. He was coming to hospital with severe malnutrition, kidney failure, and obstructive ileus.\n\nRespiratory rate was 30 times/minute. The other vital signs were within normal limit. The abdomen was blunt and mass was palpable in suprapubic region. There was abscess in umbilical region. Laboratory findings showed a hemoglobin level of 5,0\u00a0g per deciliter, 23.300 white blood cells per microliter, 757.000 platelets per microliter, blood urea nitrogen of 121\u00a0mg per deciliter, and creatinine level was 2,34\u00a0mg per deciliter with natrium level was 129 milliequivalents per liter and potassium level was 5,9 milliequivalents per liter.\n\nComputed tomography revealed a 7,33\u00a0\u00d7\u00a07,27\u00a0\u00d7\u00a09,07 cm mass that filled almost of the bladder ([Fig. 1](#fig1){ref-type=\"fig\"}). No regional lymphadenopathy was found. The kidneys showed hydronephrosis. No pulmonary metastatic was found.Figure 1Computed tomography scan showing a large"
-"1. Introduction {#sec1-sensors-16-01198}\n===============\n\nCracking is a major sign of structural aging and damage, which shortens the integrity and service life of structures. While the width of cracks for most ordinary reinforced concrete (RC) structures in civil engineering are over 0.2--0.4 mm, the service life of the structure can be severely shortened due to the erosion of inner steel rebar under harsh environments. Moreover, structures may be damaged if the cracks reach 1--2 mm. Therefore, crack monitoring is essential to guarantee the safety of structures. Currently, many approaches have been developed for crack monitoring, such as ultrasonic methods \\[[@B1-sensors-16-01198]\\], acoustic emission \\[[@B2-sensors-16-01198]\\], infrared thermography \\[[@B3-sensors-16-01198]\\], impact-echo \\[[@B4-sensors-16-01198]\\], large area electronics \\[[@B5-sensors-16-01198]\\], etc. All of the techniques mentioned above show good performance of crack detecting, however, they struggled to be applied in practical engineering due to the installation difficulties and vulnerability in the long-term harsh environment. Recently, the optical fiber sensing technology, such as the Bragg grating, the Michelson white light interferometer, and Brillouin scattering have been widely investigated for crack detecting \\[[@B6-sensors-16-01198],[@B7-sensors-16-01198],[@B8-sensors-16-01198]\\]. However, all of the fibers in the above approaches are silica fibers which are brittle (their elongation rates are only about 1%) \\[[@B9-sensors-16-01198]\\], which make it easy to"
-"Allergic rhinitis (AR) is sustained by mucosal inflammation, which is orchestrated by T helper (Th) 2 cells.^[@B1]^ Th2 cells play an important role in the pathogenesis of AR, as IL-4 promotes isotype switching to IgE synthesis.^[@B2]^ Moreover, regulatory T (Treg) cells play an important role in controlling the Th2-biased response.^[@B3]^ Indeed, a defect in Treg cells has been evidenced in allergic patients.^[@B4]^ Therefore, allergic diseases are presently considered as immunoregulatory disorders.\n\nIn this regard, interest in HLA-G antigens has been shown by the possibility that they may be involved in inflammatory diseases.^[@B5]^ HLA-G is a human, nonclassic major histocompatibility complex molecule expressed in human-privileged sites and plays an essential role in the development of maternal tolerance to genetically different fetal tissues.^[@B6]^ Soluble HLA-G (sHLA-G) derives from the secretion of soluble isoforms as well as from the shedding of proteolytically cleaved surface isoforms. Several HLA-G--mediated mechanisms have been described, including an induction of Th2-like cytokine profile, through stimulation of IL-3, IL-4, and IL-10 secretion.^[@B7]^ Numerous studies provided evidence that sHLA-G serum levels are increased in different pathological conditions, including immune-mediated disorders, transplantation, and malignancies.^[@B8]^\n\nRecently, it has been evidenced that patients with AR due to pollen allergy had significantly higher sHLA-G"
-"1.. Introduction\n================\n\nSurface Plasmon Resonance is known to be a very sensitive technique for determining refractive index variations at the interface between a metallic layer and a dielectric medium (analyte). SPR is widely used as a detection principle for many sensors operating in different application fields, such as bio and chemical sensing. In practical implementations, the biological targets are usually transported through a microfluidic system by means of a buffer fluid or a carrier fluid. In SPR sensors, the transducing media (ligands) are usually bonded on the metallic layer surface so that, when they react with the target molecules present in the analyte, the refractive index at the outer interface changes, and this change is detected by suitable optical interrogation. In the scientific literature, many different configurations based on SPR in silica optical fibers, are usually found \\[[@b1-sensors-11-11752]\\]. In general, the optical fiber employed is either a glass one or a plastic one (POF). For low-cost sensing systems, POFs are especially advantageous due to their excellent flexibility, easy manipulation, great numerical aperture, large diameter, and the fact that plastic is able to withstand smaller bend radii than glass. The advantage of using POFs is that the properties of POFs,"
-"Introduction {#Sec1}\n============\n\nRheumatoid arthritis (RA) strongly affects the properties of bone \\[[@CR1]--[@CR3]\\], while in addition bone metabolism is influenced by the intake of medication by RA patients \\[[@CR4], [@CR5]\\]. The compromising biomechanical changes in rheumatic bone could increase the risk of mechanical complications in cementless implants, such as peri-prosthetic fractures, insufficient initial implant stability and insufficient osseous integration causing early implant failure.\n\nThis systematic literature review was conducted to investigate the results of uncemented total hip arthroplasty (THA) in RA patients, with a special emphasis on mechanical complications. The research questions formulated were: (1) What are the rates of early complications such as intra-operative, peri-prosthetic fractures, implant migration and early loosening? (2) What are the failure rates with aseptic loosening as end point compared to cemented implants in RA patients, or compared with the criteria of the National Institute of Clinical Excellence (NICE) \\[[@CR6]\\]?\n\nMethods {#Sec2}\n=======\n\nThe systematic review was performed using methodology and checklists on search strategy, methods and results, according to the proposed methodology for systematic reviews of observational studies by the meta-analysis of observational studies in epidemiology (MOOSE) group \\[[@CR7]\\].\n\nSearch strategy {#Sec3}\n---------------\n\nA comprehensive search was performed on EMBASE (1993--2011), Medline (1966--2011) and"
-"Introduction {#Sec1}\n============\n\nTinnitus (TI) is the perception of sound in the absence of an external source. Approximately 10\u00a0% of the population experience TI permanently, and in around 1--3\u00a0% of these people, their quality of life is severely affected by the condition (Davis and El Rafaie [@CR8]). The current paper is concerned with chronic subjective TI, which can be heard only by the sufferer (i.e. there is no physical explanation for the perceived sound). A general assumption from animal models of TI is that the condition is due to abnormal activity in the central auditory system, as a consequence of altered patterns of neural activity following a measurable hearing impairment (Eggermont and Roberts [@CR11]). However, we acknowledge that this is just one of several explanations because not all people with hearing loss experience TI and many people with TI have clinically normal hearing (Schaette and McAlpine [@CR33]; Weisz et al. [@CR43]).\n\nOne of the more influential models within the general field of neuroscience has been the thalamocortical dysrhythmia model, which considers the reciprocal circuits between thalamus and cortex to be fundamental to a range of positive/negative symptomatology including not only TI but also neurogenic pain, depression, and Parkinson's"
-"GENOME ANNOUNCEMENT\n===================\n\nFor a concerted response action to occur in a bacterial population, each bacterium must be aware of and respond to others in unison ([@B1], [@B2]). The term \"quorum sensing\" (QS) was coined to explain bacterial communication in which synchronization of small diffusible molecules in a population stimulates a series of gene expressions ([@B3]). The aquatic environment provides a reservoir for microorganisms, and the microbial contamination of water often leads to major concerns ([@B4]). Aeromonas hydrophila, commonly known as waterborne bacteria, can cause infections, such as diarrhea, in humans, where it utilizes its QS ability to coordinate and enhance adaptation to various environments ([@B5], [@B6]). In this study, the A.\u00a0hydrophila strain M013 was isolated from the Sungai Tua waterfall. In order to further explore the genetic makeup of the QS system, whole-genome sequencing was performed.\n\nThe MasterPure DNA purification kit (Epicentre, Inc., Madison, WI, USA) was used to extract the genomic DNA, while the quality of extracted DNA was examined via a NanoDrop spectrophotometer (Thermo Scientific, Waltham, MA, USA) and a Qubit version 2.0 fluorometer (Life Technologies, Carlsbad, CA, USA). The purified DNA was subjected to whole-genome shotgun sequencing on an Illumina MiSeq personal sequencer (Illumina, Inc.,"
-"Introduction {#Sec1}\n============\n\nPalsas are peat mounds or plateaus with a perennially frozen (permafrost) core and formed primarily in subarctic wetland areas in the northern hemisphere (Fig.\u00a0[1](#Fig1){ref-type=\"fig\"}). Palsas represent marginal permafrost features and their distribution at the outer limit of the permafrost zone make them sensitive to climate variations^[@CR1]--[@CR3]^. The recognition of a cyclic development of palsas^[@CR4],[@CR5]^ complicates the assessment of possible effects of climate change on palsa development, however, these effects may be detected by general trends towards either growth or decay^[@CR6]^.Figure 1(**a**) Drone image showing part of the study area. In the foreground: the studied ridge-shaped palsa with recent peat-block erosion in the lower central part of the image (A). A minor palsa plateau (brownish colours at B) is seen beyond the ridge-shaped palsa. Photo by Mats Olvmo, Sept. 12 2019 at 9.20 AM, Location N 68.798, E 21.2104 looking southwards. (**b**) Extent and change in palsa area 1955 to 2016 of palsa shown in the foreground in Fig.\u00a01a (Area C in Fig.\u00a0[2c](#Fig2){ref-type=\"fig\"}). During these 61 years more than half (54%) of the palsa area has decayed. B/W aerial image recorded 1955 July 28, Colour orthophoto from 2016 August 18. Data sources: Ortophoto, 1\u2009m"
-"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"
-"Introduction\n============\n\nIn the 1960s, researchers first suggested a link between iron metabolism and the immune system \\[[@bib1]\\]. Since then, many iron-related genes have been found to play a role in immune function. For example, the proteins lactoferrin, hepcidin, and Hfe have all been found to modulate the host defense against bacterial infection \\[[@bib2; @bib3; @bib4; @bib5; @bib6]\\]. Moreover, the expression of several genes involved in iron metabolism, including hemojuvelin (*HJV*) \\[[@bib7]\\], hepcidin (*HAMP*) \\[[@bib8]\\], and ferroportin1 (*FPN1*) \\[[@bib9], [@bib10]\\], are modulated during inflammation. Interestingly, a recent case report described a patient with hemochromatosis who died from bacterial infection \\[[@bib11]\\]. These findings prompted us to investigate the putative role of hemochromatosis-related genes in bacterial infection. We therefore screened several hemochromatosis mouse models for their immune phenotype and susceptibility to bacterial infection.\n\nHJV is a bone morphogenetic protein (BMP) co-receptor that regulates the expression of hepcidin \\[[@bib12]\\]. In humans, mutations in the *HJV* gene cause juvenile hemochromatosis \\[[@bib13]\\]. In mice, deleting *Hjv* expression causes a similar iron-overload phenotype \\[[@bib7], [@bib14]\\]. HJV is also a member of the repulsive guidance molecule (RGM) family \\[[@bib15]\\]. However, the role of HJV in the immune response is currently unknown. Recent studies suggest that two other"
-"Introduction\n============\n\nThe long-term impact of critical illness on survivors\\' physical and mental health remains unknown. Our aim was to create a follow-up clinic for survivors of critical illness in order to quantitatively examine muscle weakness, physical functioning and mental health and relate these findings to health-related quality of life (HRQL) and ICU risk factors.\n\nMethods\n=======\n\nStudy patients were selected from a 24-bed multidisciplinary ICU. Fifty-six patients who were \u226518 years old, stayed longer than 4 days in the ICU and did not have an acute brain injury were followed-up at 2 and 4 months post hospital discharge. Peripheral muscle strength (grip, triceps, biceps, hamstrings, quadriceps and dorsiflexors) and physical functioning were objectively assessed using hand-held dynamometry and the six-minute walk test (6MWT); both were compared with age/ sex normative data. HRQL and mental health were assessed using the Short Form-36 (SF-36), EuroQol-5D (EQ-5D) and Hospital Anxiety and Depression Scale.\n\nResults\n=======\n\nThe median age of patients was 60 years, 68% were admitted for respiratory illnesses, they were severely ill (median APACHE II, 19) and had long ICU lengths of stay (median, 11 days). Muscle strength was significantly reduced when compared with normative data in all muscle groups at"
-"Introduction {#Sec1}\n============\n\nAtherosclerosis is one of the leading causes of mortality in developed countries, and with increasing incidents in the developing countries^[@CR1]^. It is a complex disease affected by the interaction of genetic and environmental risk factors^[@CR2]--[@CR4]^. In the past decade, research efforts in the biomedical field have focused on the implications of gut microbiome on human diseases. There is evidence that symptomatic atherosclerosis is associated with an altered gut microbial community in human and mice^[@CR5]--[@CR7]^. It has been demonstrated that cecal microbial transplantation from a susceptible strain to wild-type mice enhanced choline diet-dependent atheroslceorosis and TMAO (trimethylamine-*N*-oxide) levels in wild-type mice^[@CR8]^. Examination of human oral and atherosclerotic plaque microbiota in patients with clinical atherosclerosis suggests that microbes from the oral cavity and perhaps the gut may be a reservoir for bacteria found in atherosclerotic plaques^[@CR9]^. Our previous study has also shown that genetic selection for susceptibility/resistance to diet-induced atherosclerosis has affected the Japanese quail's cecal environment to accommodate distinctly different cecal microbiota^[@CR10]^. Most published studies have compared the fecal or cecal micriobial communities between atherosclerosis and healthy subjects, but there has been sparse information on the comparison of cecal and small intestinal microbiota in the same subject.\n\nMapping"
-"Background {#Sec1}\n==========\n\nIn the past decade, maternal mortality has decreased worldwide during the period that the international community was striving to attain Millennium Development Goal 5 \\[[@CR1], [@CR2]\\]. Accelerated and concerted efforts are needed to reach the ambitious Sustainable Development Goal 3 \\[[@CR1], [@CR3]\\]. Currently, the maternal mortality ratio (MMR) in Tanzania is still one of the highest in the world, with most deaths occurring during the intrapartum and immediate postnatal period \\[[@CR4], [@CR5]\\]. To design targeted interventions, data are needed on cause of death as well as underlying factors of three phases of delays. For this purpose the World Health Organization (WHO) has conceptualised the Maternal Death Surveillance and Response (MDSR) system to ensure that local data are available in timely fashion to steer efforts to reduce MMR.\n\nThe MDSR system, introduced since 2015 in Tanzania \\[[@CR6]\\], includes identification, notification and review of maternal deaths to stimulate learning from what went wrong. Typically a team of health professionals and local managers review circumstances of deaths, underlying (sometimes called primary medical) causes and contributing factors such as delays in care seeking and provision. The three-delay model provides a conceptual framework to categorize delays in maternal death \\[[@CR7]--[@CR10]\\]. After completing"
-"Dear Sir,\n\nI read with great interest the review article by Kaushik.\\[[@ref1]\\] I congratulate the author for covering this basic topic, which is still unexplored and under-reported. I appreciate the effort of the author for suggesting a basis for classification of bleeding into major and minor groups after laparoscopic cholecystectomy. I would like to add that if we lose the patient because of the bleeding, irrespective of whether any open surgical intervention was done or not, it should be grouped under major category. Though the issue has been discussed very nicely, the author has overlooked the criteria he has followed for the classification of the bleeding into major group in Table 1. It should have been clearly mentioned in materials and methods section. There is a need for consensus on this debatable issue. The author has not included the secondary haemorrhage, which could occur 7--14 days after surgery and may be precipitated by factors such as infection, pressure necrosis or malignancy.\\[[@ref2]\\] The standard classification of any bleeding related with surgery whether open or laparoscopic are primary, reactionary and secondary. One should follow the standard norm. It is true that the secondary haemorrhage after any surgery, particularly laparoscopic surgery is extremely"
-"**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"
-"All relevant data are within the paper and its Supporting Information files.\n\nIntroduction {#sec005}\n============\n\nAmniotic fluid (AF) is maintained in a dynamic equilibrium and its volume derived from the sum of inflow (from fetal urine and lung fluid) and outflow (fetal swallowing and intramembranous absorption) of fluid from the amniotic space.\\[[@pone.0144334.ref001]\\] Amniotic fluid volume (AFV) is an important parameter in the assessment of fetal wellbeing since it provides a number of functions vital to fetal development such as a supportive environment for growth,, protection from trauma and infection and a medium which allows fetal movement thus promoting the development of the musculoskeletal system. AF also prevents a possible compression of the umbilical cord and placenta thereby protecting the fetus from vascular and nutritional compromise.\\[[@pone.0144334.ref002]\\]\n\nTo date several methods are used to assess AFV ranging from subjective assessment (where the volume is described as average, above average, below average or scant) to semi-quantitative estimations including measurement of the deepest vertical pocket and amniotic fluid index (AFI).\\[[@pone.0144334.ref003]\\]\n\nWhile debate continues regarding the best method to estimate AFV, it has become evident that there are numerous maternal and fetal risk factors associated with a reduction of this parameter. \\[[@pone.0144334.ref004]--[@pone.0144334.ref008]\\] Indeed, an increased"
-"*Talaromyces marneffei* is an important pathogenic thermally dimorphic fungus that has been reported to cause systemic mycosis in southeast Asia \\[[@CIT0001], [@CIT0002]\\]. *Talaromycosis* is endemic in tropical regions, especially Thailand, Vietnam, northeastern regions of India and China, such as in Guangxi, Fujian, Hong Kong, and Taiwan \\[[@CIT0003]\\]. *Talaromyces marneffei* can cause human infections in both immunocompromised and previously healthy hosts. *Talaromycosis* is categorized as either localized or disseminated. *Talaromyces marneffei* disseminates hematogenous or via the lymphatic system throughout the body, involving the skin, respiratory, digestive, and reticuloendothelial systems \\[[@CIT0004]\\]. Given the extent of lymphoid tissue throughout the gastrointestinal system, theoretically, it should be a common site of infection. However, intestinal involvement concerning *Talaromycosis* is uncommon, and diagnosis using digestive endoscopy and tissue biopsy culture and pathology is extremely rare. As of March 2020, only 11 cases of intestinal *Talaromycosis* that were diagnosed antemortem by endoscopy have been reported in the literature \\[[@CIT0005]\\]. In this study, we report 3 patients diagnosed with *Talaromycosis* who underwent intestinal tract endoscopy examination, and we conducted a literature search of *Talaromycosis* with gastrointestinal involvement using Chinese and international databases. We describe the clinical features, treatment, patient management, and patient outcomes to provide evidence for early"
-"Vitamin D has a central role in bone health, and deficient levels are associated with an increased risk of fractures and musculoskeletal symptoms ([@bib1]--[@bib3]). Its possible role in other disease outcomes such as cancer is less certain. Most studies of cancer risk and vitamin D status have focused on cancers at the more common sites, such as colorectal, breast, and prostate cancer, but with the possible exception of colorectal cancer ([@bib4]), the evidence of an association is inconsistent ([@bib4]--[@bib7]). Few studies of less common cancers have been conducted, but of those that have, including investigations of pancreatic and esophageal cancer, researchers have found both inverse and elevated risks associated with vitamin D ([@bib8]--[@bib10]). The possible broad role of vitamin D in overall health, coupled with the high prevalence of vitamin D insufficiency and deficiency in the general population ([@bib11], [@bib12]), has led to calls for increased vitamin D supplementation and controversial recommendations to increase sun exposure in order to raise vitamin D levels ([@bib13]). However, because of the potential for harm noted in at least 1 study of a rare but highly lethal cancer ([@bib9]), additional information concerning the association of vitamin D with rarer cancers is needed.\n\nClues to"
-"Linkage analysis, positional cloning, candidate gene mutation scanning and genome-wide association study approaches have all contributed significantly to our understanding of the underlying genetic architecture of breast cancer. Taken together, these approaches have identified genetic variation that explains approximately 30% of the overall familial risk of breast cancer, implying that more, and likely rarer, genetic susceptibility alleles remain to be discovered.\n\nThe application of massively parallel sequencing has further demonstrated the complexity of human genetic variation and has raised many challenges for computational and statistical methods for searching for additional breast cancer predisposition genes. Early findings are consistent with previous indications that no single gene is likely to account for a large proportion of the remaining unexplained genetic susceptibility \\[[@B1],[@B2]\\].\n\nCoordinated international collaboration offers great potential to advance the discovery of additional breast cancer susceptibility genes by increasing the likelihood of identifying functionally relevant genetic variants in the same genes in multiple families. A new consortium, COMPLEXO (a name chosen to reflect the complexity of the exome), has been formed to facilitate collaborations between researchers actively applying massively parallel sequencing to understand the genetics of breast and ovarian cancer. The consortium has defined activities aimed at bringing together data and"
-"INTRODUCTION\n============\n\nMusculoskeletal disorders are one of the most frequent health problem for people around the world. These disorders have great consequences for public health because of their severe impact on body's disability, health care expenses, sick leave ([@b12-jer-13-2-240]). About 6% of the total healthcare costs ([@b10-jer-13-2-240]) and 30% of all sick-leave days are due to musculoskeletal problems ([@b11-jer-13-2-240]).\n\nRecently, research started to demonstrate a significant relationship between physical inactivity and variety of musculoskeletal disorders and health conditions. Several studies reported that regular aerobic exercise reduce the risk of suffering from various health conditions ([@b7-jer-13-2-240]; [@b8-jer-13-2-240]). With the greater interest of the benefits of physical activity, a more health conscious population expressed interest in exercise. In school surroundings, it is natural that students majoring sports have greater chance to participate in sport activities than nonmajoring students.\n\nIt is well known that regular exercise brings muscle strength and endurance which are two important components of muscular fitness. Diseases and disorders of the musculoskeletal system, such as osteoporosis, osteoarthritis, bone fractures, connective tissue tears, and low back syndrome, are related to physical inactivity and a sedentary lifestyle ([@b4-jer-13-2-240]).\n\nHowever, questions have been raised regarding the incidence of body deformity by participation in"
-"GENOME ANNOUNCEMENT {#s1}\n===================\n\nStreptococcus suis is a very important Gram-positive bacterium considered worldwide to be one of the most important pathogens in the swine industry. S. suis causes a wide variety of diseases in pigs, including meningitis, septicemia, and endocarditis ([@B1], [@B2]). S. suis is also an emerging zoonotic agent responsible for septicemia with or without septic shock, meningitis, and other less common infections in humans, particularly in Asian countries ([@B3]). Among the 33 known serotypes, serotype 2 (SS2) is considered to be the most prevalent and virulent in pigs and humans ([@B4], [@B5]). Two large-scale outbreaks of SS2 in China in 1998 and in 2005 have posed public health concerns worldwide ([@B6]).\n\nThe SS2 virulent strain SS2-1 was isolated from a diseased dead pig with septicemia in Jiangsu province in 1998 and has been confirmed as virulent on the basis of animal experiments ([@B7]). The complete genome sequence was determined by the Illumina HiSeq platform at Novogene (Beijing, China). Assembly was performed using SOAPdenovo. Gaps were filled by primer walking and sequencing of PCR products. The assembly of the genome was further verified by PCR. Coding sequences (CDS) were predicted using Glimmer 3.02 and GeneMarkS ([@B8]) and further"
-"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\n============\n\nThe Cox maze procedure is widely used for restoring sinus rhythm (SR) in patients with atrial fibrillation (AF) who undergo cardiac valve surgery \\[[@b1-kjtcvs-50-163],[@b2-kjtcvs-50-163]\\]. Despite a high reported success rate of 75% to 95%, a significant proportion of patients fail to recover atrial contraction (AC) after the maze operation \\[[@b3-kjtcvs-50-163]--[@b7-kjtcvs-50-163]\\]. The absence of AC could compromise the efficacy of the maze procedure by limiting the atrial contribution to ventricular performance \\[[@b7-kjtcvs-50-163]\\]. According to recently published studies, failed AC recovery was associated with an increased risk of subsequent thromboembolic stroke \\[[@b8-kjtcvs-50-163]\\] and aggravation of tricuspid regurgitation (TR) \\[[@b9-kjtcvs-50-163]\\].\n\nHowever, the clinical impact of AC recovery on the risk of subsequent permanent pacemaker (PPM) implantation after maze surgery has rarely been evaluated in this patient group. Since AF and valve surgery are associated with sinus node dysfunction (SND) \\[[@b10-kjtcvs-50-163],[@b11-kjtcvs-50-163]\\] and the risk of PPM implantation \\[[@b12-kjtcvs-50-163],[@b13-kjtcvs-50-163]\\], respectively, we hypothesized that AC recovery failure could increase the risk of PPM implantation due to additional adverse effects on the cardiac conduction system.\n\nThe objective of the present study was to assess the incidence of PPM implantation and to evaluate the potential association between the absence of AC and the subsequent risk of"
-"Paris, M. T., Lafleur, B., Dubin, J. A., and Mourtzakis, M. (2017) Development of a bedside viable ultrasound protocol to quantify appendicular lean tissue mass. Journal of Cachexia, Sarcopenia and Muscle, 8: 713--726. doi: [10.1002/jcsm.12213](10.1002/jcsm.12213).\n\nIntroduction {#jcsm12213-sec-0005}\n============\n\nQuantifying lean tissue or muscle mass in ageing and clinical populations is of increasing importance due to emerging associations between low muscle mass and poor physical function, as well as increased rates of morbidity and mortality.[1](#jcsm12213-bib-0001){ref-type=\"ref\"}, [2](#jcsm12213-bib-0002){ref-type=\"ref\"}, [3](#jcsm12213-bib-0003){ref-type=\"ref\"}, [4](#jcsm12213-bib-0004){ref-type=\"ref\"}, [5](#jcsm12213-bib-0005){ref-type=\"ref\"} Lean tissue or muscle mass can be assessed by using several accurate and precise modalities such as dual\u2010energy X\u2010ray absorptiometry (DXA), computed tomography (CT), and magnetic resonance imaging (MRI).[6](#jcsm12213-bib-0006){ref-type=\"ref\"} DXA is often used in research settings because it provides a cost\u2010effective and accurate assessment of lean tissue, with minimal exposure to radiation. These advantages have led to DXA being commonly utilized for the assessment of low lean tissue mass in ageing populations[7](#jcsm12213-bib-0007){ref-type=\"ref\"}; however, it is rarely applied for lean tissue assessment purposes in clinical centres due to the limited accessibility of these scanners for body composition analysis in these settings. In certain clinical populations, CT and MRI scans, which have been performed as part of routine care, can be utilized for muscle"
-"1.. Introduction {#s1}\n================\n\nMultiple myeloma (MM) is a neoplastic plasma cell disease with high morbidity and mortality rates. MM reportedly accounts for approximately 10--15% of haematologic malignancies in the world \\[[@RSOS192152C1],[@RSOS192152C2]\\]. Almost 6--7 individuals out of every 100 000 people in the world are diagnosed with MM each year \\[[@RSOS192152C2]\\]. In 2015, 28 850 patients were diagnosed with MM, and the number of deaths due to this illness was more than 11 000 in the United States \\[[@RSOS192152C3]\\]. However, MM is still incurable and there is a great need to develop more effective therapeutic strategies.\n\nNuclear factor-kappa B (NF-\u03baB) was reported to be abnormally activated in many types of cancer cells, including MM in the 1990s \\[[@RSOS192152C4]\\], and it inhibits the apoptosis of cancer cells by upregulating anti-apoptotic genes \\[[@RSOS192152C4],[@RSOS192152C5]\\]. A series of studies have been performed to investigate the underlying mechanism of NF-\u03baB in the pathogenesis of MM, with the aim of exploring NF-\u03baB-targeted therapies \\[[@RSOS192152C6]--[@RSOS192152C11]\\]. However, to date, no appropriate NF-\u03baB-targeted treatments have been established due to their serious side effects \\[[@RSOS192152C4]\\]. The inhibitors of NF-\u03baB similarly affect the NF-\u03baB pathway in MM and normal cells leading to serious damage. This reflects the important roles of NF-\u03baB"
-"Introduction\n============\n\nBackground\n----------\n\nWorldwide, road traffic incidents (RTIs) constitute the primary cause of death due to injuries, the tenth leading cause of all deaths, and the ninth leading contributor to the global burden of disease ^[@ref-1]^. Latin America and Peru are not exceptions to these statistics ^[@ref-2],\\ [@ref-3]^. Adequate management after the occurrence of a traffic incident can decrease the probability of death and disability, limit the severity caused by injury and ensure that survivors are optimally reintegrated into the community ^[@ref-4]^. In high-income countries, studies have shown that of those that die due to a RTI, 50% will die within minutes after the incident or on the way to the hospital, 15% die within the first 4 hours, and 35% die after 4 hours ^[@ref-5]^. In low- and middle-income countries (LMIC), the majority of deaths occur among victims before arriving at a health care facility (HCF), indicating that many deaths and complications could be prevented via adequate initial management and response ^[@ref-5]--\\ [@ref-8]^. The experiences of developing countries with regards to evaluating the care of RTI victims are scarce and unsystematic ^[@ref-9]^. Providing quality health care services to RTI victims is also important, ensuring that they are at"
-"Introduction\n============\n\nMyxopapillary ependymoma was first described as a subtype of ependymoma by Kernohan \\[[@B1]\\] in 1932. Myxopapillary ependymoma is a tumor that typically arises in the filum terminale and conus medullaris \\[[@B1],[@B2]\\]. This tumor has a significantly better prognosis than other ependymomas, because it is slow-growing, unlikely to metastasize and does not tend to infiltrate neural tissues \\[[@B3]\\]. Intracranial ependymomas represent 6%-9% of primary central nervous system neoplasms and generally present in young children, with a mean age of four-year. Spinal myxopapillary ependymomas are rarer than intracranial types. Myxopapillary ependymomas generally present within the spinal canals of adults. Spinal myxopapillary ependymomas in children \\<5 years requiring surgery are very rare.\n\nHere we describe a rare case of a 5-year-old boy who presented with cauda equina compression due to myxopapillary ependymoma, which was treated with subtotal resection and postoperative radiation therapy.\n\nCase Report\n===========\n\nA 5-year-old boy presented with a history of right popliteal pain and abnormal gait that began after March 2000, four months prior to admission. Three months before admission, the patient visited a neighborhood hospital complaining of right popliteal pain, pain in the right hip and an abnormal gait. A magnetic resonance imaging (MRI) scan of the"
-"Introduction {#s1}\n============\n\nChemothearpies are highly effective in treating most cancers, their use is limited by the potential for cardiotoxicity. All these drugs have a wide range of adverse effects the most serious one is cardiotoxicity, these severity of these effects are related to the chemotherapy regimens, patient populations and duration. The occurrence of clinical heart failure seems to be in the range of 1% to 5%, and asymptomatic decrease in left ventricular function is in the range of 5% to 20%. Toxicity can occur early (within 1 year) or late (particularly among children, where late cardiac abnormalities are detectable in two thirds of surviving patients).\n\nMany trials address the role of ACE inhibitors and beta-blockers, effective therapies for established LVSD, in preventing chemotherapy-induced cardiotoxicity. In this article we discuss the types of the cardiomyopathy, diagnosis, prognosis, prevention and managements.\n\nChemotherapy induced cardiomyopathy {#s2}\n===================================\n\nThe survival rate of cancer patients has greatly increased over the last 20 years. However, to achieve this result, a considerable price has been paid in terms of the side effects associated with the intensive anticancer treatment. Cardiotoxicity may compromise the clinical effectiveness of chemotherapy, affecting the patient\\'s survival and quality of life independently of"
-"All relevant data are within the paper and its Supporting Information files.\n\nIntroduction {#sec001}\n============\n\nChanges in diet and lifestyle are two important factors causing the worldwide dramatic increase in the incidence of diabetes \\[[@pone.0206169.ref001]\\]. Currently, about 0.7% of the world population suffer from insulin-dependent diabetes mellitus \\[[@pone.0206169.ref002]\\]. Both type I and type II diabetic patients require insulin, but because of developing insulin resistance, the late stage type II diabetes patients use larger amounts of this hormone \\[[@pone.0206169.ref003], [@pone.0206169.ref004]\\]. Due to the cumulative incidence of this metabolic disease among children and adults, insulin is now at the top of the list of therapeutic peptides in high demand \\[[@pone.0206169.ref005]\\]. Insulin controls the storage and use of sugars and if by its dysfunction, the blood sugar homeostasis is not well preserved for long periods, serious complications will appear in different tissues \\[[@pone.0206169.ref006]\\].\n\nMethods for producing insulin initially used extraction of the native hormone from the animal pancreas \\[[@pone.0206169.ref007]\\]. However, the use of bovine or pig insulin is associated with the appearance of significant adverse effects (e.g. allergy) \\[[@pone.0206169.ref008]\\]. Due to its reputable production efficiency, recombinant DNA technology is now used for human insulin production. *Escherichia coli* and *Saccharomyces cerevisiae* are the most"
-"Introduction\n============\n\nPatients with acute respiratory failure demand dynamic evaluation and interventions. Lung ultrasound is a bedside technique, very promising in this setting. Previously, Lichtenstein and colleagues proposed an algorithm approach with a diagnostic accuracy of 90.5%, named Bedside Lung Ultrasound in Emergency (BLUE protocol). However, this approach has never been validated in other populations or ultrasound operators. The aim of this study was to evaluate the diagnostic accuracy of the lung ultrasound algorithm (BLUE protocol) in ICU patients admitted with acute respiratory failure.\n\nMethods\n=======\n\nA prospective study, single-center consecutive case series evaluating critically ill adult patients in acute respiratory failure, admitted to a 23-bed general ICU between October 2011 and November 2012. The ultrasound examination was performed by an ICU physician until 20 minutes after admission, without interfering with usual care, and the ultrasound operator was blinded to the medical history of the patient. Three items were assessed: artifacts (horizontal A lines or vertical B lines indicating interstitial syndrome), lung sliding, alveolar consolidation and/or pleural effusion. BLUE protocol results were compared with clinical diagnosis by the medical assistant team at the end of the ICU stay.\n\nResults\n=======\n\nForty-two patients were evaluated (42% male), mean age was 73"
-"1. Introduction\n===============\n\nThe level of awareness towards evidence-based medicine (EBM) is growing worldwide and the acceptance of its concept is increasing. In January 2007 the British Medical Journal conducted an online poll about the 15 most important medical milestones and EBM was in seventh place, right behind germ theory and oral contraceptive pill but ahead of computer and medical imaging \\[[@R1]\\], \\[[@R2]\\]. However, fostering an EBM culture and implementing it into practice requires the skills for identifying and appraising the literature critically \\[[@R3]\\], \\[[@R4]\\], \\[[@R5]\\]. A certain knowledge of probability and statistics is mandatory as well when accessing guidelines and evidence summaries, assessing marketing and advertising material from industry, interpreting the results of a screening test, or reading research publications for staying up to date with newly developed treatments; furthermore, knowledge of biostatistics is necessary for the analysis of numerical data, for informing patients about treatment risks, and last but not least for being prepared to the Internet-literature of varying quality presented by patients \\[[@R6]\\], \\[[@R7]\\]. Actually, the question is no longer whether to teach EBM but how to teach it \\[[@R8]\\] and when. Apart from various educational methods, e.g. on the job training, problem-based or self-directed learning \\[[@R9]\\],"
-"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"
-"Background {#Sec1}\n==========\n\nThe health benefits of physical activity are well known throughout the world. Participating in regular physical activity declines mortality and has positive effect on chronic diseases, such as cardiovascular disease, hypertension, and diabetes mellitus \\[[@CR1]\\]. Additionally, physical activity has a beneficial effect on mental diseases such as anxiety or depression \\[[@CR2]\\]. It reduces stress and depression, and increases self-confidence and emotional well-being \\[[@CR3]\\]. Thus, promoting physical activity is an important part of enhancing public health.\n\nDespite these numerous benefits, physical activity levels have declined in the developed and developing countries \\[[@CR4]\\]. Members of vulnerable social groups have an especially increased incidence of participating in unhealthy behaviors, including physical inactivity \\[[@CR5]\\]. Additionally, those with lower levels of education or low economic status participate in physical activity less often compared to those of higher education and economic status \\[[@CR6]\\]. The high rate of physical inactivity among these groups can cause significant public health problems. In addition to these groups, most people who suffer from depression also do not engage in physical activity compared to the general population \\[[@CR7]\\]. According to the Epidemiology Survey of Mental Disorders in Korea 2011, the prevalence of depression is on the rise compared to"
-"Introduction\n============\n\nAdherence to antidepressant treatment is an essential step for the management of patients with major depressive disorder,[@b1-ndt-10-1433] which can change from early to late treatment stages -- it has been shown that 28% of patients discontinue medication after 1 month and that between 44% and 52% of patients discontinue medication after 3 months.[@b2-ndt-10-1433] Recent data from Saudi Arabia has reported that 52.9% of patients have low adherence to antidepressant medication.[@b3-ndt-10-1433]\n\nLow adherence to antidepressants can lead to serious complications, for example, disease recurrence, relapse, increase in the cost of treatment, and impairment in daily functioning.[@b1-ndt-10-1433],[@b2-ndt-10-1433] Several factors that influence low adherence to antidepressant treatment include environmental factors, such as poverty, homelessness, and other socioeconomic conditions. Other factors, such as persistence of symptoms, side effects, complexity of the prescription, and satisfaction with treatment, have been reported to have associations with low adherence.[@b3-ndt-10-1433]--[@b6-ndt-10-1433]\n\nTreatment satisfaction can be defined as \"the sum of the patient perceptions and expectations about the treatment\".[@b7-ndt-10-1433]--[@b9-ndt-10-1433] If the perceived expectations are met, the patient will be satisfied. Otherwise, patients have reported a low satisfaction level when there was a clear discrepancy between their high expectations and their low evaluation of treatment received.[@b10-ndt-10-1433] Additionally, satisfaction can be"
-"All relevant data have been uploaded as Supporting Information. Data are from the Radiopon study, whose authors may be contacted at <jcamps@grupsagessa.com>.\n\nIntroduction {#sec001}\n============\n\nBreast cancer (BC) is the malignant disease with the highest incidence worldwide, and is the most common cancer-related cause of death in women \\[[@pone.0188633.ref001]\\]. Genetic factors, lifestyle, and environmental agents are important contributors to the etiology of BC but, nevertheless, the molecular mechanisms underlying BC onset and development have not, as yet, been elucidated \\[[@pone.0188633.ref002]\\]. For example, oxidative stress and lipid peroxidation products play a role in oncogenesis \\[[@pone.0188633.ref003]\\] while oxidized low-density lipoproteins (LDL) have been reported as being causally associated with oxidative stress-related cancers \\[[@pone.0188633.ref004]\\]. Recent investigations have suggested that paraoxonase-1 (PON1) plays a significant role in the molecular disorders associated with cancer. PON1 is an antioxidant enzyme found in the membranes of most cells and, as well, in the circulation bound to HDL \\[[@pone.0188633.ref005]--[@pone.0188633.ref007]\\]. The original function attributed to PON1 is that of a lactonase since lipophilic lactones constitute its primary substrates \\[[@pone.0188633.ref008]\\]. It is this catalytic capacity that enables PON1 to degrade lipid peroxides within the cell and in the lipoproteins in circulation \\[[@pone.0188633.ref009]\\]. In addition, PON1 has an esterase activity and"
-"1. Introduction {#sec1-nutrients-12-01801}\n===============\n\nIn recent decades, the incidence of respiratory allergic diseases has increased dramatically \\[[@B1-nutrients-12-01801]\\]. Bronchial asthma and allergic rhinitis (AR) have become the most common chronic diseases in childhood \\[[@B2-nutrients-12-01801],[@B3-nutrients-12-01801]\\]. This rapid increase is mainly observed in Western countries. There is an urgent need to search for the methods of prevention of allergic diseases from an early age. Intervention options are sought by attempting to modulate environmental factors and lifestyle that have been identified to promote the risk of allergic diseases. Rural environment, microbiome, exposure to allergens and pollution, but also the impact of changes in diet were considered as the main elements. It has been revealed that many dietary components can influence immunological mechanisms of which we will focus here on the role of 25-hydroxyvitamin D (25(OH)D).\n\nMuch attention has been paid to the impact of 25(OH)D on the prevention and treatment of respiratory allergic diseases. The increase in asthma and allergic diseases coincided with vitamin D deficiency depicted in many populations \\[[@B4-nutrients-12-01801]\\]. The inverse relationship has raised the idea of a possible underlying association between these two opposite trends. Further research on the immunomodulatory effect of 25(OH)D in the early stages of immune system development"
-"1.. Introduction {#s1}\n================\n\nIschaemic heart disease (IHD) is the leading cause of death and disability worldwide. Therefore, novel therapies are required to protect the myocardium against the detrimental effects of acute ischaemia--reperfusion injury (I/R injury) in patients with IHD, so as to reduce lethal cardiac arrhythmias and cardiomyocyte death, preserve cardiac function and prevent the onset of heart failure, and improve patient survival.^[@CVU225C1]^\n\nDespite a large number of novel cardioprotective strategies (both pharmacological and non-pharmacological) being discovered in the research laboratory, their translation into the clinical setting to improve patient outcomes has been largely disappointing. The reasons for this failure are multiple and can be divided into two main categories: (i) the failure to rigorously test the novel cardioprotective therapy in the preclinical setting before embarking into the clinical arena.^[@CVU225C2],[@CVU225C3]^ This is the topic of the current European Society of Cardiology (ESC) Working Group (WG) Cellular Biology of the Heart Position Paper; and (ii) inadequate design of the clinical studies for testing the novel therapy. This subject has been extensively reviewed in our recently published ESC WG Cellular Biology of the Heart Position Papers^[@CVU225C4],[@CVU225C5]^ and elsewhere.^[@CVU225C2],[@CVU225C6]^ In brief, the major issues with the study design of previous clinical cardioprotection"
-"1. Introduction {#sec1-antibiotics-09-00465}\n===============\n\nIt is increasingly being recognised by 'experts' that science literacy is of key importance for the public \\[[@B1-antibiotics-09-00465]\\]. At a time where antimicrobial resistance (AMR) continues to pose significant public health threats (or indeed, at a time of a global pandemic), an understanding of statistics, epidemiology and microbiology is even more desirable. As a subject, microbiology offers many topics with which we can engage non-experts, such as microbial diversity (including fungi, algae, protozoa and viruses as well as bacteria), beneficial microbes (for example, probiotics, fermented foods, the human microbiome), and messages that can influence behaviour in a positive manner (including vaccination, hand hygiene, antimicrobial stewardship) \\[[@B2-antibiotics-09-00465],[@B3-antibiotics-09-00465],[@B4-antibiotics-09-00465]\\].\n\nBiofilms (an assemblage of microbial cells that are irreversibly associated with a surface---not removed by gentle rinsing---and enclosed in a matrix of primarily polysaccharide material \\[[@B5-antibiotics-09-00465]\\]) are of great importance to microbiologists, but also to many other professionals (such as engineers, biocide manufacturers, architects), and are found in a variety of environments (water distribution systems, industrial processing, hospitals). Biofilm research is multi-disciplinary, extensive and significant, with many applications. There are several research centres which focus on biofilm, such as the US-based Centre for Biofilm Engineering (<http://www.biofilm.montana.edu/>) and the UK-centred National"
-"INTRODUCTION {#sec1-1}\n============\n\nOver the last few years use of short message services (SMS) and smartphone-based communication applications in health care has shown its wide application and potential to improve access to health care; enhance efficiency of service delivery; improve diagnosis, facilitate timely treatment and support public health programmes.\\[[@ref1][@ref2][@ref3][@ref4]\\] This effective means of communication is providing timely and accurate results to the correct recipient, safeguarding their privacy and confidentiality and avoids misunderstanding and misinterpretation of the results. There are various uses of mobile phone message services and smartphone-based communication applications such as: Appointment remainders;\\[[@ref5]\\] to monitor chronic medical conditions;\\[[@ref6][@ref7][@ref8][@ref9]\\] to improve treatment compliance;\\[[@ref10][@ref11]\\] to provide psychological support;\\[[@ref12][@ref13]\\] managing communicable diseases via contact tracing and partner notification for sexually transmitted illnesses\\[[@ref14][@ref15]\\] and to promote health promotion programs like smoking cessation.\\[[@ref16][@ref17]\\]\n\nTata Memorial Hospital uses many modes of health related e-communications such as web based electronic medical records (EMR) where patients and families can access their medical records, blood investigations, scans and all patient-related information using an individual patient login key and password. This information can be accessed at home or any other remote setting using a computer or smartphone. The other modes of e-communications used are e-mail, short message service (SMS),"
-"Introduction {#H1-1-ZOI200404}\n============\n\nHealth care--associated infections represent an important target of efforts in the United States to connect health care quality to payment. The Affordable Care Act established 2 value-based incentive programs that link hospitals' health care--associated infection rates with financial incentives and penalties: the Hospital-Acquired Condition Reduction Program (HACRP) and the Hospital Value-Based Purchasing (HVBP) program, which includes health care--associated infection metrics in its safety domain.^[@zoi200404r1]^ In October 2014, these programs began comparing hospital performance on selected infection metrics with national benchmarks based on prospective infection surveillance data reported to the National Healthcare Safety Network (NHSN) of the Centers for Disease Control and Prevention. At present, HVBP rewards or penalizes the highest- and lowest-performing hospitals by up to 2% of the total inpatient payments the hospital received, whereas the HACRP reduces payments by up to 1% for the lowest performers.^[@zoi200404r1],[@zoi200404r2]^\n\nPrevious studies have shown worse outcomes in many targeted quality measures adopted by federal value-based incentive programs among patients with low income and among those who identify as members of racial/ethnic minority groups compared with patients without socioeconomic disadvantages.^[@zoi200404r3],[@zoi200404r4],[@zoi200404r5],[@zoi200404r6],[@zoi200404r7],[@zoi200404r8]^ Safety-net hospitals that care for a higher proportion of patients with low socioeconomic status also tend to demonstrate worse performance,"
-"Introduction\n============\n\nObesity has become a nationwide epidemic in the United States. The prevalence of obesity among adults (\\> 20 years) has consistently increased from 2001 to 2014 \\[[@b1-ophrp-10-137]\\]. Obesity is linked to increased risk for non-communicable diseases including cancer, difficulty with physical movement, heart disease, mental illness, osteoarthritis, sleep apnea, stroke, and Type 2 diabetes \\[[@b2-ophrp-10-137]--[@b5-ophrp-10-137]\\]. Obesity and overweight together are the second leading cause of preventable death (approximately 300,000 deaths per year) in the United States, right after cigarette smoking \\[[@b6-ophrp-10-137],[@b7-ophrp-10-137]\\].\n\nPrevious studies have reported that obesity rates vary greatly between socio-demographic groups in the United States. Specifically, a larger ratio of individuals are overweight or obese among lower income groups, lower-educated groups, Non-White or Hispanics than among other socio-demographic groups \\[[@b8-ophrp-10-137]--[@b10-ophrp-10-137]\\]. Women have lower obesity rates than men for self-reported height and weight \\[[@b8-ophrp-10-137],[@b11-ophrp-10-137]--[@b13-ophrp-10-137]\\]. However, other studies have shown that even though the mean body mass index (BMI) is lower for women than men, women are gaining weight quicker than men \\[[@b14-ophrp-10-137]\\]. There may no longer be a difference between men and women based on measured height and weight \\[[@b9-ophrp-10-137]\\]. According to the National Health and Nutrition Examination Survey 2015--2016, the prevalence of obesity was 35.7% among"
-"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"
-"Background {#Sec1}\n==========\n\nFor most organisms, DNA is the primary information storing molecule in the cell. Since the discovery of its molecular structure \\[[@CR1]--[@CR3]\\], it had been generally accepted that information in DNA is exclusively contained within its nucleobase sequence. At about the same time, Claude Shannon formalized the most important generalized mathematical definition of information \\[[@CR4]\\] expanding on Norbert Weiner's work in probability and thus founding the modern statistical subdiscipline of information theory. The application of information theoretics to DNA sequence did not occur until much later, after the advent of automated forms of DNA sequencing, when Schneider and Stevens \\[[@CR5]\\] utilized Shannon information in the form of the 'sequence logo' plot to describe empirically-determined binding sequence preferences of transcription factors.\n\nHistorically, studies of transcription factor binding sites (TFBS) have focused primarily upon DNA nucleobase sequence at points of major groove contact, where base sequence is directly readable at the molecular level. Thus, these studies have been largely confined to a single-dimensional bioinformatic perspective. However, recent studies have illuminated the importance of a more biophysical and less sequence-specific second mechanism involved in TF binding, whereby TF's are drawn near to their cognate sites through a process commonly referred to"
-"Sir,\n\nHajj is one of the main pillars of Islam and is mandatory for all adult Muslims who can afford the journey and are in acceptable health.\\[[@ref1]\\] Over two and half million pilgrims gather from different nationalities to perform pilgrimage in Saudi Arabia in the lunar month ZelHajjeh. A significant proportion of those performing Hajj are elderly and may suffer from chronic medical conditions. Considering the 10% prevalence of diabetes mellitus in this age group,\\[[@ref2]\\] about 250000 diabetic patients will participate in this crowded pilgrimage. Many of them are also suffering from diabetic complications like eye or coronary heart disease and diabetic foot.\\[[@ref3][@ref4]\\] The Hajj duties can be demanding in terms of physical activities and mental effort. Due to a lot of changes in usual life of diabetic patients during hajj (e.g. geography, weather, diet and physical activities), they are prone to a real challenge. Increasingly, diabetes has been reported as a leading cause of morbidity and mortality during Hajj.\\[[@ref4][@ref5]\\] At a special part of hajj duties i.e. Ihram, some acts are forbidden for pilgrims (including blood extraction). This can affect self-monitoring of blood glucose by glucometer.\n\nSome diabetic patients are at high risk for morbidities during hajj. They include"
-"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"
-"Introductions {#s1}\n=============\n\nLiving donor liver transplantation (LDLT) has been widely accepted as an effective therapeutic modality for a variety of end-stage liver diseases \\[[@r24]\\]. The success of LDLT has increased steadily over decades due to improvements in immunosuppressive therapy and postoperative care \\[[@r20]\\]. However, for patients requiring intraoperative portal vein (PV) reconstruction, one major challenge of LDLT is the portal vein stenosis (PVS), with the incidence remaining at 0.6--4.5% in recipients of a living-donor allograft, especially in children \\[[@r11], [@r12], [@r23]\\].\n\nAs we know, survival depends on the regeneration capacity of hepatocytes. It has been well documented that approximately 70--80% of hepatic blood flow in normal people is derived from the PV, and the PV has been reported to influence the impairment, regeneration, and function of the transplanted liver \\[[@r17], [@r19]\\]. Theoretically, a minimal change in the blood supply of the PV scarcely affects the graft's regeneration until the deprivation in flow of the PV reaches a certain level. Nevertheless, the tolerated limitation of PV deprivation and the optimal moment for intervention remain unknown. Recently, lots of clinical and animal studies have been performed to investigate the relationship between PV flow and liver regeneration \\[[@r2], [@r16]\\]. However, the blood"
-"Background {#Sec1}\n==========\n\nPolicy {#Sec2}\n------\n\nAfter the 2008 financial crash, austerity conditions and policies have made hospital costs and overload an increasingly salient health policy issue in many countries. In the UK, reducing hospital bed use became a pillar of fiscal control, since 67.5% of NHS costs arise from hospital care \\[[@CR1]\\]. UK policy makers attributed the rising demand for hospital care above all to unplanned admissions for older people. It has been known since the 1960s that older people, especially frail older people, used a disproportionately high share of NHS beds \\[[@CR2]--[@CR4]\\] partly because hospitals were often providing essentially residential care in the absence of alternative provision \\[[@CR2]\\]. More recently, UK policy makers have attributed part of this bed use to the increasing prevalence of dementia, which became a prominent health policy issue and remit of one of the Prime Minister's three special working groups on healthcare.\n\nFor people who require care and cannot care for themselves (or be cared for) at home, even *clinically* 'unnecessary' hospital admissions can only be avoided if non-hospital ('community based') residential care is available for them. The NHS has therefore became increasingly reliant on intermediate care, nursing and care homes as means"
-"Background {#Sec1}\n==========\n\nIn the past two decades, asthma guidelines have been revised to emphasise management based on the control of symptoms and exacerbations rather than classification of the patient by disease severity \\[[@CR1], [@CR2]\\]. The current Global Initiative for Asthma (GINA) guidelines describe the level of asthma symptom control as well-controlled, partly controlled and uncontrolled \\[[@CR1]\\].\n\nThe Gaining Optimal Asthma controL (GOAL) study was the first large study to examine whether guideline-defined asthma control can be achieved in patients who were uncontrolled on either short-acting \u03b22-agonist (SABA) alone or low- to medium-dose inhaled corticosteroid (ICS) \\[[@CR3]\\]. GOAL was a 1-year, randomised, multinational trial which included 3,421 patients from 44 countries \\[[@CR3]\\]. The study evaluated fluticasone propionate (FP) in combination with salmeterol (SAL) (FP/SAL) compared with FP alone, and demonstrated that guideline-defined asthma control could be achieved in the majority of patients \\[[@CR3]\\].\n\nThe large size and multinational nature of GOAL allows for analysis of population subgroups, for example, by ethnicity. The relatively few clinical trials evaluating asthma control in Asian patients have demonstrated that effective control can be achieved with usual therapies of ICS alone or a combination of ICS/long-acting \u03b2~2~-agonist (LABA) \\[[@CR4]--[@CR6]\\]. However, two large, population-based surveys in"
-"1. Introduction {#s0005}\n===============\n\nPregnancy is a complex event that causes alterations throughout the mother\\'s body. Notable systemic effects are those of the gastrointestinal system, renal function, cardiovascular apparatus, blood composition and coagulation, and respiratory function.\n\nThe woman\\'s body adapts to the ongoing changes ([@b0065]).\n\nAt the metabolic level there is a total average weight increase due to the development of breasts, uterus, fetus and embryofetal appendages and as a result of water retention facilitated by the fall in plasma osmolarity The woman\\'s body adapts to the ongoing changes ([@b0065]). The increase in circulating levels of progesterone and estrogen leads to a decrease in gastrointestinal motility that results in a subjective feeling of hypersalivation, often associated with nausea. The esophageal function remains normal, even if the frequency of gastro-oesophageal reflux, often due to pyrosis, increases.\n\nGastric tone and motility decrease, while the production of gastrin and gastric volume increases with a decrease in pH. All these factors predispose the subject to nausea and vomiting. Several modifications occur in oral cavity causing alterations in salivary composition, onset of caries and periodontal disease, that represent a risk factor for unfavourable outcomes during pregnancy, such as prematurity and low birth weight, as well"
-"1. Introduction {#sec1-vision-02-00011}\n===============\n\nOur social interactions rely upon the capability to understand and track a social partner's beliefs, desires, and intentions---an ability known as theory of mind (ToM) \\[[@B1-vision-02-00011]\\]. Through the act of taking another's perspective, we 'mentalise' and compute to what and where another person is attending. Mental state attributions (MSAs) guide attention to subtle social cues and information that might otherwise go unheeded, thereby allowing us to successfully integrate with the social world around us. Indeed, one influential but controversial idea is that the ability to make mental state attributions underpins the phenomenon of social attention \\[[@B2-vision-02-00011]\\] and therefore occurs prior to gaze following.\n\nSocial attention is often operationalized using a gaze-cueing task \\[[@B3-vision-02-00011]\\]. In the canonical version of this task, a participant is shown a face with the eyes averted, such that it appears to be looking at one side of the display. A stimulus is then presented on the side of the display the face is gazing at (a valid trial), or contralaterally to the direction of gaze (an invalid trial). The participant must quickly and accurately identify the target while maintaining fixation at the center of the screen. A robust finding is that reaction"
-"###### Strengths and limitations of this study\n\n-   Data comes from a large nationwide survey of patients with any cancer.\n\n-   The survey has a high (68%) response rate.\n\n-   We have not been able to directly examine the potential influence of differences in expectations of care quality between patients treated by London hospitals and hospitals elsewhere in England.\n\nIntroduction/background {#s1}\n=======================\n\nUnderstanding the variation in patient experience can help to inform priorities for improvement actions and policies. In the UK, the advent of large national surveys of patients with cancer has enabled a better appreciation of variation in cancer patient experience between different patient groups or hospitals.[@R1]^--^[@R4] A salient finding of recent cancer patient surveys is that patients treated by London hospitals reported poorer experiences compared with those treated by hospitals in other English regions.[@R1] [@R5]\n\nSeveral hypotheses can be considered to explain this type of geographical variation in crude hospital experience scores. First, London hospitals may be treating a higher proportion of patient groups known to report worse experiences of care, such as younger and ethnic minority patients or patients with certain types of cancer.[@R2] [@R3] [@R8] [@R9] Second, patient experience may vary by type of hospital, and"
-"1.. Maxwell's demon\n===================\n\nA glass of water contains about 10^24^ water molecules. A water molecule moves at several hundred meters per second and collides with other molecules approximately 10^12^ times per second. Thus, on a microscopic scale, a glass of water is a stormy chaotic world. We might then conclude that we can drive a car by using this large amount of energy contained in a glass of water. We can obtain a virtually infinite amount of water from the sea and use it to solve energy issues. However, this is in principle impossible. We cannot fully utilize the energy that is contained in the water, but we can use only a fraction of it, which is the free energy. This is one of the several equivalent expressions of the second law of thermodynamics. This arises because water molecules move randomly. In order to fully utilize the energy, we would need to have the complete information about the movement of molecules. However, only limited statistical information such as the temperature and the pressure is available to us. The lack of information about the system corresponds to the entropy. In other words, if we could somehow observe the movement of"
-"All relevant data are within the paper and its Supporting Information files. Transcriptomics data are available at NCBI Gene Expression Omnibus, GEO Series accession number GSE63023 Proteomics data are available at Peptide Atlas PASS00689.\n\nIntroduction {#sec001}\n============\n\nCaspases constitute a family of [C]{.ul}ysteine-dependent [Asp]{.ul}artate-directed prote[ases]{.ul} participating in apoptotic cell death \\[[@pone.0131411.ref001]\\]. By cleaving their targets, which include caspases themselves, caspases regulate many aspects from death signal propagation within the cell to genomic DNA degradation. Caspase gene mutation and deletion experiments unveiled their direct and evolutionally conserved implication in the control of embryonic cell death \\[[@pone.0131411.ref002]--[@pone.0131411.ref004]\\]. Interestingly, *in vivo* deletion of initiator caspase-8, which triggers the cell death intracellular signaling upon death receptor activation, or deletion of its regulators Cellular FADD-like IL-1\u03b2-converting enzyme-inhibitory protein (cFLIP) and FADD, lead to alterations in cardiac muscle differentiation \\[[@pone.0131411.ref005]--[@pone.0131411.ref007]\\]. Executioner caspase-3 and -7 function normally downstream of initiator caspases and their global deletion also impair cardiac muscle differentiation \\[[@pone.0131411.ref008]\\]. In addition, the effects of *in vitro* embryo culture in presence of caspase inhibitors suggested a role of caspase proteolytic activity in heart formation and muscle differentiation \\[[@pone.0131411.ref009], [@pone.0131411.ref010]\\].\n\nUbiquitous deletion of caspases prevented from identifying whether cardiac defects resulted from missing caspase activity in the"
-"Background {#Sec1}\n==========\n\nThe prevention of oral disease and the promotion of oral health have been established as high priorities by the World Health Organization \\[[@CR1]\\]. The etiologies of oral disease are generally progressive and cumulative, such that compared with younger individuals, elderly people are at greater risk of active dental caries and periodontal disease risk \\[[@CR2]--[@CR4]\\]. However, although middle-aged and elderly people are aware of the importance of oral health to their quality of life \\[[@CR5]\\], the majority of them seek dental care only when they experience toothaches \\[[@CR6]\\]. As consequence, middle-aged and elderly individuals usually suffer from multiple oral diseases, and obstacles to their use of dental care services are numerous \\[[@CR7]\\]. As the population ages and the retention rate of natural teeth increases, the demand for dental care becomes more urgent in middle-aged and elderly people than in adolescents \\[[@CR8]\\].\n\nIn the traditional sense, obtainment of dental care services is related to the ability to access oral health resources \\[[@CR9]\\]. If dental care-seeking behavior can be characterized in middle-aged and elderly people, then the reasons underlying the obstacles to timely and proper dental care might be identified. In addition to human resources such as dental care and"
-"Background\n==========\n\nGliomas are a particularly lethal solid tumor arising from support cells in the central nervous system, which can be divided into astrocytic tumors, oligodendrogliomas, and oligoastrocytomas. These are then graded into 4 histological degrees of malignancy, according to the WHO classification \\[[@B1]\\]. Oligodendrogliomas and oligoastrocytomas are tiered into grade II, and anaplastic is grade III lesions. Astrocytomas, which are tumors composed predominantly of neoplastic astrocytes, amount to 80-85% of all gliomas. It is graded from low (grade I) to high (grade IV), according to hallmarks of the tumor histological aberrations \\[[@B2]\\]. Grade IV astrocytomas are known as glioblastoma multiforme (GBM), the most common and lethal form of malignant gliomas. The median survival time of GBM was only 10 months for those no older than 65 and 3.5 months for 65 or older \\[[@B3]\\]. However, recent research indicated that age groups (\\<65 and \u226565 years) was not associated with survival time, with median survival 13 months and 15 months, respectively \\[[@B4]\\]. Despite the development of therapy technology, the death rate of glioblastoma patients decreases a little, which indicates that the survival time of the most common and aggressive form of glioma in adults is very poor \\[[@B5]\\]. Previous studies"
-"Neural tube defects (NTDs), major congenital anomalies of the central nervous system, result from failure of the neural tube to close between the 3^rd^ and 4^th^ week of gestation and include spina bifida, anencephaly, and encephalocele.^[@r01]^ Because previous epidemiological studies demonstrated that low folic acid intake conclusively increases the risk of NTDs, intake of folic acid is recommended worldwide for women during their reproductive years.^[@r02]^\n\nNatural folate contained in foods has rather low and variable bioavailability compared with pure folic acid, and supplementation of folic acid is recommended to increase plasma folate levels.^[@r02]^ Accordingly, the Centers for Disease Control in the United States recommended intake of folic acid supplements in 1992 to all potentially pregnant women because the critical period for NTDs occurs before pregnancy is recognized by many women. Following this global trend, the Japanese Government in 2000 recommended intake of folic acid supplements during the period from 1 month before pregnancy to 3 months of pregnancy for potentially pregnant women.^[@r03]^ The guideline recommends intake of 400 \u00b5g of folic acid supplement per day, in addition to dietary intake of folic acids. Despite the unequivocal benefits of folic acid supplementation, use of the supplement, in particular during the recommended"
-"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"
-"All relevant data are within the paper.\n\nIntroduction {#sec001}\n============\n\nWhite adipose tissue is an endocrine organ that secretes a variety of hormone-like protein factors, commonly referred to as a*dipokines*. Adiponectin is a protein hormone secreted exclusively from white adipose cells and involved in modulation of glucose and lipid metabolism \\[[@pone.0119530.ref001]\\].\n\nRegulated exocytosis has been investigated in several neuroendocrine cell types and is known to involve Ca^2+^, ATP and temperature-dependent steps \\[[@pone.0119530.ref002]\\]. Adiponectin has been suggested to be secreted via regulated exocytosis of a pre-stored pool of secretory vesicles \\[[@pone.0119530.ref003],[@pone.0119530.ref004]\\] but very little is known about stimulus-secretion coupling in the white adipocyte. Our recent work has shown that adipocyte exocytosis/adiponectin secretion is stimulated via PKA-independent cAMP-stimulation in a Ca^2+^-independent manner and is amply augmented by a combination of Ca^2+^ and ATP \\[[@pone.0119530.ref005]\\]. Thus, unlike archetypal endocrine cell types, Ca^2+^ amplifies but does not trigger exocytosis in adipocytes.\n\nCharacterisation of the steps of stimulus-secretion coupling, such as vesicle replenishment and fusion \\[[@pone.0119530.ref002]\\], is crucial in order to understand exocytosis. Several studies have shown that Ca^2+^-dependent exocytosis exhibits temperature-dependent components in both neuronal \\[[@pone.0119530.ref006]\\] and endocrine \\[[@pone.0119530.ref007]--[@pone.0119530.ref009]\\] cell types. Temperature-dependent exocytotic mechanisms were first described in catecholamine secreting chromaffin cells and the"
-"Introduction {#S1}\n============\n\nThe bacterium *Staphylococcus aureus* is a highly significant human pathogen and a major cause of bacterial infections worldwide^[@R1]^. While this bacterium is found as part of the commensal skin and mucosal microbiome in about 30% of the human population, it is usually held in check by the physical barrier of the skin. However, upon breach of host defenses, *S. aureus* can disseminate systemically, leading to life-threatening conditions such as endocarditis, osteomyelitis, meningitis and sepsis^[@R2]^. *S. aureus* often forms highly robust biofilms in which the bacterium populates synthetic surfaces, e.g. on prosthetic devices, surrounding itself in a biomolecular matrix that is largely impermeable to the immune system and many antibiotics, causing infections that are complicated and costly to monitor and treat^[@R3]^. Finally, an increased prevalence of community-acquired infections with antibiotic-resistant strains^[@R2]^ is a further reason why *S. aureus* remains a major human health threat that requires new methods for rapid detection, treatment and therapy response monitoring.\n\nHydrolytic enzymes have vital roles for maintaining bacterial homeostasis and survival at the host-pathogen interface^[@R4]--[@R10]^ and thus represent potential anti-virulence and anti-infectivity targets^[@R11],[@R12]^. Serine hydrolases are one of the largest and most diverse enzyme classes in eukaryotic and prokaryotic proteomes^[@R13]^. One of"
-"Dear Editor,\n\nWe read with great interest the article by Sohrabi et al. regarding the current 2019 novel coronavirus, SARS-CoV-2 outbreak. The article presented the timeline of the initial outbreak and response, describing key aspects such as management, transmission and symptoms \\[[@bib1]\\].\n\nIn this letter, we provide a detailed update on the supply of personal protective equipment (PPE) in the United Kingdom (UK), highlighting key statistics and updated PPE guidelines on surgical procedures. We provide comparisons to World Health Organisation (WHO) guidelines and describe recent innovations aiming to reduce hospital SARS-CoV-2 spread.\n\nSARS-CoV-2 has been shown to spread in human to human contact through aerosol droplets. Therefore, healthcare staff are at an increased risk of infection, especially during aerosol generating procedures (AGPs) including intubation, a procedure essential in maintaining ventilation of SARS-CoV-2 patients and in surgical intervention. Hence the use of PPE such as plastic face visors, filtering face pieces class 3/2 (FFP3/2) or N95 masks, which filter out 99%/94% and 95% of airborne particles respectively, are imperative in healthcare environments to prevent further spread. Government statistics state that over 761 million items of PPE have been transported to frontline staff across 58,000 different healthcare settings including hospitals, care homes"
-"Background {#Sec1}\n==========\n\nGraduate medical education training programs are faced with the challenge of developing trainee expertise despite increased work hour limitations. The majority of trainee learning takes place in the everyday clinical environment, making work-based learning opportunities increasingly valuable for trainee development \\[[@CR1], [@CR2]\\]. The role of consultation in the inpatient setting is expanding; \\[[@CR3]--[@CR5]\\] subspecialty consultation represents an important opportunity for resident work-based learning. Within academic medical centers, communication during consultation most frequently occurs between trainees \\[[@CR6]\\], making the teaching interaction between residents and fellows important. Both fellows and residents have a strong interest in teaching and learning, respectively \\[[@CR7]\\]. However, many barriers to teaching during consultation exist in the hospital environment \\[[@CR7]--[@CR10]\\]. Suboptimal communication of the consult question, fellow \"pushback\" on consult requests, lack of incentives for fellows to teach, perceptions among residents that fellows may not be interested in teaching, and among fellows that residents may not be interested in learning, may hinder the resident-fellow interaction.\n\nEffective communication between consultants and the primary team is critical for patient care and forms the cornerstone for successful resident-fellow teaching interactions \\[[@CR7], [@CR11], [@CR12]\\]. Several resident-directed interventions, such as the 5 Cs Model of Consultation (5Cs) \\[[@CR13]\\], and the"
-"Background {#Sec1}\n==========\n\nHead and neck cancer (HNC) includes malignant squamous lesions arising in the oral cavity, oropharynx, larynx or hypopharynx, and is the sixth leading cancer by incidence worldwide, with approximately 500,000 new cases annually and only 40--50% 5-year survival rate.^[@CR1]^ The use of tobacco and excessive alcohol consumption are the most important risk factors identified and they also seem to have a synergistic effect. A subgroup of HNC, particularly those of the oropharynx, is caused by infection with high-risk types of human papillomavirus (HPV). Although in the past decade the incidence of HNC has been slowly declining in the western world, probably due to a decrease in the prevalence of smoking, oral tongue and particularly oropharyngeal cancers are becoming more prevalent. This may be related to an increase in oropharyngeal HPV infections and recent studies revealed that HPV16 in particular is involved in these tumours. HPV-positive tumours form a distinct group within HNC with different aetiological factors. These tumours are different at the molecular level, changing the clinical outcome and presenting a better prognosis.^[@CR2]^ Despite their diversities, HPV-positive and HPV-negative HNC patients are treated using the same therapies, leading the scientific and medical community to reassess the current"
-"Published online: June 28, 2012\n\nIntroduction {#sec1}\n============\n\nThe Bcl-2 family includes three main subclasses: antiapoptotic proteins including Bcl-2, Bcl-xL, Bcl-w, MCL-1, and A1 that possess multiple Bcl-2 homology (BH) domains; multidomain proapoptotic proteins that include Bax and Bak, which have BH1-3 domains; and BH3-only proapoptotic proteins, including Bim, Bid, Bad, Noxa, Puma, Bmf, Bik, Bnip3, and Hrk ([@bib1]). In viable cells, Bax and Bak are monomeric and inactive. In response to death stimuli, these proteins quickly homooligomerize ([@bib44]). In the absence of both Bax and Bak, cells are resistant to a wide variety of apoptotic stimuli, including UV irradiation, TNF-\u03b1, endoplasmic reticulum (ER) stress, and BH3-only proteins ([@bib45]).\n\nBim has three different splicing isoforms, namely BimEL (the major isoform), BimL, and BimS ([@bib30]). In healthy cells, Bim is inactivated by its interaction with dynein light chain 1 (DYNLL1/LC8), which recruits it to the microtubule-based dynein motor complex ([@bib35]). After cells are exposed to apoptotic stimuli, Bim is phosphorylated by JNK at T116, which causes Bim dissociation from LC8 and the dynein motor complex ([@bib18]). Bim is essential for apoptosis induced by certain stimuli in cell culture, like cytokine deprivation and ER stress ([@bib36]), and for hematopoietic cell homeostasis in"
-"Carbapenems are often used as a last resort for treating serious infections attributable to multidrug-resistant gram-negative bacilli because these drugs are stable even to extended-spectrum and AmpC \u03b2-lactamases. However, gram-negative bacilli with acquired metallo-\u03b2-lactamase (MBL), IMP-1, emerged and spread during the early 1990s in Japan ([@R1]). IMP-1 and its variants were then detected in other countries ([@R2]).\n\nAnother type of acquired MBL, VIM-1, was first reported in *Pseudomonas aeruginosa* in Italy ([@R3]), followed by reports of VIM-2 in France and Greece. VIM-2 was detected in *P. aeruginosa* in a Korean hospital isolated as early as 1995 ([@R4]). The occurrence of the VIM enzyme has continued to evolve: VIM-3 was reported in Taiwan ([@R5]), and VIM-4 in the United States ([@R6]).\n\nThe *bla*~IMP~ and *bla*~VIM~ genes are horizontally transferable because they are inserted in integrins, and some of these integrons are located on conjugative plasmids ([@R7]). Because of its ability to spread, carbapenem resistance related to IMP and VIM \u03b2-lactamase production has become a serious concern ([@R8]). Laboratory personnel and physicians must consider the therapeutic and infection-control implications of not detecting carbapenemase-producing bacteria ([@R9]). A large number of VIM-2--producing *Pseudomonas* spp. have been detected in a Korean hospital since 1995 ([@R4]),"
-"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"
-"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"
-"Background\n==========\n\nHealth care professionals, including physicians, are at high risk of encountering workplace violence. For example, 59 per cent of Australian general practitioners reported that they had experienced work-related violence during the previous 12 months \\[[@B1]\\]. In US emergency departments, 75 per cent of physicians had encountered verbal violence and 28 per cent indicated that they had been victims of physical assault in the previous 12 months \\[[@B2]\\]. In another study, 96 per cent of physician respondents in US emergency departments reported experiencing verbal violence and 78 per cent a verbal threat during the previous 6 months \\[[@B3]\\]. In a study conducted among hospital and community physicians in Israel, 56 per cent reported verbal violence and 9 per cent physical assault during the previous year \\[[@B4]\\]. In Finland, every fifth physician reported having encountered physical violence or the threat of it in the previous year \\[[@B5]\\].\n\nWorkplace violence may have many negative ramifications for health care employees. Workplace violence has been associated with lower job satisfaction and higher levels of turnover intentions in nurses and home healthcare assistants \\[[@B6],[@B7]\\]. Moreover, workplace violence has been found to affect negatively hospital personnel's health \\[[@B8]\\] and increase sickness absences \\[[@B9]\\]. In physicians,"
-"1. Introduction {#sec1}\n===============\n\nSoil contamination by infective forms of intestinal parasites is the most important infection risk factor for both humans and animals. These parasites have been recognized as an important public health problem, particularly in developing countries \\[[@B11]\\], where adequate water and good sanitation are lacking. The commonest and well known of these parasites are hookworms (*Necator* and*Ancylostoma*), whipworm*(Trichuris)*, and the common roundworm*(Ascaris)* \\[[@B8]\\]. They are most prevalent in man and can also be found in animals. These parasites have similar epidemiological characteristics with a direct life cycle. Host contamination occurs via oral route through ingestion of infective embryonated eggs from contaminated soil, vegetables, and food products or via the percutaneous migration of infective L~3~ from the environment. Recent estimation suggests that they infect over 1 billion, 770 million, and 800 million people, respectively. These parasites have been shown to negatively impact the physical fitness and cognitive performance of the pupils \\[[@B2]\\]. Mature nematode eggs, cysts, and oocysts of protozoan parasites can remain viable in the soil for a long time depending on several factors such as climatic conditions, seasonal air temperatures, humidity or desiccation of soil, and exposure to sunlight \\[[@B21]\\]. Thus, contamination of soils with infective"
-"Introduction {#s001}\n============\n\nM[eiotic cell cycle in mammalian oocytes]{.smallcaps} is a complex process that involves several stop and go channels. It starts during fetal life and gets arrested at the diplotene stage of the first meiotic prophase. The diplotene stage oocytes are morphologically characterized by the presence of germinal vesicle and nucleolus inside the oocytes\\' cytoplasm, and this arrest may last for several months to several years depending on the mammalian species.^[@B1]^ Meiotic resumption from diplotene arrest may occur in response to a gonadotropin surge *in vivo*. The removal of follicular oocytes from ovary and their culture *in vitro* also induce meiotic resumption from diplotene arrest, so-called spontaneous oocyte maturation.^[@B4]^ This is the crucial period when oocytes achieve meiotic competence, and it determines oocytes quality, which directly affects reproductive outcome in most mammalian species, including human.^[@B5]^\n\nIt is well established that intra-oocyte cyclic 3\u2032,5\u2032-adenosine monophosphate (cAMP) plays an important role in the maintenance of meiotic arrest at the diplotene stage.^[@B3]^ The continuous transfer of cAMP through gap junctions from cumulus granulosa cells to the oocyte results in the maintenance of a high level of intra-oocyte cAMP level.^[@B5],[@B7],[@B9],[@B10]^ This increased level of intra-oocyte cAMP maintains meiotic arrest at diplotene arrest for"
-"1. Introduction\n===============\n\nWine production is of great importance in agro economic activities. The world grape production in 2012 exceeded 69 million tons and Europe was the largest producer of wine, with 66% of the total world production \\[[@B1-molecules-20-09686]\\]. The solid wastes generated by the wine industry represents between 25%--30% of the material used and it consists mainly of grape pomace (containing seeds, pulp, stem and skin) \\[[@B2-molecules-20-09686],[@B3-molecules-20-09686]\\]. It is well known that high quantities of valuable compounds like dietary fiber, oils from the seeds, anthocyanins and phenolics compounds still remain within the grape pomace after processing \\[[@B3-molecules-20-09686],[@B4-molecules-20-09686]\\]. The phenolics, such as resveratrol, have great potential due to their antioxidant capacity and health benefits against coronary diseases by the inhibition of LDL (low-density lipoproteins) and other chronic diseases, like cancer, diabetes and neurodegenerative disorders \\[[@B3-molecules-20-09686],[@B4-molecules-20-09686]\\].\n\nIn addition, from the economic point of view, the market of these compounds have been increased in the recent years by the increasing consumer demand for the use of more natural antioxidant compounds, achieving the value of US\\$30 billions, based on 2008 grape wine production data \\[[@B3-molecules-20-09686]\\]. In this sense, the valorization and reuse of these wastes from the wine-making industry would have a significant"
-"1. Introduction {#sec1-nanomaterials-09-01642}\n===============\n\nThe discovery of graphene and its unique properties has triggered the development of various types of layered materials \\[[@B1-nanomaterials-09-01642]\\]. In particular, transition metal dichalcogenides (TMDs), atomically thin semiconductors of the type MX~2~ (M = Mo, W; X = S, Se), have attracted considerable attention as their physical and electrical properties are tunable. Depending on their composition and thickness, two-dimensional (2D) TMDs have a variety of electrical properties ranging from metal, to insulator, to semiconductor, which could lead to a new dimension of atomic thickness for future device applications \\[[@B2-nanomaterials-09-01642],[@B3-nanomaterials-09-01642]\\]. TMD materials have useful device characteristics, such as a high on/off ratio, a wide range of photoluminescence, and a low subthreshold voltage, making them suitable for spintronics and optoelectronics \\[[@B4-nanomaterials-09-01642]\\]. Among the numerous TMD materials, WSe~2~ has been extensively studied because its electrical transport properties can be easily adjusted from p-type to bipolar behavior depending on the type of contact metal \\[[@B5-nanomaterials-09-01642],[@B6-nanomaterials-09-01642],[@B7-nanomaterials-09-01642]\\]. Bulk WSe~2~ crystallizes in the \"2H'' or trigonal prismatic structure (space group *P*6~3~/*mmc*; *a* = 0.330 nm, *c* = 1.298 nm), in which each W atom is surrounded by six Se atoms, defining two triangular prisms. It was also reported that the energy band structure"
-"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}"
-"Glaucoma is the second most common cause of irreversible blindness, impairing 80 million people worldwide.[@bib1] Elevated intraocular pressure (IOP) is the most common indicator for diagnosis and progression of glaucoma, with reduction of IOP the only proven glaucoma intervention.[@bib2]^--^[@bib4] IOP is controlled by the balance between production and outflow of aqueous humor. In the conventional outflow pathway, the aqueous humor travels through the trabecular meshwork and juxtacanalicular connective tissue (JCT), into Schlemm\\'s canal (SC), through collector channels (CCs) passing through the sclera, and finally emptying into the episcleral veins.[@bib5]^,^[@bib6] The increased IOP characteristic of primary open-angle glaucoma is caused by increased resistance to aqueous humor outflow.[@bib7]^,^[@bib8] Most investigations of outflow resistance have focused on the JCT and inner wall of SC, which are widely regarded as the principal sites of outflow resistance.[@bib9] However, flow resistance is also generated in SC and CCs, particularly in the former as IOP is increased.[@bib8]^,^[@bib9]\n\nIn primate, humans, and mice, SC is essentially a flat tube traveling circumferentially around the limbus of the eye, whose opening thickness, the distance from the inner wall to outer wall, decreases as IOP increases.[@bib9] Greater lengths of SC are collapsed in glaucomatous eyes than healthy eyes, even when perfused"
-"Actinomycetes are free living, saprophytic, filamentous bacteria, and a major source for the production of antibiotics ([@B1]). They are found in soil, fresh water and marine water environments ([@B2]). Actinomycetes provided many important bioactive compounds of high commercial value and screened for new bioactive substances ([@B3]). These bacteria are an important group of microorganisms due to their ability to produce a wide array of secondary metabolites, such as antibiotics, antitumor agents, immunosuppressive agents, cosmetics, vitamins, nutritional materials, herbicides, pesticides, anti-parasitic agents and enzymes ([@B1], [@B4], [@B5]). Around 23000 bioactive secondary metabolites produced by microorganisms have been reported. Over 10000 of these compounds are produced by actinomycetes, representing 45% of all bioactive microbial metabolites discovered. Among actinomycetes, around 7600 compounds are produced by *Streptomyces* species ([@B6]). As the frequency of novel bioactive compounds obtained from terrestrial actinomycetes decreased, it had been emphasized that actinomycetes from marine sediments might be valuable for the isolation of novel strains which could potentially yield a broad spectrum of secondary metabolites ([@B7]-[@B9]). However, it has been resolved whether actinomycetes forms part of the marine microbial community of sediment samples originated from terrestrial environments and was simply carried out to sea in the form of resistant spore"
-"Data are available from the National Institute for Communicable Diseases (NICD) on request for those who meet criteria for access to confidential data after completion and approval of the NICD Data Sharing Agreement. The data contain information that could compromise patient confidentiality. Data requests may be sent to the institute\\'s Executive Director, Prof Shabir Madhi (email address: <ShabirM@nicd.ac.za>).\n\nIntroduction {#sec005}\n============\n\nInfluenza A and B viruses co-circulate globally during winter in the Northern and Southern hemispheres causing seasonal influenza epidemics, while epidemics are sporadic in the tropics \\[[@pone.0177655.ref001]--[@pone.0177655.ref003]\\]. Influenza B viruses were first identified in 1940 and, unlike influenza A, they cause disease primarily in humans \\[[@pone.0177655.ref004], [@pone.0177655.ref005]\\]. Studies have found that the symptoms and duration of illness due to infection with influenza A and influenza B are similar \\[[@pone.0177655.ref006]\\]. During the mid-1980's, evolutionary changes in the haemagglutinin (HA) gene by antigenic drift separated influenza B viruses into two antigenically distinct lineages represented by B/Yamagata/16/88 and B/Victoria/2/87 \\[[@pone.0177655.ref007]\\]. Phylogenetic studies from different parts of the world demonstrated that influenza B viruses evolve through progressive antigenic drift at a slower rate compared with influenza A viruses \\[[@pone.0177655.ref005], [@pone.0177655.ref007]--[@pone.0177655.ref009]\\]. Influenza B disease burden has been reported to be higher in children (0--17"
-"Introduction {#S0001}\n============\n\nThe development of chemotherapy has significantly improved the survival of cancer patients, especially for those who were diagnosed at advanced stages.[@CIT0001] Endometrial adenocarcinoma (EA) is the most common type of endometrial cancer, which is the major type of common gynaecological cancer in developed countries.[@CIT0002] EA is characterized by its extreme aggressive nature and low early diagnosis rate.[@CIT0003] A considerable portion of EA patients are initially diagnosed with the existence of tumor invasion, which are not candidates for radical tumor resection.[@CIT0004] Although chemotherapy is helpful for EA patients, chemo-resistance will inevitably develop, leading to poor treatment outcomes.[@CIT0005]\n\nIt has been reported that chemotherapy modulates the expression of endogenous genes in the body of cancer patients, and the altered expression of certain genes may induce the sensitivity of cancer cells to chemical drugs.[@CIT0006],[@CIT0007] Recent studies also showed that long non-coding RNAs (lncRNAs, longer than 200 nt) were critical regulators of cancer cell behaviors[@CIT0008] and also participate in the development of chemo-resistance during chemotherapy.[@CIT0009] Therefore, regulation of lncRNA expression may assist the use of chemical drugs in cancer treatment. PMS1 Homolog 2, Mismatch Repair System Component Pseudogene 2 (PMS2L2) is a novel lncRNA that has protective effects on chondrocytes during"
-"1. Introduction\n===============\n\nMelanomas are the most potentially lethal of all the skin cancers. Although major changes have been made in the surgical procedures and in the therapy for melanoma, the incidence of this skin cancer is still increasing. These changes eliminate the need for grafts thereby greatly reducing hospital and recovery time. However they do not appear to improve the survival rate \\[[@B1-cancers-02-01155],[@B2-cancers-02-01155]\\]. Diagnosis of all four types of melanoma at an early stage is the key to the best prognosis and to possibly preventing death. This requires that the tumour be diagnosed before it has reached Grade 4, infiltrated the lymph nodes or metastasised to other body organs. Since the most common type, the Superficial Spreading Melanomas, can grow extremely fast and the Nodular, Lentigo Maligna and Aeral Lentiginous melanomas are not easily recognised in the early stages, many patients present too late. In this paper we present a possible alternative diagnostic test using fibre x-ray diffraction of a skin biopsy.\n\nThis use of x-rays is completely different from the familiar standard shadow patterns from routine medical examinations where the full wavelength spectrum of hard x-rays \\[energy range 20 to 120 keV (0.10 to 0.010 nm wavelength)\\] are"
-"Introduction and Motivations {#Sec1}\n============================\n\nThe current approach to forecasting modelling consists of simulating explicitly only the largest-scale phenomena, while taking into account the smaller-scale ones by means of \"physical parameterisations\". All numerical models introduce uncertainty through the selection of scales and parameters. Additionally, any computational methodology contributes to uncertainty due to discretization, finite precision and accumulation of round-off errors. Finally the ever growing size of the computational domains leads to increasing sources of uncertainties. Taking into account these uncertainties is essential for the acceptance of any numerical simulation. Numerical forecasting models often use Data Assimilation methods for the uncertainty quantification in the medium to long-term analysis. Data Assimilation (DA) is the approximation of the true state of some physical system at a given time by combining time-distributed observations with a dynamic model in an optimal way. DA can be classically approached in two ways: as variational DA \\[[@CR16]\\] and as filtering \\[[@CR5]\\]. In both cases we seek an optimal solution. The most popular filtering approach for data assimilation is the Kalman Filter (KF) \\[[@CR15]\\]. Statistically, KF seeks a solution with minimum variance. Variational methods seek a solution that minimizes a suitable cost function. In certain cases, the two approaches"
-"Background {#Sec1}\n==========\n\nDisability of the upper extremity is common after stroke and almost 50\u00a0% of those affected have remaining impairments more than three months post-stroke \\[[@CR1], [@CR2]\\]. The impairments often lead to difficulties in performing daily hand activities \\[[@CR3]\\], especially those that require the use of both hands, i.e., bimanual activities \\[[@CR4]\\]. The ability to perform bimanual activities is therefore an important goal in stroke rehabilitation, regardless of which hand that is affected \\[[@CR5]\\].\n\nThe ability to perform daily activities can be objectively assessed by observations of different tasks in a standardized environment or by patient-reported questionnaires. The advantage of using questionnaires is that they often provide a better understanding of an individual's self-reported everyday difficulties and thereby enable clinicians to design more individually targeted rehabilitation interventions \\[[@CR6]\\]. One questionnaire that is recommended for persons with disability of the upper extremity after stroke is the ABILHAND Questionnaire \\[[@CR4], [@CR7], [@CR8]\\]. It assesses self-perceived ability to perform daily bimanual activities. Previous studies have focused on evaluating the psychometric properties of the ABILHAND \\[[@CR4], [@CR8]\\], but no study has thoroughly described which activities persons in a stable phase post stroke perceive difficult to perform.\n\nIn order to improve functioning of"
-"Background\n==========\n\n**4**D Flow has been used to study flow patterns, mainly in the aorta. In the Pulmonary Artery (PA) an abnormal Vortex (VO) has been described in association with pulmonary hypertension \\[[@B1]\\]. However, a systematic analysis of flow patterns in the PA has not been performed.\n\nObjective\n=========\n\nTo perform hemodinynamic analysis in the PA in volunteers and patients with CHD after Glenn procedure.\n\nMethods\n=======\n\nEighteen volunteers and two patients underwent 4D Flow scan on a Phillips system (25 frames, 2.5mm^3^). Flow was visualized by streamlines and particle traces (\\\"GTFlow\" software). 2D planes placed in 5 locations were used to grade flow patterns: 1) just after to the pulmonary valve, 2) before the PA bifurcation, 3) between plane 1 and 2, 4) Right-PA, and 5) Left-PA. Sagital and coronal planes were also analyzed. VOs that lasted at least 2 frames were registered (start, finish and peak-frame; direction, size, and distance between vortex-center and vessel-center).\n\nResults\n=======\n\nTwo VOs were identified in the PA in volunteers (Fig. [1a](#F1){ref-type=\"fig\"}). VO~1~ was seen in all volunteers and VO~2~ in sixteen. Both vortices started at peak-systole and ended at late-systole. VO~1~ was located on posterior wall and VO~2~ on anterior wall, with"
-"Introduction\n============\n\nRelapse is the most frequent outcome of people who stop smoking; typically, several quit attempts are required to achieve sustained tobacco abstinence ([@R1]). Relapsed smokers are interested in treatment but generally do not seek it proactively ([@R2]--[@R6]). Most smoking cessation programs lack strategies to encourage relapsed smokers to make another quit attempt (\"recycle\"). Research suggests that relapsed smokers experience decreased self-efficacy and feelings of disappointment and guilt that may hinder them from proactively seeking treatment ([@R2]). They may also have limited knowledge about treatment and health coverage for repeated quit attempts ([@R4]). Effective interventions are needed to reconnect relapsed smokers with cessation support.\n\nCarlini and colleagues ([@R3],[@R4]) conducted 2 randomized controlled trials that tested the feasibility and efficacy of proactive interventions inviting unsuccessful quitters to enroll in a new quitline-supported quit attempt. In the first trial, quitline staff contacted the participants by telephone. In the second trial, they used an automated telephone system (Interactive Voice Response \\[IVR\\]). In both studies, motivational and information barriers to a new quit attempt were addressed, followed by an immediate option to connect with quitline support. Recycling rates in both trials were 8 to 12 times higher among participants in the intervention group"
-"###### Strengths and limitations of this study\n\n-   The surveys were population-based, which provide an updated examination of disability trends among Chinese adults in Hong Kong aged 65\u2005years and older.\n\n-   This study includes the adjustment for multiple potential cofounders, including sociodemographic characteristics, lifestyle factors, comorbidities as well as self-rated health, which are known to influence functional status.\n\n-   The surveys ended in the birth cohort 1947. Therefore, we were unable to examine the cohort differences on disability between prewar generations and postwar baby boomers, whose early-life and mid-life experiences were remarkably different from each other.\n\n-   Information on birth place or risk factors in early-life and mid-life that may affect disability at older ages was not available, limiting the ability to identify causes of the increased disability burden in late life.\n\n-   Finally, our results only apply to the community-dwelling elderly. Disability prevalence in institutions tends to be higher than that in the community.\n\nIntroduction {#s1}\n============\n\nLife expectancy at birth of Hong Kong has taken one of the world\\'s leading positions and reached 81.2\u2005years in men and 86.9\u2005years in women in 2014.[@R1] The lengthening of life, however, does not mean that Hong Kong people have"
-"Anterior temporal lobe resection (ATLR) is an effective treatment for refractory temporal lobe epilepsy (TLE).^[@R1]^ Surgical damage to Meyer loop, the most anterior part of the optic radiation, results in a visual field deficit (VFD) in between 48%^[@R2]^ and 100% of patients.^[@R3]^ This precludes driving, a key goal of surgery,^[@R4]^ in 4%--50% of patients even if seizure-free.^[@R5][@R6][@R7]^\n\nOptic radiation fibers passing from the lateral geniculate nucleus (LGN) anteriorly over the roof of the lateral ventricle before turning backwards (Meyer loop) represent the superior visual quadrant so surgery may cause a contralateral superior quadrantanopia. VFD are hard to predict as the anterior extent of Meyer loop is variable^[@R8]^ and cannot be visualized intraoperatively. Diffusion tensor imaging tractography enables in vivo delineation of the optic radiation that can be used for epilepsy surgery planning.^[@R9],[@R10]^ Preoperative imaging has been used in neuronavigation systems to guide surgery^[@R11]^ but brain shift following craniotomy renders preoperative imaging inaccurate.^[@R12]^\n\nIntraoperative MRI (iMRI) allows updated images to be acquired during surgery. Tractography can be repeated using deterministic algorithms,^[@R13]^ but these depict Meyer loop poorly.^[@R14]^ More accurate probabilistic algorithms can be performed on preoperative data but are too time-consuming to employ during surgery. While preoperative tractography can be superimposed"
-"Introduction {#s1}\n============\n\nRemembering the place of an object (object-location memory, OLM) is crucial for adapting to changing environments in every-day life. However, this ability is known to decline during aging (Hedden and Gabrieli, [@B34]; Kessels et al., [@B50]) and may represent an incipient marker of neurodegenerative disease (Iachini et al., [@B42]). Advanced age increases risk of cognitive impairment and other age-related diseases (Salthouse, [@B87]; Niccoli and Partridge, [@B68]; Harada et al., [@B30]). Hence, early preventative strategies aiming to activate cognitive and brain resources in order to retain cognitive health, autonomy, and a better quality of life (Depp and Jeste, [@B17]) are of paramount importance. A variety of approaches have been investigated for its therapeutic and neuro-enhancing potential, including cognitive training, dietary regimes, physical training, use of pharmacological agents, as well as non-invasive brain stimulation (Perceval et al., [@B78]).\n\nCognitive training (CT) usually involves strengthening of neural networks through repeated co-activation of specific neurocognitive circuits active during task performance (Santarnecchi et al., [@B89]). The literature indicates that CT is beneficial for older adults\\' memory, but gains are much smaller than in young subjects (c.f. Passow et al., [@B77]). Moreover, evidence for generalizing effects that go beyond trained domain (transfer effects)"
-"1. Introduction {#sec1-antibodies-07-00022}\n===============\n\nNowadays, monoclonal immunoglobulin gamma (IgG) antibodies have become a major framework in cancer therapy and therapy for many other critical diseases. IgG molecules bind to their cognate antigens and the immune complexes subsequently interact either with type I or type II Fc receptors on effector cells and on B cells, modulating both humoral immune processes and innate immune processes \\[[@B1-antibodies-07-00022]\\]. Structurally, IgG contains four polypeptide chains, including two light chains (LC) and two heavy chains (HC). The four chains fold into three domains ([Figure 1](#antibodies-07-00022-f001){ref-type=\"fig\"}), that is, two Fab domains, which bind antigen and one Fc domain, which bind Fc receptors for effector function \\[[@B2-antibodies-07-00022]\\]. The Fab domains contain variable domain and constant domain. The variable domains, especially complementarity determining regions (CDRs), are mainly responsible for specificity and affinity \\[[@B3-antibodies-07-00022]\\], while the constant domains modulate the isotype/effector functions \\[[@B4-antibodies-07-00022]\\]. The Fc domain contains CH2 and CH3 domains. The CH2 domain mainly interacts with Fc receptors (FcRs), which are on the cell surface and play pivotal roles in humoral and cellular protection. Other regions, including the hinge region and glycan, also affect antibody activities, (e.g., binding \\[[@B5-antibodies-07-00022]\\], pharmacokinetics \\[[@B6-antibodies-07-00022]\\], and effector functions \\[[@B7-antibodies-07-00022]\\]).\n\nInterestingly, numerous evidences have"
-"Introduction {#Sec1}\n============\n\nThromboangiitis obliterans (TAO), or Buerger's disease, is an inflammatory, thrombotic-occlusive, medium- and small-sized vasculitis that usually occurs in young males with a history of tobacco use \\[[@CR1]\\]. The pathophysiology of the disease is not well understood. However, recently, the possible role of infectious pathogens as the trigger of TAO has been suggested \\[[@CR1]\\]. For instance, the antibody for the main oral pathogen responsible for gingivitis, *Porphyromonas gingivalis* (*P. gingivalis*), has been detected in the sera of TAO patients, and this pathogen has also been isolated from vascular lesions using polymerase chain reaction (PCR) \\[[@CR2], [@CR3]\\]. However, since smoking might be responsible for gingivitis and related immunologic responses in TAO patients \\[[@CR4]\\], this hypothesis has neither been confirmed nor disproved.\n\nIn addition to oral bacteria pathogens, since the 1980s, the possibility of Rickettsia infection has also been suggested as a trigger for TAO \\[[@CR5], [@CR6]\\]. In recent studies, Rickettsia infection was detected using PCR in 3 of 25 biopsies from a below-knee amputated limb in a TAO patient \\[[@CR7]\\]. Following the study, the antibodies for the Rocky Mountain spotted fever (RMSF) group were detected in the sera of TAO patients using micro-immunofluorescence (MIF) \\[[@CR8]\\].\n\nAccording to our recent"
-"**Correction to**: Molecular Systems Biology 5: 246. doi:10.1038/msb.2009.4; published online 17 February 2009\n\nIn our previously published study ([@b1]), we offered quantitative measurements and a kinetic model to delineate Ras- and phosphoinositide 3-kinase-dependent pathways that contribute to the activation of extracellular signal-regulated kinase (ERK). As a part of that study, we reported on the perturbation of the network by expression of a constitutively active variant of Ras, G12V H-Ras. The attendant effects on ERK and Akt phosphorylation kinetics were shown in Figure 1D and Figure 2D of the article, respectively.\n\nSince the publication of the above article, we submitted the vector harboring what was thought to be G12V H-Ras (from the same glycerol stock) for resequencing. The results from multiple sequencing reactions definitively showed the gene to be wild-type H-Ras, not G12V H-Ras. We regret that this error occurred; however, it does not substantively change our interpretation of the data. Overexpression of wild-type Ras results in the same qualitative effect that was desired: an increase in the amount of intracellular Ras-GTP. Perhaps more importantly, the data presented in Figures 1D and 2D were not used in any way in the formulation or parameterization of the kinetic model.\n\nGiven that the"
-"Background\n==========\n\nInherited defects in DNA mismatch repair (MMR) genes, usually *hMLH1*or *hMSH2*, lead to microsatellite instability (MSI) and subsequent malignancy in hereditary nonpolyposis colon cancer (HNPCC) \\[[@B1]\\]. While typical of HNPCC cancers, MSI also occurs in a minority of sporadic cancer \\[[@B2]\\]. Recently, a distinct type of MSI has been described where microsatellite alterations are present at selected tetranucleotide repeat regions; this is referred to as \\'elevated microsatellite alterations at selected tetranucleotide repeats\\' (EMAST) \\[[@B3]-[@B5]\\]. Although the genetic basis for MSI associated with defective MMR is being increasingly clarified, the mechanism underlying microsatellite alterations for EMAST tumors remains to be unclear \\[[@B3]\\]. Recent work has suggested that EMAST may be associated with alterations in the tumor suppressor gene p53 \\[[@B4],[@B6]\\].\n\nThe incidence of MSI in endometrial carcinoma has recently been described in several articles. It has been shown to be present in 25% to 30% of type I endometrial carcinoma, which is related with estrogenic stimulation, and has been rarely demonstrated in type II endometrial carcinoma, which is unrelated with estrogen \\[[@B10]-[@B12]\\]. However, EMAST in endometrial carcinoma has not yet been studied. The aim of the current study was to evaluate the prevalence and clinicopathologic significance of MSI including"
-"INTRODUCTION\n============\n\nRecent advancements of Reproductive Medicine, especially in some technical aspects, such as hormonal stimulation, *in vitro* fertilization (IVF), and the intracytoplasmic sperm injection (ICSI), made it possible to solve many causes of male and female infertility.^(^ [@B1] ^)^ For those women with absolute infertility, the traditional options of maternity are adoption or surrogate pregnancy.^(^ [@B2] ^)^\n\nHowever, in many countries, surrogate pregnancy is not accepted due to legal, ethical and religious issues.^(^ [@B3] ^)^ Thus, women submitted to hysterectomy when young due to malignant gynecological diseases or benign conditions, such as leiomyoma, endometriosis, and adenomyosis; patients with significant blood loss after a delivery resulting in hysterectomy, and finally, women with congenital anomalies of the genital tract, such as the Mayer-Rokitansky-K\u00fcster-Hauser syndrome, are condemned to not bearing children. Unquestionably, for many women this perspective affects their quality of life very negatively.^(^ [@B4] ^--^ [@B7] ^)^\n\nThe diverse issues related to surrogate pregnancy have led these women to 'dream' of the possibility of a uterine transplant that would relieve the anguish of the immense desire to conceive and bear a child.^(^ [@B8] ^)^\n\nUterine transplant mimicks a normal situation, with the primary constituent of genetic, gestational, and legal maternity. Additionally,"
-"1. Introduction {#sec1}\n===============\n\nThe most common etiology of spontaneous excess cortisol production is Cushing\\'s disease due to hypersecretion of pituitary adrenocorticotropic hormone (ACTH) by a corticotroph adenoma \\[[@B1]\\]. Cushing\\'s disease is a rare disorder, with an annual incidence of 1--3 per million and a female\u2009:\u2009male ratio of 3\u2009:\u20091, that is responsible for significant morbidity and mortality resulting from cardiovascular complications, infections, and psychiatric disturbances \\[[@B2]\\]. It is now recognized that, in a small proportion of cases, Cushing\\'s disease is accompanied by an elevated prolactin (PRL) level. For example, Lado-Abeal and colleagues identified a mildly elevated serum PRL in 20% of women with Cushing\\'s disease and menstrual abnormalities \\[[@B3]\\], and both Mahler et al. \\[[@B4]\\] and Sherry et al. \\[[@B5]\\] have presented a patient with Cushing\\'s disease and symptomatic hyperprolactinemia. Although Cushing\\'s disease with hyperprolactinemia due to mixed ACTH- and PRL-secreting adenomas occurs rarely, elevated preoperative PRL levels in Cushing\\'s disease are of diagnostic significance. Despite the abundance of published data concerning various aspects of the clinical course and treatment of Cushing\\'s disease, very few investigations have focused on the characteristics of patients with Cushing\\'s disease and hyperprolactinemia, and there is a paucity of studies comparing"
-"Background\n==========\n\nAging is a risk factor for chronic obstructive pulmonary disease (COPD) \\[[@B1]\\]. Recent evidence indicates that cellular senescence of various types of cells is accelerated in COPD patients, including alveolar type II cells, endothelial cells, fibroblasts, and peripheral blood lymphocytes \\[[@B2]-[@B5]\\]. Cellular senescence is a state of essentially irreversible growth arrest that occurs either as a result of a large number of cell divisions (replicative senescence) or exposure to any of wide range of stimuli, including oncogene activation, oxidative stress, and DNA damage (premature senescence) \\[[@B6],[@B7]\\]. Unlike apoptotic cells, senescent cells remain metabolically active and are capable of altering their microenvironment for as long as they persist \\[[@B6],[@B7]\\]. Since senescent cells accumulate in vivo, they are presumed to contribute to the pathogenesis of age-related diseases, such as COPD and atherosclerosis, in at least two distinct ways, first inhibiting tissue repair, because they remain viable but are unable to divide and to repair tissue defects, and second, by acting as a source of chronic inflammation, because senescent cells have been shown to secrete pro-inflammatory mediators \\[[@B1],[@B6]-[@B10]\\]. However, whether the senescence of airway epithelial cells contributes to the development of airway diseases is unknown.\n\nClara cells are the principal progenitors"
-"introduction {#s0010}\n============\n\nInfluenza virus is an enveloped virus belonging to the Orthomixoviridae. Peculiar to this virus is the segmented and single-stranded negative-sense RNA genome, which enhances its potential for recombination. Three types of influenza virus (A, B, and C) have been so far recognized, but only influenza virus type A and B have been associated with seasonal epidemics, and only influenza virus type A can occasionally give rise to worldwide pandemics \\[[@bb0010]\\].\n\nThree HA antigens (H1, H2, and H3) and two NA antigens (N1 and N2) of influenza A viruses have caused widespread disease and sustained human-to-human transmission while, in birds, 16 different HA antigens (H1--H16) and 9\u00a0NA antigens (N1--N9) are currently known. Minor antigenic variants arise yearly within the specific H1N1 and H3N2 subtypes during seasonal epidemics. Influenza B viruses also undergo antigenic drift and a significant part of the annual influenza burden is caused by two co-circulating, antigenically distinct lineages called the Yamagata and Victoria lineages.\n\nInfluenza virus type A and B show similar pathogenic potential in humans, and co-circulate during seasonal epidemics. More complex is the mechanism at the basis of pandemic events. In these cases, major antigenic variants of influenza A (antigenic shift) may"
-"Liver dysfunction caused mostly due to exposure to toxic chemicals, certain drugs and environmental pollutants, has been on the increase for the past few decades. In many countries hepatopathy is increasingly being managed using herbal treatment\\[[@ref1]\\]. Ginger (*Zingiber officinale* Roscoe, Zingiberaceae), a commonly used flavoring agent and cooking spice is added as a herbal supplement. It has a large variety of pharmacological activities such as antibacterial, antioxidant, and antiinflammatory effect as well as attenuation of lipid peroxidation and oxidative stress\\[[@ref2][@ref3]\\]. It has been reported to improve various gastrointestinal illnesses\\[[@ref4][@ref5]\\] and immunologic dysfunction\\[[@ref6]\\]. It also has been reported to exert antidiabetic activity, reduce liver damage\\[[@ref7]\\] and possess anticarcinogenic effect\\[[@ref8]\\]. It also has been reported to be used in hypertension and for exerting cardioprotective and antioxidant property\\[[@ref4][@ref9]\\].\n\nChicory (*Cichorium intybus*, Asteraceae) is a root vegetable whose green leafy tops are also used in salads or as a coffee supplement. Recently pharmacological actions of chicory have attracted the attention of many researchers. It was reported to induce hypocholesterolemia\\[[@ref10]\\], protect against hepatocellular damage\\[[@ref11][@ref12]\\] and inhibit lipid peroxidation\\[[@ref13][@ref14]\\]. It also has an antihyperglycaemic effect\\[[@ref15]\\], regulate appetite and carbohydrate and lipid metabolism\\[[@ref16]\\]. It was the aim of this work to explore the hepatoprotective effect of the"
-"Introduction {#s1}\n============\n\nThe vertebrate retina derives from common, multipotent progenitor cells that give rise to six classes of neurons and one type of glial cell organized into three nuclear layers. The rod and cone photoreceptors reside in the outer nuclear layer (ONL), three types of interneurons including the horizontal, bipolar and amacrine neurons, together with the M\u00fcller glial cells are found in the inner nuclear layer (INL) and the displaced amacrine and ganglion cells are in the ganglion cell layer (GCL) [@pone.0013232-Wallace1], [@pone.0013232-Ohsawa1]. The photoreceptors are the primary sensory neurons responding to light stimuli, the interneurons process a highly complex array of spatial and frequency information and convey this information to the retinal ganglion cells, the final output neurons of the retina. Mammalian retinal development starts at mid-gestation (embryonic day 12 for the mouse) and continues into the first two weeks after birth. Retinal ganglion cells, amacrine cells, cone photoreceptors, and horizontal cells differentiate first and the process is almost complete at birth (gestation period being 21 days in mice). In contrast, bipolar cells, rod cells and M\u00fcller glial cells continue to be generated from neural precursors up to two weeks after birth (see review [@pone.0013232-Ohsawa1]).\n\nMany transcription factors"
-"Background\n==========\n\nCardiovascular diseases (CVDs) are a leading cause of death both worldwide (29% of all deaths, 2004) \\[[@B1]\\] as in the Netherlands (28% of all deaths, 2011; Statistics Netherlands). CVDs are to a large extent preventable \\[[@B2]\\]. In 2009, in Dutch family practice, \u20ac39 million was spent on non-pharmaceutical cardiovascular preventive activities, i.e. risk profiling, blood pressure (BP) measurements and lifestyle counselling \\[[@B3]\\]. Annual costs at patient level were estimated for the Dutch situation, including doctor's visits, repeat prescriptions, drug costs and excluding diagnostics and productivity costs, as \u20ac293 for statin use and \u20ac258 for antihypertensives \\[[@B4]\\].\n\nLifestyle interventions appear to be cost effective in reducing cardiovascular risk \\[[@B5]\\]. A Dutch study found that preventive cardiac medication, following a 2006 revised guideline, was also cost effective \\[[@B4]\\]. This guideline recommended a broader indication for starting medication than previous guidelines and was also the basis for SPRING study (Self-monitoring and Prevention of RIsk factors by Nurse practitioners in the region of Groningen), of which the cost effectiveness is discussed in this paper. Drug treatment of hypertension and dyslipidaemia for cardiovascular prevention according to Canadian guidelines appeared to be cost effective as well \\[[@B6]\\]. However, Grover et al. concluded that treatment"
-"We present this special issue of the *Canadian Journal of Diabetes* at a very unusual time in all of our lives. Not only has the COVID-19 pandemic had an impact on populations worldwide, the mortality and health-related consequences of this disease have been magnified in some communities over others, specifically for individuals with diabetes. Clearly, we are living through a global crisis that not only affects our health and mental health, but also has disrupted the economy, education and employment. As difficult as it is for us all, living with diabetes during this time of uncertainly caused by the COVID-19 pandemic heightens the already daunting task of diabetes self-management. Routines are disrupted, finances may be challenged and in this era of self-isolation, social supports are not as available. As diabetes care providers, the more we can help patients cope with the mental health impact of the pandemic, the better equipped they will be to perform all the behaviours necessary to keep their blood glucose levels in target. It is in this context that we offer this special issue on mental health and diabetes.\n\nPlanning this special issue started prior to the pandemic and was based on the beliefs that diabetes"
-"After the publication of this article \\[[@pone.0220356.ref001]\\], concerns were raised that Actin panel lanes 3, 4 in Fig 7A appear similar to lanes 5, 6.\n\nThe authors explained that this duplication was due to an error during figure preparation and provided an updated figure along with the original, underlying images to the journal. The underlying images provided did not fully match the updated figure thus not resolving the concerns satisfactorily. A member of our Editorial Board concluded that the updated figure did not support p-ERK 1/2 activation as described in the results.\n\nIn light of the unresolved concerns that question the validity of the findings, the *PLOS ONE* Editors retract this article.\n\nSS, MS, RT, MG agreed with retraction. IWYM did not respond."
-"To the Editor: A 71-year-old male was admitted to Department of Urology, The 3^rd^ Xiangya Hospital, Central South University on June 26, 2014, because of lateral distending pain in the left back in recent 3 months. The patient\\'s past medical history included retroperitoneoscopic left pelvilithotomy at 6 years ago. Physical examination showed left costovertebral angle tenderness when slightly tapped at left kidney region (affected area). In addition, plain X-ray of the kidney, ureter, and bladder (KUB) and abdominopelvic computed tomography scan showed multiple left renal stones with hydronephrosis \\[Figure [1a](#F1){ref-type=\"fig\"}--[1d](#F1){ref-type=\"fig\"}\\]. After meticulous preoperative preparation, the patient, stayed at lithotomy position under general anesthesia, was admitted for flexible ureterorenoscopy with holmium laser lithotripsy. Unexpectedly, two stones were found at the left ureteral pelvis and subrenal calyx, respectively. The core of pelvic calculus was white strip funicular substance, which strongly attached to the pelvic mucosa and could not be removed by flexible ureterorenoscopy. The patient then was admitted for percutaneous nephroscopy with the guidance of B ultrasound. First, removing calculus at subrenal calyx out and then locating foreign body at renal pelvis \\[[Figure 1e](#F1){ref-type=\"fig\"}\\]. Thereafter, the foreign body at pelvis was removed using alligator plier. Finally, double-J tube and fistula were indwelled."
-"1 Introduction\n==============\n\nCircular RNAs (circRNAs) represent an emerging type of regulatory RNA with 3' and 5' ends covalently join together as 'back-spliced junctions'. circ RNAs have been reported to have multiple functions. Beside serving as miRNA sponges, many circRNAs are important for brain function, synaptic plasticity ([@btz705-B44]; [@btz705-B36]; [@btz705-B46]) and fetal development ([@btz705-B42]). Cell free circRNAs are found stable in saliva ([@btz705-B4]) as well as exosomes ([@btz705-B29]), which makes circRNA a promising diagnosis biomarker. Most circRNAs are originated from circularization of coding gene exons, which leads to the hypothesis that circRNA biogenesis competes with pre-mRNA splicing ([@btz705-B2]). Literature evidences suggest that the biogenesis of each circRNA subset may likely be regulated by different mechanisms ([@btz705-B9]; [@btz705-B11]; [@btz705-B19]; [@btz705-B20]; [@btz705-B28]; [@btz705-B30]; [@btz705-B49], [@btz705-B47], [@btz705-B48]), which supports the existence of multiple subclasses of circRNAs and each with specific roles.\n\nIn this study, we aim to decipher the relationship between the sequence features and circRNA subclasses. To this end, we have developed a computational model to predict whether a genomic locus would generate circRNA based on the presence of the following sequence features within the flanking regions of the circular RNA back-spliced junction sites: CpG islands, enhancers, RNA binding protein (RBP) binding"
-"Introduction {#s0001}\n============\n\nAlzheimer\\'s disease (AD) is the most frequent case of age-related neurodegenerative dementia, characterized by progressive loss of memory and other cognitive functions[@CIT0001] ^,^ [@CIT0002]. AD is a heterogeneous disease, driven by the interaction between multiple deleterious factors. However, the exact mode of how these factors contribute to impair neuronal functions and neuronal survival still remains undetermined. One of the main markers of AD is the accumulation of \u03b2-amyloid plaques (A\u03b2) in nerve cells. In healthy brain, these aggregates of proteins are degraded and eliminated[@CIT0003]. However, in AD the aggregates accumulate to form insoluble plaques[@CIT0003]. Another characteristic is the presence of insoluble neurofibrillary filaments that is associated with tau protein (PTau)[@CIT0004]. In AD, however, PTau becomes hyperphosphorylated, denaturing and resulting in its dissociation of microtubules, followed by formation of neurofibrillary filaments that aggregate, acting as physical barriers to microtubules[@CIT0004]. In addition, the occurrence of glial cell neuroinflammation, synaptic loss, and specific neuronal death is common in AD[@CIT0005] and can be aggravated by oxidative stress[@CIT0006].\n\nThe knowledge of neurotransmitter disorders in AD has led to the approval of drugs with symptomatic effects[@CIT0007]. The cholinergic hypothesis of AD states that the degeneration of cholinergic neurons in basal forebrain nuclei causes"
-"Introduction {#s1}\n============\n\nIn plants, sugars are the key carbon source for energy production and macromolecule biosynthesis, and they are important for carbohydrate accumulation in crop organs consumed as food by humans ([@CIT0007]). Thus, sugar allocation between source leaves (net exporters) and sink organs (net importers), such as young leaves, flowers, and storage organs, is of primary importance for organ development and plant growth, and as a sustainable food supply ([@CIT0001]; [@CIT0055]). For long-distance allocation, sugars are primarily synthesized by photosynthetic carbon fixation in source leaves and are loaded, mostly as sucrose, into phloem-specific companion cell (CC)--sieve element (SE) complexes. This loading occurs either symplasmically via plasmodesmata or via the apoplasmic route, with fine-tuned regulation of sugar partitioning ([@CIT0078]; [@CIT0053]; [@CIT0086]). Regarding the apoplasmic route, plasma membrane-localized sugar transporters facilitate sucrose efflux and import between adjunct CCs and parenchyma cells of minor veins, promoting mass flow in the phloem for continuous sugar allocation ([@CIT0059]; [@CIT0013]; [@CIT0034]).\n\nDuring sucrose loading, SWEET ([s]{.ul}ugar [w]{.ul}ill [e]{.ul}ventually be [e]{.ul}xported [t]{.ul}ransporters) proteins, especially clade III SWEET members localized in the plasma membrane of phloem parenchyma cells, are probably the main efflux mechanism to facilitate sucrose export into the apoplast in both dicot ([@CIT0016]; [@CIT0020]) and"
-"1. Introduction {#sec1}\n===============\n\nCystic echinococcosis (CE), also known as cystic hydatid disease, is a zoonotic infection caused by larval stage of *Echinococcus granulosus* \\[[@B1], [@B2]\\]. Nowadays, benzimidazole compounds, particularly the albendazole (ABZ), have been reported to be effective against CE \\[[@B3]\\]. However, these compounds, with poor water solubility, were classified as type II drugs on the Biopharmaceutical Classification System \\[[@B4]\\]. The low dissolution rate of ABZ triggers insufficient absorption in the gastrointestinal tract, resulting in a low plasma drug level \\[[@B5]\\]. Moreover, long-term medication of ABZ results in severe adverse events in these patients. Therefore, novel chemotherapeutic agents with good efficacy are urgently required.\n\nArtemisinin, an ancient Chinese herbal, was initially isolated in 1972 from *Artemisia annua*. L. The World Health Organization (WHO) recommends the artemisinin-based combination therapy (ACT) as the first-line treatment for *Plasmodium falciparum* infection \\[[@B6]\\]. In recent years, artemisinin and its derivatives have been reported to show curative effects on protozoans \\[[@B7]\\], nematodes \\[[@B8]\\], trematodes, and tumor \\[[@B9]\\]. These findings prompted us to investigate the potency of artemisinin for treating CE. Artemisinin and its derivatives including artesunate (AS) showed high efficiency with low toxicities. The effects of AS were further evaluated using the BALB/c mouse model"
-"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"
-"All relevant data are within the paper and its Supporting Information files.\n\n1 Introduction {#sec001}\n==============\n\nOne of the most important properties that is common to complex systems is the presence of critical thresholds in its dynamics \\[[@pone.0181953.ref001]\\] at which the system shifts abruptly (relative to its own long-range time scales) from one state to another. These abrupt changes in the state of a system occur near bifurcation points. At a bifurcation, the state of the system becomes unstable and the system jumps to an alternative (usually radically different) stable state. Stable states are related to a minimum in the potential energy and are separated by a potential barrier associated with unstable states. The point at which the bifurcation begins is called a critical point (CP). At this point the potential barrier flattens almost to the point of disappearing, giving place to a phenomenon known as critical slowing down (CSD) \\[[@pone.0181953.ref001]\\], the fact that the recovery time of a system after a perturbation increases when the system approaches a bifurcation in the dynamics. There are several examples of this across many fields: in medicine, asthma attacks or epileptic seizures; in global finances, in the vicinity of market crashes; in Earth"
-"1.. Introduction {#S1}\n================\n\nPulmonary mucormycosis is a form of mucormycosis that affects the lungs. Fungal entry into the body occurs by inhalation, and once in the respiratory tract, fungal hyphae may enter lymphatics, arteries, and veins, resulting in disseminated disease and infarct \\[[@R2]\\]. Typical presentation resembles that of community-acquired pneumonia and includes productive cough, fever, and pleuritic pain \\[[@R3]\\]. Diagnosis is made by transbronchial biopsy, bronchoalveolar lavage, or thoracic fluid sampling with visualization of fungal hyphae \\[[@R2],[@R3]\\]. Treatment includes antifungal therapy, aggressive surgical debridement or excision of necrotic tissue and stabilization of underlying comorbidities \\[[@R6]\\]. Mortality is estimated to be 50--80%, with the severity of comorbidities positively correlating with death rate \\[[@R1]\\]. Incidence and management of pulmonary mucormycosis in children is poorly described. One review article described 44 definitive cases identified by registry, of which 63% were associated with malignancy or bone marrow transplant, and 48% of all patients were treated with a combination of antifungal medication and surgery \\[[@R4]\\]. Combination therapy was associated with lower mortality; however, additional details, such as underlying etiology and surgical intervention, were not reported \\[[@R4]\\].\n\n1.1.. Case report {#S2}\n-----------------\n\nA 15-year-old boy with insulin-dependent type two diabetes (HbA1C 13.3) and obesity presented"
-"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],"
-"INTRODUCTION {#s1}\n============\n\nAPP plays a central role in the pathogenesis of both sporadic and familial AD. Indeed, *APP* mutations that alter APP processing either protect from sporadic AD or cause familial AD; additionally, mutations in genes that regulate APP processing -such as *PSENs* and *BRI2/ITM2B*- cause FAD, FBD and FDD \\[[@R1]-[@R12]\\].\n\nAs briefly mentioned above, mutations in *BRI2/ITM2B* cause the AD-like autosomal dominant FBD and FDD \\[[@R5], [@R7]\\]. FBD is characterized by the early onset of personality changes, memory and cognitive deficits, spastic rigidity, and ataxia \\[[@R5]\\]. FDD patients present early onset cataracts, deafness, progressive ataxia and dementia \\[[@R7]\\]. BRI2 is a type II membrane protein of 266 amino acids that is cleaved at the C terminus into a peptide of 23 amino acids (Bri23) plus a membrane-bound mature BRI2 (mBRI2) product \\[[@R13], [@R14]\\]. In FBD patients, a point mutation at the stop codon of *BRI2* results in a read-through of the 3\u2032-untranslated region and the synthesis of a BRI2 molecule containing 11 extra amino acids at the COOH terminus. Cleavage by convertases generates a normal mBRI2 plus a longer peptide, the ABri peptide. FDD is caused by a10- nucleotide duplication before the stop codon of the *BRI2* gene,"
-"All relevant data are within the paper and its Supporting Information files.\n\nIntroduction {#sec001}\n============\n\nHuman experience is strongly influenced by how much external stimuli are perceived as self-related. When stimuli are viewed as self-referential, associated neural activity can index a conscious reflection on oneself, which is referred to as self-referential processing (SRP) \\[[@pone.0149554.ref001]\\]. Previous studies have shown a specific pattern of neural activity during various expressions of SRP. For example, recognition of one's own face elicits activity in brain regions that is distinct from activity evoked by other-faces, and these regions include the medial prefrontal cortex (MPFC), anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), precuneus, and anterior insular cortex \\[[@pone.0149554.ref002],[@pone.0149554.ref003]\\]. Based on these results, the existence of a self-specific network has been proposed \\[[@pone.0149554.ref004]\\]. A previous study has shown that a functional response within this network is more pronounced during processing of negative stimuli than positive ones \\[[@pone.0149554.ref005]\\].\n\nThere is an emerging consensus that the MPFC is strongly linked to self-related information processing \\[[@pone.0149554.ref006],[@pone.0149554.ref007]\\]. In terms of self-relatedness a functional dissociation between the dorsal and ventral portions of the MPFC is proposed, though this distinction remains controversial \\[[@pone.0149554.ref008]--[@pone.0149554.ref011]\\]. Indeed there is evidence that the role of the MPFC"
-"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"
-"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 {#S0001}\n============\n\nProviding continuity of care and managing chronic disease are outlined as core skills for trainees by the American College of Graduate Medical Education and Liaison Committee on Medical Education \\[[1](#CIT0001),[2](#CIT0002)\\]. According to the American Association of Medical Colleges national survey, 94% of US medical schools use standardized patient (SP) experiences \\[[3](#CIT0003)\\]. Longitudinal standardized patient (LSP) experiences involve a medical student interacting with the same 'patient' over time in various scenarios. LSP experiences have been described as a means to provide structured opportunities for practice, assessment, and feedback in clinical skills and foster an appreciation for the continuum of care \\[[4](#CIT0004)--[6](#CIT0006)\\]. These interactions are designed to provide students with clinical experiences as well as individualized, developmentally sequenced assessment of clinical skills \\[[7](#CIT0007)\\]. Students and faculty participating in a four-encounter LSP program in the Netherlands rated their program favorably on the authenticity of the experience and similarity of LSPs to real patients \\[[8](#CIT0008)\\]. One study describing the integration of an LSP program into a family medicine clerkship reported increased student confidence in managing chronic disease and establishing relationships \\[[9](#CIT0009)\\]. SPs described the approach as one which facilitates skill development through immediate feedback and performance adjustment \\[[10](#CIT0010)\\]. However, the nature"
-"Introduction {#S0001}\n============\n\nGuided bone regeneration (GBR) is the most common and reliable therapy used to treat bone defects around dental implants.[@CIT0001] The GBR method is based on the creation of a closed space by a barrier membrane to protect the newly formed bone from the fast-growing fibrous connective tissue invading the bone defect area. This maximizes the regeneration ability of the bone tissue.[@CIT0002] In clinical practice, the barrier membrane is classified into a resorbable and non-resorbable membrane.[@CIT0003] Polymers and titanium have been employed in the fabrication of non-resorbable membranes whereas collagen is used as the main material for the construction of a resorbable membrane.[@CIT0004] An ideal GBR membrane should possess properties that are suitable for bone regeneration. First, the membrane should have optimal mechanical strength that matches that of natural bone tissue and gingival tissue to keep the bone regeneration space and prevent damage to the surrounding tissue during surgery.[@CIT0005] Second, the membrane should induce osteoconductivity and act as a scaffold to promote stem cells attachment and guide the migration of bone cells.[@CIT0006] Third, an ideal GBR membrane should provide sufficient osteoinductivity to induce the differentiation of stem cells into osteoblasts.[@CIT0007] However, existing GBR membranes have weak structural integrity"
-"1. Case report {#sec1}\n==============\n\nA 78-year old patient was implanted with a biventricular defibrillator (Medtronic Viva Quad CRT-D with a 6935 Sprint Quattro Secure right ventricular lead and a 4298-88 quadripolar left ventricular lead) in 2014 for dilated non-ischemic cardiomyopathy with left ventricular ejection fraction (LVEF) of 25%, left bundle-branch block (LBBB) and New York Heart Association (NYHA) class II heart failure. Initial follow-up was unremarkable, with average percentage of biventricular (BiV) pacing of \\>97%, until December 2015 when a scheduled 6-month follow-up revealed a reduction in BiV pacing to 88%, associated with an increase in heart-failure symptoms. Device parameters are shown in [Table\u00a01](#tbl1){ref-type=\"table\"}. Interrogation of the device revealed a loss of BiV pacing of 12% due to ventricular sensed events (Vs) without any sustained arrhythmia. However, the electrocardiogram showed sinus rhythm with alternating wide unpaced and narrower paced QRS complexes ([Fig.\u00a01](#fig1){ref-type=\"fig\"}). Further device interrogation revealed excellent R-wave amplitude (\\>20mV) but with T-wave oversensing (TWOS, see [Fig.\u00a02](#fig2){ref-type=\"fig\"}) on all ventricular paced beats (BV), with the sensed T-waves at a coupling interval of 320\u00a0ms (188bpm) interpreted as ventricular events falling in the slow ventricular tachycardia (VT) zone (labelled TS). The sinus atrial beats following these TS"
-"Regulatory T (T~reg~) cells are central players in establishing homeostasis of the immune system by suppressing activation, proliferation and effector functions of various immune cells^[@R1]^. They develop in the thymus from CD4^+^ single-positive (CD4SP) cells or differentiate from na\u00efve CD4^+^ T cells^[@R2]^. The cytokine TGF-\u03b2 drives differentiation of T~reg~ cells by up-regulating expression of Foxp3 transcription factor that is necessary for suppressive activity and serves as a marker of T~reg~ cells^[@R3]--[@R5]^. Deregulation of T~reg~ cell development and function leads to autoimmune diseases and immunopathology^[@R1],[@R6]--[@R8]^. Because of their important roles in numerous diseases including allergy^[@R9]^, autoimmunity^[@R1],[@R6]--[@R8]^, microbial infections^[@R10]^ and cancer^[@R11]^, T~reg~ cells have become a focus for development of various therapies aiming to treat autoimmune disorders and graft-versus-host disease^[@R12],[@R13]^. Thus, a thorough understanding of the regulatory processes that govern T~reg~ cell differentiation is necessary.\n\nCell specification is under control of cell-specific enhancers. Foxp3 is the signature transcription factor that defines T~reg~ cells, which is regulated by three distal enhancer elements including conserved noncoding-sequence (CNS) 1, CNS2 and CNS3 at different stages of T~reg~ cell development^[@R14]^. The genome-wide enhancer landscape in T~reg~ cells has been recently described^[@R15]^. Foxp3 does not establish T~reg~-specific enhancer landscape but instead exploits previously established already existing enhancers^[@R16]^."
-"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\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"
-"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"
-"Introduction\n============\n\nTransition metal dichalcogenides (TMDs)[@cit1],[@cit2] are an emerging type of two-dimensional (2D) materials consisting of a single layer of atoms. In particular, tungsten disulfide (WS~2~) displays a graphene-like structure in which each individual layer of W atoms is hexagonally packed between two trigonal atomic layers of S atoms. Such a structure offers 2D permeable channels for electron transport whereas a potential barrier along the vertical layers hinders electron jumping. This results in strong quantum confinement of electrons, which along the ultrahigh specific surface results in superior charge transfer.[@cit3],[@cit4] Such a unique combination of physical, optical, chemical and electronic properties has been exploited in a myriad of applications such as electronic devices,[@cit5] photocatalysis,[@cit6]--[@cit8] energy storage,[@cit3],[@cit9]--[@cit11] sensing[@cit12]--[@cit14] and biomedicine.[@cit15]--[@cit17] The fabrication of continuous WS~2~ films has been achieved by top--down exfoliation of the bulk material[@cit18] or bottom--up approaches such as chemical vapor deposition, hydrothermal synthesis or sulfurization.[@cit18]--[@cit20] Electrochemical synthesis is a simple approach that can be performed under ambient conditions using aqueous precursors, yielding excellent nanostructures for (photocatalytic) processes.[@cit21]--[@cit23]\n\nThe field of micromotors has only recently started to benefit from the outstanding properties of TMDs. Micromotor design and the synthetic route adopted will exert a strong influence on the overall catalytic"
-"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"
-"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"
-"INTRODUCTION\n============\n\nThe preventive treatment of latent tuberculosis infection (LTBI) has gradually gained a vital role in tuberculosis (TB) control worldwide since the 1950s. Currently, the global strategy in the treatment of TB is divided into two basic parts: in areas with a high incidence of TB, the main goal is to treat the active cases, but in areas with a low incidence of TB, the goal also includes prophylactic treatment for LTBI. According to the World Health Organization (WHO), approximately 2--3 billion people in the world are latently infected with *Mycobacterium tuberculosis* (Mtb), and 5%--15% of these people will suffer from reactivation of TB during their lifetime.^[@bib1]^ Therefore, the treatment of LTBI directly influences the future global prevention of TB infection. At present, the study of LTBI relies heavily on screening for high-risk populations and on treatment strategies for the disease.\n\nSCREENING FOR LATENT TUBERCULOSIS INFECTION\n===========================================\n\nCurrently, a golden standard for the diagnosis of the LTBI is lacking. Because the amount of *Mycobacterium tuberculosis* is small in LTBI patients, diagnosis of LTBI mainly depends on the immune reaction of the host rather than the bacteria itself. There are two currently available screening tests for LTBI: the tuberculin skin"
-"INTRODUCTION {#SEC1}\n============\n\nIn all domains of life, the biological function of RNAs is often associated with the presence of posttranscriptional chemical modifications. These modifications influence the stability, the folding pathways, the structure and the function of RNAs by e.g. modulating hydrogen bonding capabilities, stacking and hydrophobic interactions between nucleotides or the local charge distribution ([@B1]). Ribosomal RNAs (rRNAs) and transfer RNAs (tRNAs) contain particularly large numbers of modified nucleotides. Most modifications of nucleotides in rRNA are chemically simple. The most frequent nucleotide modifications in rRNAs are methylations of ribose 2\u2032-hydroxyl groups and the isomerization of uridines to pseudouridines. Other chemically simple modifications in rRNA are methylations or acetylations of exocyclic or endocyclic nitrogen atoms in the nucleobases. The chemically most complex modification found for rRNA nucleotides so far is an *N*1-methyl-*N*3-(3-amino-3-carboxypropyl) pseudouridine (m^1^acp^3^\u03a8) present at a single conserved position in the small ribosomal subunit RNA of eukaryotes ([@B2]). In archaea such as *Haloferax volcanii* an *N*3-(3-amino-3-carboxypropyl)-uridine (acp^3^U) nucleotide is found in an equivalent position ([@B3]).\n\nIn tRNAs, the frequency of posttranscriptional modifications and also their chemical variety and complexity is much higher than in rRNAs. The chemical structures of tRNA modifications, their enzymatic synthesis and their biological impact were"
-"Introduction {#Sec1}\n============\n\nInfectious diseases of the lower respiratory tract are exacerbated by the lack of sufficient treatment options, which is underlined by the 3.2 million reports of death in 2015 (World Health Organization; WHO). Although less frequently observed in wealthy countries, the increasing number of nosocomial infections constitutes a substantial public health problem worldwide^[@CR1]^. Treatment of lower respiratory tract infections becomes particularly problematic, if the invasive microorganisms are resistant to standard or reserve antibiotic therapy as observed with increasing frequency for infections triggered by *Pseudomonas aeruginosa* (*P. aeruginosa*), one of the most common pathogens responsible for severe nosocomial infections^[@CR2]^. In fact, the most recent global priority list of antibiotic-resistant bacteria to guide research, discovery, and development of new antibiotics from the WHO, states carbapenem-resistant *P. aeruginosa* as one of the three most critical pathogens for which new treatment options are urgently required^[@CR3]^.\n\nOne promising alternative to antibiotic therapy might be a cell-based immunotherapy approach applying phagocytes to enhance pulmonary immunity. As of yet, generating the therapeutically required amount of immune cells from peripheral blood or other sources remains challenging. In contrast to somatic cells, human-induced pluripotent stem cells (hiPSC), with their unlimited potential for proliferation and differentiation, may---in principle---enable"
-"Introduction\n============\n\nWound healing is often a clinical challenge, as wound pain, non-healing wounds with a variety of pathogenetic factors, and a limited wound healing velocity, even in undisturbed wound healing, decrease quality of life and cause tremendous costs, especially in chronic wounds \\[[@R1]\\]. A variety of strategies, methods or substances including wound dressings are used to overcome such problems. Beside negative pressure wound therapy and hyperbaric oxygenation the application of heat belongs to the group of technical methods for improving wound healing. Positive effects with pre-operative \\[[@R2]\\] and post-operative \\[[@R3]\\] warming of the operative field have been shown.\n\nWater-filtered infrared-A (wIRA), as a special form of heat radiation (in the range 780--1400 nm) with a high tissue penetration and a low thermal load to the surface of the skin, is a substance-free non-contact, pleasant feeling method, which can be used in both acute and chronic wounds.\n\nMethodological aspects\n======================\n\nThis review presents an overview of seven prospective clinical studies, of which six were randomised controlled (RCTs), and other experiences related to the application of wIRA for the improvement of healing in acute and chronic wounds (reviews: \\[[@R4]\\], \\[[@R5]\\], \\[[@R6]\\], \\[[@R7]\\], \\[[@R8]\\], \\[[@R9]\\], \\[[@R10]\\], \\[[@R11]\\], \\[[@R12]\\], \\[[@R13]\\], \\[[@R14]\\]).\n\nThe main"
-"1. Introduction {#sec1}\n===============\n\nObesity has reached pandemic proportions worldwide, significantly contributing to reduce life quality and lifespan at a global scale [@bib1]. This condition is characterized by abnormal and excessive fat accumulation and is influenced by both genetic and environmental determinants. While several genetic loci have been associated with obesity, they explain only a fraction of the total variance within populations; moreover, genes deemed obesity-predisposing interact with environmental factors to regulate, for instance, satiety and energy expenditure [@bib2]. Among the environmental determinants of obesity and its associated dysmetabolic conditions, dietary habits play a central role. Diet\u00a0also strongly influences our \"other genome\" (*i.e.*, the metagenome), modeling gut microbial community structure [@bib3] and impacting host metabolism and energy partitioning [@bib4]. Research conducted throughout the last decade has revealed a clear association between obesity and gut microbial dysbiosis, which is generally characterized by a reduction in bacterial richness and by major taxonomic and functional changes [@bib5].\n\nThe consumption of fiberless diets rich in simple sugars and saturated fat (often referred to as Western diets) generates well-known detrimental metabolic consequences, leading to insulin resistance and glucose intolerance in the early-term, which later evolves to overt obesity, type 2 diabetes, and cardiovascular complications."
-"Background\n==========\n\nThe Clinical Global Impression Scale (CGI) is a brief clinician-rated instrument that consists of three different global measures. 1. *Severity of illness:*overall assessment of the current severity of the patient\\'s symptoms (CGI-S); 2. *Global improvement:*overall comparison of the patient\\'s baseline condition with his current state (CGI-I); 3. *Efficacy index:*overall comparison of the patient\\'s baseline condition to a ratio of current therapeutic benefit and severity of side effects (CGI-E). Since its first publication the CGI has become one of the most widely used assessment tools in psychiatry \\[[@B1]\\]. For example, the CGI, especially the CGI improvement scale (CGI-I) has been widely utilized as an efficacy measure in clinical drug trials in different mental disorders \\[e.g., depression, schizophrenia; \\[[@B2],[@B3]\\]\\]. Its popularity is mainly based on its conciseness and easiness of administration.\n\nIt is widely accepted and some studies presented evidence arguing that the CGI is a valid assessment instrument. Moreover, the CGI was used as external criterion to test the validity of other outcome measures such as the Beck Depression Inventory \\[BDI; \\[[@B4]\\]\\], the Hamilton Depression Rating Scale \\[HAMD; \\[[@B5]\\]\\] or the Montgomery-Asberg Depression Rating Scale \\[MADRS; \\[[@B6]-[@B9]\\]\\].\n\nDespite its general acceptance and extensive use as outcome measure and criterion"
-"ORGANELLE MOVEMENT IN PLANT CELLS\n=================================\n\nPlant cells are characterized by a powerful flow of intracellular components, generally termed as \"cytoplasmic streaming\" ([@B79]). This mechanism allows the efficient transport and the uniform redistribution of membranes and molecules in plant cells, especially in very large cells ([@B91]) such as those of the alga *Chara* that are considered the model par excellence in which to investigate this process ([@B29]). It is largely accepted that cytoplasmic streaming is based upon the interaction between actin filaments and myosins ([@B79]). The *Arabidopsis* genome contains 17 myosin members ([@B46]) and only two plant-specific subfamilies (myosin VIII and myosin XI) have been identified ([@B80]). The rice genome contains 14 myosin genes, with only two of the predicted sequences belonging to class VIII and the others to class XI ([@B36]). Both myosin XI and myosin VIII subfamilies are closely related to animal and fungal myosin V. Myosins XI are motor proteins showing high processive velocity and are therefore candidates to drive cytoplasmic streaming in plant cells. However, it remains to understand if plant myosins XI interact with specific organelles. Immunolocalization analysis have not clarified this question, since a myosin XI was found to be associated with various particles"
-"INTRODUCTION\n============\n\nWith a recent successful series of endovascular recanalization through stent-retrivers,[@B1][@B2][@B3][@B4][@B5] fast and unblemished recanalization of occluded cerebral arteries has become an achievable goal in the treatment of hyperacute ischemic stroke. Therefore, the latest clinical practice guideline recommends an endovascular recanalization strategy for an acute ischemic stroke of moderate severity if the intervention can be applied within 6 hours from last seen normal.[@B6] However, stroke physicians worldwide are still waiting for a reasonable decision strategy to initiate this treatment in individual cases, since 29% to 59% of cases show profound functional dependence or mortality even after applying groundbreaking treatment. A strategy therefore needs to be developed for identifying the best candidates for endovascular recanalization treatment.\n\nCurrently, the suggested indications for endovascular recanalization include the baseline neurological severity, time delay from onset, and extent of irreversible infarction.[@B6] However, these conventional indicators are representative characteristics only for those patients who show a favorable clinical response to treatment, and so they are of limited relevance to the condition of the ischemic brain in individual cases. Among the various advanced imaging techniques used to measure personalized ischemic/perfusion status, collateral imaging based on computed tomography (CT) angiography has been suggested as a good alternative"
-"Background\n==========\n\nThe discovery of RNA interference (RNAi) and its use as an experimental tool has heralded a new era in functional genomics \\[[@B1],[@B2]\\]. The ability of short interfering RNA (siRNA) to perturb expression of any gene target highlights the enormous potential of this technique. However, siRNA delivery into primary cells, cell lines that are difficult to transfect and delivery to specific cell types *in vivo*remains a key technical issue.\n\nA variety of vector-based approaches, which express siRNAs as short hairpin (sh)RNAs, have been developed to permit delivery through viral vectors \\[[@B3]\\]. Designing such shRNA in the context of a naturally occurring RNA polymerase (pol) II-driven microRNA transcript (miR-shRNA; Fig. [1a](#F1){ref-type=\"fig\"}) increases the flexibility of this approach allowing for conditional and cell type-specific expression \\[[@B4]-[@B11]\\]. The observation that some endogenous microRNAs (miRNA) are processed from single transcripts containing multiple primary miRNA sequences \\[[@B12],[@B13]\\] adds to the potential experimental utility of this approach to RNAi. In using RNAi as an experimental tool, the ability to effectively deplete multiple gene targets is vital to address the issue of isoform redundancy, especially in mammalian cell systems. Thus, a flexible vector platform that allows for effective multi-gene knockdown in essentially any cell system would"
-"(J Am Heart Assoc. 2020;9:e014591 DOI: 10.1161/JAHA.119.014591.)32204665\n\n {#jah34890-sec-0004}\n\nClinical PerspectiveWhat Is New?Untreated mixed aortic valve disease (defined as concomitant presence of at least moderate aortic stenosis and regurgitation) is associated with poor prognosis even in the presence of normal ejection fraction.What Are the Clinical Implications?Given that aortic valve replacement dramatically improves survival independent of symptoms, early intervention in patients with mixed aortic valve disease may be warranted.\n\nIntroduction {#jah34890-sec-0008}\n============\n\nConcurrent presence of aortic stenosis (AS) and aortic regurgitation (AR) is termed mixed aortic valve disease (MAVD). Although multiple articles addressed patients with \"isolated\" AS or AR, the natural history, impact, and outcome of MAVD are not well defined. Decision making regarding treatment with either surgical or transcatheter interventions is extrapolated from evidence from either isolated AS or AR and is usually guided by the dominant lesion.[1](#jah34890-bib-0001){ref-type=\"ref\"} Therefore, intervention is usually recommended in the presence of symptoms and specific structural or hemodynamic factors such as left ventricular (LV) ejection fraction (LVEF), aortic valve area (AVA), mean aortic gradient, maximum aortic velocity, and LV volumes.[2](#jah34890-bib-0002){ref-type=\"ref\"}, [3](#jah34890-bib-0003){ref-type=\"ref\"} However, in MAVD, the development of symptoms and progression of structural and hemodynamic parameters may have a different pattern than in isolated AS or AR."
-"I[NTRODUCTION]{.smallcaps} {#sec1-1}\n==========================\n\nThe liquid or fluid applied in Doppler ultrasound flow phantoms and for testing the object models *in vitro* must preferably have similar properties and features which mimic real human blood (*in vivo*).\\[[@ref1][@ref2]\\] Furthermore, for estimating the achievements of Doppler instrument, blood itself may seem to be the best liquid to use. However, there are several difficulties connected with utilizing blood and its ingredients. There is a possible biohazard and care should be taken into consideration to minimize this hazard. The lifespan of blood is finite and red blood cells *in vitro* are easily deteriorated. This avoids utilizing the blood like a standard liquid in long-term research studies of measurements. The room temperature plays an important role in changing the acoustical and physical properties of blood, especially with a temperature of more than at 37\u00b0C.\\[[@ref3]\\]\n\nThe nature of human blood is non-Newtonian.\\[[@ref2][@ref4][@ref5][@ref6][@ref7][@ref8][@ref9]\\] In other words, the human viscosity of blood is highly based on shear rate. Thus, the non-Newtonian feature of blood is idea happen in the small or tiny vessels. However, in the large or main vessels, it is proper to consider that the blood is Newtonian.\\[[@ref2][@ref4][@ref5]\\] Thus, the BMF applied in Doppler medical ultrasound (*in vitro*)"
-"Globally, 15 million neonates (11% of the total births) are born preterm every year[@ref1]. Preterm infants face lifelong morbidity with increased risk of respiratory disease[@ref2], intellectual disability, cerebral palsy[@ref3][@ref4] and vision impairment[@ref5]. With a high risk of acquiring infection, preterm birth (PTB) is one of the major contributors to infant mortality. There are various known factors such as hormonal imbalance, oxidative stress, genetic disposition, gene environment interaction, low socio-economic status, *etc*. which may lead to PTB[@ref6].\n\nOrganochlorine pesticides (OCPs) are widely used in India under public health and agricultural programmes[@ref7]. OCPs are xenoestrogenic in nature, slow in degradation and highly lipophilic. These pesticides tend to bio-accumulate in lipid-rich tissues because of their strong lipophilic nature and slow biodegradability[@ref8]. Earlier studies, including those from our laboratory, have reported that OCPs may increase the risk of PTB[@ref7][@ref9][@ref10]. Further, we have also reported that polymorphisms in xenobiotic metabolizing genes along with more than 50^th^ percentile of OCPs (\u2265 median value) may lead to a significant decrease in the period of gestation (POG)[@ref10].\n\nAn exaggerated inflammatory response is an emerging mechanism in conditions such as spontaneous abortion, PTB, preterm premature rupture of the membranes (PPROM), preeclampsia, and other \"great obstetrical syndromes\"[@ref11]. Increased inflammation occurs"
-"Background {#Sec1}\n==========\n\nIn many healthcare settings, waiting lists help streamline the uncertain flow of requests and providers' workload. Their presence in healthcare services is of paramount importance in order to rationalize capacity and hence costs \\[[@CR1]\\]. However, as the demand for services exceeds supply, these lists can grow quickly and result in unacceptable wait times. Patients from countries with publicly funded healthcare systems frequently experience excessive wait times \\[[@CR2]\\] that have significant consequences, such as a negative impact on pain and function and deterioration in the quality of life \\[[@CR3], [@CR4]\\]. Reducing wait times in order to improve access to healthcare services has become one of the main concerns of modern healthcare systems. Many strategies can be used to manage waiting lists with the aim of improving patient flow and reducing wait times. Examples of such approaches include increasing capacity (e.g., hiring more staff or purchasing more equipment), setting maximum wait time targets, and reorganizing patterns of services (e.g., introducing methods to reduce missed appointments) \\[[@CR1], [@CR5]\\]. However, wait times for non-urgent health services such as elective surgery or the prescription of wheelchairs is often unavoidable \\[[@CR6]\\]. Therefore, waiting lists should be managed as fairly as possible to ensure"
-"Introduction\n============\n\nSolitary plasmacytomas (SPs) are rare and are characterized by a localized accumulation of neoplastic monoclonal plasma cells, without proof of systemic myelomatosis. The tumors represent \u22645% of all plasma cell neoplasms ([@b1-ol-09-01-0191]) and mostly occur in the spine, pelvis, ribs and pectoral girdle ([@b1-ol-09-01-0191]--[@b3-ol-09-01-0191]), while rarely occurring in the sternum. Radiologically, SP of the bone typically appears as an osteolytic lesion; the tumor usually destroys the cortex in several places and invades the soft tissues ([@b2-ol-09-01-0191],[@b4-ol-09-01-0191]). In rare cases, the radiological findings may take unusual forms, for example, they can manifest as bony spicules on the surface of the bone, which resemble the appearance of sunrays ([@b5-ol-09-01-0191]--[@b12-ol-09-01-0191]). The sites of bony spiculation in the lesions previously described in the literature are the mandible, orbit, vertebral body and skull vault ([@b5-ol-09-01-0191]--[@b12-ol-09-01-0191]).\n\nThe current study presents a case of a solitary plasmacytoma of the sternum with a spiculated periosteal reaction on radiological imaging. Written informed consent was obtained from the patient.\n\nCase report\n===========\n\nA 74-year-old female presented with neck and anterior chest wall pain, along with swelling in the chest area that had persisted for one month. The past medical history consisted of type II diabetes mellitus and hypertension."
-"Even when living in relative prosperity, adolescents frequently report low levels of life satisfaction (Huebner, Drane, & Valois, 2000; [@B37]). At the same time, a substantial number of adolescents reports feelings of depression (Lewis, Jones, & Goodyer, 2016). This is a severe problem as feelings of dissatisfaction and depression negatively affect almost all spheres of psychosocial functioning (e.g., physical health, the quality of interpersonal relationships) and are associated with a significant impairment in multiple life domains ([@B23]; [@B24]; [@B25]; [@B41]).\n\nNumerous studies have tried to understand how life satisfaction and depression develop in adolescence. These have mainly focused on family-related factors such as parental styles ([@B47]), social influences such as relationships with peers, the school teacher and the neighborhood ([@B53]; Sarkova et al., 2014), and individual difference variables such as introversion and neuroticism ([@B12]). Up to now, no study has considered the relationship between mental health of adolescents and the combination of school with part-time work. Figures, however, show that a substantial number of adolescents combine school with student work. For example, in the United States about 31% of students are engaged in paid employment ([@B70]) while in Europe, 24% of 15--24 years old engage in part-time work ([@B21]).\n\nWe"
-"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"
-"Introduction {#Sec1}\n============\n\nEach year, millions of people are exposed to serious health risks due to emerging infectious and communicable diseases. This poses a severe threat to the public health security at local, regional or national level; especially in underdeveloped countries. This is primarily due to the lack of infrastructure for timely collection, reporting, and analysis of epidemic data; non-existent early warning and forecasting systems; inadequate preparedness and emergency response management\u00a0\\[[@CR22]\\].\n\n3.9 billion people in 128 countries are at risk of contracting dengue, with estimated 96 million cases annually. The worldwide incidence of dengue has risen 30-fold in the past 30\u00a0years. Pakistan is among the 110 countries in the world which are badly affected by the mosquito-borne dengue virus. The first outbreak of dengue fever (DF) in Pakistan was confirmed in 1994. The country is currently experiencing among worst-ever dengue outbreaks, recording about 45,000 confirmed cases\u00a0\\[[@CR27]\\]. Even today, an effective dengue vaccine offering balanced protection is still elusive. Unfortunately, existing dengue vaccines are known to have limited efficacy and cure\u00a0\\[[@CR8]\\]. This underscores the critical need of preventing dengue transmission and eventual outbreak by: (i) investigating favorable conditions for the dengue epidemic to occur\u00a0\\[[@CR21]\\]; (ii) plummeting"
-"Introduction {#s1}\n============\n\nIdiopathic type 2 macular telangiectasia (mactel), also referred to as juxtafoveolar retinal capillary telangiectasia, was first classified in detail in 1982 by Gass and Oyakawa^[@i2164-2591-6-6-7-b01]^ with further elaboration on classification made in 1993 by Gass and Blodi.^[@i2164-2591-6-6-7-b02]^ This is a bilateral disease characterized by progressive changes in the macular capillary network that follow a slowly progressive course, which begins temporal to the foveal center, in association with neurosensory atrophy and loss of luteal pigment, resulting in encroachment of paracentral scotoma into the foveal center.^[@i2164-2591-6-6-7-b03]^ Visual acuity remains stable for many years in the early stages of the disease and, therefore, is not a suitable clinical endpoint in neuroprotective treatment trials.^[@i2164-2591-6-6-7-b03]^ Microperimetry now has been adopted as a promising functional endpoint for monitoring visual decline in this disease.\n\nMicroperimetry is a modified visual field test that allows assessment of retinal differential light sensitivity at selected and known retinal loci and fixation characteristics without the need for stable and foveal fixation.^[@i2164-2591-6-6-7-b04]^ This technique currently is used as an outcome measure in five type 2 mactel clinical trials registered with the United States National Institutes of Health clinical trial registry (clinicaltrials.gov--NCT 00685854; NCT 01327911; NCT 00685503; NCT 00504400; NCT 01949324).^[@i2164-2591-6-6-7-b05]^"
-"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 {#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\n============\n\nOral cancer is the sixth leading cancer worldwide ([@B1],[@B2]). Risk factors such as alcohol and tobacco have an harmonizing effect, other than from infection with human papilloma virus is considered in oral cancer ([@B1]). Most of the oral cancer develops from oral premalignant lesions such as leukoplakia, erythroplakia, and lichen planus ([@B3]). Oral leukoplakia, submucous fibrosis and lichen planus are major known precursor lesions. The prevalence of malignant transformation of oral lichen planus is around 0.5% and for leukoplakia is around 1% ([@B3]). Early detection of oral cancer considerably increases survival rates and diminish other health effects ([@B4]). Despite of advancement in technologies, oral cancer cases are diagnosed at very late stage due to lack of awareness of the symptoms and risk factors between public as well as lack of prevention and early detection by oral physicians ([@B5]-[@B7]). Presently, diagnosis depends mostly on a thorough clinical oral examination and histopathological examination by taking a biopsy. A definite diagnosis is based on biopsy. Various technologies such Chemiluminescence, autofluorescence, Toluidine Blue, Brush biopsy, OralCDx Brush Test, ViziLite Plus with TBlue, VELscope Vx, Sapphire Plus, MicroLux(\u2122) /DL, Identafietc have been proposed, but these technologies need strong evidences to be used in"
-"Black phosphorus (BP), an emerging layered two-dimensional (2D) semiconductor, is presently attracting immense research interest on the global level due to its high mobility and suitable band gap for potential applications in novel electronic and optoelectronic devices[@b1][@b2][@b3][@b4][@b5]. Unlike other well-studied 2D materials, such as semimetallic graphene[@b6] with zero band gap and MoS~2~[@b7] with a direct band gap of \\~1.5\u2009eV only in its monolayer form, BP has a tunable thickness-dependent direct band gap varying from \\~0.3\u2009eV (bulk) to \\>1.4\u2009eV (monolayer)[@b4][@b5]. This prominent feature benefits layered BP in optoelectronic applications such as phototransistors, *p-n* diodes and solar cells[@b2][@b8][@b9][@b10][@b11]. So far, BP has been shown to have some remarkable properties, such as high mobility[@b1][@b2], semiconductor-metal transition[@b12] as well as superconductivity[@b13] under high pressure. Additionally, as shown in [Fig. 1(a)](#f1){ref-type=\"fig\"}, owning to the puckered honeycomb lattice in each P atom layer, much work has been involved to explore the anisotropic thermal transport properties in bulk BP[@b14][@b15][@b16], indicating that BP could be also used as a novel thermoelectric material in which the anisotropic properties might be used. Similar as the anisotropic thermal conductivity, it was theoretically predicted that BP has a large direction-dependent photonic[@b17][@b18] and magneto-transport anisotropy[@b1]. Investigations on magneto-transport properties of"
-"1. Introduction {#sec1-sensors-19-02010}\n===============\n\nAmong structural health monitoring (SHM) techniques, Lamb-wave-based methods have shown great potential for fast damage detection in plate-like structures \\[[@B1-sensors-19-02010]\\]. Lamb waves can propagate a distance with low attenuation and are highly sensitive to small imperfections \\[[@B2-sensors-19-02010],[@B3-sensors-19-02010]\\]. These waves have been significantly utilized for SHM and determination of surface defects in large metallic structures \\[[@B4-sensors-19-02010]\\]. Accurately estimating the damage not only requires the construction of damage images for its localization but also an accurate quantification of both the location and size of the damage. The presence of damage in a structure results in the forward and backward scattering of waves. The change in Lamb wave propagation due to this reflection and transmission can be detected and analyzed to evaluate the damage \\[[@B5-sensors-19-02010]\\]. There are a variety of methods to excite and receive Lamb wave signals. These methods can be grouped into five broad categories based on the transducers \\[[@B6-sensors-19-02010]\\]: ultrasonic probes, lead zirconate titanate (PZT) transducers and piezocomposite transducers, laser-based ultrasonic transducers, interdigital transducers (IDTs), and fiber-optic transducers. Comparing these methods, PZT transducers can be directly mounted on the surface of the target structure to excite/receive the Lamb waves through in-plane strain coupling \\[[@B7-sensors-19-02010],[@B8-sensors-19-02010]\\]. As a"
-"Background {#s1}\n==========\n\nVirus-associated hemophagocytic syndrome (VAHS) is classified within acquired hemophagocytic lymphohistiocytosis (HLH) and is a rare and life-threatening disease resulting in pathological findings secondary to abnormal proliferation of activated lymphocytes and histiocytes leading to high levels of inflammatory cytokine release ([@B1]). Because neonatal HLH shows non-specific symptoms, it is difficult to distinguish it from other diseases. Diagnosis and treatment are often delayed, with mortality as high as 60%. Although the ideal therapy for patients with VAHS remains unknown, many of the therapies, such as immunosuppressant therapy, antitumor agent therapy, exchange blood transfusion, and blood purification methods, have potentially severe side effects. A case of severe VAHS in the neonatal period associated with echovirus type 7 that was successfully treated with intravenous immunoglobulin (IVIG) therapy is reported.\n\nCase Presentation {#s2}\n=================\n\nA 37-week gestational age male infant was transferred to the neonatal intensive care unit (NICU) on the 4th day of life with apnea and lethargy. His two brothers had had fever and diarrhea 1 week before his birth. The maternal past medical history was unremarkable. At 37 weeks\\' gestation, his mother was suspected to have appendicitis due to fever and abdominal pain. She underwent cesarean section on that"
-"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"
-"This study is funded by the US Centers for Disease Control and Prevention Preventive Health and Health Services Block Grant, award number 2B01OT009042\u201015, and by the US Department of Agriculture Nutrition Education and Obesity Grant Program, award numbers G\u20101415\u201017\u20100847 and G\u20101617\u20100452, and the Centers for Disease Control and Prevention Health Promotion and Disease Prevention Research Center supported by Cooperative Agreement Number 1U48DP005030. We are grateful to the data collection team, study participants, and partners involved in this research.\n\nChildhood obesity rates among US children aged 2 to 19\u2009years have tripled during the past few decades from about 5% in the 1980s to 17% from 2011 to 2014.[1](#josh12747-bib-0001){ref-type=\"ref\"} Substantial racial and economic disparities in childhood obesity rates remain of great public health concern. For instance, African American (19.5%) and Hispanic (21.9%) children are disproportionately affected by obesity, compared to their white counterparts (14.7%).[2](#josh12747-bib-0002){ref-type=\"ref\"} Furthermore, childhood obesity increases risk for preventable chronic diseases such as hypertension and type 2 diabetes that manifest both in the short\u2010term as well as over the life course.[3](#josh12747-bib-0003){ref-type=\"ref\"}\n\nOne strategy to shift childhood obesity trends is to implement interventions designed to establish healthy dietary behaviors during childhood.[4](#josh12747-bib-0004){ref-type=\"ref\"}, [5](#josh12747-bib-0005){ref-type=\"ref\"}, [6](#josh12747-bib-0006){ref-type=\"ref\"} A key behavioral target for these types"
-"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 {#s01}\n============\n\nNeuroendocrine neoplasms (NENs) are rare, heterogeneous malignancies that are steadily rising in both prevalence and incidence ([@b1]). Due to the body-wide distribution of neuroendocrine cells, NENs can originate from various organs, with most primary cases occurring in the gastrointestinal track and the bronchopulmonary system ([@b1],[@b2]). In 2010, the revised World Health Organization (WHO) classification of NENs defined three grades based on the mitotic count and Ki-67 index (G1, G2, and G3) ([@b3]). In 2015, the National Comprehensive Cancer Network (NCCN) recommended the addition of tumor differentiation to NEN classification ([@b4]), which classified well-differentiated neoplasms as neuroendocrine tumors (NETs, G1 or G2) and poorly differentiated neoplasms as neuroendocrine carcinomas (NECs, G3). Studies have shown that NETs and NECs have distinct prognoses and responses to treatment ([@b3],[@b5]), with pancreatic NETs (PanNETs) responding better to traditional chemotherapy than NECs ([@b6]). However, the histopathologic classification can be challenging due to the lack of well-defined histological criteria ([@b7]), and this dichotomization is far from perfect since some NETs are shown to behave like NECs ([@b8]). Furthermore, although NETs are mostly G1/G2 grade, regions of excessive proliferation comparable to G3 can also be found within NETs, which is associated with reduced disease-specific survival"
-"Introduction {#s1}\n============\n\nSoil nitrogen (N) and phosphorus (P) are the most common macronutrients limiting plant growth under natural conditions. Inventories of global soil P found that soil P amount is lowest in the tropical and subtropical regions [@pone.0088070-Taylor1], [@pone.0088070-Zhang1] that account for about 40% of the global gross primary production and net carbon uptake over the past two decades [@pone.0088070-Beer1], [@pone.0088070-Pan1]. It is generally accepted that the total soil P gradually decreases as the result of weathering [@pone.0088070-Walker1], ecosystems may decline at their advanced stage [@pone.0088070-Wardle1], which resulting in a decrease of biomass and diversity due to soil P limitation [@pone.0088070-Hooper1], [@pone.0088070-Wassen1]. Previous studies also found that available soil P reduced the responses of tropical forests to increasing CO~2~ concentrations [@pone.0088070-Lloyd1], [@pone.0088070-Vitousek1]. Under global increasing atmospheric CO~2~ and N deposition in the future, P limitation of net primary production (NPP) in terrestrial ecosystems, particularly tropical and subtropical forests, will likely exacerbate. However, a number of continuous eddy covariance measurements and long-term biomass inventories showed that old-growth forests can be significant carbon sinks, including tropical and subtropical forests [@pone.0088070-Phillips1]--[@pone.0088070-Yan1].\n\nThe Dinghushan Biosphere Reserve (DBR) is located in the southern China experiencing a typical subtropical monsoon climate. The monsoon evergreen broadleaved"
-"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"
-"Background\n==========\n\nIntravenously injectable contrast agents (CA) consisting of gas-filled microbubbles (MBs) with a mean diameter of 2--5\u00a0\u03bcm can be used for improved image quality during ultrasound examinations, which results in diagnostic benefits. An ideal ultrasound CA must be biocompatible, stable during image acquisition, and circulate without causing obstructions or negative physiological effects. In addition, it should have the ability to increase backscattering efficiency when exposed to an acoustic field. In 1968, the first contrast-enhanced echocardiography examination was described \\[[@B1]\\]. At that time, fragile free-air MBs with a short lifetime of a few seconds were used. Since then, more stable CAs have been developed by encapsulating a low-solubility gas within a stabilizing shell \\[[@B2]\\]. In parallel, the development of specific ultrasound contrast pulse sequences, which use the nonlinear response generated by the MBs when exposed to acoustic pressure, has further improved the possibility of successfully using these CAs during ultrasound examinations \\[[@B3],[@B4]\\].\n\nAlthough commercially available ultrasound CAs are relatively stable and used in various diagnostic procedures, there is still a need for improvement and extended applicability. One such example is targeted imaging, which would enable the visualization of specific areas, e.g., inflammatory tissue. Local deposition of drugs might also"
-"Background\n==========\n\nSuccessful management of chronic disease in routine practice is an elusive task \\[[@B1],[@B2]\\]. As the number of patients with chronic medical illness and the literature regarding their optimal management have grown, attempts have been made to improve their care by implementing new models of care delivery. Implementation of these models involves intervening in specific ways in clinical settings and organizations, and each model has organizational elements that are considered necessary for model implementation. For example, in the chronic care model, delivery system design and information systems are among the elements that are specifically identified \\[[@B3]\\].\n\nThe number of interventions on an organizational level to improve delivery of care and outcomes for patients with chronic disease has grown. However, these care models and organizational strategies have not met with uniform success \\[[@B4]-[@B14]\\]. We believe that an important reason for this variation in outcomes is that interventions do not adequately take into account the characteristics of clinical systems in which patients receive care.\n\nClinical microsystems are the building blocks of healthcare delivery: the individual clinics, units, or other areas where care is delivered. The complex adaptive system (CAS) framework has been applied to clinical microsystems as a theoretical model for"
-"**African economies brace for a fully\u2010fledged Covid\u201019 outbreak.**\n\nAfter a slow start, the number of coronavirus cases in Africa is rising. By mid\u2010March African leaders were preparing for the outbreak to spread as doctors and experts fear it could only be a matter of time before the virus spirals out of control. Several African countries have been rolling out measures to prevent further contamination. Conferences, sporting events and concerts are being suspended one after the other, and flights suspended (*see p.22910*). Rapid testing and quarantines have been put in place to limit transmission. But concerns are growing about the continent\\'s ability to handle the disease.\n\n**South Africa**, already in a recession, declared a national state of emergency and banned travel to and from **China**,**Europe** and the **US.** \"We are at this very early phase where it is critically important that we contain the virus,\" said Richard Friedland, head of South Africa\\'s largest private healthcare provider Netcare.\n\n\"The key issue is with people living in informal settlements, in shacks... that (are) very difficult to self\u2010isolate,\" he told *AFP (13/3),* warning that a spread to such areas could be \"catastrophic\" for the continent.\n\nThough South Africa has a young population, there are"
-"Introduction {#Sec1}\n============\n\nChronic inflammatory rheumatic diseases (CIRDs), of which rheumatoid arthritis (RA) and axial spondyloarthritis (axSpA) are the most frequent, are progressive diseases that evolve with an unpredictable and fluctuating course over the patient's lifetime. The chronic nature of these diseases, the heterogeneity of physical manifestations between patients, and the difficulty in foreseeing disease flares and long-term progression create uncertainty and stress for the patient. In addition, they make it difficult for patients to develop a valid internal representation of their disease \\[[@CR1]\\]. This may in turn lead to misplaced disease perceptions and treatment expectations \\[[@CR2], [@CR3]\\], and the development of inappropriate behaviors for managing disease manifestations and coping with their consequences \\[[@CR4], [@CR5]\\]. For example, patients who believe that disease flares are triggered by physical activity may actively pursue a sedentary lifestyle, with detrimental consequences for their CIRD and their general health \\[[@CR6]\\]. The erroneous assumption that diet has an impact on disease may also lead the patient to make poor nutritional choices \\[[@CR7]\\]. In addition, expectations about the benefits and risks of treatment with disease-modifying anti-rheumatic drugs (DMARDs) may influence treatment adherence \\[[@CR8]\\] or perceptions of tolerability \\[[@CR9]\\].\n\nTherefore, it is important for physicians to understand their"
-"Background {#Sec1}\n==========\n\nThe patella is the biggest sesamoid bone inside the human body, located between the quadriceps tendon and the patella tendon. As an important module in the knee extension system, the patella can function as a lever and increase the moment of quadriceps, enabling the extension of the knee and helping maintain the stability of knee joint \\[[@CR1]\\]. The incidence of patella fracture in young people (18--49\u2009years) is 0.01% \\[[@CR2]\\]. What's more, the incidence of patella fractures in adult including elder people is as high as 1.5%, accounting for 10% of all fractures \\[[@CR3]\\]. Comminuted patella fractures (AO/OTA 34C2 and 34C3) are common challenges for orthopedic surgeons. Anatomical reduction and stable fixation are standard management to restore disrupted extension system and articular surface. Regardless of what kind of treatment was applied, there are still some patients who suffered poor outcomes from those comminuted patella fractures \\[[@CR4], [@CR5]\\].\n\nWhile the operative techniques of patella fractures have undergone many changes over the past few decades, anterior tension band remains the most widely accepted method \\[[@CR6]--[@CR8]\\]. It can transfer tension into pressure force to achieve dynamic compression between fragments, allowing early joint motion. However, the tension band still has many"
-"Introduction {#Sec1}\n============\n\nThe construction of narrow-bandwidth emitting organic lasers relies on the accuracy of technical equipment, such as deposition techniques for the construction of optical waveguides and optical techniques for writing periodic resonant structures^[@CR1]^. As an alternative approach, the concept of random lasers in which optical modes are guided and supplied with feedback within a disordered medium has been elaborated^[@CR2]--[@CR4]^. A wide range of gain materials have been developed, which are normally prepared on flat or structured substrates^[@CR5],[@CR6]^. In the past decade, however, there has been an increased interest in simple material systems that are inexpensive, easy to build, flexible, and do not require many preparation steps to be operational. Recently, paper has emerged as a promising candidate to fulfil these requirements^[@CR7]^. As a renewable resource, paper is an economically accessible, abundant and biodegradable composite that is already used in a variety of industrial applications (including, but not limited to copy paper, filters and weighting papers). Consisting of interconnected cellulose fibres often filled with mineral fillers, such as calcium carbonate, this composite material achieves better stability and smoothness as well as opaqueness compared to just cellulose fibres^[@CR8]^. In order to improve the brightness and to maintain a white impression"
-"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"
-"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"
-"Introduction {#sec1}\n============\n\nEncapsulation technology has been widely used in the field of agrochemicals, as encapsulation can reduce the volatilization and degradation of the active ingredient to prolong its persistence.^[@ref1]\u2212[@ref4]^ To date, more than 150 kinds of pesticide microcapsules (MCs) have been registered in China, including insecticides, fungicides, herbicides, and plant growth regulators. The advancements of pesticide MCs in China also stem from the limitations of using organic solvents in pesticide emulsifiable concentrate (EC), which was officially issued in the *Limit of Harmful Solvents of Emulsifiable Concentrate Pesticides*.^[@ref5]^ Petroleum derivatives, such as benzene, toluene, xylene, and *N*,*N*-dimethylformamide, are widely used as solvents for the production of EC. However, these solvents are not biodegradable and can be hazardous to the environment.^[@ref6]^ The development of water-based formulations is one of the most significant developments for EC. Among the extensive developments, capsule suspension is a promising orientation that accommodates the encapsulated pesticide in water.^[@ref7]\u2212[@ref9]^\n\nPendimethalin (*N*-(1-ethylpropyl)-3,4-dimethyl-2,6-dinitrobenzenamine; [Scheme S1](http://pubs.acs.org/doi/suppl/10.1021/acsomega.7b01651/suppl_file/ao7b01651_si_001.pdf) in the Supporting Information) is a dinitroaniline primarily preemergent herbicide; pendimethalin is one of the top herbicides and can control various annual grasses and certain broadleaf weeds in a variety of crops. At present, the dominant formulation for pendimethalin is still an EC. Thus, the"
-"Introduction {#S1}\n============\n\nInsulinoma is a very rare neuroendocrine tumor with a reported incidence of 0.5--5 per million person-years. It is also the most common cause of hypoglycemia associated with endogenous hyperinsulinemia ([@B6]). Clinical clues suggest that insulinoma continues to be diagnosed based on the physician's recognition of the presence of hypoglycemic symptoms, such as sweating, hunger, tremors, and palpitations. When the relationship between symptoms and possible hypoglycemia is missed, in most clinical settings, the blood glucose levels are not be checked. In addition, hypoglycemic symptoms are varied, lack specificity, and mimic many common neuropsychiatric disorders, such as epilepsy ([@B3]).\n\nComplex partial seizures are characterized by an aura, impaired consciousness, automatisms, and sometimes psychopathology, also known as temporal lobe seizures (TLE) or psychomotor seizures. Sometimes they are easily confused with metabolic diseases, such as hypoglycemia ([@B3]).\n\nIn this study, we report a case of insulinoma with impaired consciousness and behavioral disorders, which resulted from hypoglycemia and which were misdiagnosed as complex partial seizures based on the normal fasting blood glucose and glycosylated hemoglobin levels prior to admission. In clinical practice, for atypical complex partial seizures, in addition to eliminating epilepsy, the idea should be broadened and positive; finding other causes"
-"1. Introduction {#sec1}\n===============\n\nA time record consisting of beat-to-beat RR intervals is referred to as the heart rate tachogram. This forms the basis for a number of metrics of heart rate variability (HRV). The simplest measures of HRV are based on variance determined over a range of time periods. More complex measures can be derived from power spectrum density (PSD) estimations. The two most commonly used PSDs are the Welch Periodogram, based on the DFT, and the AR Spectrum, based on an autoregressive process model \\[[@B1]\\]. Both approaches require the data to be sampled regularly. Resampling the raw HRV data onto a regular time axis introduces noise into the signal and the information quality is compromised \\[[@B1]\\]. Conventionally, the HRV power is reported over 3 bandwidths: \\[0.01 \u22ef 0.04\\] Hz (Very Low Frequency, VLF) \\[0.04 \u22ef 0.15\\] Hz (Low Frequency, LF), and \\[0.15 \u22ef 0.4\\] Hz (High Frequency, HF) \\[[@B1], [@B2]\\].\n\nPrior to transformation into the frequency domain, normal practice requires that the time series data are \"detrended\" or \"high-pass filtered\" at a very low frequency, say \\~0.005\u2009Hz. There is no universally formal justification for such detrending other than it minimises the effects of medium-term nonstationarity within the"
-"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 {#Sec1}\n============\n\nWasting is prevalent among patients with chronic kidney disease (CKD). Eighteen to 75% of adults with end-stage renal disease (ESRD) undergoing maintenance dialysis showed some evidence of wasting \\[[@CR1], [@CR2]\\]. The differences in prevalence of wasting may be due to the different ESRD patient population mix reported, in the context of race, age, and prevalence of comorbid conditions such as congestive heart failure, diabetes mellitus, and liver disease. Wasting, defined by the World Health Organization as low weight for height \\[[@CR3]\\], was thought to be the direct consequence of inadequate nutrition intake or malnutrition. As a result, the terms, \"wasting\", \"cachexia\", and \"malnutrition\" were used interchangeably. Although inadequate nutrition may contribute to wasting or cachexia, other factors including systemic inflammation, perturbations of appetite-controlling hormones from reduced renal clearance, aberrant neuropeptide signaling, insulin and insulin-like growth factor resistance, and metabolic acidosis, may be important in the pathogenesis of CKD-associated wasting \\[[@CR4]--[@CR12]\\]. The wasting/cachexia syndrome in CKD patients consists of anorexia, increased energy expenditure, decreased protein stores characterized by a low serum albumin, and loss of body weight and loss of muscle mass. Importantly, the individual components of this syndrome all represent risk factors for mortality in patients with"
-"Klahs, P. C., T. J. Gallaher, and L. G. Clark. 2018 A refined method for digitally modeling small and complex plant structures in 3D: An example from the grasses (Poaceae). Applications in Plant Sciences 6(8): e1177.\n\nThe creation of three\u2010dimensional (3D) models is a valuable tool for exploring a wide range of questions in biological research. The choice of technique used to generate 3D models in a particular study is important for the resolution quality, the investment of time, and production cost. Modeling intricate plant structures generally involves extracting two\u2010dimensional (2D) images of a desired structure, interpreting those shapes, and then recreating the morphology in 3D. High\u2010resolution X\u2010ray computed tomography has been used to construct virtual 3D models of plant structures (Dhondt et\u00a0al., [2010](#aps31177-bib-0004){ref-type=\"ref\"}) and even fossilized plants (Gee, [2013](#aps31177-bib-0007){ref-type=\"ref\"}) by extracting 2D slices linearly through a structure, and then reconstructing a 3D surface from those images. Another method, optical photogrammetry (Eulitz and Reiss, [2015](#aps31177-bib-0005){ref-type=\"ref\"}), accomplishes the same task by rotating the object to collect 2D images from multiple angles. The method that we describe here operates similarly to X\u2010ray computed tomography, but uses refined microscopy techniques to produce conventional anatomical slides containing serial sections. Imaging those serial sections"
-"INTRODUCTION\n============\n\nOwing to reduction of genotyping cost and availability of high density single nucleotide polymorphism (SNP) panels, genome assisted selection method has become a popular selection method in animal breeding. The genomic estimated breeding values are used in genomic selection to predict the genetic merit of the candidate. Genomic selection refers to incorporation of DNA marker information, often the whole genome SNP data, to predict the genomic breeding values (genomic estimated breeding values, GEBV) used to make selection decisions. Genomic prediction is believed to provide better genetic gain for quantitative traits than could be achieved by phenotypic data alone \\[[@b1-ajas-30-7-907]\\]. Selection based on genomic data can be applied to young animals without sacrificing the selection candidates, which is apparently the most important advantage of this method. Bayesian methods for GEBV have proven to be accurate and efficient for phenotypes controlling few genes with large effects; however, the high-density SNP data sets demand computation power for the parameter estimation algorithms. The accuracy of genomic prediction using different methods (genomic best linear unbiased prediction \\[GBLUP\\] and Bayesian methods) depends on the genetic structure controlling the phenotypes \\[[@b2-ajas-30-7-907]\\]. Recently many reports suggested genomic selection to be better than traditional best linear unbiased"
-"INTRODUCTION {#s1}\n============\n\nThe lens of the eye is a key optical element that, together with the cornea, refracts light to the retina. Unlike the cornea, the lens has the capacity to alter ocular focus so as to enable clarity of vision for objects over a range of distances. This functional capacity, termed accommodation, which decreases progressively with age leading to a loss of ability to focus on near objects, is achieved by the lens changing its shape under forces mediated by the contraction and relaxation of the ciliary muscle. Accommodative capacity is effectively lost by the sixth decade of life for, though the rates can vary in individuals based on a number of internal and external factors \\[[@R1], [@R2]\\], by the end of the sixth decade when atrophy of the ciliary muscle occurs \\[[@R1]\\] lenses have no ability to accommodate. Refractive power for distant objects is not affected or altered with age. The growth of the lens continues throughout life by accrual of layers of fibre cells over existing tissue without concomitant cellular loss creating a lamellar structure with the oldest cells in the central layers and the most recently synthesised cells on the lens surface. This renders the"
-"Introduction\n============\n\nCarbohydrates coat most cell types in nature and are involved in a multitude of essential biological processes such as cell signalling, cell--cell communication, inflammation and fertilisation.^[@cit1]--[@cit4]^ However, bacteria, their toxins and viruses can exploit these cell surface oligosaccharides for adhesion to host tissues and is the first step in many infectious diseases.^[@cit4],[@cit5]^ The proteins that mediate these interactions are known as lectins, they interact with carbohydrates non-covalently and reversibly with a high level of specificity.^[@cit6],[@cit7]^ Protein--carbohydrate interactions are typically weak with values for *K* ~d~ in the range of 10^--3^--10^--6^ M. This intrinsically weak protein--carbohydrate affinity is circumvented in nature by the involvement of multiple protein--carbohydrate interactions leading to the high affinity and specificity, this is known as the 'cluster glycoside effect', which is regarded as the enhancement in the activity of a multivalent ligand beyond the simple linear sum of the total number of ligands.^[@cit8],[@cit9]^ This simple, but still not fully understood enhancement effect, presents huge opportunities in macromolecular and nanoscale science to probe glycan function.^[@cit4]--[@cit6],[@cit10]^\n\nThe ubiquitous nature of carbohydrate--lectin interactions in infectious diseases presents new opportunities in drug design and biosensing. For example, urinary tract infections in humans are strongly associated with *Escherichia coli* producing"
-"Data are available upon request to the authors. No authorization for public deposition was given by the relevant ethical authority: Geneva Hospital CRC (Centre de Recherche Clinique) committee.1310.\n\nIntroduction {#sec001}\n============\n\nSelective attention, which has traditionally been associated with modulation of perceptual processing based on dimensions such as spatial location or stimulus feature, can also operate dynamically in time \\[[@pone.0164613.ref001]\\]. Orienting attention to specific moments in time, referred here as temporal attention or temporal expectation, enhances the processing of upcoming events during this interval \\[[@pone.0164613.ref001]--[@pone.0164613.ref003]\\]. In addition to influencing motor preparation, temporal attention improves perceptual performance and reaction times in tasks requiring stimulus discrimination or identification \\[[@pone.0164613.ref004], [@pone.0164613.ref005]\\]. Strikingly, temporal attention has also been found to determine the extent to which subliminal stimuli influence response priming \\[[@pone.0164613.ref006]--[@pone.0164613.ref008]\\]. However, the neural underpinning of these effects remains unknown.\n\nBehavioral studies have typically investigated the effect of temporal attention on the perception of visual stimuli flashed rapidly in a continuous sequence (e.g. rapid serial visual presentation tasks) or briefly presented below the threshold of consciousness (i.e. masked priming paradigms). For instance, generating temporal expectations regarding target onset reduces the attentional blink \\[[@pone.0164613.ref009], [@pone.0164613.ref010]\\]. Using a task where participants judged whether visible target numbers"
-"Coronal ISH data for 4345 genes obtained from the Allen Mouse Brain Atlas (<http://mouse.brain-map.org/>) at 200 \u03bcm resolution in male, 56-day-old C57BL/6J mice at 25-\u03bcm sections. Code to download and analyze data sets are supplied as Supporting Information.\n\nIntroduction {#sec001}\n============\n\nThe mammalian neocortex is classified into a series of anatomically and functionally distinct regions or cortical areas \\[[@pone.0212898.ref001],[@pone.0212898.ref002]\\]. Areas are often identified using histochemical stains and antibodies to visualize differences in protein expression across cortex. Examples include cytochrome oxidase histochemistry and antibodies against m2 muscarinic receptors \\[[@pone.0212898.ref003]\\]. Numerous differences in expression across cortical areas have been observed, including abrupt changes in expression at area borders, more graded changes between areas, gradients in expression across an area, and changes in cell-specific expression \\[[@pone.0212898.ref004]--[@pone.0212898.ref011]\\].\n\nWe reasoned that there may be genetic markers of cortical areas that have not been identified and that we might identify additional markers by screening the Allen Mouse Brain Atlas, a database containing in situ hybridization information for thousands of genes \\[[@pone.0212898.ref012]\\]. We developed numerical tools to screen the many thousands of images in the database, using a random forest algorithm to identify changes in gene expression at the boundaries of cortical areas defined in the Allen"
-"INTRODUCTION {#s1}\n============\n\nLipopolysaccharide (LPS) known as a trigger of inflammatory responses has been suggested to be implicated in several cancer invasion or angiogenesis \\[[@R1]--[@R3]\\]. Recent studies also indicated that toll-like receptors (TLRs) are expressed in many tumors and might play key roles in tumor progression. The role of TLR4, specific receptor for LPS, in tumor progression has been studied in various cancers involving colon, pancreas, liver and breast cancers \\[[@R4]--[@R7]\\]. Particularly, it has been shown that LPS/TLR4 has critical role in stimulation of invasiveness of breast cancer cells, and status of TLR4 expression is deeply linked to metastasis \\[[@R6]\\]. Breast cancer is known to be one of common cancers in women and metastatic breast cancer still retains poor prognosis. However, little is known about the underlying mechanism by which LPS/TLR4 regulates breast cancer progression involving migration, invasion or metastasis.\n\nIt has been shown that T-LAK cell-originated protein kinase (TOPK), serine/threonine mitogen-activated protein kinase (MAPK)-like protein kinase, was highly expressed in several cancer cells and closely implicated in tumorigenesis \\[[@R8], [@R9]\\]. Recently, TOPK has been suggested to act as a prognostic factor in some of cancers such as oral, ovarian, or lung cancer \\[[@R10]--[@R12]\\]. In particular, TOPK has been shown"
-"Introduction {#sec1-1}\n============\n\nPatients undergoing induction chemotherapy for acute leukemias are at a particularly high risk of developing neutropenic fever (NF) due to the prolonged duration of severe neutropenia. In the majority of these cases, the rapid administration of broad spectrum antimicrobials decreases the risk of progression to septic shock and death. Despite advances in antimicrobial therapy and supportive care measures, infection-related complications frequently prolong the duration of hospitalization and continue to be the main causes of early mortality in patients undergoing chemotherapy for acute leukemias.^[@ref1],[@ref2]^ Strategies to further decrease these complications are needed to improve patient outcomes.\n\nThe initiation of broad-spectrum antimicrobials for NF generally occurs at the time of fever. Although most patients stabilize after starting treatment, a subgroup of patients deteriorates rapidly into septic shock despite prompt initiation of antimicrobials. A strategy to improve outcomes is the use of antibiotic prophylaxis which has been shown to reduce infection-related mortality, especially with the use of fluoroquinolones.^[@ref3]^ However, antibiotic resistance, fungal overgrowth, and antibiotic-related adverse effects (*e.g. Clostridium difficile* colitis and allergic responses) have limited the routine use of antibiotic prophylaxis. An alternative strategy is to initiate antimicrobial therapy just prior to the onset of fever. This strategy may"
-"Introduction {#s1}\n============\n\nThere is no consensus on the health consequences of lactose intolerance (LI)\\[[@B1],[@B2]\\]. The commonest form of LI, primary LI, results from either a genetic inability to produce lactase, an enzyme that breaks down lactose to glucose and galactose, or from an age-related down-regulation of lactase production\\[[@B3]\\]. Bacterial fermentation of the non-digested lactose leads to the production of short chain fatty acids and gas including hydrogen, carbon dioxide, and methane\\[[@B4]\\]. The degree of elevation of these gases as measured by the hydrogen breath test forms the basis of the clinical diagnosis of LI\\[[@B4]\\]. The associated bloating, diarrhea, and abdominal pain lead to the avoidance of dairy products\\[[@B5]\\]. A central hypothesis in LI is that dairy avoidance leads to reduced intake of protein and calcium, which consequently results in poor growth, short stature and low bone mineral density, respectively \\[[@B6]\\]. However, no systematic study has been conducted in prepubertal children to accurately assess this hypothesis.\n\nEven though the studies that demonstrated an association between LI and low bone mineral density have provided important information in this field \\[[@B6]-[@B8]\\], they failed to articulate a coherent biochemical basis for the reported low bone mineral density and increased fracture risk in their"
-"Background {#Sec1}\n==========\n\nSubtotal esophagectomy for esophageal cancer is one of the most invasive gastrointestinal surgeries and is associated with high morbidity and mortality rates, though there have been recent advances in surgical techniques and perioperative management \\[[@CR1], [@CR2]\\]. The intestinal tract is the largest immune organ in the human body. The intestinal epithelial barrier allows absorption of dietary nutrients and prevents passage of pathogens and toxins into the body. Severe insults have a negative impact on the intestinal environment, which may decrease intestinal barrier function and cause bacterial translocation. We previously reported that esophagectomy in patients with esophageal cancer disturbed the intestinal microbiota and decreased the concentrations of organic acids, while the administration of perioperative synbiotics significantly shortened the duration of the postoperative systemic inflammatory response syndrome and nonsignificantly reduced postoperative infectious complications by maintaining the intestinal microbiota and the concentrations of organic acids \\[[@CR3]\\].\n\nThe fermentation of carbohydrates by the intestinal microbiota produces organic acids. Among them, short chain fatty acids (SCFAs) play a variety of important roles in maintaining intestinal mucosal barrier function and preventing bacterial translocation \\[[@CR4]\\]. Bacterial translocation, which can cause infectious complications, is the passage of microbes or their products from the gastrointestinal tract"
-"Background {#Sec1}\n==========\n\nMedical knowledge bases (KBs) play an important role in healthcare research. Existing KBs vary from coding systems such as ICD10 \\[[@CR1]\\], terminology systems such as UMLS \\[[@CR2]\\], clinical ontology systems such as SNOMED CT \\[[@CR3]\\] to medical databases such as DrugBank \\[[@CR4]\\]. The major objectives for these KBs are to provide knowledge to medical workers and to promote standardization and interoperability for biomedical information systems and services. Besides, there exist many different types of biomedical KBs. For example, SIDER \\[[@CR5]\\], and AMDD \\[[@CR6]\\] contain drug-related information. Diseasome \\[[@CR7]\\], ParkDB \\[[@CR8]\\], and ChemProt \\[[@CR9]\\] describe disease and disease-related gene information. These KBs are necessary in automatically processing and analyzing electronic medical records (EMRs) and then form the basis of the upper information applications such as clinical decision support systems.\n\nCurrently there are many general-purpose KBs built by automatic approaches. The DBpedia project \\[[@CR10]\\] extracted structured information from Wikipedia and published them on the Web. YAGO \\[[@CR11]\\] was derived from Wikipedia, WordNet, and GeoNames. NELL \\[[@CR12]\\], SOFIE \\[[@CR13]\\], and PROSPERA \\[[@CR14]\\] extracted data from the Web. The input data for NELL consisted of an initial ontology as well as a small number of instances. SOFIE extracted ontological facts from"
-"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"
-"Introduction {#Sec1}\n============\n\nLymphomas are the second most common indication for autologous hematopoietic stem cell (HSC) transplantation (HSCT). The most common method for mobilizing HSCs from the peripheral blood is treatment with granulocyte-colony stimulating factor (G-CSF) alone or combined with chemotherapy \\[[@CR1], [@CR2]\\]. However, a sizable minority of patients fail to mobilize sufficiently with G-CSF-based regimens \\[[@CR3], [@CR4]\\].\n\nPlerixafor has a mode of action different from other HSC mobilizing agents and acts by binding to chemokine (C-X-C motif) receptor 4 (CXCR4), preventing the binding of its ligand stromal cell-derived factor 1 (SDF-1, now C-X-C motif chemokine 12, CXCL12) and thereby inhibiting events downstream of CXCL12 including SDF-1-mediated G-protein activation, receptor internalization, calcium flux, and chemotaxis \\[[@CR5], [@CR6]\\]. The CXCL12/CXCR4 interaction is an integral part of the mechanism of homing and retention of HSC in the bone marrow and inhibition of this interaction by plerixafor mobilizes HSCs from the bone marrow \\[[@CR7], [@CR8]\\]. Unlike cytokines used for HSC mobilization (e.g., G-CSF), plerixafor is not a growth factor and does not cause cell proliferation or expansion. Therefore, the approved use for plerixafor is in combination with G-CSF \\[[@CR9], [@CR10]\\].\n\nAs there is a theoretical risk of tumor cell mobilization with any stem"
-"Background {#Sec1}\n==========\n\nThe monogenean *Gyrodactylus salaris* Malmberg, 1957 has been an important pathogen of juvenile freshwater stages of Atlantic salmon, *Salmo salar* L. in Norway since the 1970s, when it is thought to have been introduced from the Baltic region \\[[@CR1]\\]. An early conclusion was that, following the introduction of this parasite, Norwegian (Eastern Atlantic) salmon stocks were especially susceptible due to a lack of co-adaptative evolutionary experience of *G. salaris*, contrary to Baltic salmon stocks \\[[@CR2]\\]. This hypothesis has been repeated, with numerous studies comparing parasite performance on different salmon stocks and other salmonids, generating one of the largest available data sets using a common garden experimental approach to examine host specificity of a metazoan parasite infecting vertebrates. Studies with other gyrodactylid-host systems have shown that parasite infra-populations grow rapidly to a peak, followed by decline and eventual elimination \\[[@CR3]--[@CR14]\\], a pattern interpreted as exponential increase before induction of immunity after a short period of recognition and activation \\[[@CR15]--[@CR19]\\]. The continuous growth of *G. salaris* on susceptible Norwegian salmon was therefore interpreted as evidence of impaired immunity \\[[@CR20]\\], despite earlier suggestions that even on these fish, parasite population growth rates could decline throughout infection \\[[@CR21]\\]. The resulting 'Atlantic"
-"Introduction {#S1}\n============\n\nParkinson's disease (PD) is the most common neurodegenerative movement disorder and is likely to increase due to the aging population ([@B1]). PD is principally attributed to the death of dopamine (DA) neurons in the substantia nigra, but other neurotransmitters, such as glutamate, are also affected ([@B2]). There is no cure for PD but symptomatic treatments are available ([@B3]). Restoring lost DA with its precursor, [l]{.smallcaps}-3,4-dihydroxyphenylalanine ([l]{.smallcaps}-DOPA), remains the most effective treatment ([@B4]). However, many patients (\u226540%) develop motor complications after 5--10\u2009years of treatment ([@B5]). These motor complications include motor fluctuations and abnormal involuntary movements, such as [l]{.smallcaps}-DOPA-induced dyskinesias (LID), and contribute to limit the quality of life in PD patients and can be very difficult to manage ([@B6]). Motor fluctuations such as \"wearing-off\" are also common. Wearing-off is defined as a reduced duration of benefit from an individual [l]{.smallcaps}-DOPA dose and a recurrence of parkinsonian symptoms before the next normal dose of [l]{.smallcaps}-DOPA ([@B7]).\n\nNo drug is yet available for LID, aside from some benefit with amantadine that has anti-glutamatergic properties ([@B8]). Glutamatergic transmission is increased in the basal ganglia in PD ([@B9]) and is also believed to be involved in LID ([@B10], [@B11]).\n\nThe mechanisms"
-"Introduction {#sec1-1}\n============\n\nHIV counseling and testing services are a key entry point in HIV prevention and treatment of people with HIV. These services provide accurate information about HIV and help the clients to undergo HIV test in a supportive and confidential environment.\\[[@ref1]\\] With the introduction of antiretroviral therapy (ART), the scope of voluntary counseling and testing centers (VCTCs) further expanded to include preparedness and adherence along with counseling for people on ART. HIV counseling and testing services were provided to 66.62 lakh persons in the year 2010.\\[[@ref2]\\] Barriers to voluntary counselling and testing (VCT) include low perceived risk for HIV infection, negative perceptions of testing services, lengthy pre- and post-test counseling, and shortages of counselors.\\[[@ref3][@ref4][@ref5]\\] To provide integrated services, earlier VCTCs and prevention of parental to child transmission were brought under one roof to cater general and ANC clients and was renamed as integrated counseling and testing centers (ICTCs).\\[[@ref6]\\] In India, the ICTC services are provided through 4486 standalone ICTCs, 4071 Facility ICTCs at 24 \u00d7 7 PHCs and 902 ICTCs under public--private partnership model. A total of 90.52 lakh clients tested for HIV in the year 2011--2012.\\[[@ref7]\\] Evaluation of counseling, testing, and referral services increase the effectiveness, efficiency,"
-"The data set was assembled from public Instagram posts from January 2017 and July 2018 using InstaLooter. InstaLooter and its documentation are publicly available at the following webpage: <https://github.com/althonos/InstaLooter>.\n\nIntroduction {#sec001}\n============\n\nPeople's perceptions about health risks are impacted in part by who they see portrayed as at risk, including media portrayals \\[[@pone.0231155.ref001]\\]. Specifically, theories in communication and social psychology posit that the perception of prevalence (commonly called the descriptive norm) governs how individuals assess their own risk and adopt prophylactic behaviors \\[[@pone.0231155.ref002],[@pone.0231155.ref003]\\]\\[[@pone.0231155.ref004],[@pone.0231155.ref005]\\]. Accordingly if an individual perceives there is low risk among persons they know or see, they likely infer they too are at low risk. In the case of media and disease, these theories assume that when viewers engage with media they ask themselves \"do I look like the people who are portrayed as at risk?\" \\[[@pone.0231155.ref006],[@pone.0231155.ref007]\\].\n\nIt is also well established in the literature on persuasion and health behaviors that people that are perceived as similar to oneself are more influential than people who are perceived as not similar \\[[@pone.0231155.ref008]\\]. For instance, through constant social comparison processes, individuals adjust their risk prevalence estimate by changing the reference group to persons who share their traits. Consequently, messages for"
-"Background {#Sec1}\n==========\n\nOligodendrocytes (OLs) are responsible for generating myelin, a lipid-rich structure that envelops central nervous system (CNS) axons, allowing for rapid communication between neurons. OLs generate myelin as they differentiate by extending multiple processes that contact adjacent axons, forming concentric wrappings of lipid-rich OL membrane mostly devoid of cytoplasm and stabilized by myelin structural proteins \\[[@CR1]\\]. Prior to the onset of myelination, newborn OL precursor cells (OPCs) undergo a transient period of local proliferation followed by migration \\[[@CR2]\\], their direction and extent governed by patterning molecules. Proper myelination is therefore highly dependent on the capacity of OPCs to migrate to target destinations and initiate the differentiation program. As such, researchers have endeavored to dissect the extracellular cues and the intracellular machinery governing OPC migration. This is especially relevant in neurological diseases like multiple sclerosis (MS) where the capacity for endogenous repair may be limited partly by the hampered migration of OPCs into lesions \\[[@CR3]\\].\n\nOver the years, our understanding of OL biology has vastly improved through the study of rat OLs in vitro, for which several isolation methods exist \\[[@CR4]--[@CR6]\\]. However, these strategies are often not ideal for isolating mouse OPCs for a number of reasons. First and"
-"1. Introduction {#sec1}\n===============\n\nThe existence of free radicals, known in chemistry since the beginning of the 20th century \\[[@B1]\\], was discovered in biological systems in 1954 \\[[@B2]\\]. In the same year, Gerschman et al. proposed that the noxious effects of hyperbaric oxygen and X irradiation had a common mechanism which involved radical and nonradical species, resulting from partial reduction of oxygen \\[[@B3]\\]. Soon after, Harman suggested that these species, at present referred to as reactive oxygen species (ROS), might play a role in the aging process \\[[@B4]\\].\n\nProgress in the free radical knowledge occurred in 1969 when the enzyme superoxide dismutase (SOD) was isolated \\[[@B5]\\]. The SOD discovery inspired a large number of studies, which contributed to the knowledge of the ROS, even though for several decades they were thought to cause exclusively damaging effects. This view was mainly supported by the finding that ROS readily react with most biological macromolecules, causing their oxidative modification, ultimately resulting in the loss of their function \\[[@B6]\\]. Actually, ROS include species, such as the hydroxyl radical (^\u2022^OH), whose reactivity is so high that it reacts very close to its site of formation \\[[@B7]\\], and other species, such as superoxide (O~2~ ^\u2022\u2212^) and"
-"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"
-"Cancer Sci 108 (2017) 136--142\n\n**Funding Information**\n\nNational Cancer Center Research and Development Fund (23\u2010A\u201016); Japan Society for the Promotion of Science (KAKENHI 26108007).\n\nDespite advances in therapy, the prognosis of patients with advanced NSCLC remains poor with a 5\u2010year survival rate of \\<20%.[1](#cas13110-bib-0001){ref-type=\"ref\"} Distant metastasis is the most important prognostic factor and play a major role in choice of treatment. Squamous cell carcinoma accounts for approximately 30% of lung cancer and is the second most common histological type behind adenocarcinoma.[2](#cas13110-bib-0002){ref-type=\"ref\"} Lung SqCC has a lower rate of distant metastasis than other histological type, but not of LN metastasis. Furthermore, local recurrence including LN is more frequent after the resection of early stage of lung SqCC than adenocarcinoma.[3](#cas13110-bib-0003){ref-type=\"ref\"}, [4](#cas13110-bib-0004){ref-type=\"ref\"} As lymph node metastasis is an important prognostic factor,[5](#cas13110-bib-0005){ref-type=\"ref\"} an improved knowledge of the mechanism of lymphatic metastasis in lung SqCC might be of potential clinical benefit.\n\nMetastasis is a complex multistep process. In the PT, tumor cells detach from their surrounding cells by EMT and intravasate into blood or lymphatic vessels. The tumor cells float in the circulation and some of them survive without anoikis. The cells adhere to the endothelium, extravasate, and begin reproliferation. To facilitate an increase in"
-"Background\n==========\n\nDespite prevention campaigns and easy access to highly active antiretroviral therapy (HAART), the number of new HIV diagnoses in Western Europe continues to increase, with unprotected sex between men being reported as the main mode of transmission \\[[@B1]-[@B3]\\]. The design of prevention measures calls for a thorough understanding of the HIV epidemiology. As such, reconstruction of transmission networks based on interview data can provide valuable insights in the spread of the virus \\[[@B4]-[@B6]\\]. For several years now, international guidelines recommend baseline testing for drug resistance in all HIV-1 infected patients \\[[@B7]\\]. This has led to a substantial increase in the availability of viral sequence data and has permitted a new approach to study the HIV epidemiology \\[[@B8]\\]. More specifically, phylogenetic analysis allows the identification of mutual characteristics of so-called clusters, i.e. specific groups of patients in which multiple transmissions of HIV-1 have taken place. Studies using phylogenetics based on the *pol*gene of HIV were performed throughout the world to map local HIV epidemics in correlation with transmission pathway, drug resistance, risk behaviour and cluster size. Some focussed on the contribution of primary infection to onward transmission \\[[@B9]\\], while others investigated the transmission of drug resistant viruses \\[[@B10]-[@B12]\\] or"
-"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"
-"Introduction\n============\n\nIntracellular Na^+^\u2010activated K^+^ (K~Na~) channels were first described in guinea pig cardiomyocytes 30 years ago (Kameyama et al. [@b15]) and later in cultured trigeminal ganglion neurons from quail embryos (Bader et al. [@b1]; Haimann et al. [@b12]). K~Na~ channels in neurons can either be activated by Na^+^ ions that are conducted by voltage\u2010activated Na^+^ channels during the rapid upstroke phase of action potentials (Bader et al. [@b1]) or by a persistent inward Na^+^ current (Budelli et al. [@b5]). However, in the heart it appears that K~Na~ channels are only activated under pathological conditions such as hypoxia or ischemia (Kameyama et al. [@b15]). The molecular basis of K~Na~ channels was discovered in 2003 with the cloning of Slo2.1 (Bhattacharjee et al. [@b4]) and Slo2.2 (Yuan et al. [@b23]). Based on RT\u2010PCR, Slo2.1 is expressed in most tissues, including the brain, heart, skeletal muscle, lung and liver, whereas Slo2.2 is highly expressed within specific regions of the brain, and to a lesser extent in the kidney, testis, and very weakly in the heart (Yuan et al. [@b23]). The Slo2.1 channel was first described as a functional hybrid between a K~Na~ and K~ATP~ channel because it was activated by intracellular Na^+^"
-"Chagas disease ranks highly among the main neglected tropical diseases in the Americas ([@B20]). The main vector for Chagas disease, *Triatoma infestans* (Klug, 1834) (Hemiptera: Reduviidae), has historically played a crucial role in the Southern Cone Region. Although the geographical range of *T. infestans* has been strongly reduced over the last three decades, this species still persists in the Gran Chaco eco-region of Argentina, Bolivia and Paraguay, where it represents a serious health problem ([@B20]). Chagas disease affects approximately 1.6 million people in Argentina, and *T. infestans* is present in a large fraction of the territory ([@B30]).\n\nChagas disease in the Argentine Chaco is characterised by a complex eco-epidemiological scenario with high levels of house infestations by *T. infestans* ([@B11]) and increasing professional vector control efforts over the last decade ([@B23]). Several efforts have been made to understand the processes related to *T. infestans* house infestation and re-infestation patterns as well as the transmission of *Trypanosoma cruzi* (Chagas, 1909) ([@B17]). However, the eco-epidemiology of Chagas disease remains mostly unknown in western Argentina, where the SW extreme of the Gran Chaco creates a biogeographic transition area known as the Monte Desert ([@B25]). Mendoza province is located at the heart of the"
-"Background\n==========\n\nThe vertebral column is the defining character of vertebrates providing the organism with a unique ability of movement, form and function. Obviously, abnormalities to this organ can lead to severe and often painful pathological conditions. Spinal disorders are a major cause of disability for humans and an important health problem for intensively farmed animals. A number of animal models have been used to further explore the pathology and revealed that vertebral deformities present a complex but comparable cross species etiology \\[[@B1],[@B2]\\]. Morphological changes like altered bone formation and cell density, thinning of osteoblasts along with increased cell proliferation and cell death are changes found in spinal deformities and intervertebral disc degeneration (IDD) in mammals \\[[@B3],[@B4]\\]. Discs from patients with spinal deformities further have ectopic calcification of the vertebral endplates and sometimes in the disc itself \\[[@B5]\\]. Cells of the mammalian disc are derived directly from the phylogenetically conserved notochord \\[[@B6]\\]. Whereas only remnants of the notochord exists in the nucleus pulposus (NP) in humans by the age of 4, the notochord persist throughout all life stages in teleosts. Spinal disorders in teleosts like sea bass, sea bream, rainbow trout, halibut and salmon \\[[@B7]-[@B12]\\] have mostly been descriptive and"
-"Introduction\n============\n\nEsophageal squamous cell carcinoma (ESCC) is one of the most malignant tumors worldwide ([@b1-ijo-52-05-1443]--[@b3-ijo-52-05-1443]) and the sixth most fatal cause of cancer-related death. Squamous cell carcinoma (SCC) is the main histological type of this cancer. Northern and central China is part of the \\'Asian belt\\' which has a very high incidence of ESCC; there are \\>100 cases per 100,000 annually. The urgency of preventing and curing ESCC is obvious ([@b4-ijo-52-05-1443],[@b5-ijo-52-05-1443]).\n\nSimilar to other types of cancer, the development of ESCC is believed to be a multi-step process caused by the accumulation of activated oncogenes and inactivated tumor suppressor genes (TSGs) ([@b6-ijo-52-05-1443]). TSGs can be inactivated by both genetic and epigenetic mechanisms. Genetic deletions and point mutations disrupt TSG functions, and epigenetic mechanisms, including CpG island promoter methylation and histone modifications, frequently lead to the loss of TSG functions and are involved in tumor development and progression ([@b7-ijo-52-05-1443]). The aberrant methylation of CpG islands leads to gene silencing, resulting in TSG inactivation, which can increase the rate of tumor formation by disabling multiple normal cellular processes, such as apoptosis and cell cycle progression ([@b7-ijo-52-05-1443]). In breast cancer and renal clear cell carcinoma ([@b8-ijo-52-05-1443]), methylation of erythrocyte membrane protein band"
-"INTRODUCTION\n============\n\nLiver transplantation (LT) is a revolutionary treatment for patients with acute liver failure or end-stage liver disease, and it prolongs survival and allows for full recovery \\[[@b1-kjim-2019-044],[@b2-kjim-2019-044]\\]. LT can be divided into deceased-donor and living-donor LT (DDLT and LDLT, respectively) according to the organ delivery method \\[[@b3-kjim-2019-044]\\]. In Western countries, where social systems are well established to enable a smooth process of organ procurement from deceased donors, DDLT is the preferred procedure. In Eastern countries, where organ procurement systems are not well established and still developing, LDLT is more common \\[[@b4-kjim-2019-044],[@b5-kjim-2019-044]\\].\n\nThe management of complications occurring after LT is very important for the patient and graft survival. Patients with complications post-LT may experience frequent hospitalization, increased treatment costs, and, rarely, liver failure. Biliary stricture is the most common (approximately 40%) biliary complication occurring after LT \\[[@b6-kjim-2019-044],[@b7-kjim-2019-044]\\]. The incidence of biliary stricture is approximately 5% after DDLT and approximately 24% and 60% for left and right lobe grafts, respectively, after LDLT \\[[@b8-kjim-2019-044]-[@b10-kjim-2019-044]\\].\n\nThis article provides an overview of the pathogenesis, diagnosis, endoscopic management, and long-term outcomes of post-LT biliary stricture, with a focus on anastomotic stricture (AS).\n\nPATHOGENESIS OF BILIARY STRICTURE\n=================================\n\nBile duct epithelium is more vulnerable to"
-"Chemical context \u00a0 {#sec1}\n==================\n\nFor the last several decades, Schiff bases have remained an important and popular area of research for the scientific community due to their simple synthesis, versatility and extensive range of applications (Cozzi, 2004[@bb5]; Chen *et al.*, 2008[@bb4]). A number of carbonyl compounds and amines have been utilized for the synthesis of Schiff bases (Zheng *et al.*, 2009[@bb18]; Hussain *et al.*, 2014[@bb9]). However, there are only a few reports where de\u00adhydro\u00adacetic acid (DHA) has been used for the preparation of Schiff bases for various applications (Liu *et al.*, 1991[@bb10]; Luo *et al.*, 1995[@bb11]). In some cases, DHA-based Schiff bases are used for the synthesis of metal complexes, leading to their utilization in various biomedical applications due to their anti\u00adfungal, anti\u00adbacterial, anti\u00admalarial and anti\u00adcancer activities (Chan & Wong, 1995[@bb3]; Erkkila *et al.*, 1999[@bb6]; Ganjali *et al.*, 2007[@bb7]; Gupta & Sutar, 2008[@bb8]). In general, the compounds are formed *via* a condensation product of hydrazine and the respective aldehyde or ketone in a 1:1 molar ratio. Structurally, a Schiff base (also known as an imine or azomethine) is a nitro\u00adgen analogue of an aldehyde or ketone in which the carbonyl group (C=O) has been replaced by an imine or azomethine"
-"1 INTRODUCTION {#SEC1}\n==============\n\nAs genomes evolve, they undergo mutational processes that can alter not only individual nucleotides but also the large-scale structure of chromosomes. Although genome sequencing has helped to characterize the rates and patterns of such chromosomal evolution, communicating findings to a broad audience can be challenging.\n\nModern inference methods can reconstruct likely evolutionary histories using genome sequence data alone. Methods such as GRAPPA (Tang and Moret, [@B8]) can infer inversion histories and phylogenies on single chromosomes, while GRIMM/MGR (Tesler, [@B9]) can be applied to multi-chromosomal genomes. Yet another method, BADGER (Larget *et al.*, [@B6]), implements a Bayesian framework to sample likely phylogenetic inversion histories and can report the uncertainty in individual reconstructions (Darling *et al.*, [@B3]). Bayesian methods have also been developed to sample histories of inversions and transposition (Miklos, [@B7]), duplications (Zhang, [@B10]), gene gain and loss and gene conversion and nucleotide substitution (Didelot and Falush, [@B4]). Similar methods have been applied to mammals (Blanchette *et al.*, [@B1]). All of these inference methods are typically predicated on a multiple-genome alignment (Darling *et al.*, [@B2]). Although no method currently infers mutation histories under a single model incorporating all these mutation types, inferences from each method can potentially"
-"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"
-"1. Introduction {#sec1}\n===============\n\nHead and neck squamous cell carcinoma (HNSCC), the sixth most common cancer worldwide, often generates from critical organs including the larynx, pharynx, oral cavity, and tongue that play indispensable roles in social, respiratory, communicative, and nutritional functions \\[[@B1]\\]. Surgical intervention for these organs often leads to a considerable impairment of the patient\\'s quality of life (QOL), albeit recent remarkable progresses in reconstructive surgery. Accordingly, the intensity of conventional DNA-damaging therapies (i.e., irradiation and chemotherapy) has been strengthened to the upper limit of human tolerance of acute toxicities during the last decade \\[[@B2]\\]. Short-term results of these treatments seem to be promising. However, it is still under debate whether these dose-intensified types of protocols would lead to the long-term overall survival as well as \"functional\" organ preservation, because these protocols occasionally cause considerable complications (e.g., requirement for feeding tube due to severe laryngeal and pharyngeal dysfunction) and potential treatment-related death \\[[@B2]--[@B4]\\]. Ongoing molecular targeted therapies in HNSCC revealed only marginal effects so far \\[[@B5]\\]. In addition, the frequent occurrences of second primary tumor further worsen the prognosis of patients with HNSCC \\[[@B1], [@B6]\\]. As a result, the dishonorable phrase that is routinely used in the *Introduction* of"
-"1. Introduction\n===============\n\nColorectal cancer is an important disease, one of the leading causes of cancer death, across ages and in all countries. There have been many advances in preventing colorectal cancer. Screening by colonoscopy is useful for detecting colorectal adenomas and helps in reducing colorectal cancer. However, the current challenging issue includes how to reduce interval colorectal cancer (ICC), especially for the right colon (RC), which colonoscopy is less effective.^\\[[@R1]\\]^\n\nColonoscopic withdrawal time (CWT) and adenoma detection rate (ADR) are widely used quality indicators for screening colonoscopy.^\\[[@R2]\\]^ Barclay et al^\\[[@R3]\\]^ suggested that CWT should be longer than 6 minutes for higher ADR, whereas Simmons et al^\\[[@R4]\\]^ suggested that it should be longer than 7 minutes for higher polyp detection rate. Lee et al^\\[[@R5]\\]^ suggested that CWT should be longer than 6 minutes, and that around 10 minutes is necessary for higher ADR. In addition, shorter CWT has been associated with lower ADR, which can increase the risk of ICC.^\\[[@R6]\\]^ ICCs often arise in the RC.^\\[[@R7]\\]^ Therefore, improvement of ADR in the RC may decrease the incidence of the ICCs. One recent study published in Taiwan found that shorter withdrawal time in the ascending colon was associated with the development"
-"Published: April 21, 2020\n\nIntroduction {#sec1}\n============\n\nA series of recent discoveries has uncovered how cells of the innate immune system such as monocytes and macrophages undergo functional reprogramming to mount a de facto immune memory of an infectious or inflammatory injury by a process called trained immunity, which facilitates augmented responses to subsequent pathogenic encounters ([@bib30]). In the context of infections or vaccination, trained immunity provides beneficial heterologous effects by the enhanced cytokine response to stimulation with non-related pathogens. Prototypical stimuli of trained immunity include the fungal cell wall component \u03b2-glucan ([@bib35]) and the bacillus Calmette-Gu\u00e9rin (BCG) vaccine ([@bib26]). Recent attention has also turned to endogenous drivers of inflammation as inducers of trained immunity ([@bib5], [@bib41]). These stimuli shape innate immunological memories by reprogramming metabolic and transcriptional profiles ([@bib3], [@bib8]).\n\nPosttranslational methylation of proteins conveys information to cellular pathways, including those that regulate gene expression. *In\u00a0vitro* experiments with pan-methyltransferase inhibitors revealed the pivotal importance of this chemical modification for trained macrophages ([@bib8], [@bib35]). Changes in histone lysine methyl modifications (H3 histones monomethylated \\[H3K4me1\\] or trimethylated \\[H3K4me3\\] at lysine 4) underlie \u03b2-glucan-induced trained immunity ([@bib32]). Signaling factors derived from local tissue environments play key roles in determining macrophage fate,"
-"1. Introduction {#s0005}\n===============\n\nThere are various molecular markers distinguishing animals from plants, fungi, protists and bacteria. Amongst these are glycan modifications of peptides and proteins which appear to be rather restricted to the Metazoan lineage---such as proteoglycans based on *O-*linked xylose (Xyl) linked to serine or mucins based on *O-*linked *N-*acetylgalactosamine (GalNAc) linked to serine or threonine. These types of animal-specific glycosylation are also strongly evolutionarily conserved throughout the animal kingdom, indicating a specific and fundamental role in animal development and physiology. Indeed, gel-forming mucins emerged early during metazoal evolution and are found, e.g., in the cnidaria ([@bb0245]). The modification of proteins by GalNAc residues is initiated by the action of a family of *N*-acetylgalactosaminyltransferases (ppGalNAc-T, ppGaNTase or GalNAc-T enzymes encoded by *GALNT* genes in vertebrates; EC 2.4.1.41). Recent data from model organisms such as *Drosophila melanogaster* and *Xenopus laevis*, as well as the discovery of the basis of familial tumoral calcinosis, have indicated that the modification of proteins by *N-*acetylgalactosamine to form 'mucin-type' O-linked oligosaccharides is required for normal animal development. For instance, lethal mutations are associated with two *D. melanogaster N*-acetylgalactosaminyltransferase genes (*pGaNT35A* and *pGaNT5*) ([@bb0075; @bb0085]), whereas the association of mutations in the human *GALNT3* gene"
-"***Background.***\u2003Nosocomial outbreaks of *Klebsiella pneumoniae* carbapenemase-producing Enterobacteriaceae (KPC) are being reported increasingly. The first recognition of KPC in metropolitan Chicago was in 2007. Prevalence rose rapidly thereafter, especially in long-term acute care hospitals (LTACHs). Using mathematical models we studied the spread of KPCs in LTACHs, determined the transmission capacity of KPC, and investigated the effect of cohorting.\n\n***Methods.***\u2003Data on room occupancy, admission cultures, and every-other-week point prevalence cultures were available from four LTACHs in the Chicago region from June 2012 until June 2013. Three different cohort strategies were adopted at the LTACHs: a pure cohort (all KPC-positive patients on one floor), single rooms for KPC-positive patients, and a mixed cohort (all KPC-positive patients on one floor, supplemented with KPC-negative patients). A data-augmented Markov chain Monte Carlo method with Metropolis-Hastings algorithm was developed to model the transmission process in the LTACHs and to study the effect of different cohort strategies. The transmission process was described by the background transmission rate *\u03b1* (including transmissions independent of the colonization pressure, such as endogenous selection) and the patient-dependent transmission rate *\u03b2* (including transmissions dependent on the colonization pressure: *\u03b2* \\* ward prevalence).\n\n***Results.***\u2003The average point prevalence of KPC among patients as"
-"Third-party data from ecoClimate was used for this study and are accessible at: <http://ecoclimate.org/downloads/>. Those interested would be able to access the data in the same manner as the authors. The authors had no special access privileges to this data.\n\nIntroduction {#sec001}\n============\n\nAn accurate knowledge of species geographic distributions is critical to preserve biodiversity in a changing world. Despite the increasing availability of digitized information on biodiversity data and species occurrence, our knowledge about the geographic distribution of most species is regretfully incomplete \\[[@pone.0205164.ref001]--[@pone.0205164.ref003]\\]. This shortcoming, called the Wallacean shortfall, is more evident in highly diverse tropical ecosystems \\[[@pone.0205164.ref004]--[@pone.0205164.ref006]\\], which are paradoxically the most threatened ecosystems \\[[@pone.0205164.ref007],[@pone.0205164.ref008]\\]. Moreover, the lack of data on species distribution is frequently biased toward small, inconspicuous, and not easily detectable species \\[[@pone.0205164.ref001],[@pone.0205164.ref009]\\]. Even with the wide use of methodological tools to predict species ranges, large gaps still exist for these species, particularly because the primary data used in predictive models are scarce or incomplete, precluding a clear understanding of the threats from climate change and assessments of their conservation status.\n\nOngoing climate changes have already impacted organisms' distributions around the world in recent years \\[[@pone.0205164.ref010]--[@pone.0205164.ref013]\\]. Snakes are especially sensitive to climate changes \\[[@pone.0205164.ref014]--[@pone.0205164.ref016]\\] because"
-"Introduction {#s1}\n============\n\nHealth systems in low and middle-income countries (LMIC) like India struggle to provide quality clinical services to rural populations. An important constraint facing these countries is the scarcity of physicians in rural areas. In India, for example, almost 60% of health workers reside in urban areas even though 74% of the country's population is rural [@pone.0082984-Rao1]. This rural scarcity is particularly stark when compared to the urban availability of clinical care providers. In rural (urban) India there are 1.2(11.3) physicians and 0.7(4.3) nurses and midwifes per 10,000 population [@pone.0082984-Rao1].\n\nEfforts to reduce the scarcity of rural clinicians in LMICs have broadly focused on three strategies. One is to make rural service compulsory; however, this has generally been unpopular and unsuccessful [@pone.0082984-Kalantri1]. A second strategy is to make rural service more attractive by offering monetary and non-monetary incentives. Several studies have shown that job choices are driven by salary, as well as, non-monetary job characteristics such as living conditions, educational opportunities for children, opportunities for training, and future career prospects [@pone.0082984-Blaauw1]--[@pone.0082984-Vujicic1]. A third strategy of task shifting involves deploying non-physician clinicians (e.g. nurse-practitioner or medial assistant) to perform many of the functions of a doctor [@pone.0082984-Fulton1]. Studies have"
-"Introduction\n============\n\nIndividuals differ widely in their ability to accurately perceive, understand, and reason about emotional information, and to effectively apply that knowledge to enhance cognitive and behavioral performance---a capacity known as emotional intelligence (EI) ([@nsx088-B73]). People who possess high EI are skilled at reasoning about emotional issues and are effective at using emotional information to solve problems and achieve goals ([@nsx088-B58]). Because EI capacities are often highly predictive of important aspects of social/interpersonal functioning and professional success ([@nsx088-B14]; [@nsx088-B15]; [@nsx088-B22]; [@nsx088-B87]; [@nsx088-B52]; [@nsx088-B65]), it is of critical importance to understand the neurobiological underpinnings of these capacities and the extent to which they can be improved through training. The goal of the present study is to address the existing knowledge gap regarding the neurocircuitry that underlies EI.\n\nSince EI was first proposed in the early 1990s ([@nsx088-B57]; [@nsx088-B73]), two different approaches to conceptualizing and assessing this construct have emerged---the \"trait\" and the \"ability\" models ([@nsx088-B94]). The *Trait* model considers EI as a set of emotional self-perceptions and dispositions that are best assessed via introspection and self-report, similar to personality traits ([@nsx088-B69]; [@nsx088-B77]), while the *Ability* model considers EI as a set of cognitive capacities that permit an individual to accurately"
-"Introduction\n============\n\nMolecular scatology, the use of fecal samples for genetic analyses, is increasingly being used in ecological and conservation studies of wild animals. Traditionally, scat was used for documenting the abundance and distribution of focal species, or for studying diet based on bone fragments and other prey hard parts ([@ref-22]). [@ref-18] was among the first to recognize the value of scat as a source of DNA. Since then, scat-derived DNA has been applied to study various animals, including brown bears (*Ursus arctos*; [@ref-25]), chimpanzees (*Pan troglodytes verus*; [@ref-14]), seals (*Halichoerus grypus* and *Phoca vitulina*; [@ref-21]), and gray wolves (*Canis lupus*; [@ref-24]). Scat samples are one means of obtaining DNA for threatened or endangered species when capture or handling is undesirable ([@ref-24]). Data from noninvasive DNA sampling can provide important insights on sex ratios, population size, demography, mating and breeding system, population structure, gene flow, diet and disease ([@ref-8]), and can help address important questions in conservation.\n\nMany important questions in conservation genetics are investigated using next generation sequencing (NGS). To reliably use fecal samples for NGS libraries, we first must have a method to quantify the amount of target DNA. Fecal samples contain DNA from both the focal species"
-"1. Introduction {#sec1-sensors-19-01971}\n===============\n\nLocalization of a source is a technique in which a source is located by detecting propagated signals received in several sensors and the analysis of them \\[[@B1-sensors-19-01971]\\]. There are many localization techniques proposed for wireless sensor networks \\[[@B2-sensors-19-01971],[@B3-sensors-19-01971]\\]. However, in this article, a three-dimensional localization to solve the estimation of an acoustic source in a homogeneous medium is introduced. The use of acoustic sensors to locate sound sources in such practical systems is of great interest but needs further development and improved performance systems. This research has significant potential for many applications in medicine, physics, engineering, and underwater acoustics. The method to locate the tumor tissue is based on a computed tomography scan to find the area that will then be radiated by heavy particles in the Bragg peak region \\[[@B4-sensors-19-01971]\\]. However, uncertainties in the patient positioning and/or in the anatomical parameters can increase the uncertainty during the radiotherapy. In these cases, acoustic source localization in medical applications has gained a lot of interest in recent years, which ought to be the necessity for improving the monitoring of tumor tissue in hadrontherapy treatments. Linear sensors can be employed for acoustic source localization in a noise environment"
-"REFER TO THE PAGE 30-36\n\nThere are a number of systemic diseases with cardiovascular manifestations in which echocardiography plays a valuable role for surveillance and follow-up of anticipated cardiovascular abnormalities. Systemic autoimmune disorders are frequently associated to cardiac involvement such as pericarditis, myocarditis, valvular abnormalities or ischemic coronary disease.\n\nAnkylosing spondylitis (AS) is also a chronic systemic inflammatory rheumatic disorder that primarily affects the axial joints and mainly involves young male. Extra-articular manifestations vary widely in terms of both frequency and severity. The most common extra-articular manifestations are uveitis, bowel disease, skin, lung and kidney involvement; less frequently cardiovascular involvement occurs.[@B1] Screening for extra-articular manifestations in patients with AS is important for appropriate management as the presence of extra-articular manifestations may be a consequence of uncontrolled systemic inflammation and may influence treatment decisions.[@B2] The prevalence of cardiac pathologies in patients with AS has been reported to be 10% to 30%.[@B3] It is related to a sclerosing inflammatory process that primarily involves the aortic root and the aortic valve, and the chronic inflammation may extend into the ventricular septum, atrioventricular node, proximal bundle of His and bundle branches or fascicles. Thus, various studies indicate a higher rate of conduction disturbances, valvular"
-"Immune-mediated diseases along with lesions in oral cavity. Immunology is defined as the study of the molecular cells, organs and system for the recognition and disposal of foreign materials.\\[[@ref1]\\] Factor responsible for differences in immunity are age, nutrition and genetic factors. Clinical appearance may not lead to a final diagnosis, but can be achieved by a biopsy of 4 mm in diameter at the perimeter.\\[[@ref2]\\]\n\nClassification {#sec1-1}\n==============\n\nHypersensitive reactionPemphigus vulgarisParaneoplastic pemphigusCicatricial or mucocutaneouspemphigoidCutaneous, bullous pemphigoidLinearIgAEpidermolysisbullosaLichenplanusErythemamultiformeSystemic drug reactionLupus erythematosusSclerodermaCrest syndromeBechets syndromeReiter\\'s syndrome.\\[[@ref3]\\]\n\nHypersensitve Reaction {#sec1-2}\n======================\n\nMucosal surfaces are exposed to many dietary proteins and infectious agents, the immune system normally will not react to these antigens. Unresponsiveness or tolerance to these antigens are maintained by three principle mechanism namely energy or functional unresponsiveness; apoptosis; and immune suppression by regulatory T-cells.\\[[@ref4]\\]\n\nAnaphylaxis is the most serious hypersensitive reaction, which commences immediately after the exposure to allergens. The clinical presentation may be redness or whiteness of mucosa, swelling of lips, tongue, cheek or ulcers and blisters.\n\nLichen planus {#sec2-1}\n-------------\n\nLichen planus is believed to result from an abnormal T-cell mediated immune response in which basal epithelial cells are recognized as foreign because of changes in the antigenicity of cell surface.\\[[@ref5]\\]"
-"Introduction\n============\n\nAbsence of melatonin or its inefficient production affects people who work on night shift, undergo changes in time zone, and suffer from insomnia[@B16]. In addition, melatonin interferes with bone healing in several ways: through modulation of inflammatory process, collagen fibril formation, osteoblast differentiation, and oxidative stress[@B6] ^,^ [@B9] ^,^ [@B10] ^,^ [@B15] ^,^ [@B26] ^,^ [@B28].\n\nA lower production of melatonin, either by genetic modifications or pinealectomy, results in alterations in morphology and bone metabolism[@B8] ^,^ [@B30]. The literature describes that its action is related to differentiation and increase in osteoblastic activity, as well as osteoprotegerin increase, thus decreasing the action of osteoclasts[@B18] ^,^ [@B29]. In addition, it can promote bone cell proliferation and increase in production of type I collagen[@B21], thus increasing bone mass[@B19]. In this context, the absence of melatonin has been shown to delay alveolar repair after exodontia[@B9] ^,^ [@B17]. Melatonin replacement could regulate this alteration, which would emphasize the role of this neurohormone in biological responses that drive bone metabolism, especially in conditions in which a decrease occurs in the circadian release capacity of this hormone by the pineal gland[@B15].\n\nWith the popularization of dental implants, the understanding of structural characteristics and the reversion"
-"A 60-year-old woman presented with the complaints of recurrent swelling on her upper back \\[[Figure 1](#F1){ref-type=\"fig\"}\\]. It was present since her childhood and was small, painless, and did not change in size. Two years back, due to trauma, the swelling started increasing in size, with the complaint of pain and also bloody discharge. The patient then got it excised one-and-a-half years back. On histopathologic examination, the diagnosis of dermatofibrosarcoma protuberans (DFSP) was made. Six months later the swelling recurred and gradually increased in size. This time a wide local excision was performed. Grossly, the specimen received was a skin covered soft tissue piece measuring 6.5 \u00d7 6.0 \u00d7 1.0 cm. On cutting, it revealed a well-circumscribed grayish white mass in the subepidermal tissue measuring 3.5 \u00d7 2.0 \u00d7 1.0 cm \\[[Figure 2](#F2){ref-type=\"fig\"}\\]. Microscopically, a section covered by stratified squamous epithelium with uninvolved zone of dermis was seen. The underlying tissue showed a well-demarcated tumor composed of uniform population of slender fibroblasts arranged in a storiform pattern. The cells showed mild nuclear pleomorphism and rare mitosis. The tumor was seen infiltrating subcutaneous fat \\[[Figure 3](#F3){ref-type=\"fig\"}\\]. Furthermore, immunohistochemical analysis revealed tumor cells positive for CD34. And hence, the diagnosis of DFSP was"
-"I[NTRODUCTION]{.smallcaps} {#sec1-1}\n==========================\n\nThe greatest challenge in managing dental caries process is to sort how the contributing factors interact in a way that translates into effective strategies for disease diagnosis, prevention, and therapy. The focus of the management of dental caries has shifted from intervention to prevention in the past few decades. The aim of prevention is to diagnose the disease before any irreversible carious lesion has been established. However, because of the nature of this disease process, there can be no single \"preventive program\" to be superimposed uncritically on all populations.\\[[@ref1]\\] The important question remains how to control caries lesion as cost-effectively as possible. The severe \"old\" recommended preventive programs are no longer effective, not just because the caries incidence rate has changed but as the environment and changing trends among the population.\\[[@ref2][@ref3]\\]\n\nAmong various means for prevention of dental caries, fluoride has emerged among a plethora of elements as the redeeming messiah to the plague of dental caries. It has been postulated that the ability to conquer this indomitable disease lies within the folds of the widespread and judicious use of fluoride.\\[[@ref4]\\] In fact, the most developed countries have benefited from the use of fluoride.\\[[@ref5][@ref6]\\] Over the years,"
-"Introduction {#Sec1}\n============\n\nThe regulation of food intake is a critical mechanism with major physiological impacts. On the one hand, the rate of food intake determines the rate of growth, and anomalous feeding behaviours are associated with an assortment of chronic diseases such as obesity, type 2 diabetes, cardiovascular diseases and some cancers^[@CR1]--[@CR3]^. On the other hand, dietary restriction has implications and beneficial effects on health and longevity^[@CR4]--[@CR6]^. Hence the growing interest and the increasing efforts to understand the processes and mechanisms that control feeding actions and its anomalies.\n\nDespite their evolutionary distance, metabolism and central signalling pathways are highly conserved between mammals and *Caenorhabditis elegans*, and the regulation of feeding is not an exception^[@CR7]^. Human and *C. elegans* genomes show a relevant orthology degree^[@CR8]^. At least 50% of *C. elegans* genes have a human ortholog, and approximately 70% of genes related with human diseases have homologs in *C. elegans*^[@CR9]^. Therefore*, C. elegans* has emerged as a powerful model to study food-related behaviours, shedding light in the underlying factors and mechanisms involved in the genetic regulation of feeding^[@CR10]--[@CR15]^.\n\n*C. elegans* feeding occurs as a consequence of two motions: the cyclic contraction of the pharynx (pumping) and the isthmus peristalsis, being"
-"Background\n==========\n\nThree main issues have been identified in addressing the problem of health care providers and their approach to people with disabilities: lack of disability-specific knowledge; discomfort with working with people with disabilities; and attitudes and misperceptions about disability. People with disabilities have cited negative attitudes and behaviors of health care providers as the most formidable barriers to accessing health care services\\[[@B1]-[@B5]\\].\n\nNegative attitudes held by health care providers about patients with disabilities may affect care that the patient receives. Although these attitudes and misconceptions are usually not overtly hostile, they may result in patients with disabilities not receiving appropriate treatment or not receiving indicated preventive care\\[[@B2],[@B6]-[@B8]\\]. For example, physicians might defer a pelvic exam in a patient with a disability due to the misconception that these patients are generally not sexually active. The assumption that a patient with a disability has a baseline quality of life which is low may lead the physician to defer aggressive treatment of acute problems\\[[@B3],[@B9]\\]. Adverse outcomes may be compounded and services available to patients may be limited if these subtle attitudes unduly affect the physician\\'s judgment and actions. \\[[@B5]\\]\n\nUntil recently, disability has not been appropriately addressed in medical school curricula \\[[@B2],[@B6],[@B10]-[@B14]\\]."
-"INTRODUCTION {#sec1-1}\n============\n\nSince many years, oral route is most preferable amongst all routes for drug administration.\\[[@ref1]\\] In a recent era near everyone prefers to use sustained release (SR) mode of drug administration as a substitute to conventional dosage form because it has guaranteed features that eventually affects enormity of the pharmacologic response. It reduces ratio between peak and trough which properly maintains the therapeutic level of drug concentration, reduces the dosing frequency and enhance patient\\'s compliance.\\[[@ref2][@ref3]\\]\n\nDiclofenac sodium (2-(2,6-dichloranilino)phenylacetic acid) is a nonsteroidal anti-inflammatory drug usually administered to manage a variety of anti-inflammatory disorders such as rheumatoid arthritis, polymyositis, osteoarthritis, and spondylarthritis and so on.\\[[@ref4][@ref5]\\] SR tablets of diclofenac sodium using natural gums such as Xanthan gum, Guar gum, and synthetic polymers have previously been reported.\\[[@ref6][@ref7][@ref8]\\]\n\nAlthough the synthetic polymers such as ethyl cellulose\\[[@ref9]\\] and hydroxy propyl methyl cellulose (HPMC)\\[[@ref10]\\] are widely used to formulate SR preparations, at the present researchers are aiming to implement the use of natural polymers to design and develop the sustain release drug delivery system. Literature reveals that previous work has been conducted on sustainable formulations using natural polymers like Guar gum,\\[[@ref11]\\] Karaya gum,\\[[@ref12]\\] Chitosan,\\[[@ref13]\\] and Xanthan gum.\\[[@ref14][@ref15]\\] Natural polymers are widely used because"
-"Introduction {#Sec1}\n============\n\nDespite progress in malaria control over the last two decades, *Plasmodium* parasites continue to cause more than 200 million cases every year^[@CR1]^. After their inoculation into the skin by infected *Anopheles* mosquitoes, *Plasmodium* sporozoites rapidly migrate through tissues and blood vessels to reach the liver, using active gliding motility and cell traversal activity. Once in the liver, they first traverse hepatocytes before invading them and developing into exo-erythrocytic forms (EEFs), surrounded by a parasitophorous vacuole (PV) membrane. Inside the PV, they differentiate into thousands of merozoites, which are eventually packed in merosomes and released into the blood circulation, where they invade red blood cells, provoking the symptomatic phase of the disease.\n\nSeveral host and parasite factors implicated in sporozoite invasion have been identified but the underlying molecular interactions remain unknown. Human and murine parasites share similar invasion routes, with two distinct invasion pathways that depend on the tetraspanin CD81 or the scavenger receptor class B type 1 (SR-B1)^[@CR2]--[@CR5]^. The human parasite *P. falciparum* and the murine parasite *P. yoelii* both require CD81^[@CR3]^, whereas *P. vivax* enters human hepatocytes using SR-B1^[@CR4]^*.* Interestingly, the murine parasite *P. berghei* can invade cells in vitro using either CD81 or, alternatively, a"
-"Dear editor,\n\nA patient with sudden complete loss of vision is presented, which ultimately turned out to be caused by a pituitary adenoma coincidentally infected with MRSA.\n\nA 39-year-old male patient woke up with complete blindness of both eyes. History taking revealed slightly blurred vision for several weeks. Also, the patient suffered from a nose bleeding and nasal discharge for which he visited his general practitioner. No further action was taken at that time. On physical examination, we saw an acutely ill patient (body temperature, 39 \u00b0C) with complete blindness, but without any focal neurological deficit. Magnetic resonance imaging (MRI) showed a sellar mass with suprasellar expansion and compression of the optic chiasm (Fig.\u00a0[1a](#Fig1){ref-type=\"fig\"}). Also, the right sphenoid sinus was filled with debris, possibly in continuity with the suprasellar region. Laboratory testing did not reveal any endocrine disturbances, while leukocyte and C-reactive protein count were slightly elevated. Fig.\u00a01**a** Preoperative T2-weighted coronal MR image showing a sellar mass with suprasellar expansion and severe compression of the chiasm. It has a somewhat dumbbell shape. **b** Postoperative T1-weighted contrast-enhanced, coronal MR image showing a contrast-enhancing sellar mass remnant, while the optic chiasm is adequately decompressed\n\nAn emergency left-sided pterional craniotomy was"
-"Introduction\n============\n\nTenosynovitis is defined as inflammation of a tendon and its synovial sheath. Pyogenic tenosynovitis is often caused by hematogenous spread of infection or by trauma with direct inoculation of a tendon. A high-pressure environment may develop, due to increased purulence contained within the tendon sheath, which impedes vascular flow to the tendon leading to ischemia and necrosis \\[[@B1], [@B2]\\]. Symptoms and clinical examination findings associated with pyogenic tenosynovitis may be confused with superficial soft tissue infections as both include pain over the affected digit or tendon sheath region, tenderness with movement of associated musculoskeletal anatomy, and soft tissue fullness or swelling \\[[@B3]\\].\n\nThese symptoms commonly are present in superficial infections such as cellulitis, felons, and traumatic injuries; however, management plans vary significantly. In patients with pyogenic tenosynovitis, operative intervention provides surgeons visual confirmation of the disease process and the subsequent irrigation and debridement offers definitive therapy \\[[@B4]\\]. Point of care ultrasound (US) has become ubiquitous within emergency departments (ED), and most ED's have a dedicated ultrasound machine available at all times. Ultrasound imaging for soft tissue infections was shown to improve diagnostic accuracy and alter management plans \\[[@B5], [@B6]\\] and can be utilized for tendon injury and fluid"
-"Introduction\n============\n\nMesenchymal stem cells (MSC), a distinct type of adult stem cell, are easy to isolate, culture, and manipulate in ex vivo culture \\[[@b1-cm-86-65]\\].\n\nRat mesenchymal stem cells (MSCs) represent a small portion of the cells in the stromal compartment of the bone marrow. MSCs are defined as a self-renewing population and have the potential to differentiate into several mesenchymal cell lineages (bone, cartilage, fat, new blood vessel and other tissues) and represent a promising source for therapeutic applications \\[[@b2-cm-86-65]\\]. MSCs can be isolated from the bone marrow and can be easily separated from the hematopoietic stem cells (HSCs) due to their plastic adherence \\[[@b3-cm-86-65]\\].\n\nCritical limb ischemia is recognized as the most severe stage of peripheral arterial disease, and is associated with a high risk of amputation, along with significant morbidity and mortality.\n\nMSCs therapy generates new blood vessels and promotes neovascularization and tissue repair. MSCs transplantation in tissues from critical limb ischemia model in rat can represent therapeutic applications of vascular regeneration.\n\nThus, designing, describing and validating these new therapies in an experimental model of critical limb ischemia is essential.\n\nAim\n===\n\nThe aim of this study was to isolate with a simple method the rat bone"
-"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\n============\n\nThe ANGPTLs (angiopoietin-like proteins) are a family of secreted proteins which share tertiary structural domains with angiopoietins \\[[@B1]\\], with N-terminal CCD (coiled coil domain) and C-terminal FLD (fibrinogen-like domain) of which the CCD is functionally associated with reduced plasma TAGs (triacylglycerols) \\[[@B2]\\]. *ANGPTL3* is almost exclusively expressed in the liver with minor expression found in kidney \\[[@B3],[@B4]\\]. ANGPTL3 has been shown to inhibit LPL (lipoprotein lipase) *in\u00a0vitro* and *in\u00a0vivo* \\[[@B5]--[@B7]\\], and mice lacking ANGPTL3 protein have increased LPL activity and reduced levels of plasma TAG \\[[@B8],[@B9]\\].\n\nGWAS (genome wide association studies) in humans have shown that SNPs (single nucleotide polymorphisms) at loci near *ANGPTL3* are associated with plasma TAG levels \\[[@B10]--[@B12]\\]. Sequencing of the coding region of *ANGPTL3* revealed additional loss-of-function mutations associated with low levels of plasma TAG \\[[@B4]\\]. Furthermore, Musunuru et al. \\[[@B13]\\] have identified E128X and S17X as two novel nonsense mutations in *ANGPTL3.* Loss of function in *ANGPTL3* results in a condition referred to as FHBL2 (familial combined hypolipidaemia, OMIM \\#605019), featuring reduction in all major plasma lipoproteins VLDL (very-low-density lipoprotein), LDL (low-density lipoprotein) and HDL (high-density lipoprotein). In addition to FHBL2 phenotype also plasma NEFAs (non-esterified fatty acids), insulin, fasting plasma"
-"Introduction {#Sec1}\n============\n\nRecent progress in the field of cell therapies^[@CR1],[@CR2]^ and the increasing understanding of the complex interplay between different cell populations^[@CR3]--[@CR5]^ have created a demand for novel *in vivo* methods to longitudinally study the fate of specific cell populations or even individual cells. Optical techniques such as confocal or two-photon microscopy are well established for cell tracking, but require invasive procedures such as installation of cranial windows or skin-fold chambers^[@CR6],[@CR7]^. This approach is therefore not suitable for all animal models, and has limited potential for clinical translation. Non-invasive cell tracking is possible by a number of different methods such as fluorescence or radionuclide imaging^[@CR8],[@CR9]^ and different Magnetic Resonance Imaging (MRI) approaches using T2\\*w MRI of iron nanoparticle (ION)-labelled cells, ^19^F-MRI, or highly shifted proton MRI^[@CR10]--[@CR12]^. All of these methods have unique advantages which, however, are accompanied by drawbacks such as limited tissue penetration, instability of the marker, low spatial resolution, high background signal or limited sensitivity. With regards to potential clinical translation, T2\\*w MRI using ION-labelled cells offers the advantages of unlimited tissue penetration, stability of the marker substance, high spatial resolution, and additional morphological information^[@CR13]--[@CR20]^. However, due to the long image acquisition times, MRI and other non-invasive"
-"INTRODUCTION {#s1}\n============\n\nBreast cancer is the most common cancer in women worldwide, and at least 50% of breast cancer occurrences and 62% of deaths occur in less-developed countries.^[@B1]^ This pattern is attributed to limited availability of screening, late presentation, and poor access to treatment, which includes surgery, chemotherapy, and radiation therapy. The availability of such treatments in sub-Saharan Africa is limited because of lack of skilled manpower, surgical equipment, and radiation facilities. According to a review in 2010 from the International Atomic Energy Agency, 29 of 52 countries in Africa have no radiation treatment facilities; more than half of the existing machines are located in southern and northern Africa.^[@B2]^ Pathology services, in general, are lower than the recommended standards required for adequate management decision making. Delays in reporting of test results invariably affect local control and survival outcomes. Multidisciplinary tumor boards are mandatory in most institutions worldwide, but the practicality of operating tumor boards in sub-Saharan Africa is limited by the lack of physicians with oncology skills and the existence of few tertiary institutions that can organize tumor boards on a consistent basis. Comparatively, however, better-performing economies located in the southern and northern parts of Africa have well-equipped centers"
-"Introduction {#sec1}\n============\n\nChanges in training load -- particularly in the frequency, duration, and intensity of training sessions -- are associated with the principle of training stimulus variability that seeks to optimize sports performance ([@ref16]). Training load monitoring can be categorized into two forms: external load and internal load ([@ref23]). External load is understood as the physical repercussions of training performed by an athlete, encompassing indicators such as distance, duration, and race intensity ([@ref21]). Internal load is associated with the biological response of the athlete to the external load imposed by training ([@ref5]).\n\nIn the training's prescription, it is essential that the external and internal loads be appropriate and that there is a balance between them, allowing for improvements in the performance of the athlete and for the reduction of overload or underload ([@ref2]). The correct planning of the training load through microcycles allows an approximation of the training regarding the requirements of races ([@ref26]), causing fundamental specific adaptations in the athlete ([@ref25]).\n\nThe monitoring of training loads requires an accurate and reliable evaluation of the determinants of the training process ([@ref28]). However, the use of different methods and/or techniques is dependent on the context, namely considering the applicability and"
-"Introduction\n============\n\nYucca Mountain, NV, is the designated site for a permanent geologic repository for high-level nuclear waste in the USA. The current waste package design consists of a double-walled container with an inner barrier of stainless steel, an outer barrier of highly corrosion resistant nickel--chromium--molybdenum alloy, and a titanium alloy drip-shield that covers the containers. Corrosion resistance and long-term integrity of the metal containers and shields are important for the safe disposal of the waste. Characterization of the compositional evolution of waters that affect waste package corrosion is necessary. If the site is licensed, the waste packages will be placed in tunnels several hundred meters below the ground surface and above the groundwater table in partially saturated volcanic tuff. Once the waste packages are in place, the repository will heat up due to the thermal energy of the nuclear waste. Although the waste packages will be above the groundwater table, pore water present in rock formations within (Topopah Spring Tuff) and above (Paintbrush Tuff) the repository may come into contact with the metal containers and shields. Additionally, brines may form from the deliquescence of salts found in dusts deposited on the containers.\\[[@B1]\\] In this study we focus on seepage"
-"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"
-"Introduction\n============\n\nSelf-assembled monolayers (SAMs) have raised considerable interest in the past decades because of their potential applications in various areas such as biomaterials, tissue engineering, biosensors and electronics \\[[@R1]--[@R3]\\]. The seminal work of Nuzzo and Allara on the adsorption of disulfides on gold surface has triggered numerous research activities in the preparation and applications of sulfur-based SAMs on Au surfaces \\[[@R4]\\]. Important contributions have been notably driven by the implementation of reactive end groups in the monolayers enabling the chemical functionalization of solid surfaces \\[[@R3],[@R5]--[@R7]\\]. Within this context, noncovalent and covalent strategies have been investigated for the immobilization of a target molecule through a reaction with the terminal groups of the SAMs. The most common methods to covalently functionalize these materials involve the Huisgen cycloaddition between an azide and an alkyne \\[[@R8]--[@R9]\\], Thiol-Michael addition \\[[@R10]--[@R11]\\], amide formation \\[[@R12]--[@R14]\\], Diels--Alder reaction \\[[@R15]--[@R16]\\] or the imine/oxime condensation \\[[@R17]--[@R18]\\]. These reactions tend to produce strong covalent interactions between the surface and the molecules in solution which ensure a stable immobilization. One limitation of the covalent strategy lies in the irreversible permanent functionalization of the SAMs which precludes reusable properties. A reversible strategy could find applications in a wide range of fields such"
-"Introduction\n============\n\nThe novel coronavirus, 2019-nCoV, emerged in Wuhan, China in December 2019 and has rapidly spread across the world ([@ref-12]; [@ref-35]). In February 2020, the World Health Organization (WHO) renamed this epidemic disease coronavirus disease (COVID-19) as it is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The number of COVID-19 cases has rapidly increased worldwide ([@ref-30]; [@ref-8]). As of 29 February 2020, there were 85,403 confirmed COVID-19 cases and 2,924 fatalities across 49 countries ([@ref-30]; [@ref-10]). Although the emerging threat of COVID-19 has drawn global attention, the optimal strategies to reduce the spread of disease remain largely undetermined ([@ref-7]).\n\nSeveral studies have investigated the virology, transmission, risk factors and protection associated with COVID-19 ([@ref-4]; [@ref-13]; [@ref-14]; [@ref-28]; [@ref-31]; [@ref-33]). COVID-19 spreads by human-to-human transmission, primarily through respiratory droplets and direct contact with groups of infected family members, friends, colleagues, or medical health workers. However, even asymptomatic patients can be a source of infection. COVID-19 has dramatically higher rates of transmission compared to SARS and Middle East respiratory syndrome, but an observed lower fatality rate. The median age of COVID-19 patients ranged from 47 to 56 years old; approximately 65% of patients were male and 35% were female."
-"The views expressed in this Perspective do not necessarily reflect the views of the journal or of ASM.\n\nINTRODUCTION {#h0.0}\n============\n\nZoonotic influenza viruses circulating in poultry and swine pose an ever present threat to human health. In particular, the rapid geographical expansion of highly pathogenic avian influenza (HPAI) A(H5N1) throughout Asia and then into Europe, the Middle East, and Africa during the 2000s galvanized the global community in an attempt to control this rapidly growing threat. Despite successful control efforts in some countries, the virus remains endemic in poultry in at least six countries and continues to cause human illness and deaths as well as countless outbreaks in birds. During the past decade, 668 cases and 393 deaths were detected and reported to the World Health Organization (WHO) ([@B1]). During the 17\u00a0years since human infections with HPAI A(H5N1) were first identified in Hong Kong, Special Administrative Region, People's Republic of China, in 1997, these viruses have evolved substantially through mutation and reassortment, resulting in multiple divergent genotypes and clades ([@B2]).\n\nOngoing H5N1 circulation has appropriately resulted in a focus on sequencing viral genomes to understand the evolution of these viruses and the significance of observed genetic changes. Expanded"
-"Introduction {#s1}\n============\n\nProteases represent one of the largest and most important protein families known, and their importance in processes that govern the life and death of a cell cannot be overestimated. The last decades, it has become evident that proteolysis of bioactive molecules plays an essential role in the regulation of many biological processes, such as signal transduction, RNA-transcription, apoptosis, and development [@pone.0016136-LpezOtn1], [@pone.0016136-Doucet1]. In addition, proteases are widely used as virulence factors by many infectious microorganisms, viruses and parasites [@pone.0016136-Duesbery1]. Consequently, proteases and their substrates are therefore of great interest as potential drug targets. In fact, in humans, proteases represent 5--10% of all drug targets [@pone.0016136-Overall1], [@pone.0016136-Turk1].\n\nThe function of proteases is regulated either by controlling the spatial and temporal activity or through their ability to discriminate among potential substrates, of which the last is probably the most important mechanism. Accordingly, efficient methods for characterization of proteases and their associated substrates could enhance our understanding of biological systems, which ultimately may result in new therapeutic strategies.\n\nWhile various biological and chemically based approaches have been developed to study protease substrate specificity and activity [@pone.0016136-Marnett1], [@pone.0016136-Overall2] they do have their limitations. Many suffer from being insensitive, time consuming, labor"
-"Introduction {#Sec1}\n============\n\nChromaffin cells are neuroendocrine cells that synthesize and secrete catecholamines in response to sympathetic nervous system stimulation and therefore participate in regulation of stress-modified parameters such as heart rate and blood pressure. A variety of additional agents are costored and released along with the catecholamines from the chromaffin granules, including neuropeptides such as the enkephalins and adenosine triphosphate (ATP) \\[[@CR1]\\]. In addition to being released into the circulation, these agents may regulate chromaffin cell activity in an autocrine or a paracrine manner, allowing the cells to adjust to varying levels of stimulation.\n\nThe role of ATP in chromaffin cell function has not been well defined, even though it is secreted in high concentrations from chromaffin cells \\[[@CR1]\\]. It has been suggested that ATP regulates chromaffin cell secretion, either positively \\[[@CR2]\\] or negatively \\[[@CR3], [@CR4]\\], and that ATP regulates the function of voltage-dependent calcium channels \\[[@CR5]\\]. ATP exerts its effects through either G-protein-coupled receptors, designated P2Y; or ion channels, designated P2X. These receptor types are further divided into subtypes, including P2Y~1~, P2Y~2~, P2Y~4~, P2Y~6~, and P2Y~11--14~ for the G-protein-coupled P2Y receptors and P2X~1--7~ for those that activate ion channels \\[[@CR6]\\]. Previous work with chromaffin cells indicated ATP stimulation"
-"Background {#Sec1}\n==========\n\nA robust clinical training experience is essential in producing physicians capable of delivering high quality health care. Effective clinical teachers have been described in previous studies as clinically knowledgeable, compassionate, having strong integrity and possessing solid teaching skills. Additionally, effective teachers actively involve their students in patient care and provide constructive feedback and guidance \\[[@CR1]\\].\n\nReview studies have found that over 32 different instruments have been developed to assess clinical teachers \\[[@CR2]\\]. A small number of these instruments assesses only student performance \\[[@CR3]\\]. Some of those instruments are not validated, while some studies argue that instruments must be validated against the specific context they are being applied to \\[[@CR4]\\].\n\nSuch questionnaires are essential for the continuous development of medical students' education and for the ongoing improvement of clinical teaching skills. Because students at different stages of their educational careers may be looking for different attributes in a clinical teacher \\[[@CR5], [@CR6]\\], these instruments should be administered to a wide variety of samples at different points in the learning process. This will support the criterion validity of the instrument. It has been suggested that for an instrument to be used by specific groups or in different cultural and"
-"The filtering properties of synapses are modulated by a form of short term depression arising from the depletion of neurotransmitter vesicles. The uptake and release of these vesicles is stochastic in nature, but a widely used model of synaptic depression does not take this stochasticity into account. While this model of synaptic depression accurately captures the trial-averaged synaptic response to a presynaptic spike train \\[[@B1]\\], it fails to capture variability introduced by stochastic vesicle dynamics \\[[@B2]\\]. Our goal is to understand the impact of stochastic vesicle dynamics on filtering and information transfer in depressing synapses.\n\nWe derive compact, closed-form expressions for the synaptic filter induced by short term synaptic depression when stochastic vesicle dynamics are taken into account and when they are not. We find that stochasticity in vesicle uptake and release fundamentally alters the way in which a synapse filters presynaptic information. Predictably, the variability introduced by this stochasticity reduces the rate at which information is transmitted through a synapse. Additionally, this variability introduces frequency-dependence to the transfer of information through a synapse: a model that ignores synaptic variability transmits slowly varying signals with the same fidelity as faster varying signals \\[[@B3],[@B4]\\], but a model that takes this variability"
-"Background\n==========\n\nGuillain-Barre syndrome is an autoimmune disorder of peripheral nervous system causing progressive weakness and areflexia. Since the marked decline in poliomyelitis incidence, the syndrome is now the most common cause of acute flaccid paralysis in many countries \\[[@B1]\\]. Epidemiologic studies have reported an annual incidence of 0.16--4 (mostly between 1--2) cases per 100 000 population from different countries \\[[@B2]-[@B10]\\]. Although the disease is considered to be sporadic without significant variation over time, some studies have shown annual and seasonal trends \\[[@B5]-[@B8],[@B11]-[@B13]\\].\n\nThe aim of this study was to investigate the incidence, annual time trend and some epidemiological and clinical features of Guillain-Barre syndrome in children in the north west of Iran.\n\nMethods\n=======\n\nEast Azerbaijan is located in the northwest of Iran, a cold climate zone. It has a total area of 47 821 km^2^. According to the official census data, the total population of children 0--15 years was estimated 6465267 over the study period.\n\nIn this population-based cross sectional research, medical history and clinical features of 143 cases with Guillain-Barre syndrome between 2001 and 2006 were studied. The setting of the study was Tabriz Children Medical Centre, is the largest children medical center in the north-west area"
-"Chemical context \u00a0 {#sec1}\n==================\n\nChalcone (systematic name 1,3-diphenyl-2-propene-1-one) is an aromatic ketone that represents the central core for various derivatives with inter\u00adesting properties, known as chalcones (Kostanecki & Tambor, 1899[@bb23]). For example, chalcones are found in fruits, vegetables, spices, tea or soy, and find applications as pharmaceuticals (Di Carlo *et al.*, 1999[@bb5]). Chalcones are also major inter\u00admediates in the synthesis of natural products and are widely used in synthetic and pharmaceutical chemistry (Dhar, 1981[@bb4]; Ansari *et al.*, 2005[@bb1]) because they have anti\u00adtumor (Modzelewska *et al.*, 2006[@bb14]), anti\u00adfungal (L\u00f3pez *et al.*, 2001[@bb11]), anti-inflammatory (Lee *et al.*, 2006[@bb9]), anti-bacterial (Batovska *et al.*, 2009[@bb3]) or anti\u00adtubercular properties (Lin *et al.*, 2002[@bb10]). In general, chalcones consist of two aromatic rings that are linked by a three-carbon \u03b1,\u03b2-unsaturated carbonyl system, leading to a completely delocalized \u03c0-electron system. Recently, chalcones have also been used in the field of materials science as non-linear optical devices (Raghavendra *et al.*, 2017[@bb15]). As part of our studies in this area, we report herein the synthesis, crystal structure and Hirshfeld surface analysis of a new chalcone.\n\nStructural commentary \u00a0 {#sec2}\n=======================\n\nIn the title mol\u00adecule (Fig.\u00a01[\u25b8](#fig1){ref-type=\"fig\"}), the cyclo\u00adhexa\u00adnone ring (C1/C2,C7/C8,C9/C10) has an envelope conformation with the flap atom C9 deviating by"
-"1. Introduction {#sec0005}\n===============\n\nLumbar-peritoneal (LP) and ventriculo-peritoneal (VP) shunt placement is the treatment of choice for diversion of cerebrospinal fluid (CSF) from the subarachnoid space into the peritoneal cavity. In conditions where there is obstruction of CSF absorption or elevated CSF pressure such as hydrocephalus, LP works as an alternative route for removal of excess cerebrospinal fluid. However this invasive procedure has been associated with several complications, most commonly infection and obstruction. Perforation of the bowel is an extremely rare complication occurring in less than 0.1% of cases. Although infrequent, this delayed complication can be fatal if it goes unrecognized. We report a case of a 72 old female patient with LP shunt for raised intracranial pressure, who presented with LP shunt catheter protruding from anus. This was due to bowel perforation in the recto-sigmoid junction by the distal tip of lumbar-peritoneal shunt. She was surgically treated with removal of the distal part of the shunt, external drainage of the proximal part and primary closure of the perforation. The case report has been the work has been reported in line with the SCARE criteria. \\[[@bib0080]\\] Clinical suspicion of abdominal complications by the LP should be raised when patient with"
-"INTRODUCTION {#sec1}\n============\n\nSmall bowel obstruction (SBO) in pregnancy is a high risk situation for both mother and baby with maternal mortality ranging from 2 to 4% and fetal/neonatal loss from 13 to 17%. Preterm delivery occurs in \\~45% of the cases. Adhesions were the most common pathology in 30--50% followed by internal hernias and volvulus \\[[@ref1], [@ref2]\\].\n\nIn a systematic review \\[[@ref2]\\] of 78 studies describing 92 pregnancies from 2006, the most common risk factor for SBO in pregnancy was previous abdominal surgery (49%). The most common presenting symptoms were abdominal pain (88%), vomiting (67%), examination findings of tenderness (49%) and distension (28%). Abnormal laboratory parameters were seen only in 26%. Webster *et al.* \\[[@ref1]\\] reviewed cases from 1992 to 2014 with 46 cases of SBO identified. Of the case reports, five out of six (83%) women with adhesive SBO were treated surgically. One was treated successfully with conservative management. Of the case series, 16 cases of adhesive SBO were treated surgically (94%) with 1 case successfully managed conservatively.\n\nThis case occurred in public (state-funded) hospital, which is the only type of hospital of which acute surgery is managed in New Zealand.\n\nCASE REPORT {#sec2}\n===========\n\nA 37-year-old female"
-"Introduction\n============\n\nThe incidence of colorectal carcinoma in the United States is among the highest in the world, affecting \\~52/100,000 individuals, and the incidence of colorectal cancer in India is among the lowest, affecting \\~7/100,000 individuals, suggesting that lifestyle factors may contribute to the development of the disease ([@b1-mmr-14-05-4559]). Previous epidemiological and dietary intervention studies have suggested that diet-derived flavonoids may have a beneficial contribution to cancer therapy, primarily due to their pro-apoptotic or anti-angiogenic activities ([@b2-mmr-14-05-4559]--[@b4-mmr-14-05-4559]). Quercetin (also termed 3,3\u2032, 4\u2032, 5,7-pentahydroxyflavone) is a ubiquitous flavonoid found in various fruits, vegetables, nuts and red wine. Its antitumor effects have been confirmed in various cancer cells, including leukemia, breast, ovarian, colon, cervical, prostate and lymphoma ([@b5-mmr-14-05-4559]--[@b8-mmr-14-05-4559]). Different molecular mechanisms underlying the antitumor activity of quercetin have been identified, including upregulation of cell cycle inhibitors, downregulation of oncogene expression and the inhibition of glycolysis ([@b5-mmr-14-05-4559],[@b9-mmr-14-05-4559]--[@b12-mmr-14-05-4559]). However, the precise target for quercetin and its mechanisms of action remain to be elucidated.\n\nThe constitutive photomorphogenesis 9 (COP9) signalosome (CSN), is an evolutionarily conserved multiprotein complex that is present in all eukaryotes. It consists of eight subunits termed CSN1-CSN8 ([@b13-mmr-14-05-4559]). Previous studies have identified that CSN6 of the COP9 complex is crucial for proteasome-mediated"
-"See related commentary by Ikeda and Kudva, <http://stemcellres.com/content/4/6/159>\n\nIntroduction\n============\n\nThe success of islet transplantation over the last decade suggests that diabetes can be cured by a replenishment of deficient beta cells \\[[@B1],[@B2]\\]. However, according to the transplantation protocol of Edmonton, the transplanted islets into each patient should be isolated from two to three pancreatic donors, exceeding ten thousand islet equivalent (IEQ)/kg \\[[@B3]\\]. As a result, a widespread use of islet transplantation is severely limited by the shortage of donor organs. Stem cells have the capacity of self-renewal and the potential of differentiating into various cell types, making them an ideal candidate to address this issue.\n\nAlthough the possibility of generating insulin-producing cells routinely from both human embryo stem cells (ESC) and human induced pluripotent stem (iPS) cells is quite encouraging, significant challenges still remain \\[[@B4]\\]. Lumelsky \\[[@B5]\\] and Assady \\[[@B6]\\] found that islet-like cells could be generated *in vitro* by differentiation of ESC under conditions resembling those of physiological development for pancreatic beta cell development. However, insulin secretion by these cells was low and lacked a full response to glucose. Clinically, applying ESC-derived cells in treatment presents more challenges including the risk of cancer formation, functional deficiency of such"
-"All relevant data are within the paper.\n\nIntroduction {#sec001}\n============\n\nRice is the staple food crop for a large segment of the world population \\[[@pone.0167152.ref001]\\]. China is one of the main rice production countries, and improving rice productivity in China is very important for world food security \\[[@pone.0167152.ref002]\\]. In the past five decades, rice yield has more than tripled in China \\[[@pone.0167152.ref003]\\]. Unfortunately, the increase in rice yield has been associated with a major decline in nutrient use efficiency, especially nitrogen (N) \\[[@pone.0167152.ref004]\\]. Agronomic N use efficiency in rice systems in China was 15--20 kg kg^--1^ in the early 1960s and declined to approximately 9 kg kg^--1^ in the early 1980s and to only about 6 kg kg^--1^ in the 2000s \\[[@pone.0167152.ref005], [@pone.0167152.ref006], [@pone.0167152.ref007]\\]. The low N use efficiency is mainly attributed to overfertilization \\[[@pone.0167152.ref003], [@pone.0167152.ref004]\\]. The average rate of N application for rice production in China is 180 kg ha^--1^, about 75% higher than the world average \\[[@pone.0167152.ref003]\\]. Because of the high rate of N application, only 20--30% of N is taken up by the rice plant and a large proportion of N is lost to the environment \\[[@pone.0167152.ref007], [@pone.0167152.ref008]\\]. The lost N has caused substantial environmental problems such"
-"Introduction\n============\n\nCystic fibrosis (CF) is a severe, autosomal recessive, multi-system condition, predominantly affecting the respiratory and digestive systems. CF is caused by mutations, of which there are more than 1900, in the cystic fibrosis transmembrane conductance regulator (*CFTR*) gene. The prevalence of CF is 1 in 2500 to 1 in 3500 live births, and for people with Northern European ancestry, the carrier frequency is 1 in 25.[@b1] Advances in multi-disciplinary care have improved long-term outcomes for people with CF. In the UK, median survival is now 43\u2009years.[@b2],[@b3]\n\nPrenatal diagnosis of CF currently requires an invasive test to obtain fetal genetic material and so carries a small risk of miscarriage[@b4] but is an option that is valued by carrier couples as it allows them to either plan and prepare for the birth of an affected child or make decisions about termination of pregnancy.[@b5] Non-invasive prenatal diagnosis (NIPD) based on analysis of cell-free fetal DNA (cffDNA) in maternal plasma has been reported to exclude the paternal mutation in couples carrying different CF mutations.[@b6]--[@b8] However, these reports described analyses developed for individual families, a labour-intensive approach for implementation into routine clinical practice. Here, we describe the development of a next-generation sequencing"
-"Background\n==========\n\nIncreasing concern over foreign energy supplies, global greenhouse gas emissions and the need for rural economic development has driven the interest in sustainable biomass production for bioenergy and bio-products. It has been suggested that by 2025, the world energy demand will likely be increased by more than 50% \\[[@B1],[@B2]\\]. This demand, and societal concerns about the environmental impact of burning fossil fuels are key factors stimulating the development of national and regional strategies aimed at the growth of renewable energy supplies, primarily focused on biofuels. To reduce the reliance on fossil fuels, the USA, the world's major energy consumer, released the Energy Independence and Security Act of 2007 that aims to increase the production of renewable fuels from 9.0 billion gallons in 2008 to 36 billion gallons by 2022 \\[[@B3]\\]. The recent USDA/DOE National Biofuels Action Plan \\[[@B4]\\] has helped to delineate the priority areas required to accelerate sustainable biofuel industry development. Within this document, Action Area 2 was identified as feedstock production and improvement. Various feedstocks, such as perennial rhizomatous grasses, can provide sources of lignocellulosic biomass, serving as new sources of crop growth and income for regional farmers.\n\nOne of the most promising feedstocks capable of"
-"1. Introduction {#sec1}\n===============\n\nAcrylamide, a white odorless crystalline solid, has been identified in heat-treated carbohydrate-rich foods such as fried cookies, potatoes, bread, and breakfast cereals \\[[@B1]\\]. Research observations revealed that acrylamide levels appeared to rise as food is subjected to heat for longer periods of time, which might be produced by the reaction between asparagine and reducing sugars (fructose, glucose, etc.) or reactive carbonyls at temperatures above 120\u00b0C \\[[@B2]\\]. Many scientists proposed that the Maillard reaction \\[[@B2], [@B3]\\], which was a vital factor to produce brown color and specific taste of bakery food, was responsible for the formation of acrylamide. However, this substance originated toxic effects on nervous system and on fertility \\[[@B4]\\]. In addition, acrylamide may induce carcinogenesis and heritable mutations in rats when orally administrated in high-dose experiments in laboratory, which implies that it is probably carcinogenic to humans \\[[@B5], [@B6]\\]. Consequently, the potential harmfulness of acrylamide cannot be ignored.\n\nIn recent years, some studies have demonstrated that acrylamide-induced cytotoxicity was relevant to oxidative stress \\[[@B7], [@B8]\\]. The cytotoxic properties of acrylamide by affecting the cellular redox status might lead to generation of reactive oxygen speices (ROS), which would ultimately cause cytotoxic and genotoxic effects. Considering this,"
-"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"
-"Background\n==========\n\nThe purpose of this study is to investigate if S-uPAR correlates with expected length of patients\\' hospitalization. This could be useful in emergency medicine, due to the acute departments treating patients hospitalized for 48 hours or less. S-uPAR (Urokinase Plasminogen Activator, CD87) is a potential biomarker thought to be related to inflammatory immune cell activation. It is expressed on various immune cells including neutrophils, monocytes, macrophages, and lymphocytes. Upon inflammation, it is cleaved from the cell surface and released into serum. S-uPAR has shown prognostic and clinical value in the triage of patients as described in an editorial comment in the Journal of Internal Medicine 2012 \\[[@B1]\\].\n\nMethods\n=======\n\nIt is a follow-up study including 60 unselected patients (n = 60) above 60 years of age and is the first sample of a larger study including 500 patients. Blood samples in this study have been collected from patients at admission. The samples were frozen afterwards and the patients have been examined retrospectively by physicians and stratified into groups: hospitalized \\< 24 hours, 24-72 hours, and \\> 72 hours.\n\nResults\n=======\n\nThe mean S-uPAR value for the \\< 24h group (n = 14) was 2.75 (1.5 - 24.3). This"
-"Introduction {#s1}\n============\n\n*Xanthomonas citri* subsp. *citri* (Xac) is the causal agent of citrus canker, a severe disease that affects citrus crops, decreases fruit production and causes economic losses (Gottwald et al., [@B19]). This disease is currently present in South and North America, Asia, Africa, and Oceania (Stover et al., [@B55]; Davis et al., [@B14]; Leduc et al., [@B30]; Behlau et al., [@B6]). The current strategy to combat citrus canker in the state of S\u00e3o Paulo, Brazil, the largest producer of concentrate orange juice in the world, comprises the eradication of symptomatic trees along with spraying copper-containing bactericides in a radius of 30 m having the symptomatic tree as the center point (Gottwald et al., [@B19]; Behlau et al., [@B5]). However, this strategy is costly and has limited effectiveness (Behlau et al., [@B4], [@B6]).\n\nThe genome of Xac was fully sequenced 14 years ago, opening up several possibilities for molecular and genetic characterization of this plant pathogen (da Silva et al., [@B13]). Since then, some studies have expanded upon the knowledge we have about biological processes in Xac, mostly concerning pathogenicity mechanisms (Alegria et al., [@B2]; Casabuono et al., [@B12]; Li and Wang, [@B31]; Huang et al., [@B24]; Alexandrino et"
-"1. Introduction\n===============\n\nResearch addressing the measurement and dissemination of ultrasonic power levels began at the National Bureau of Standards (NBS) in the 1970s, in response to the increasing needs of the medical ultrasonics community. The initial outcomes of this research included the design and construction of two instruments---a calorimeter \\[[@b1-v113.n05.a03]\\] and a radiation force balance (RFB) \\[[@b2-v113.n05.a03]--[@b5-v113.n05.a03]\\]---and the establishment, in 1977, of an ultrasonic power measurement service.\n\nThe most frequently requested measurement service was the determination of the effective radiation conductance, *G~r~*, of transducers intended to be used as power transfer standards. Defined by $$G_{r} = P/V^{2}$$where *P* is the output power level in watts and *V* is the root-mean-square (rms) radio-frequency (rf) voltage applied to the transducer, this parameter can be used by the customer to generate arbitrary power levels by simply applying accurately known rf voltages.\n\nBy 1980, it was evident that, with the equipment available to typical customers, the accuracy of calibration transfer based on values of *G~r~* was critically affected by the systematic errors associated with rf voltage measurements. Because their missions did not support a standards-lab-grade approach to rf voltage measurements, these customers were fundamentally constrained by the use of radiation conductance.\n\nAccordingly, a"
-"Introduction\n============\n\nSurgery is the major treatment method for lung cancer, especially for non-small cell lung cancer (NSCLC). The prevalence of chronic obstructive pulmonary disease (COPD) in patients with lung cancer is 73% in men and 53% in women.[@b1] Postoperative pulmonary complications (PPC) are the main cause of mortality during the postoperative period[@b2] and pulmonary infection is the most common of these.[@b3],[@b4] Various reports have highlighted the need to improve lung function and quality of life in patients with COPD.[@b5],[@b6] However, the value of pre-operative pulmonary rehabilitation in lung cancer patients with COPD, who are candidates for lung resection, is controversial.[@b7],[@b8] Previous studies have included small sample sizes, using conventional pulmonary function tests (PFTs) for determination of COPD level, and treating with simple physical pulmonary rehabilitation without medication.[@b9] However, none of these studies have included patients with cardiopulmonary high risks who could be determined by cardiopulmonary exercise testing (CPET).[@b10][@b11] There has been no research evaluating CPET and pre-operative pulmonary rehabilitation in lung cancer. Our study was designed to evaluate CPET and pre-operative pulmonary rehabilitation, which may improve postoperative complications and fast-track recovery in high-risk patients who undergo resection for lung cancer.\n\nMaterial and method\n===================\n\nClinical data and grouping\n--------------------------"
-"INTRODUCTION {#s1}\n============\n\nGastric cancer (GC) is a heterogeneous disease and recent effort has been focused on exploring subsets of patients who may potentially benefit from molecularly targeted agents \\[[@R1]\\]. Despite of tremendous effort in attempting to prove the survival benefit from targeted agents in a \"target\" population (i.e. MET inhibitor in MET overexpressed gastric cancer patients), many trials have failed to show survival benefit \\[[@R2]\\]. The survival outcome for metastatic gastric cancer patients is still near one year after diagnosis and thus, exploration of novel targets in \"target\" population in GC is urgently needed \\[[@R2]\\].\n\nMER proto-oncogene tyrosine kinase (MerTK) belongs to the family of TYRO3, AXL, MER (collectively, TAM) receptor tyrosine kinases (RTKs) which are normally expressed in macrophages, dendritic cells and natural killer cells \\[[@R3]\\]. MerTK overexpression has been demonstrated in several cancer types such as melanoma \\[[@R4], [@R5]\\], lung cancer \\[[@R6]\\], prostate cancer, glioblastoma \\[[@R7], [@R8]\\], HCC \\[[@R9]\\], and head and neck cancer \\[[@R10]\\]. We recently showed that 8.3% (16 of 192) of GC patients demonstrated strong positive MerTK total protein expression and overall they have poor survival outcome \\[[@R11]\\]. In addition, we showed that MerTK-overexpressing GC cells were profoundly inhibited after MerTK knockdown, suggesting that"
-"Introduction {#s0005}\n============\n\nHuntington\\'s disease (HD) is the most prevalent of a set of human neurodegenerative disorders linked to expansion of polyglutamine (polyQ) tracts in specific proteins [@bb0005; @bb0010]. The full-length protein associated with HD, huntingtin (HTT), is found predominantly in the cytosol. In the disease state, however, N-terminal proteolytic fragments of mutant forms of HTT (mHTT), which are characterized by aberrant expansions of the wild-type polyQ tract of \\>\u00a036 residues, are found to accumulate as insoluble inclusions in cellular nuclei [@bb0015; @bb0020; @bb0025; @bb0030]. The proteolytic fragment of mHTT that is found to be most pathogenic is the exon1 fragment of mHTT, and overexpression of this fragment has been shown to be sufficient to produce rapid HD pathology in cells and organotypic tissue, as well as in yeast and animal models, including *Drosophila* and mouse models [@bb0035; @bb0040; @bb0045; @bb0050].\n\nThe sequence of the HTT-exon1 fragment can be divided into three regions: a 17-residue N-terminal region \\[HTT(1-17)\\], immediately followed by the polyQ tract of variable length and a proline-rich region at the C-terminal end of the peptide [@bb0055]. The HTT(1-17) region is highly conserved, has a high propensity to adopt an amphipathic \u03b1-helical structure and has been shown"
-"The Corona-virus (2019-nCoV) is a kind of zoonotic virus that has been first proclaimed in Wuhan (China). By 10th April 2020, the pandemic (COVID-19) has infected more than one and a half million (1698881) people across the world. During the last couple of weeks a sharp surging trend (COVID-19 infection) has been recorded \\[[@CR1]\\]. The community dissemination is a major cause behind this exponential growth. The substantial growth of this pandemic virus (COVID-19) has created a scary and stressful environment \\[[@CR2]\\]. The consequence of the stress is so high that fear of infection forces the persons to suicide \\[[@CR3]\\]. The key intention of this analysis is to highlight the escalating cases of COVID-19 and its refection in the growing search trend and concern of the people from 01st March to 10th April 2020.\n\nDuring this observation period, the worldwide COVID-19 infected cases have been raised from 88,585 to 1,698,881 (\\~1.7 million). The highest number of new cases (101736) have been observed on 3rd April. An average growth rate of 7.58% (new_cases\\>70,000) has been witnessed. As of 10th March, the growth in the global contaminated cases has been intensified. Moreover, in the last five days of this study, 349,830 new cases"
-"Hypertension is the number one attributable risk factor for death within the general population worldwide ([@B1]) and remains particularly prevalent among individuals with diabetes ([@B2]), despite the broad availability of effective treatment regimens ([@B3]). Among individuals with type 1 diabetes, the presence of hypertension has been associated with a significantly increased risk of both microvascular ([@B4]) and macrovascular ([@B5]) complications, and it also raises overall mortality risk ([@B6]). Given the increased incidence of cardiovascular and kidney complications in this population, the control of arterial blood pressure is of imminent importance, as is the management of risk factors for hypertension incidence itself.\n\nModifiable lifestyle factors, such as obesity and physical inactivity, and dietary factors, including excess alcohol consumption, increased dietary sodium intake, and inadequate fruit, vegetable, and potassium intakes, have been shown to significantly increase the risk of new-onset hypertension in the general population ([@B3],[@B7],[@B8]). Although, traditionally, individuals with type 1 diabetes were thought to be of normal or subnormal weight, the adoption of unhealthy lifestyle behaviors and/or intensive insulin therapy have led to an increasing prevalence of overweight and obesity in individuals with this diabetes type ([@B9]). Moreover, the presence of hyperglycemia has been suggested to further contribute to the"
-"Evidence-based medicine is the integration of best research evidence with clinical expertise and patient values [@CIT0001]. The International Lyme and Associated Diseases Society (ILADS) has adopted the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system as its basis for evidence assessment and the development of recommendations to ensure a transparent and trustworthy guideline process [@CIT0002].\n\nThese guidelines address three fundamental treatment questions: the usefulness of antibiotic prophylaxis for known tick bites, the effectiveness of erythema migrans (EM) treatment and the role of antibiotic retreatment in patients with persistent manifestations of Lyme disease. ILADS anticipates performing GRADE assessments on additional topics related to the diagnosis and treatment of tick-borne diseases in the future.\n\nThe GRADE scheme classifies the quality of the evidence as high, moderate, low or very low. The quality of evidence from randomized controlled trials (RCTs) is initially rated as high, but may be downgraded based on five limitations: study bias, publication bias, indirectness (generalizability), imprecision and inconsistency. Evidence quality from observational studies is generally low, but may be upgraded based on a large effect or dose--response gradient [@CIT0006]. Rather than labeling recommendations as strong or weak, these guidelines use the terms 'recommendation' or 'strong recommendation' for or"
-"INTRODUCTION\n============\n\nMagnetic resonance imaging (MRI) provides effective visualization of normal alignment and morphology of the posterior cruciate ligament (PCL) ([@B1][@B2]). Besides, it can demonstrate injury of the PCL and associated structural abnormalities. On MRI, the normal PCL is shown as a well circumscribed very low signal intensity band coursing between the medial femoral condyle and the posterior tibia. Sagittal plane imaging, with the ability to best demonstrate cruciate ligament along its anatomic course, is the most widely applied and studied imaging plane for detecting PCL abnormality ([@B1][@B3][@B4]). Due to the complex nature of the PCL anatomy, coronal image serves an important supplementary role to sagittal image in detecting PCL abnormality ([@B1][@B5]). The posterior segment of PCL is the vertically oriented portion that is located in the intercondylar notch adjacent to the lateral aspect of the medial femoral condyle ([@B6]). The PCL then curves anteriorly and the horizontal portion appears, which is depicted as ovoid shaped, low signal structure within the intercondylar notch on coronal MRI ([@B7]). The injuries involving horizontal and vertical portions of the PCL may be more readily identified on coronal images, even though they are often detected on sagittal images ([@B1]).\n\nIn daily practice, we occasionally"
-"Background\n==========\n\nRestless legs syndrome (RLS) is a common neurological disorder in Western countries with a lifetime prevalence of 7 to 10% \\[[@B1]\\]. Approximately 1 to 3% of patients require treatment \\[[@B2]\\]. The disease specific, health-related, and psychosocial quality of life of this population is reduced compared to the general population and is comparable to that of patients with type 2 diabetes mellitus and osteoarthritis \\[[@B2],[@B3]\\]. The lifetime prevalence of comorbid depression and anxiety disorders is elevated by odds ratios of 2.1 to 5.3 in RLS compared to the community at large \\[[@B4]-[@B6]\\]. Sleep problems, leg dysaesthesias, and the psychological sequelae of the disorder are all particularly implicated in contributing to impaired daily functioning \\[[@B7],[@B8]\\]. RLS is considered to be a chronic disorder as causative treatments do not exist except of a few secondary forms such as iron deficiency. Dopamine agonists, the first-line treatment in RLS, show efficacy which is, however, moderate \\[[@B9]\\] and the majority of patients do not experience full remission in drug trials \\[[@B10],[@B11]\\]. Little is known about the psychopathological state and psychological wellbeing of RLS patients. This issue is, however, of major clinical relevance as psychological factors may contribute to an unfavourable treatment outcome as seen"
-"Introduction\n============\n\nEnteral nutrition has surpassed parenteral nutrition in terms of safety and physiological benefits \\[[@B1],[@B2]\\]. For a patient who has problems swallowing but has an intact intestinal tract, enteral nutrition is primarily recommended \\[[@B1]\\]. Semi-solid enteral nutrition has the advantage of lowering the risk of diarrhea and esophageal reflux \\[[@B3]\\]. Here we report a case in which malnutrition, diarrhea and a pressure ulcer were improved by high viscosity semi-solid nutrition via a large-bore nasogastric tube.\n\nCase presentation\n=================\n\nA 67-year-old man (mongoloid race, Japanese) was admitted to our hospital because of a 3-day history of fever. Acid-fast bacilli was found to be smear-positive in his sputum, and a chest radiograph and computed tomography examinations showed parenchymal opacities with scattered fine nodules in his right apical region. He was diagnosed with pulmonary tuberculosis, so he was started on anti-tuberculosis therapy with isoniazid, rifampicin, ethambutol, and pyrazinamide on the first day that he was hospitalized. He had developed a cerebral hemorrhage 18 months before this hospitalization, and he had right hemiplegia, dysphagia, and aphasia as sequelae. He had been receiving 600 kcal/day of liquid nutrition via a nasogastric tube for 6 months before the current hospitalization.\n\nOn admission to our hospital,"
-"Introduction {#s1}\n============\n\nMulticellular development relies on the formation of cell-type-specific gene expression programmes that support differentiation. At the most basic level, these expression programmes are defined by cell signaling pathways that control how transcription factors bind DNA sequences in gene regulatory elements and shape RNA polymerase II (RNAPolII)-based transcription from the core gene promoter (reviewed in \\[[@bib74]\\]). In eukaryotes, the activity of RNAPolII is also regulated by a large multi-subunit complex, Mediator, which can directly interact with transcription factors at gene regulatory elements and with RNAPolII at the gene promoter to modulate transcriptional activation. The Mediator complex functions through regulating pre-initiation complex formation and controlling how RNAPolII initiates, pauses, and elongates. Therefore, Mediator is central to achieving appropriate transcription from gene promoters (reviewed in \\[[@bib4]; [@bib56]\\]).\n\nIn mammalian genomes, CpG dinucleotides are pervasively methylated and this epigenetically maintained DNA modification is generally associated with transcriptional inhibition, playing a central role in silencing of repetitive and parasitic DNA elements ([@bib44]; [@bib70]). Most gene promoters, however, are embedded in short elements with elevated CpG dinucleotide content, called CpG islands, which remain free of DNA methylation ([@bib10]; [@bib38]; [@bib48]). Interestingly, mammalian cells have evolved a DNA-binding domain, called a ZF-CxxC domain, which"
-"Background\n==========\n\nEach year 200 children and adolescents in Denmark are diagnosed with cancer. Over recent decades the increased understanding of cancer biology, improved surgery and chemotherapy, and generally intensified treatment, have resulted in 5-year survival rates above 80% \\[[@B1]-[@B3]\\]. However, the disadvantages of this improvement include severe acute and late effects \\[[@B2]-[@B4]\\], often involving isolation for long periods of time, both when in hospital and at home. This isolation reduces participation in activities with peers at school and in sporting activities \\[[@B1],[@B5],[@B6]\\]. As a result, important social interactions and the natural development of social skills with classmates are disrupted \\[[@B5],[@B6]\\]. Following diagnosis, children are absent from school for an average of 85\u00a0days \\[[@B7]\\] during the first 12 to 18\u00a0months, and 3\u00a0years after diagnosis their school attendance is still irregular and many fail classes \\[[@B8],[@B9]\\]. Childhood and adolescent cancer survivors report being bullied, feeling isolated \\[[@B10]-[@B13]\\], and having few or no friends \\[[@B14]-[@B16]\\]. Although register-based data show that they achieve the expected educational level post-treatment \\[[@B17]\\], such data do not address social and physical functioning \\[[@B18]-[@B20]\\]. Attending school may help provide normality, continuity, and security, in an abnormal life situation \\[[@B21]\\]. Few intervention studies have addressed children's"
-"Introduction\n============\n\nAtmospheric CO~2~ concentration has varied tremendously over geological time, from as high as 3000 ppm in the lower Devonian (Royer [@b42]) to as low as 180--280 ppm during the past 2.1 Ma of the Pleistocene (Honisch et al. [@b22]). About 17.5 Ka ago, atmospheric CO~2~ concentration started to rise from 180 ppm, levelled off at 280 ppm around 15 Ka ago and broadly remained at 280 ppm until the Industrial Revolution. Since the start of the Industrial Revolution, CO~2~ levels have risen to 390 ppm today, levels not experienced by plants for over 25 Ma (Royer [@b42]) and are expected to increase even further; common model estimates go up to 700 ppm by 2100 (IPCC [@b23]). A CO~2~ atmosphere of 700 ppm has not been observed since 42 million years ago (Royer [@b42]). The atmosphere today and as predicted for the end of the century is thus increasingly different from that experienced by plants during a large part of the recent past.\n\nCO~2~ plays a pivotal role in a number of important ecophysiological processes: it is an essential ingredient for photosynthesis and plant growth, and it is highly likely that plants\\' morphological and physiological traits and their plastic"
-"Introduction {#sec1-1}\n============\n\nA dairy cow is the backbone of the Indian dairy industry as it contributes about 38% of the national \\[[@ref1]\\] and 8.7% of the world total cow milk production (FAO, 2012). FAO \\[[@ref2]\\] had reported that there were 620 million dairy cows in the world, out of which India had a total of 54 million (8.7% of world production). The Jersey breed of dairy cattle originated on the Island of Jersey, a small British Island located in the English Channel off the coast of France. The ability of Jerseys to make more profit per acre is one of the most important reasons for the breed's popularity. The breed's greater efficiency in converting feed into milk and the ability of the dairymen to keep more animals on an acre of ground are principal reasons why Jerseys make more profit per acre. They cost less to raise than other dairy cattle because they reach a productive age from 2 to 10 months earlier than other dairy breeds. They are especially tolerant to hot temperature, yet perform well in the northern climates.\n\nHowever, the genetic improvement of the Indian cow was not good. The genetic improvement of dairy cow done"
-"Introduction {#S1}\n============\n\nSince the introduction of antiretroviral therapy (ART), life expectancy of people living with HIV (PLHIV) has notably improved, and the gap between the uninfected population ranging from 60 to 90%, of normal life expectancy is narrowing in regions of the world among those with access to ART ([@B1]). Before the availability of ART, immune suppression-related complications represented the predominant cause of mortality among HIV-infected individuals. Incidence rates of non-Hodgkin lymphoma (NHL) and Kaposi sarcoma (KS) were more than 100 times higher in the pre-ART era and were classified, together with cervical cancer, as AIDS-defining cancers (ADCs) ([@B2]). Overtime, as ART became the standard of care, prolonged use has lead to a remarkable improvement in immune status, dramatically reducing ADC rates (ratio of ART to no-ART) by 0.61 per year ([@B3]).\n\nIn the United States, despite the sharp decline in the incidence of ADCs, increased risk of developing specific types of NHL such as Burkitt lymphoma and classical Hodgkin lymphoma (HL) has evolved ([@B4], [@B5]). A meta-analysis of standardized incidence ratios from 18 studies showed that infection-related cancers such as anal, liver and HL, as well as smoking-related cancers such as lung, kidney, and oral cancers, had an"
-"Clinical translation of advances in understanding the genetics of common disease will require primary care practitioners to play an increasing role in providing genetic advice ([Qureshi *et al*, 2004](#bib21){ref-type=\"other\"}). Cancer genetics provides a model for the genetics of common disease and their clinical implications for primary care ([Emery *et al*, 2001](#bib10){ref-type=\"other\"}). The discovery of genes that place individuals at increased risk of breast, ovarian and colorectal cancer has had important and immediate clinical applications ([Wooster and Weber, 2003](#bib29){ref-type=\"other\"}). Key tasks for primary care practitioners include identifying individuals likely to be at increased genetic risk and advising those for whom genetic testing and increased disease surveillance offer little benefit. Previous audits of referrals to familial cancer clinics in the UK show that approximately 30% of referrals from general practice are for patients whose risk is not significantly raised on current evidence ([Wonderling *et al*, 2001](#bib28){ref-type=\"other\"}).\n\nPreviously we reported experimental and qualitative evaluations of a prototype computer decision support tool for the management of familial cancer risk in primary care ([Emery *et al*, 1999](#bib11){ref-type=\"other\"}, [2000](#bib12){ref-type=\"other\"}). These demonstrated the functionality and design of the software, and also demonstrated its potential to improve general practitioners\\' management decisions in simulated cases. This work underpinned the"
-"Background {#Sec1}\n==========\n\nThe latest European Perinatal Health Report identified 22.6% of German women as being overweight (body mass index (BMI) 25.0--29.9 kg/m^2^) and 13.7% as obese (BMI \u2265\u200930.0 kg/m^2^) at the onset of pregnancy \\[[@CR1]\\]. Maternal overweight and obesity can affect the course of pregnancy, as well as delivery and the postpartum health of both mothers and their infants \\[[@CR2], [@CR3]\\]. In addition to a high pre-pregnancy BMI, excessive gestational weight gain (GWG) is an increasing public health concern due to its potential contribution to pregnancy and obstetric complications, maternal postpartum weight retention and childhood obesity. With reference to the recommendations for adequate weight gain during pregnancy provided by the United States' Institute of Medicine (IOM) \\[[@CR4]\\], there is a significant trend towards excessive GWG \\[[@CR5]\\]. In Germany, more than 40% of pregnant women currently exceed the recommended weight gain thresholds \\[[@CR6]\\].\n\nPregnant women who gain weight excessively are more likely to develop gestational diabetes mellitus (GDM) \\[[@CR7], [@CR8]\\] and to retain weight in the postpartum period \\[[@CR9]\\]. These risks not only affect overweight women or those with obesity, but also those entering pregnancy with a normal BMI \\[[@CR8], [@CR10], [@CR11]\\]. Further, high maternal weight gain in pregnancy"
-"Dear Editor,\n\nAirway management is a key element of resuscitation procedures. However, due to the current COVID-19 pandemic, medical personnel should complete medical procedures wearing full personal protective equipment (PPE) for aerosol-generating procedures (AGP) \\[[@bb0005]\\]. PPE-AGP should be used especially during cardiopulmonary resuscitation, including airway management \\[[@bb0010]\\]. Emergency intubation using direct laryngoscopy carries a significant risk of failure. As many authors indicate, the effectiveness of the first intubation attempt with a Macintosh laryngoscope is from 57.6% to 89.9% \\[[@bb0015],[@bb0020]\\]. The use of PPE-AGP may reduce the efficiency of medical procedures and prolong their duration \\[[@bb0025],[@bb0030]\\]. intubation methods alternative to Macintosh laryngoscope may be a suitable solution. An example of a new type of laryngoscope is Vie Scope\u00ae (Androit Surgical, Oklahoma City, USA), which is a self-contained, battery-powered, disposable scope that takes advantage of a closed circular tube with a beveled end to visualize the vocal cords ([Fig. 1](#f0005){ref-type=\"fig\"} ). The light is transmitted through the sidewall of the tube from end to end as well as within the lumen of the tube. The intubation procedure using Vie Scope\u00ae should be based on the following steps -- the intubator should: (1) insert scope and identify glottis opening between vocal cords, (2)"
-"Background {#Sec1}\n==========\n\nMortality due to cancer is becoming unacceptably high and is therefore a worldwide concern. Statistics indicate that the total number of cancer deaths in 2007 was 7.6 million, of which 62% were in developing countries and 38% in developed countries \\[[@CR1]\\]. By 2050, 27 million new cases and 17.5 million cancer deaths are expected globally \\[[@CR1]\\]. Therefore, serious efforts have been made to reduce the threat of cancer all over the globe.\n\nHistorically, natural products have served as a rich source of lead compounds for drug development against a wide array of biological targets, including various forms of cancer. Search continues in rigorous footing to discover unexplored plants and animals as potential new sources of anticancer drugs. Since 1940, almost 75% of approved small molecules for the treatment of cancer have been either natural products, semi-synthetic derivatives of natural product scaffolds, or synthetic compounds inspired by natural products pharmacophores \\[[@CR2]\\].\n\nThe genus *Cephalotaxus* has received a great level of scientific interest as it contains anticancer potential ingredients \\[[@CR3]--[@CR6]\\]. Homoharringtonine, an alkaloid isolated from *Cephalotaxus harringtonia* was recently approved by USFDA for the treatment of adult patient with chronic myeloid leukemia \\[[@CR7]\\]. In view of the importance of"
-"Introduction\n============\n\nPatients with cholangiocarcinoma (CAA) have extremely poor prognosis with an average 5-year survival rate of 5%--10%.[@b1-cmo-2009-121] Among the clinicopathologic factors influencing the survival after surgical treatment, curative surgery, lymph node metastases, tumor size and cancer-free margin are the most predictive factors.[@b2-cmo-2009-121]--[@b8-cmo-2009-121] Recently, in a large series of CCA, multivariate analysis showed that EGFR expression was a risk factor for recurrence of intrahepatic CCA[@b9-cmo-2009-121] with a five-year survival rate at around 20% and in hilar bile duct cancer, after curative resection, 40% of the patients had disease recurrence.[@b8-cmo-2009-121] In these patients with high risk factors, adjuvant therapy may play a role in prolonging survival. The aim of this pilot study was to assess the efficacy and safety of adjuvant chemotherapy (GEMOX) in high-risk patients with intrahepatic and hilar CAA after curative surgery.\n\nPatients and Methods\n====================\n\nPatients and treatment\n----------------------\n\nPatients were eligible for entry into this pilot study if they fulfilled the following criteria: age \u226518 years, Karnofsky Performance Status (KPS) \u2265 80%, histologically confirmed diagnosis of CCA tumor tissue available for immunohistochemical EGFR detection and curative surgery. Laboratory acceptance parameters included an absolute neutrophil count of \u22651,500 cells/\u03bcL, a platelet count of \u2265100,000 cells/\u03bcL, a serum creatinine"
-"Introduction\n============\n\nAcquired hemophilia A is a rare but potentially life-threating bleeding disorder that is caused by autoantibodies against factor VIII. Acquired hemophilia A is usually suspected in patients with an isolated prolongation of the activated partial thromboplastin time (aPTT). We herein present a case of acquired hemophilia A with a normal aPTT, intramuscular hematoma and cerebral hemorrhage.\n\nCase Report\n===========\n\nA 73-year-old man with a history of hypertension, gastric cancer and abdominal aortic aneurysm visited our emergency department complaining of gait disturbance, pain and swelling in his right leg. His leg had become swollen five days ago and he was not able to walk smoothly. He had not experienced any trauma or fever and had not undergone an operation in the past month. On examination, his blood pressure was 162/81 mmHg, heart rate was 81 beats per minute and body temperature was 36.4\u2103. His right thigh demonstrated tender swelling, and the neurological findings revealed a shot-stepped gait without any paralysis or sensory disturbance. Laboratory test results revealed a hemoglobin level of 10.4 g/dL (normal, 13.2-17.2 g/dL), hematocrit of 30.4% (normal, 40.4-51.1%), a von Willebrand factor activity of 203% (normal, 60-170%), elevated fibrinogen of 569 mg/dL (normal, 200-400 mg/dL) and"
-"1. Introduction\n===============\n\nSepsis, one of multiple severe symptoms of patients with trauma, burn, shock, and infection, will induce multiple organ dysfunction syndrome (MODS), septic shock, and other more severe complications. The progression of sepsis is very fast, making it hard to predict, and its death rate is extremely high, which makes its clinical diagnosis and treatment more difficult.^\\[[@R1]\\]^ There are approximately 20 million patients with sepsis in the world each year, and the corresponding mortality rate is 28% to 50%.^\\[[@R2]\\]^ In addition, sepsis is closely associated with the intensive care unit (ICU) stay rate, the elongation of total days of hospital stay, and hospital mortality. Data from Australia and New Zealand have shown that the inpatient number due to sepsis accounts for more than 50% of the total number of ICU patients.^\\[[@R3]\\]^ Some investigations have found that the treatment cost of sepsis each year is as high as \\$1.7 million, accounting for 40% of ICU expenses.^\\[[@R4]\\]^ Early identification, timely diagnosis, and select effective treatment methods are the key to enhancing the success rate of sepsis treatment.\n\nMany reports have confirmed the effectiveness of traditional Chinese medicine (TCM) Xuebijing injections (XBJI) and ulinastatin for treating sepsis in the Chinese population."
-"**To the Editor:** Hantavirus pulmonary syndrome (HPS) is characterized by fever, gastrointestinal symptoms, respiratory distress, elevated hematocrit, hypoalbuminemia, and thrombocytopenia. Most cases in North America are acquired from rodent vectors and are caused by the Sin Nombre virus. Person-to-person transmission has been reported for Andes virus ([@R1]*,*[@R2]) but not for Sin Nombre virus ([@R3]). We describe a patient with fatal hantavirus pulmonary syndrome.\n\nThe patient was a previously healthy 15-year-old Canadian girl. In the spring of 2006, she had traveled to the Santa Cruz-San Jose de Chiquitas corridor of Bolivia with her parents and siblings for a 4-week visit ([Figure](#F1){ref-type=\"fig\"}), where they stayed with family and friends on their farms. The family noted rodent droppings outside but no rodents were seen. The patient had no known exposure to rodents or rodent droppings after her return to Canada.\n\n![Map of Bolivia with an inset map of North America showing the location of British Columbia (BC) and its relation to Bolivia.](07-0708-F){#F1}\n\nOn day 26 after her return from Bolivia, the patient sought treatment at a community hospital at 6:30 [am]{.smallcaps} for malaise and mild fever. During the night before seeking treatment, she had mild confusion. Her initial blood pressure was 99/50, heart"
-"Introduction {#s1}\n============\n\nThe concept of \"receptor\" was independently proposed by Ehrlich and Langley ([@B1]) at the beginning of the 20th century to explain the selective effects of drugs and suggested that the action of a drug involved the formation of specific complexes with molecular agents in the target cells, thereby eliciting a cell response. In the decades that followed, this hypothesis was demonstrated, receptor molecules were biochemically identified, and their structures discovered, thus enabling the key role that they play in physiology to be fully understood. More than 4% of the human genome encodes cell receptors ([@B2]); these are organized into different families \\[see ([@B3])\\] including matrix receptors (e.g., integrins), ligand-gated (LGIC, 76 members in the human genome) and voltage-gated (VGIC, 143 members) ion channels, intracellular receptors, such as nuclear hormone receptors (NHRs, 48 members), enzyme-linked receptors, such as receptor tyrosine kinases (RTKs, 58 members), and G protein-coupled receptors (GPCRs). GPCRs constitute the largest family; in mammals, they contribute to almost all physiological processes and are currently very common targets for drugs ([@B2], [@B4]). In humans, the GPCR family is made up of about 800 receptors; these are classified in five major groups, namely classes A (the largest group),"
-"INTRODUCTION {#cesec10}\n============\n\nThe extensor mechanism of the knee is a complex structure formed basically by three structures that are interlinked with each other: quadriceps muscle and tendon, patella and patellar tendon. In addition to these, the mechanism also includes the patellar retinacula, restrictor ligaments, Hoffa\\'s fat pad and the pre-patellar tissue^(^[@bib1], [@bib2]^)^.\n\nThe extensor apparatus is responsible for knee extension and stabilization of the patellofemoral joint. Loss of joint congruence and stability failure between the patella and femur are abnormalities resulting from lack of synergy between the structures of this mechanism. These abnormalities may be congenital or may be due to traumatic episodes of patellofemoral dislocation. Because of the high incidence of patellofemoral disorders, there is great interest in understanding the anatomy of the structures that make up the extensor mechanism and the function of each of these structures^(^[@bib3]^)^.\n\nDespite several classical anatomical studies on cadavers, doubts persist regarding the presence, location, anatomical variations and function of some structures in the joint dynamics of the knee extensor mechanism^(^[@bib2], [@bib4], [@bib5], [@bib6]^)^.\n\nThe aim of our study was to demonstrate the anatomy of the extensor apparatus by means of three-dimensional photographs, highlighting the medial and lateral ligament structures between the"
-"Background {#Sec1}\n==========\n\nApproximately 15 % of the world's population lives with disabilities. This means there are almost one billion people who face everyday inequality, marginalization, and discrimination through inequitable opportunities, as compared to persons without disabilities \\[[@CR1]\\]. People with psychosocial disabilities face particularly acute social challenges and continue to be subjected to human rights violations worldwide \\[[@CR2]\\]. The stories of discrimination, mistreatment, and exclusion are harrowing. For example, in response to rising substance abuse, many countries in Southeast Asia, such as Cambodia and Myanmar, have adopted laws that allow for compulsory detention as a treatment for persons living with drug addictions. These compulsory drug detention centres have drawn international outrage for subjecting patients to forced labour, physical and sexual abuse, inadequate provision of healthcare, lack of consent for treatment, and involuntary imprisonment \\[[@CR3]\\]. In Eastern Europe, Romas with disabilities have been found to face even higher levels of discrimination than Romas without disabilities, who already encounter numerous obstacles in accessing basic goods, services, healthcare, and rights protection \\[[@CR4]\\]. Mental health care is also woefully lacking in South Africa, where it remains near the bottom of the government's list of priorities. In the South African province of KwaZulu-Natal, only 32"
-"Airway epithelial cells form a paracellular barrier through apical junctional complexes that physically separate the host from its external environment. This barrier serves several important functions including protection from harmful microorganisms and regulation of the bi-directional flow of ions and macromolecules across the lung epithelial barrier. Interestingly, several studies have recently reported structural and functional defects in airway epithelial cells of individuals with allergic disease \\[[@R1]\\]. Although environmental factors such as allergens, viruses and pollutants have been shown to damage the epithelial barrier and increase allergen sensitization, genetic factors also likely play a role in epithelial dysfunction of susceptible individuals. In support of this concept, a study recently published by our laboratory provides insight into a novel intracellular pathway associated with epithelial barrier integrity and susceptibility to allergic disease \\[[@R2]\\].\n\nMicroarray analyses revealed a reduction in expression of a lipid transport gene, Stard7, in nasal epithelial cells isolated from individuals experiencing an acute asthmatic exacerbation compared to those with stable asthma or nonatopic controls \\[[@R3]\\]. To further explore the significance of this gene in asthma, we generated mice globally deficient in Stard7. Although the majority of mice homozygous for the disrupted allele died at embryonic day 11 (likely of cardiovascular"
-"1. Introduction\n===============\n\nOcular toxoplasmosis (OT) has been reported as the most common cause of infectious posterior uveitis in immunocompetent patients.^\\[[@R1]\\]^ The prevalence of OT ranges from 3.8% to 17.7% of infectious uveitis.^\\[[@R2]\\]^ Ocular toxoplasmosis usually presents as posterior uveitis with a chorioretinal lesion associated with vitritis.^\\[[@R3],[@R4]\\]^*Toxoplasma gondii* may induce a latent disease characterized by tissue cysts in various organs, thereby leading to delayed OT or recurrence from a retinochoroidal scar.^\\[[@R5]\\]^ It has been estimated that approximately 2% of individuals experiencing toxoplasmosis will develop ocular manifestations, suggesting that 1 in 400 persons across the world might have posterior uveitis due to *Toxoplasma gondii*.^\\[[@R6]\\]^\n\nOcular toxoplasmosis sometimes causes visual impairment and blindness in the affected eye, even in young adults. In one previous study, 24% of OT patients developed legal blindness.^\\[[@R1]\\]^ Because OT is primarily an infectious disease, it remains a preventable cause of blindness. In this aspect, epidemiologic studies on OT are important for further advancement in its knowledge and prevention.\n\nHowever, there are limited data on the incidence, clinical characteristics, and disease course in Korea compared to other countries. This is because Korea is a low-endemic area of *Toxoplasma gondii*. Therefore, the objective of this study was to describe"
-"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"
-"Introduction {#s1}\n============\n\nOther's actions affect one's own cognitive processing and task performance. For example, the perceived direction of another's eye gaze is widely known to elicit reflexive attentional shifts, even when the gaze direction is non-predictive or counter-predictive (Friesen and Kingstone, [@B10]; Driver et al., [@B8]; Ristic and Kingstone, [@B39]; Galfano et al., [@B11]). Eye gaze has also been shown to activate responses on the side of its direction, eliciting the spatial compatibility effect (Ansorge, [@B1]; Zorzi et al., [@B49]; Ricciardelli et al., [@B37]): the phenomenon in which performance is better when a spatial stimulus feature (such as a location or symbolic spatial meaning) is congruent with a spatial response feature than when they are incongruent, irrespective of whether the spatial stimulus feature is relevant to the task (Kornblum et al., [@B24]; Simon, [@B43]; Umilt\u00e0 and Nicoletti, [@B46]; Lu and Proctor, [@B28]; Hommel and Prinz, [@B20]; Proctor and Vu, [@B36]). Additionally, humans tend to imitate the gaze direction of other individuals (Ricciardelli et al., [@B38]).\n\nIn daily life, referential pointing with an extended index finger is ubiquitous. The index finger pointing gesture is used as a social cue to communicate spatial information; the performer's intent to indicate spatial direction"
-"Introduction\n============\n\nAcute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia (AML) that is characterized by its morphology, t(15;17) translocation leading to the formation of the PML/RAR\u03b1 fusion gene, and life-threatening coagulopathy.[@b1-ott-8-3297] The prognosis of APL has changed from the worst among AMLs to currently the best among AMLs due to the application of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO).[@b2-ott-8-3297]--[@b5-ott-8-3297] A consensus has been reached that ATRA alone or in combination with ATO, with the proper addition of anthracyclines according to white blood cell (WBC) count, is able to achieve complete remission (CR) and results in negativity for the PML/RAR\u03b1 fusion gene.[@b6-ott-8-3297],[@b7-ott-8-3297] Currently, there is no consensus regarding the optimal consolidation and maintenance therapies after induction therapy. Additionally, whether the early involvement of maintenance therapy benefits low-risk patients who have already achieved molecular CR is still being debated. Because the regimen administered after remission determines the long-term survival rate of APL, in this article, we explored an effective, safe, and simple therapeutic strategy for APL that would potentially provide a remedy to this issue.\n\nPatients and methods\n====================\n\nEthics statement\n----------------\n\nThis study was approved by the Institutional Review Board of Sun Yat-sen University Cancer"
-"1. Introduction\n===============\n\nHepatocellular carcinoma (HCC) ranks the sixth as the most frequent cancers and is the third most common cause of cancer-related mortalities in the world.^\\[[@R1]\\]^ The most common risk factor for HCC is chronic hepatitis B virus (HBV) infection, which causes over 50% of all cases. The relative risk of tumor development is higher among HBV-carriers than noncarriers, and HBV-carriers with cirrhosis share an even higher risk.^\\[[@R2]\\]^ Hence, it is urgently demanded to seek effective biomarkers which are significantly associated with the pathological characteristics and patients' survival outcomes. However, the potential tissue-based biomarkers for the diagnosis and prognosis remain obscure and need further characterization.^\\[[@R3]\\]^\n\nRecent advances in genomics, proteomics, and metabolomics technologies have led to the discovery of novel biomarkers in HCC. MicroRNAs are considered to be ideal biomarkers because they are easy to detect, stable, and are strongly related to clinical outcomes compared with other biomarkers such as genetic and epigenetic alterations, posttranslational protein modifications, and metabolites.^\\[[@R4]\\]^ microRNAs are a variety of small noncoding RNAs that are involved in multiple oncological processes. miR-204-5p is a type of microRNA, and recent studies have reported that miR-204-5p was decreased in tumors and may serve as a prospective tumor suppressor"
-"Background {#Sec1}\n==========\n\nPostnatal period is the time period from birth to 42\u00a0days after birth. It is a period where most of the maternal and new-born death occur. Immediately after birth, bleeding and infection pose the greatest risk to the mother's life, while preterm birth, asphyxia, and severe infections pose the greatest risk to newborn \\[[@CR1], [@CR2]\\]. Most maternal and newborn deaths are avoidable because healthcare solutions to prevent or manage complications related to pregnancy and birth are well known. All these maternal and neonatal problems could be reduced if women receive appropriate postnatal care \\[[@CR1]\\].\n\nPostnatal care (PNC) is one of the recommended strategies to reduce the maternal and new-born deaths during the postpartum period \\[[@CR3], [@CR4]\\]. Hence, World Health Organization (WHO) recommends mothers and newborns should receive PNC in health facilities for at least 24\u00a0h after birth, if birth is in a health facility. While, if birth is at home, the first postnatal contact should be as early as possible within 24\u00a0h of birth. At least three additional postnatal contacts are recommended for all mothers and newborns on day 3 (48--72), between days 7--14 after birth, and six weeks after birth \\[[@CR4]\\]. However, In Africa,"
-"Introduction {#Sec1}\n============\n\nThis joint position paper, composed by an author group of members of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) and the European Society of Hypertension (ESH), is being published jointly in the Cardiovascular and Interventional Radiology Journal and the Journal of Hypertension. The paper attempts to review the evidence and provide some guidance and forward direction for this new and potentially still valuable technique. The article presented here is a brief executive summary of the full paper which can be found on the CIRSE and ESH websites.\n\nMethodology {#Sec2}\n===========\n\nCIRSE and the ESH produced this joint position paper using the following process. The formal decision of the two societies to draft a multidisciplinary joint position paper was taken in November 2013, following the discussion on the potential benefits of a joint statement on the occasion of the CIRSE annual meeting 2013 in Barcelona.\n\nBoth societies identified and nominated recognised experts as members of the joint writing group for the document. In the case of CIRSE, the renal denervation task force, an already established group of senior interventional radiologists and CIRSE members with significant experience in performing renal artery denervation, represented the society in the"
-"Background\n==========\n\nAutism is a heterogeneous disorder characterized by impairments in social interaction, deficits in verbal and nonverbal communication, restricted interests and repetitive behaviors \\[[@B1]\\]. Autism comprises the severe end of a group of autism spectrum disorders (ASD) \\[[@B2]\\]. The prevalence of autism is estimated at 0.2%, with males being more likely than females to have a diagnosis of autism (ratio of approximately 4:1) \\[[@B3]\\].\n\nThere is compelling evidence from twin and family studies indicating a strong genetic component in autism. The average risk of recurrence of autism in siblings is approximately 10% \\[[@B4]\\] in families with one affected sibling, which is much higher than the prevalence in the general population, but much lower than would be expected for a single-gene disease \\[[@B2]\\]. Indeed, cases of autism have only rarely been associated with mutations in single genes or with chromosomal duplications or other abnormalities \\[[@B5]-[@B9]\\]. Furthermore, the inheritance pattern in most cases of autism is complex and not compatible with simple Mendelian inheritance \\[[@B10],[@B11]\\]. A series of common autism susceptibility genes has been identified in the literature, but taken individually, the risk associated with these genes remains modest. Although spontaneous mutations may help explain isolated cases of autism, the inheritance"
-"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\nHigh-grade gliomas are the most common brain malignancy in adults and represent approximately 10% of childhood brain tumors.^[@R1]^ Outcomes for adult and pediatric *glioblastoma multiforme* (GBM) are poor with 2-year survival rates less than 20% despite multimodality therapy including surgery, chemotherapy, and radiotherapy.^[@R2],[@R3]^ Novel therapies are desperately needed, and oncolytic engineered herpes simplex virotherapy (oHSV) is one such therapy that offers a promising approach by targeting glioma cells while sparing normal cells. Normal cells are unharmed through deletions of various dispensable genes such as the neurovirulence gene \u03b3~1~34.5, which enables the wild-type virus to overcome a host cell\\'s defense mechanism to prevent virus replication.^[@R4]^ Oncolytic HSVs with \u03b3~1~34.5 deleted cannot evade protein kinase R (PKR)-mediated translational arrest which occurs in normal cells in response to HSV double-stranded RNA and prevents viral replication, rendering the virus safe for normal cells. Mutant \u03b3~1~34.5-deleted viruses may replicate in tumor cells with defective signaling pathways that result in an attenuated PKR response. Non-essential genes can be replaced with therapeutic foreign genes that augment the oncolytic effect, such as the human cytolomegalovirus (HCMV) *IRS1* gene. The *IRS1* gene product restores a critical function that is lost with the \u03b3~1~34.5-deletion by facilitating late"
-"INTRODUCTION\n============\n\n*Coriolus versicolor*, known as Yun-zhi in Korean, is a mushroom and belongs to the class Basidiomycetes. Medicinal mushrooms have been used to treat various diseases. Of theses, *Coriolus versicolor* has been demonstrated to possess a wide range of biological activities, which include anti-tumor, anti-bacterial, anti-viral, and immune-potentiating activities ([@B27]; [@B3]).\n\nNitric oxide (NO) is a reactive free radical gas and a messenger molecule with many physiological functions ([@B30]; [@B38]). NO is generated from L-arginine by nitric oxide synthase (NOS), and it is synthesized in neurons, astrocytes, microglial cells, endothelial cells, and many other cell types ([@B9]). Moreover, in the mammalian central nervous system, NO modulates many physiological functions including neurotransmission, synaptic plasticity, and memory ([@B11]; [@B13]). However, excessive NO formation is now believed to be a mediator of neurotoxicity, and NO is known to induce apoptosis in a variety of disorders, such as Alzheimer disease, acquired immune deficiency syndrome (AIDS) dementia, and multiple sclerosis ([@B10]; [@B8]).\n\nApoptosis, also known as programmed cell death, is a biological process that plays a crucial role in normal development and tissue homeostasis ([@B34]). However, this type of cell death also contributes to a variety of human disorders ([@B32]). The characteristic morphological changes"
-"1. Introduction {#sec1-sensors-19-03618}\n===============\n\nWearable devices have been developed to track the human body in a number of different areas, such as fitness \\[[@B1-sensors-19-03618]\\], healthcare \\[[@B2-sensors-19-03618]\\], entertainment \\[[@B3-sensors-19-03618],[@B4-sensors-19-03618]\\], and fashion \\[[@B5-sensors-19-03618]\\]. However, in early wearable computer research, the sensors and computing system were put into a pocket to be carried on the body \\[[@B6-sensors-19-03618]\\]. Since the 1970s and 1980s, clothing, accessories, and even the body itself were developed as an interface for various analog and digital functions by researchers \\[[@B7-sensors-19-03618]\\]. The exploration of digital textile interfaces provides the opportunity for wearable technology to be integrated into our daily lives and could provide access to data generated by the body.\n\nMore recently, with an increasing range of applications for wearable devices research into intelligent textiles has attracted considerable attention \\[[@B8-sensors-19-03618],[@B9-sensors-19-03618],[@B10-sensors-19-03618]\\]. Clothing is regarded as a second layer of skin for the human body---it keeps our body warm and protects us from the environment. On the basis of enhancing the basic functionality of clothing, researchers have started to explore its connectivity and interaction with surrounding objects and environment. \"Smart clothing\" \\[[@B11-sensors-19-03618]\\], \"wearables\" \\[[@B12-sensors-19-03618]\\], and \"wearable computing\" \\[[@B6-sensors-19-03618]\\] are innovating what otherwise would be generic clothing \\[[@B13-sensors-19-03618]\\]. Electronic textiles (e-textiles) combine textile technology"
-"All relevant data are within the paper and its Supporting Information files.\n\nIntroduction {#sec005}\n============\n\nThe prevalence and incidence of renal and ureteral lithiasis are increasing worldwide \\[[@pone.0237068.ref001], [@pone.0237068.ref002]\\]. Surgical treatments are evolving and flexible ureterorenoscopy (f-URS) has been shown to outperform extracorporeal shockwave lithotripsy (ESWL) and percutaneous nephrolithotomy (PCNL) in a number of indications \\[[@pone.0237068.ref003], [@pone.0237068.ref004]\\]. This depends mainly on the size, number and location of the stones. ESWL is a minimally invasive technique but often requires several procedures. PCNL seems to be the most successful but is the most invasive procedure \\[[@pone.0237068.ref005]\\]. f-URS also gives excellent results and is associated with a low complication rate \\[[@pone.0237068.ref006]\\]. Furthermore, f-URS is a safe and efficient option in specific populations such as obese patients \\[[@pone.0237068.ref007]\\].\n\nMany studies have evaluated the factors affecting the success rate of these procedures. Preoperative scores and nomograms have been developed and are available to predict the stone-free rate (SFR) with varying degrees of accuracy. Several factors affecting the outcome of ESWL and PCNL have been described and nomograms have been established \\[[@pone.0237068.ref008]--[@pone.0237068.ref011]\\].\n\nFor f-URS, four scores have been developed. Two of these have been compared and validated in different cohorts: the Resolu Unsal Stone Score (RUSS)"
-"Introduction {#s1}\n============\n\nOxidative stress has been considered to be an important intermediary step in the pathogenesis of preeclampsia [@pone.0012202-Hubel1]; however, several randomized clinical trials have failed to demonstrate any beneficial effect of concomitant supplementation of vitamin C (1000 mg) and vitamin E (400 IU) on the reduction of the rates of preeclampsia [@pone.0012202-Rumbold1]--[@pone.0012202-Xu1]. Instead, concomitant use of these antioxidants during pregnancy has been observed to increase the risk of low birth weight (less than 2500 g), preterm premature rupture of membranes (PROM), and fetal loss or perinatal death in women at risk for preeclampsia [@pone.0012202-Poston1], [@pone.0012202-Spinnato2], [@pone.0012202-Xu1]. The reasons why concomitant supplementation of vitamins C and E differentially affects pregnancy outcomes in healthy pregnant women and women at risk for preeclampsia are unclear.\n\nOne of the most common characteristic features in placentas from pregnancies complicated by preeclampsia is insufficient trophoblast invasion of maternal endometrial spiral arteries [@pone.0012202-Khong1]. As a result, perfusion of the placenta is impaired, and oxygen concentration within the intervillous space is more variable in comparison to a healthy pregnancy, resulting in an ischemia-reperfusion type injury [@pone.0012202-Hung1]. Such a change in the prevailing oxygen concentration may lead to a difference in the susceptibility of cytotrophoblasts and syncytiotrophoblast"
-"Mitochondria are among the prime suppliers of energy (ATP) in virtually all living cells[@b1][@b2] and empirical evidence suggests that their dysfunction is involved in the pathomechanism of Parkinson's disease (PD)[@b3][@b4][@b5]. Despite considerable progress, the potential role of mitochondrial (dys)function during PD development remains poorly understood. One of the main reasons for this lack of insight is the fact that there is no direct *in vivo* access to nigrostriatal dopaminergic neurons, the loss of which is one of the main pathological features of PD[@b6]. The latter study hypothesized the gastrointestinal tract may be the starting point of the disease and thus enteric neurons may reliably reflect fundamental disease characteristics. Indeed, both Lewy neurites and Lewy bodies (LB), abnormal protein aggregates that develop in nerve cells during PD, have been demonstrated in the submucosal colon nerve layer of patients with early PD[@b7][@b8][@b9][@b10][@b11]. This suggests that pathological aberrations observed in enteric neurons might represent an early stage of PD manifestation[@b7][@b8]. Furthermore, animal studies of enteric neurons suggest a direct involvement of mitochondrial dysfunction in PD. It was suggested that inhibitory enteric neurons are particularly vulnerable to mitochondrial dysfunction induced by Parkinsonian neurotoxins[@b12]. In this sense, mice treated with a chemical inhibitor of the"
-"Introduction\n============\n\nHeterotopic ossification (HO) is a process of benign bone formation and growth outside of normal skeletal locations. It is associated with numerous local and systemic conditions. These include hip replacement and acetabular surgery, soft-tissue and bony trauma, burns, rare congenital diseases such as fibrodysplasia ossificans progressiva, rheumatologic diseases such as ankylosing spondylitis, and neurological conditions including tumours of the central nervous system, encephalitis, traumatic brain injury and spinal cord injury.^[@r1]-[@r4]^\n\nNeurogenic heterotopic ossification (NHO) is a devastating complication of major central nervous system trauma seen in more than 20% of patients with traumatic brain injury and/or spinal cord injury,^[@r1]^ appearing in characteristic patterns around major joints. Significant morbidity can be observed at the site of this formation of new bone, including pain and loss of motion especially around joints. In addition, the development of NHO increases the risk of complications such as urinary tract infection (UTI) and pressure ulcers, which can significantly impair quality of life.^[@r2]^ The aetiology is not clearly known; however, there is some evidence of a complex interplay between local and systemic factors including neuroendocrine, genetic and extrinsic factors. Mainstays of management include primary and secondary prevention with radiation and non-steroidal anti-inflammatory drugs (NSAIDs). Traditionally,"
-"The authors confirm that all data underlying the findings are fully available without restriction. The data have been published previously and can be accessed through the following accession numbers GSE36063 (Brogaard, 2012), E-MEXP-1172 (Lee, 2007), GSE25133 (Valouev, 2011), and SRA030538.1 (Zhang, 2011), and the following URL <http://bioinfo.stats.northwestern.edu/~jzwang/Yigit2013NAR.html> (Yigit, 2013).\n\nIntroduction {#s1}\n============\n\n*In vivo*, promoters are characterized by a nucleosome free region (NFR) that is followed by a periodic phasing of well-positioned nucleosomes continuing into the gene body. In yeast, this phasing is absent *in vitro*, but can be restored by the addition of a whole cell extract (WCE) and ATP, presumably a result of ATP-dependent chromatin remodelers (CRs) [@pone.0110479-Zhang1]. The promoter NFR, however, is largely preserved *in vitro* because yeast promoters contain sequences that are inherently refractory to nucleosome formation, such as low G/C content [@pone.0110479-Tillo1] and poly-dA:dT tracts [@pone.0110479-Kaplan1].\n\nYeast promoters have a biased distribution of poly-A and poly-T elements flanking nucleosome free regions [@pone.0110479-Wu1], [@pone.0110479-Hampson1], which cannot be explained solely by the biased base content ([**Figure 1**](#pone-0110479-g001){ref-type=\"fig\"}). This asymmetric poly-A/poly-T arrangement has no known function and is incongruous with the model that poly-dA:dT tracts simply exclude nucleosomes via a rigid DNA structure [@pone.0110479-Iyer1] since the DNA should"
-"Introduction\n============\n\nThe combined actions of neural input, muscles, and the joint(s) about which those muscles act serve to produce sufficient endpoint force for physical function, allowing the performance of activities of daily living, as well as the spectrum of athletic endeavors. Due to the complexity of the neuromuscular and musculoskeletal systems, many factors can influence strength, including, but not limited to, muscle moment arm, muscle size, activation, muscle architecture, and normalized muscle force (or specific tension) ([@ref-74]). Muscle size is of particular interest, as (1) it is highly plastic ([@ref-33]) and (2) a clear positive relationship exists between baseline muscle cross-sectional area (CSA) and strength, with greater CSAs correlating with greater strength capacities ([@ref-55]; [@ref-56]; [@ref-68]). However, this relationship is not necessarily linear, as several additional factors interactively influence strength capacity ([@ref-74]); studying the role of and relationship between muscle size and strength is therefore less straightforward under longitudinal contexts.\n\nWhile the cross-sectional correlation between muscle mass and strength remains well-established, some researchers have recently challenged the belief that resistance training (RT)-induced hypertrophy significantly impacts the ability to produce force, claiming improvements in these outcomes are separate and unrelated adaptations ([@ref-17]). Indeed, data remain somewhat equivocal on the relationship"
-"INTRODUCTION {#s1}\n============\n\nCancers can be intrinsically resistant to chemotherapy or may develop resistance to chemotherapy during treatment. Both intrinsic and acquired resistance to anticancer drugs are major causes of treatment failure in patients with cancer. Most anticancer drugs, chemotherapeutic agents (such as 5-FU, gemcitabine, cisplatin, oxaliplatin, and paclitaxel) and molecularly targeted agents (such as imatinib, vemurafenib, and bortezomib) induce apoptosis. However, many cancer cells evade apoptosis by modulating pro- and anti-apoptotic proteins and eventually become resistant to anticancer drugs. Apoptosis evasion by drug resistance is a major factor in cancer cell survival and limits chemotherapy effectiveness \\[[@R1], [@R2]\\]. Moreover, despite the performance of increasing numbers of studies regarding pro-apoptotic anticancer drugs, no strategies designed to overcome the limitations of these drugs have been established.\n\nNecrosis is characterized by cytoplasmic swelling and cytoplasmic translucency, as well as the loss of plasma membrane integrity and the release of intracellular contents into the extracellular environment, which usually stimulates inflammation. Necrosis has also been regarded as an uncontrolled form of cell death \\[[@R3], [@R4]\\]. However, the results of recent studies indicate that necrosis, like apoptosis, can also occur through a regulated process, namely, necroptosis \\[[@R5]\\]. Necroptosis is caspase-independent and is mediated by receptor-interacting"
-"Background {#Sec1}\n==========\n\n4-1BB (CD137; TNFRSF9) is an inducible costimulatory molecule. It and its ligand were discovered in the 1980s in activated T cells and antigen-presenting cells (APCs) \\[[@CR1], [@CR2]\\]. 4-1BB, a Type I membrane glycoprotein, is a member of the tumor necrosis factor receptor (TNFR) superfamily. It augments cellular immunity via signal transmission through protein--protein interactions that either extend survival or enhance costimulatory signals. The 4-1BB gene is localized on chromosome 1p36, close to other TNFR family members, including TNF-RII, OX40 and CD30. T-cell activation upregulates the expression of 4-1BB \\[[@CR3]--[@CR5]\\].\n\n4-1BB is induced within 24\u2009h of activation. Signaling through the T-cell receptor (TCR) or CD3 can stimulate it on T cells \\[[@CR4], [@CR6], [@CR7]\\]. Its expression has also been found on NKT cells, monocytes, macrophages, activated B cells, dendritic cells, eosinophils, neutrophils, epithelial and hepatoma cells, CD11^+^ dendritic cells and regulatory T cells \\[[@CR8]\\].\n\n4-1BB binds to its ligand (4-1BBL or CD137L), a transmembrane molecule of the TNF family that is expressed by APCs. 4-1BBL is induced after cell activation and can be regulated by LPS, Ig or CD40 signals \\[[@CR4], [@CR6], [@CR7], [@CR9]\\]. In addition to T-cell costimulation through the 4-1BB receptor, 4-1BBL has the ability"
-"Sequence data has been deposited to the European Nucleotide Archive under accession number PRJEB33774. Additionally, a fully reproducible workflow of the analysis presented in this manuscript can be found at (<https://github.com/chandni177/BacterialViralMicrobiome_of_GrowthVelocity_in_EED>) along with the required data files.\n\nIntroduction {#sec001}\n============\n\nStunting, defined as height for age greater than two standard deviations below the median, is a neglected tropical disease. One-third of the half-billion preschool children in low and middle-income countries are stunted \\[[@pntd.0008387.ref001]\\], an anthropometric status that is strongly associated with \\~20% of all-cause mortality before age five. Stunted individuals who survive early childhood are predisposed to long-term cognitive deficits, poor school performance, lower economic productivity \\[[@pntd.0008387.ref001]\\], and metabolic syndrome \\[[@pntd.0008387.ref002]\\]. Stunting has intergenerational consequences, since maternal short stature, presumably a legacy of childhood stunting, is a risk for intra-uterine growth retardation \\[[@pntd.0008387.ref003]\\] and perinatal mortality \\[[@pntd.0008387.ref004]\\].\n\nEnvironmental enteric dysfunction (EED) was first described in healthy adults in resource poor settings \\[[@pntd.0008387.ref005]\\], then in Peace Corps volunteers in South Asia \\[[@pntd.0008387.ref006]\\], and later in children in regions of the world with inadequate dietary intake, sanitation and hygiene \\[[@pntd.0008387.ref007]\\]. EED is characterized by diffuse villous atrophy of the small bowel. EED has been defined through biopsies: decreased villus height, lymphocytic infiltration"
-"INTRODUCTION {#s1}\n============\n\nThe receptor VPAC1 belonging to class B G-protein coupled receptors (GPCR) family is shared by pituitary adenylate cyclase activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) with identical binding affinity \\[[@R1]\\]. VPAC1 not only localizes in central nervous system such as forebrain, thalamus, cerebral cortex and hippocampus, but also spreads in numerous peripheral organs, including liver, kidney, prostate, breast, spleen, lung, gastrointestinal tract, and in almost all epithelial tissues \\[[@R2]\\]. Moreover, the expression of VPAC1 is also reported associated with some special physiological and pathological processes \\[[@R3]\\]. For example, high expression level of VPAC1 has been found in various malignant epithelia-derived tumors and their metastases, such as colorectal carcinoma \\[[@R4]\\], breast carcinoma \\[[@R5]\\], prostate carcinoma \\[[@R6]\\] and lung carcinoma. On the other hand, the lower expression level of VPAC1 is corresponding to the more severe inflammation and the higher disease activity in rheumatoid arthritis \\[[@R7], [@R8]\\]. Since the variation of VPAC1 expression is always correlated with the occurrence and development of diseases such as tumor and immune disorders, the structure-activity-relation study of VPAC1 not only help to explain the physiological and pathological functions of VPAC1, but also provide the research basis for the drug screening and development"
-"Introduction\n============\n\nMelamine (2,4,6-triamino-1,3,5-triazine) is an organic base, found usually in the form of white crystals, with a high nitrogen content, \\~66% by mass.[@b1-aci-10-2015-053] It is used for the manufacturing of several laminates, plastics, dishware, and kitchenware, as well as in the synthesis of melamine formaldehyde resins. It can migrate from these household items into food under acidic conditions or at higher temperatures.[@b2-aci-10-2015-053] It has also been illegally added as a nitrogen source in animal feeds and human foods, such as milk and milk products, to increase the protein concentration because it increases the nitrogen content, which is actually measured by the Kjeldahl method.[@b3-aci-10-2015-053] It can also be found in animal products due to the degradation of cyromazine present in animal feed, since melamine is one of the primary metabolites of cyromazine. By forming an insoluble salt, it may precipitate in kidneys and lead to renal function failure.[@b4-aci-10-2015-053] European Commission has agreed a maximum acceptable limit of 2.5 mg/kg for melamine in imported foods and 1 mg/kg in infant formula.\n\nCyromazine (*N*-cyclopropyl-1.3.5-triazine-2.4.6-triamine) is a triazine derivative used as pesticide and insect growth regulator. It is effective against blowfly larvae on sheep and lambs. It is also effective against other Diptera"
-"**What's Known**\n\nChemotherapy with cyclophosphamide (CTX) damages ovaries.Transplantation of bone marrow stromal cells (BMSCs), as a type of mesenchymal stem cells, repairs damaged ovaries following chemotherapy.Granulocyte colony-stimulating factor (G-CSF), as a growth factor, has beneficial effects on damaged ovaries.\n\n**What's New**\n\nG-CSF may have the potential to regenerate ovaries damaged by chemotherapy with CTX.Coadministration of BMSCs and the G-CSF may be more effective than either of them alone on ovaries damaged by chemotherapy \u2022with CTX.\n\nIntroduction {#sec1-1}\n============\n\nOvarian dysfunction is common in premenopausal women receiving chemotherapy, and approximately 30% of women aged less than 35 years and 50% of women aged between 35 and 40 years tend to experience menstrual function cessation after chemotherapy, leading to premature ovarian failure (POF) or menopause.^[@ref1]^ POF is described as secondary infertility with elevated gonadotropin levels before age 40, with an estimated incidence rate of 1%.^[@ref2]^ The use of chemotherapy increases the cure rate in young cancer patients, but some side effects such as ovarian failure and infertility may occur. POF due to chemotherapy causes cytotoxic effects, which will damage granulosa cells (GCs) and will, thus, possibly lead to folliculogenesis disruption.^[@ref3]^ Cyclophosphamide (CTX) is one of the most commonly used chemotherapy drugs, and"
-"Background\n==========\n\nChronic pancreatitis (CP) as a chronic and progressive condition requires a specific approach for quality of life (QOL) assessment. As a chronic disease with debilitating symptoms, consequences of diabetes mellitus, malabsorption and weight loss and possibility of complications (including cancer), CP severely affects QOL \\[[@b1-medscimonit-17-10-cr583]--[@b3-medscimonit-17-10-cr583]\\].\n\nNumerous studies have shown the heterogeneous character of the disease, with the interaction of physical, psychological and social factors \\[[@b1-medscimonit-17-10-cr583],[@b4-medscimonit-17-10-cr583],[@b5-medscimonit-17-10-cr583]\\].\n\nAs long as the pathophysiological background of pain in CP remains uncertain, the management of CP patients is based on a trial and error approach. Commonly used therapeutic methods of treatment remain insufficient because patients' quality of life is highly impaired \\[[@b1-medscimonit-17-10-cr583]--[@b3-medscimonit-17-10-cr583]\\]. Chronic pancreatitis cannot be cured and may require many clinical interventions and frequent hospitalization. Quality of life is the priority outcome measure in chronic untreatable diseases. This also requires a high level of patient-doctor communication and compliance. Alcohol abuse and disease-related unemployment have negative impacts on coping with the disease. Chronic pancreatitis affects all aspects of patients' lives: work, leisure, travel and relationships. It is not surprising that the multidimensional approach should be taken with these patients \\[[@b1-medscimonit-17-10-cr583]--[@b3-medscimonit-17-10-cr583]\\].\n\nIt is well documented that quality of life is an important variable and"
-"Introduction {#sec1}\n============\n\nThe apolar membrane creates an ideal environment for making strong hydrogen bonds. Nevertheless, direct measurements of hydrogen bonds made between amino acid side chains in membrane proteins indicate that their full potential strength is rarely realized, presumably because side-chain flexibility and water penetration into membrane proteins afford many opportunities for competing hydrogen bonds.^[@ref1]\u2212[@ref10]^ However, backbone hydrogen bonds might be generally stronger than side-chain hydrogen bonds because there are fewer alternative hydrogen bonding partners. On the other hand, strong backbone hydrogen bonds would make it difficult to create the many transmembrane (TM) helix distortions and breaks^[@ref11]\u2212[@ref13]^ often required for function.^[@ref14]\u2212[@ref18]^ We previously argued that one important mechanism for generating TM helix distortions is through the formation of alternative backbone hydrogen bonds, i.e., shifts from canonical *i*+4 \u03b1-helical hydrogen bonds to *i*+3 or *i*+5 hydrogen bonds, thereby maintaining hydrogen bonding, yet allowing for conformational flexibility.^[@ref19]^ It also remains possible that that the sequences evolved to optimize hydrogen bond strengths, sometimes to create weak points in TM helices as needed to satisfy functional requirements.\n\nTo test the possibility that backbone hydrogen bond strengths might be variable we sought a direct way to measure backbone hydrogen bond free energies. While the"
-"Background\n==========\n\nVascular endothelial growth factor (VEGF), a diffusible glycoprotein produced by normal and neoplastic cells, is an important regulator of physiologic and pathologic angiogenesis. Increased VEGF levels in serum or tumor tissue have been reported to correlate with poor survival; therefore, efficacy of anti-VEGF therapy is expected in clinical application \\[[@B1],[@B2]\\].\n\nBevacizumab is a humanized monoclonal antibody to human VEGF that inhibits VEGF-mediated angiogenesis in many types of tumors. In the US and EU, bevacizumab is used in combination with standard chemotherapies for patients with colorectal cancer, non-small cell lung cancer, breast cancer, and glioblastoma. Although bevacizumab improves progression-free survival (PFS) in these cancers, it is not effective for all patients. Predictive markers of bevacizumab efficacy have been assessed in many clinical trials \\[[@B3]\\], however, no validated biomarker is available to predict bevacizumab efficacy and identify the patients who could benefit from bevacizumab. Therefore, it is important to investigate the biomarker of bevacizumab efficacy from the phase of clinical development for other cancer types.\n\nGastric cancer is one of the most malignant cancers and second leading cause of cancer death in the world \\[[@B4]\\]. The incidence is reportedly highest in Asia, South America, and Southern Europe \\[[@B5]\\]. Increased levels"
-"Background\n==========\n\nCommonly, the musculoskeletal physical exam is focused on measures of range of motion (ROM) and muscular strength of the affected segment that could not provide enough information about overall segment functional level of activity \\[[@B1]\\]. Thus, shoulder evaluation could be improved by including techniques those assess functional movements and biomechanical impairment present in professional or daily life activities \\[[@B1]\\]. Functional tests could be considered a valuable complementary low-cost clinical tool to provide quantitative data about the functional ability and performance of a body segment \\[[@B2],[@B3]\\]. Some tests also can be used to record the progress of a rehabilitation protocol by measuring, for example, performance and ability of a patient during physical task \\[[@B4]-[@B7]\\].\n\nThe *Closed Kinetic Chain Upper Extremity Stability Test* (CKCUES Test) is a performance test that provides quantitative data (score) for a upper extremity task in closed kinetic chain (CKC) with no needs of high technology to be realized in sportive or clinical settings. The test consists in counting how much times, during 15\u00a0seconds, the subject assuming a push-up position is able to touch his/her supporting hand with the swinging hand. The test is considered easy for clinicians to apply and also easy for clients"
-"**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"
-"Background {#Sec1}\n==========\n\nRecent advances in metabolic engineering enable the use of microbes such as *E. coli* and *S. cerevisiae* for the production of chemicals \\[[@CR1]--[@CR12]\\]. Compared to traditional fossil fuel-based processes, bio-processes can be advantageous for their mild production conditions and good selectivity toward a specific product \\[[@CR13]\\]. Also, the chemicals can be produced directly using microbes instead of being converted via multiple conversion steps (some of which can have low yield and high cost) from fossil fuel feedstocks.\n\nTerpenes (also known as isoprenoids or terpenoids) are a class of organic compounds biosynthetically derived from isoprene (C~5~H~8~: CH~2~=C(CH~3~)--CH=CH~2~) and can be classified into groups according to the number of carbons they contain: hemiterpene (C~5~, i.e., isoprene), monoterpenes (C~10~; major interest of many studies), sesquiterpenes (C~15~), diterpenes (C~20~), triterpenes (C~30~), etc. \\[[@CR14]--[@CR17]\\]. Terpenes have been attracting substantial attention due to their relatively high prices and wide applications in chemical, food, cosmetics, pharmaceutical, fragrance, flavor and biotechnology industries \\[[@CR14], [@CR18]--[@CR23]\\]. Some terpenes, such as limonene and linalool, are also potential drop-in biofuels and platform chemicals to produce other value-added products \\[[@CR24]--[@CR26]\\].\n\nThe microbial conversion of terpenes from sugar via microbes has been reviewed extensively \\[[@CR14], [@CR27]--[@CR36]\\]. Terpenes can be produced mainly"
-"Introduction\n============\n\nChronic obstructive pulmonary disease (COPD) is a common chronic condition associated with a rapidly increasing physical, social, and economic burden in terms of both direct healthcare costs including hospitalisations and medication and indirect costs (productivity loss, work absenteeism, premature retirement).^[@bib1]^ It is estimated that approximately 210 million people worldwide have COPD,^[@bib2]^ and its incidence is believed to be rising.^[@bib3]^ Mortality predictions suggest that COPD will become the third leading cause of death in 2020 and the fourth leading cause of death in 2030.^[@bib4]^ There is therefore an urgent need to develop innovative COPD management models. In this context, nurses are uniquely positioned to make a substantial contribution as they are often the first point of contact for patients and are actively engaged throughout the disease management process, frequently providing palliative care.\n\nIn this discussion paper we explore the role of nurses in the management of COPD and highlight some of the barriers which are currently preventing nurses from expanding and strengthening their role. We also suggest some possible strategies to help nurses overcome these obstacles.\n\nCOPD and nursing: from prevention to palliation\n===============================================\n\nThe nursing role in COPD --- and essentially in all chronic diseases --- is becoming"
-"The DNA damage response (DDR) is a coordinated signalling network involving a large number of interacting proteins controlled by post-translational modifications and includes signalling, cell--cycle checkpoint enforcement and DNA repair[@b1][@b2]. Following DNA double-strand break (DSB) generation, the apical DDR kinase ataxia telangiectasia mutated (ATM) undergoes activation and phosphorylates the histone H2AX at serine 139 (named \u03b3H2AX); this event is necessary for the recruitment of DDR proteins to sites of DNA damage, including ATM phosphorylated at serine 1,981 (pATM) itself and p53-binding protein 1 (53BP1). Recently, a class of small non-coding RNAs (ncRNAs), termed DNA damage response RNAs (DDRNAs), has been shown to be generated on transcription of the damaged locus following DSB induction and then processed by the endoribonucleases DICER and DROSHA[@b3][@b4][@b5]. DDRNAs are dispensable for the direct recognition of DNA damage and \u03b3H2AX phosphorylation, but necessary for the secondary recruitment of DDR proteins to DSBs to form the so-called DDR foci[@b6]. A similar set of small ncRNAs, named damage-induced RNAs, has been shown to be involved in DNA repair by homologous recombination (HR) in plants and human cells[@b7][@b8], and by non-homologous end-joining (NHEJ) in plants[@b9].\n\nTelomeres are the nucleoprotein complexes located at the tips of eukaryotic chromosomes, composed 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"
-"Background\n==========\n\nThe bacterial genus *Arsenophonus*corresponds to a group of insect intracellular symbionts with a long history of investigation. Although many new *Arsenophonus*sequences have been published in the last several years, along with documentation of diverse evolutionary patterns in this group (Figure [1](#F1){ref-type=\"fig\"}), the first records of these bacteria date to the pre-molecular era. Based on ultrastructural features, several authors described a transovarially transmitted infection associated with son-killing in the parasitoid wasp *Nasonia vitripennis*\\[[@B1]-[@B3]\\]. Later, they were formally assigned to a new genus within the family Enterobacteriaceae with a single species, *Arsenophonus nasoniae*\\[[@B4]\\]. The same authors proposed a close relationship of *Arsenophonus*to free-living bacteria of the genus *Proteus*. Independently, other microscopic studies revealed morphologically similar symbionts from various tissues of blood-sucking triatomine bugs \\[[@B5],[@B6]\\]; a decade later these bacteria were determined on molecular grounds to belong to the same clade and were named *Arsenophonus triatominarum*\\[[@B7]\\]. Interestingly, the next record on symbiotic bacteria closely related to *A. nasoniae*was from a phytopathological study investigating marginal chlorosis of strawberry \\[[@B8]\\]. Since available sequence data were insufficient for reliable phylogenetic placement, the phloem-inhabiting pathogen was described as a new genus, *Phlomobacter*, with a single species *P. fragariae*\\[[@B8]\\].\n\n![**An increase of records on *Arsenophonus*bacteria from"
-"Introduction\n============\n\nOvarian cancer remains one of the leading causes of death from gynecologic cancer worldwide [@B1]. One of the reasons for this dismal prognosis is that, on most occasions, ovarian cancer is diagnosed at an advanced stage [@B2]. To improve survival of advanced ovarian cancer patients, cytoreductive surgery to achieve a largest residual tumor mass of 1 cm or less in maximum diameter (e.g., optimal cytoreduction) followed by postoperative chemotherapy is recommended [@B3], [@B4]. However, if patients fail to achieve optimal cytoreduction, they may experience major morbidity without survival benefit [@B5]. In addition, interval debulking surgery has not been considered to be useful for patients with a largest residual tumor more than 1 cm in maximum diameter after primary surgical cytoreduction [@B6]. To overcome situations in which it is difficult to achieve optimal cytoreduction, interval cytoreduction following neoadjuvant chemotherapy (NAC) has been suggested as an alternative treatment to primary cytoreductive surgery plus postoperative chemotherapy [@B2], [@B5]. Therefore, the precise pretreatment discrimination of patients\\' not amenable to optimal cytoreduction may be one of the principal determinants of prognosis in ovarian cancer [@B7].\n\nSeveral researchers have endeavored to identify the specific predictors of cytoreductive outcomes. With respect to age, optimal cytoreduction"
-"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"
-"Background\n==========\n\nJuvenile xanthogranuloma (JXG) is a benign idiopathic cutaneous granulomatous tumor occurring primarily in infants less than 1\u00a0year old, and less commonly found in older children and adults \\[[@B1],[@B2]\\]. Cutaneous lesions appear as orange-red macules or papules, predominantly over the face, neck, and upper trunk and usually resolve spontaneously over 1 to 5\u00a0years \\[[@B1]\\]. Ocular JXG occurs up to 10% of patients with JXG, usually as a solitary mass in the iris. This can cause spontaneous hyphema or secondary glaucoma, threatening the vision of affected individuals \\[[@B1],[@B3]\\]. Ocular JXG may also involve the eyelid, corneoscleral limbus, conjunctiva, orbit, retina, choroid, disc, and optic nerve \\[[@B2],[@B4],[@B5]\\].\n\nAlthough JXG mainly occurs in infants, it is occasionally encountered in adults, with several adults reported with corneoscleral limbal JXG \\[[@B6]-[@B11]\\]. To date, however, there have been no reports of patients older than 50\u00a0years of age with corneoscleral JXG without limbal involvement. Here, we describe a 58-year-old woman who presented with subconjunctival JXG without limbal involvement.\n\nCase presentation\n=================\n\nThis study has been granted an exemption from requiring ethics approval by the Institutional Review Board of the Ethics Committee of Asan Medical Center, Seoul, Korea, under the tenets of the Helsinki"
-"1. Introduction {#sec1}\n===============\n\nLiving with limited resources on the planet represents a tremendous challenge due to our increasing global population.^[@ref1]^ The growing demand for fuels and chemicals and the society's dependence on nonrenewable petroleum should be addressed simultaneously through the development of sustainable technologies that would enable the efficient utilization of renewable resources.^[@ref2]\u2212[@ref5]^ Such an attractive, carbon-neutral and nonedible starting material is lignocellulose, generated in considerable quantities from forestry and agricultural activity worldwide.^[@ref5],[@ref6]^ Moreover, food waste has been put forward as an economically significant, lignocellulose-rich resource.^[@ref7]^ In the past decade, significant advances have been achieved regarding the development of biorefineries suitable for the fractionation of lignocellulose to its main constituents: cellulose, hemicellulose, and lignin.^[@ref8]\u2212[@ref10]^ However, in order to create economically feasible biorefineries and overcome the initial energy cost associated with processing and pretreatment, all three major constituents should be fully valorized.^[@ref7]\u2212[@ref10]^ Novel chemo- or biocatalytic routes should enable the conversion of these biobased starting materials to chemicals and fuels. In this regard, the catalytic conversion of lignin was found extremely challenging,^[@ref11]^ mainly due to the robustness and complexity of its structure.^[@ref12]\u2212[@ref14]^\n\nDespite these encountered challenges, the catalytic conversion of lignin has remained a scientifically intriguing research problem that can"
-"All datasets, config files, documentation, and scripts used in this analysis or to generate figures are available publicly at \\<<https://github.com/blab/siv-cst>\\>.\n\nIntroduction {#sec001}\n============\n\nAs demonstrated by the recent epidemics of EBOV and MERS, and by the global HIV pandemic, viral cross-species transmissions (CST) can be devastating \\[[@ppat.1006466.ref001],[@ppat.1006466.ref002]\\]. As such, understanding the propensity and ability of viral pathogens to cross the species barrier is of vital public health importance. Of particular interest are transmissions that not only \"spillover\" into a single individual of a new host species, but that result in a virus actually establishing a sustained chain of transmission and becoming endemic in the new host population (\"host switching\") \\[[@ppat.1006466.ref003]\\].\n\nHIV is the product of not just one successful host switch, but a long chain of host switch events \\[[@ppat.1006466.ref004],[@ppat.1006466.ref005]\\]. There are two human immunodeficiency viruses, HIV-2 and HIV-1. HIV-2 arose from multiple cross-species transmissions of SIV*smm* (simian immunodeficiency virus, *sooty mangabey*) from sooty mangabeys to humans \\[[@ppat.1006466.ref006]--[@ppat.1006466.ref008]\\]. HIV-1 is the result of four independent cross-species transmissions from chimpanzees and gorillas. Specifically, SIV*cpz* was transmitted directly from chimpanzees to humans twice; one of these transmissions generated HIV-1 group M, which is the primary cause of the human pandemic \\[[@ppat.1006466.ref009]\\]. SIV*cpz*"
-"Introduction {#s1}\n============\n\nBovine tuberculosis (bTB) is an insidious, progressive disease of livestock that has cost the United States livestock industry millions of dollars in losses prior to and since the establishment of a national eradication campaign in 1917 [@pone.0050147-Essey1]. Despite this large-scale eradication effort, bTB is a reemerging infectious disease in the U.S. It is endemic in select areas of Michigan and recent outbreaks have occurred in Minnesota, California, and New Mexico.\n\n*Mycobacterium bovis*, the causative agent of bovine tuberculosis, creates significant problems for agriculture at both the state and national levels. From a management and animal health perspective, it is essential that infected animals are reliably detected and removed to prevent the spread of the disease. Current diagnostic tests are primarily based on immune responses to crude protein extracts from *M. bovis* (PPDb) injected intradermally. Three days after injection of PPDb, excessive swelling at the injection site indicates that the animal may be infected with *M. bovis*.\n\nThe sensitivity (*Se*) and specificity (*Sp*) of the single intradermal test (SIT) depends on a cut-off value, and there is an inverse relationship between test *Se* and *Sp* values [@pone.0050147-delaRuaDomenech1]. For example, the SIT test *Se* could be as high as"
-"Phendimetrazine (PDM) is a clinically available and widely prescribed anti-obesity medication[@b1]. Recently, 14--21 day PDM treatment was shown to decrease cocaine self-administration in preclinical cocaine addiction models[@b2][@b3], and it is currently being evaluated as a candidate pharmacotherapy in human laboratory cocaine self-administration studies (NCT02233647 and NCT0252235). Structurally, PDM is an *N*-methyl analog of the monoamine transporter substrate phenmetrazine (PM; [Fig. 1](#f1){ref-type=\"fig\"}) and is hypothesized to function as a prodrug that requires biotransformation to PM as its active metabolite to produce its effects[@b4][@b5]. From a clinical therapeutic perspective, prodrugs are advantageous for multiple reasons[@b6]. As one example, prodrug formulations may slow onset of central nervous system-active drug effects reducing abuse liability[@b7][@b8]. A recent example is the amphetamine prodrug lisdexamfetamine[@b9][@b10][@b11]. However, research regarding whether PDM functions as an inactive prodrug or has pharmacological activity on its own has produced inconsistent results.\n\nThere are two main lines of evidence supporting the hypothesis that PDM functions as an inactive prodrug. First, *in vitro* studies found that PDM possessed measurable but very low potency to block the dopamine transporter (DAT) in rat brain synaptosomes (IC~50~\u2009=\u200919\u2009\u03bcM)[@b5]. By contrast, PM was approximately 30-fold more potent to block DAT (IC~50~\u2009=\u20090.6\u2009\u03bcM) and 100-fold"
-"Introduction {#sec001}\n============\n\nCockayne syndrome (CS) is an autosomal recessive disorder with shunted growth and developmental defects involving a wide range of tissues and organs \\[[@pone.0128558.ref001]\\]. Among these, progressive neurological abnormalities including demyelination, ataxia, and cerebellar atrophy are the hallmarks of this syndrome. Two genes (*CSA and CSB*) have been implicated in the pathogenesis of Cockayne syndrome and patients with mutations in *CSB* are more frequent \\[[@pone.0128558.ref002], [@pone.0128558.ref003]\\]. The CSB is a member of the SWI/SNF ATP dependent chromatin remodeling family of proteins \\[[@pone.0128558.ref004]\\] and plays a role in transcription-coupled repair (TCR), an important sub-pathway of nucleotide excision repair (NER) \\[[@pone.0128558.ref005]--[@pone.0128558.ref007]\\]. Patients afflicted with CS exhibit multiple pathological symptoms and some of which may not be solely explained by DNA repair defects. This has led to the hypothesis that CSB has additional roles in processes other than the TCR pathway \\[[@pone.0128558.ref007]--[@pone.0128558.ref010]\\]. Consistent with this notion, CSB protein has been shown to interact and stimulate the transcriptional complexes of all the three nuclear RNA polymerases (I, II and III), indicating a regulatory role for CSB in basal transcription \\[[@pone.0128558.ref011]--[@pone.0128558.ref018]\\]. Additionally, CSB has been demonstrated to be a key regulator of p53 pathway \\[[@pone.0128558.ref019]--[@pone.0128558.ref022]\\]. Unraveling additional novel functions of CSB is likely"
-"This is the Coat of Arms of the College of Anaesthetists in Dublin granted to the College in 1999 ([fig 1](#fig1){ref-type=\"fig\"}). In central position, representing anaesthesia is a shield containing poppy heads. The cloud above represents the downwards drift to unconsciousness with the healing hand of the physician in attendance. The cloud might have another interpretation for there can hardly be a treatment in medicine which is so widely applied and yet so little understood. The supporters are unusual in heraldry taking the form of dolphins and these provide a link to one of the founders of this Society, James MacDonnell ([fig 2a](#fig2){ref-type=\"fig\"}) whose family coat of arms also bears this heraldic symbol ([fig 2b](#fig2){ref-type=\"fig\"}).\n\n![Coat of Arms of the College of Anaesthetists](umj7803-146-f1){#fig1}\n\n###### \n\nBust (left) and coat of arms (right) of James MacDonnell\n\n![](umj7803-146-f2a)\n\n![](umj7803-146-f2b)\n\nAs most of you will know James was a son of the Glens and the first of a family of doctors all of whom rose to distinction in different ways. His thesis entitled 'On the Drowned' is the first formal account of resuscitation methods, and perhaps he might have been attracted to emergency medicine or even anaesthesia, had he lived a generation later. As"
-"Adults with a history of childhood-onset GH deficiency or with hypothalamic/pituitary disease, surgery, or irradiation to these areas, head trauma, or evidence of other pituitary hormone deficiencies are at risk for adult GH deficiency (AGHD). Because symptoms are usually nonspecific, in the absence of panhypopituitarism and low serum IGF-I levels, the diagnosis of AGHD requires biochemical confirmation with at least 1 GH stimulation test ([@B1]). The insulin tolerance test (ITT) is considered the gold standard test for AGHD, having a sensitivity of 96% and a specificity of 92% ([@B1]). However, because it induces hypoglycemia, the test is contraindicated in patients with coronary artery disease, seizures, and in the elderly ([@B1]). GHRH combined with arginine (arginine+GHRH) has been endorsed by several consensus guidelines ([@B2][@B3][@B4]) as the main alternative when the ITT is contraindicated, having a sensitivity of 95% and a specificity of 91% ([@B1]); but when GHRH analog (Geref Diagnostic; Serono Laboratories, Rockland, Massachusetts) was withdrawn in the United States in 2008, the need for an alternative to the ITT increased ([@B2]). The diagnosis of AGHD is important, given that the treatment of this condition, although expensive, has consistently shown improvements in body composition, exercise capacity, endothelial function, inflammatory biomarkers, bone"
-"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 {#j_pp-pp-2018-0108_s_006}\n============\n\nPeritoneal carcinomatosis (PC) represents end stage disease in many types of cancer (e.g. gastric, pancreatic, liver, colo-rectal, ovarian) and, if left untreated, the majority of patients with PC will die from their disease within 6 months \\[[@j_pp-pp-2018-0108_ref_001]\\]. Platinum-based systemic chemotherapy (SC) may prolong survival in selected patients, but poor performance status and low response rates have led to nihilistic treatment strategies in these patients. However, patients with PC who are in good condition and with a remaining life expectancy of more than a few months, may still have an unmet need for additional treatment in order to be able to perform with a high quality of life for as long as possible. These patients have often tried several lines of SC with disappointing results, and alternative and more effective treatment strategies are needed.\n\nThe installation of chemotherapeutic agents within the peritoneal cavity would seem a simple and effective treatment of PC -- at least from a theoretical point of view. Unfortunately, the effect of intraperitoneal chemotherapy on PC is disappointing. Like with SC, the poor response rates may be explained by the poor penetration of the active chemical substances into the PC plaques \\[[@j_pp-pp-2018-0108_ref_002]\\]. Combining cytoreductive surgery"
-"It has long been known that the body moves with each heartbeat[@b1]. These subtle movements represent the body's recoil to cardiac expulsion of blood into the arteries. Various \"ballistocardiography (BCG)\" instruments have been developed (ranging from tables to wearables[@b2][@b3][@b4]) to measure the periodic, reactionary forces experienced by the body. [Figure 1](#f1){ref-type=\"fig\"} illustrates an example of a measured BCG waveform for one heartbeat. The example shows several waves such as the \"I\", \"J\", and \"K\" waves, which are typical of BCG recordings. Current understanding of the curious BCG waves is based mainly upon empirical correlations with other measurements such as the electrocardiogram, phonocardiogram, and blood pressure (BP) waveform[@b5][@b6]. However, theoretical efforts to explain the underlying mechanism have been relatively rare. Further, while a few mathematical models of the BCG waveform have been proposed, these models have either failed to reproduce the key BCG waves[@b7] or were too complicated to glean any mechanistic insight[@b8]. Hence, despite increasing interest in BCG[@b9], the origin of the BCG waves has remained mysterious. In this study, we formulated and validated a simple mathematical model of the BCG waveform. The model reveals the primary mechanism of the BCG waves as well as their meaning in terms of"
-"INTRODUCTION {#s1}\n============\n\nProlonged immobilization reduces passive range of motion of joints, creating joint contractures[@r1],[@r2],[@r3],[@r4],[@r5],[@r6]^)^. This may cause inconveniences with regard to activities of daily living; thus physiotherapy is often used to treat problems related to joint movement limitation. In previous studies, we have reported the histopathological changes that occur in the rat knee joint components during immobilization; however, the changes have not been fully clarified. In addition, controversies still remain regarding the pathosis of joint contracture. Joint immobilization induces muscle atrophy, articular cartilage loss, and proliferation of connective tissue within the joint space[@r1], [@r7]^)^. Immobilization of joints surrounded by edematous soft tissue often produces joint stiffness more quickly and more severely than immobilization of nonedematous extremities[@r8]^)^. After two weeks of joint immobilization, the number of synoviocytes in the posterior synovial intima was increased compared with a control group[@r9]^)^. Watanabe reported atrophy of fat cells, proliferation of fibroblasts, and narrowing of the spaces between collagen fibers in the rat knee joint after immobilization[@r10]^)^. Some studies reported changes in joint components caused by remobilization after immobilization[@r8], [@r11],[@r12],[@r13],[@r14],[@r15]^)^. The range of motion of rat knees immobilized for 8 weeks remained substantially reduced after a 4-week period of unassisted remobilization[@r16]^)^. But histopathological findings"
-"Background {#Sec1}\n==========\n\nKomatsu and Tamai reported the first successful finger replantation in 1968 \\[[@CR1]\\]. Over the ensuing four decades, many refinements and advances had been made in microsurgical techniques resulting in a success rate of 92--99% for digital replantation, but replantation surgery is still a challenge because the surgeon needs to perform the operation quickly while potentially be facing limited amount of tissue to work with \\[[@CR2], [@CR3]\\]. Many factors can affect the prognosis, but impaired arteria digitalis communis is a particular problem for finger replantation surgery. Most surgeons treat digital amputation with damaged arteria digitalis communis as a complication of replantation. Both the proximal and distal neurovascular bundles are extensively damaged, making it difficult to estimate the level of tissue injury even with the help of an operating microscope. The aim of this study is to highlight the technical advantage of using cross-finger revascularization in salvage of digits with damaged arteria digitalis communis and the positive functional prognosis this can bring to the table.\n\nMaterials and methods {#Sec2}\n=====================\n\nFrom July 2012 to June 2018, a retrospective study was conducted on 554 hands with total finger amputations treated by replantation of finger/fingers. Seven of these cases were complicated"
-"In order to carry out nuclear DNA replication during G1 and S phase, many factors are recruited to the chromosomal origin, one of which is the GINS complex composed of SLD5 and [p]{.ul}artner of [S]{.ul}ld[5]{.ul} (Psf) \u22121, \u22122, and \u22123), identified in eukaryotes in 2003[@b1]. The GINS complex has been reported to regulate DNA polymerase \u03b5 (DNA poly \u03b5)[@b1]. In budding yeast, cyclin-dependent kinases (CDK) activate and load GINS complexes at origins[@b1][@b2] to regulate the initiation of DNA replication.\n\nRecently, several studies have shown that each GINS member is associated with malignant progression in several different tumor histotypes, i.e., PSF1 for breast cancer[@b3], colon cancer[@b4], and lung cancer[@b5], PSF2 for cholangiocarcinoma[@b6], and PSF3 for colon cancer[@b7] and non-small cell lung cancer[@b8]. Although we previously reported on the levels of expression of SLD5 in different cancer cell lines[@b7], to the best of our knowledge there have been no reports thus far on its expression and malignant tumor progression. We did report that targeted disruption of the SLD5 gene led to disturbance of epiblast proliferation and resulted in early embryonic lethality[@b9]. Moreover, we found that SLD5 is involved in protection from DNA damage in mice[@b10]. It has also been suggested that SLD5"
-"INTRODUCTION\n============\n\nDermatomyositis as a connective tissue disease syndrome is an idiopathic inflammatory myopathy that affects cutaneous characteristics and striated muscles. The disorder is rare, with a prevalence of one to 9.63 cases per million in adults and one to 3.2 cases per million in children ([@R1]). It indicates solitarily or could be associated with other disorders of connective tissue (overlap syndrome) and also malignancy ([@R2]).\n\nThe etiology of dermatomyositis is not perfectly recognized yet however the most agreeable cause is reported due to genetics and particular genes over expression (e.g. type 1 interferon--inducible transcripts) leading to autoimmune responses that cloud be triggered by endotheliotropic viruses and underlying neoplasia. Uncommon drugs, namely the lipid-lowering agents, also have been reported to implicate dermatomyositis ([@R3]). Although the disease can onset at any age, 40 years is the most reported average age at the diagnosis, and women are affected almost three times more than men. Dermatomyositis can indicate in children too which is called juvenile dermatomyositis. It could onset at the average age of 5 to 14. These subgroups have a better prognosis than adults ([@R4], [@R5]).\n\nThe pathologic features of dermatomyositis including autoantibody production, endothelial damage, dysregulation of both complement and mannose"
-"Introduction {#jcmm12717-sec-0001}\n============\n\nRheumatoid arthritis (RA) is a chronic autoimmune disorder that is characterized by systemic and joint synovial chronic inflammation and/or by bone and cartilage destruction [1](#jcmm12717-bib-0001){ref-type=\"ref\"}. Despite extensive efforts, the molecular pathogenesis and aetiological factors of RA are not entirely obvious, and effective treatments with limited side\u2010effects remain lacking. We are now beginning to understand that the functions of dendritic cells (DCs), especially maturation and migration, are important constituents in the pathogenesis of RA.\n\nDendritic cells, the professional antigen\u2010presenting cells, are specialized cells that acquire and process protein antigens, assemble antigenic peptides on the major histocompatibility complex (MHC) and present them to T cells. DCs are critical sentinels to induce and regulate most adaptive immune responses [2](#jcmm12717-bib-0002){ref-type=\"ref\"}, [3](#jcmm12717-bib-0003){ref-type=\"ref\"}. Dendritic cells play central roles in linking innate and adaptive immunities, which likely contribute to the pathogenesis of RA in several ways: (*i*) Immature DCs infiltrate the synovial tissues and fluids of the involved joints in RA patients and mature within the inflammatory microenvironment [4](#jcmm12717-bib-0004){ref-type=\"ref\"}; (*ii*) In the presence of chemotactic ligands, mature DCs rapidly transit through the endothelium of lymphatic vessels and migrate to the draining secondary lymphoid organs, where they present antigens to na\u00efve T cells and induce"
-"1. Introduction {#sec1-sensors-18-02443}\n===============\n\nThe micro-machined Coriolis vibratory gyroscope (MCVG) has been widely used in many fields, including for motor vehicles, robotics, and smartphones, because of its low cost and power, and high yield rate. However, its low performance limits further high-end applications of the MCVG. One important factor limiting its performance is the inevitable zero-rate output drift of the gyroscope, also known as the bias drift \\[[@B1-sensors-18-02443]\\].\n\nIn order to reduce the bias and suppress bias drift, the bias sources resulting from various aspects have been analyzed, and corresponding control schemes have also been discussed in the published literature. First, the drive voltage will be coupled to the sense mode through the parasitic capacitances between the wire bonding pads, wires, proof mass, substrate, etc. \\[[@B2-sensors-18-02443],[@B3-sensors-18-02443],[@B4-sensors-18-02443]\\] Researchers have aimed to reduce this in either the microfabrication process \\[[@B5-sensors-18-02443]\\] or circuit design based on the trans-impedance amplifiers \\[[@B6-sensors-18-02443]\\]. Second, the phase error in the circuits will inevitably result in an incomplete demodulation, which is also an important bias source \\[[@B7-sensors-18-02443],[@B8-sensors-18-02443],[@B9-sensors-18-02443],[@B10-sensors-18-02443]\\]. This error is suppressed by selecting the reference phase of the drive-mode control circuits. Third, the mechanical movement in the drive mode will be coupled to the sense mode because both"
-"Introduction {#s1}\n============\n\nGuanine nucleotide binding proteins (G proteins) are involved in important cellular processes, including signal transduction, translation, vesicle trafficking and exocytosis [@pone.0014246-Wennerberg1]. G proteins function as GDP/GTP-regulated switches with an \"inactive\" GDP-bound state and an \"active\" GTP-bound state [@pone.0014246-Vetter1]. The subcellular trafficking of GTPases coordinates their activity in time and space and regulates their function. The mechanisms controlling the localization of the proteins from the Ras family of small GTPases have been extensively studied. Small GTPases display a general affinity for localization to cellular membranes, which depends on structural signals [@pone.0014246-Vogler1]. More specifically, GTPases are characterized by the presence of a carboxyl-terminal \"CaaX\" motif for prenylation (where \"C\" represents cysteine, \"a\" is an aliphatic amino acid and \"X\" is any amino acid). Prenylation is a posttranslational modification leading to the attachment of a lipid hydrophobic moiety which allows the protein to anchor to cellular membranes. The process of prenylation involves the addition of a C15 farnesyl or a C20 geranylgeranyl isoprenoid to the cysteine residue of the CaaX motif by a farnesyl transferase (FTase) or geranylgeranyl transferase type I (GGTase-I), respectively [@pone.0014246-Roskoski1]. Additional structural signals have been described that further increase membrane affinity; these signals include the presence"
-"INTRODUCTION {#S1}\n============\n\nBuilding a functional nervous system is staggeringly complex and depends critically on the coordinated proliferation, differentiation, and survival of diverse neuronal and glial cell types. Interactions within and across these cell types regulate a wide range of processes, from cell migration to axon guidance, necessary for establishing neural circuitry. How neuronal and glial diversity arises from precursor cells and how they participate in circuit formation remain central questions in developmental neurobiology.\n\nWe used the complex but spatially ordered visual system of *Drosophila* to investigate neurogenesis and gliogenesis fate decisions during development. Glial cells comprise 10% of the *Drosophila* nervous system and can arise from dedicated precursors (glioblasts) or from precursors with mixed neuronal and glial potential. For the latter case, a neuroblast (NB) generates either intermingled neurons and glia or a glioblast and an additional NB that form bifurcating lineages of glia and neurons ([@R7]; [@R11]; [@R60]; [@R61]; [@R69]).\n\nThree types of NBs have been described in *Drosophila*. Type I NBs undergo multiple asymmetric divisions to self-renew and produce ganglion mother cells (GMCs). Each GMC terminally divides to produce two differentiated cells, two neurons or a neuron and a glia (reviewed in [@R19]). Type II NBs generate"
-"Background {#Sec1}\n==========\n\nAlthough global morbidity and mortality have decreased substantially, malaria is still a great public health concern, especially in Africa \\[[@CR1]\\]. The World Malaria Report 2018 draws on data from 87 countries and areas with ongoing malaria transmission. Recent research shows that after an unprecedented period of success in global malaria control, progress has stalled. An estimated 219 million (95% confidence interval \\[CI\\]: 203--262 million) persons suffer from malaria infections worldwide, with 435,000 malaria deaths in 2017. Fifteen countries accounted for 80% of global malaria deaths in 2017, and the 10 highest burdened African countries saw an estimated 3.5 million more malaria cases in 2017 compared with the previous year \\[[@CR2]\\]. Malaria is endemic in Equatorial Guinea, a country in Central West Africa with a population of around 1 million inhabitants. In 2004, the government and private parties formed a Public--Private Partnership that has spent the last 15\u00a0years controlling malaria on Bioko Island and parts of the mainland in an effort to reduce malaria's burden on the population. The Bioko Island Malaria Control Project (BIMCP) implemented by the U.S. NGO, Medical Care Development International (MCDI) and the Ministry of Health and Social Welfare of the Government of"
-"Background {#Sec1}\n==========\n\nTetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease (CHD). In neglected untreated cases, the mortality rate is about 33% in the first year of life and about 50% in the first 3\u2009years of life \\[[@CR1]\\]. However, advances in diagnosis, surgical techniques, and postoperative treatment have led to increasing number of patients reaching adulthood with a dramatic increase in survival rate to almost 90% at 30\u2009years. TOF was originally named after the French scientist \"Arthur Louis Etienne Fallot\" who published a paper in 1988 entitled \"Contribution a 'l'anatomie pathologique de la maladie bleue\" \\[[@CR2]\\]. He described four anatomical features that were almost always present in all post-mortem specimens of the blue patients \"la maladie bleue\" in his own words. These anatomical features consist of a tetrad of (1) ventricular septal defect (VSD), (2) aortic overriding, (3) right ventricular outflow tract (RVOT) obstruction, and (4) right ventricular (RV) hypertrophy \\[[@CR3]\\].\n\nPathophysiology {#Sec2}\n---------------\n\nThe main pathophysiological features of TOF are the antero-cephalic deviation of the cono-ventricular septum and hypertrophy of the septoparietal trabeculations of the RVOT \\[[@CR3]\\]. The antero-cephalic deviation of the cono-ventricular septum results in a mal-aligned VSD in continuity of the"
-"Introduction {#Sec1}\n============\n\nAntibodies against RSV proteins play an important role in preventing disease with RSV by various mechanisms including virus neutralization, antibody-dependent cellular cytotoxicity (ADCC), and complement-mediated neutralization. The RSV attachment (G) and fusion (F) proteins are the major targets of RSV-specific neutralizing antibodies but antibodies against other virus proteins are also induced by infection and can contribute to serological diagnosis of infection. EIA detects both neutralizing and non- neutralizing antibodies and use of RSV lysate antigen in EIA provides a way to detect antibodies against multiple RSV proteins. Use of F or G gene-expressed antigens, e.g., in a HEp-2 cell line, can be used to determine protein-specific antibody response. The 30-amino acid synthetic peptides are from a region of the G protein that is immune active and antibodies to this region can prevent some aspects of RSV disease.\n\nMaterials {#Sec2}\n=========\n\nProduction of RSV Virus and HEp-2 Lysate Antigens {#Sec3}\n-------------------------------------------------\n\nClass II biosafety laminar flow cabinet.175 cm^2^ Vented cell culture flasks.HEp-2 cells.RSV virus stock.37 \u00b0C Incubator with 5\u2009% CO~2~.SF-MEM: Serum-free minimum essential medium (MEM).5\u2009% Fetal bovine serum-minimum essential medium (FBS-MEM): MEM, 5\u2009% v/v FBS, 1\u00d7 penicillin/streptomycin, 1\u00d7 glutamine.\u221280 \u00b0C Freezer.15 mL Conical tubes.50 mL"
-"1. Introduction {#sec1-nutrients-12-02150}\n===============\n\nExtra-virgin olive oil (EVOO) is the superior olive oil category extracted from olives by the mechanical extraction process. EVOO is one of the main components of the Mediterranean diet and it is considered worldwide as one of the healthiest oils. The European Union (EU) is the largest EVOO producer worldwide, and production is concentrated in three Mediterranean countries: Spain produces about 57.5% of EU EVOO output, Italy over 19.5%, and Greece about the 15.8% \\[[@B1-nutrients-12-02150]\\]. Due to increasing consumption in non-producing countries, both within the EU (e.g., UK and Germany) and outside Europe (e.g., China, Japan, Russia, Australia, Brazil, Canada, and the US), demand for European EVOO is expected to rise until 2030 \\[[@B2-nutrients-12-02150],[@B3-nutrients-12-02150]\\]. Rising EVOO consumption in non-producing countries leads Mediterranean EVOO producers to export their EVOO to other markets \\[[@B2-nutrients-12-02150],[@B3-nutrients-12-02150]\\]. The steadily increasing demand for EVOO in non-producing countries has led Italy to export a large share of domestically produced EVOO, which is no longer sufficient to satisfy the domestic market. Such supply imbalance is constantly re-balanced by importing EVOO from Spain and non-European Mediterranean countries, such as Tunisia and Turkey. This EVOO is usually priced lower than Italian EVOO. Compared to Italian EVOO"
-"The Japanese encephalitis (JE) virus of genus *Flavivirus* (*Flaviviridae*) has a positive sense RNA genome and presents an enzootic cycle involving mosquitoes[@ref1] and amplifying vertebrate hosts. It causes viral encephalitis which is primarily a disease of children. According to the World Health Organization (WHO), annually, there are about 68,000 global cases of JE, of whom 20-30 per cent are fatal, 30-50 per cent of survivors have significant neurological sequelae and three billion people are at the risk of infection in endemic countries including WHO South-East Asia and Western Pacific Regions[@ref2]. The causative agent, JE virus (JEV) is vector borne with *Culex* mosquitoes as its main vectors and water birds such as egrets and herons as reservoirs[@ref3][@ref4]. Pigs serve as amplifying hosts in human epidemics[@ref5], and the virus causes reproductive disorder in pigs. Pathological and pathogenesis studies have been conducted on JEV infection in rabbit, guinea pig, monkey, hamster, rat and mouse models using different routes of infection, including intravenous (*i.v.*), intraperitoneal (*i.p.*), subcutaneous (*s.c.*), intracerebral (*i.c.*), intradermal and intranasal (*i.n.*) routes, but neuronal invasion has been confirmed in some of these models[@ref6]. However, footpad inoculation closely mimics the conditions of human infection by natural route[@ref7][@ref8]. Rabbits and guinea pigs develop"
-"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"
-"Background\n==========\n\n\\\"Migrants from impoverished hinterlands, living without security, public health, and, often, clean water in the shantytowns of S\u00e3o Paulo, Lagos, Karachi, Dhaka, and Jakarta, have as much in common with each other as \\\"People Like Us\\\"--the global class of businessmen, journalists, academics, and anti-terrorism experts--do among themselves.\\\" --Pankaj Mishra, *Bombay: The Lower Depths*, New York Review of Books, November 18, 2004\n\nThey are known as *favelas*, *kijiji*, *johpadpatti*, *gecekondu*, *aashiwa\\'i*, *barriadas*, *kampungs*, and *mudukku*(see Figures [1](#F1){ref-type=\"fig\"} and [2](#F2){ref-type=\"fig\"}) \\[[@B1]\\]. They describe human settlements known in English as slums in Brazil, Kenya, India, Turkey, Egypt, Peru, Malaysia, and Sri Lanka, respectively \\[[@B1]\\]. In year 2000, the United Nations Millennium Declaration pledged to tackle the challenge of setting specific goals of achieving \\\"significant improvement in the lives of at least 100 million slum dwellers by the year 2020\\\" \\[[@B2]\\]. This historic declaration formally recognized the existence and need to improve the lives of a large group of people living in places in what are likely to become central to this century\\'s most expensive health crisis. Today, nearly 1 billion people, or 32% of the world\\'s urban population are estimated to live in slums \\[[@B3]\\]. In 30 years, this population is"
-"Haplotype refers to a group of alleles inherited on a single chromosome. Haplotype analysis plays an important role for mapping disease genes, elucidating population histories, studying the evolutionary genetics, and exploring *cis*-interactions in the regulation of gene expression [@R1],[@R2]. Statistical and computational methods have been developed to reconstruct haplotypes from conventional genotype data. Although statistical and computational methods can provide highly accurate estimates of haplotypes in most situations, even the best method can have a large error rate of more than 35% for some real datasets [@R3]. The accuracy of statistical methods for haplotype reconstruction can be greatly improved when they are applied to trio datasets using information from relatives [@R2]; however, the parental samples are not always available to make this feasible. Experimental approaches have been developed to determine haplotypes [@R4],[@R5] with limited capability of haplotyping SNPs across a large chromosomal region spanning megabase distances, except the conversion technology, which can determine the long-range haplotypes by creating human-mouse hybrid cells that contain a subset of human chromosomes [@R6],[@R7], and the polony (polymerase colony) technology, which can determine the long-range haplotype of a pair of distant SNP loci on the same immobilized colony within an acrylamide gel [@R8],[@R9]. Conversion technology"
-"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"
-"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"
-"Introduction {#s1}\n============\n\nMalaria and lymphatic filariasis (LF) are the two most important vector borne parasitic diseases worldwide [@pone.0028347-WHO1], [@pone.0028347-WHO2]. In Africa these diseases are both primarily transmitted by *Anopheles* species. Nigeria has the largest burden of malaria and lymphatic filariasis in Africa -- yet very little is known about the distribution of *Anopheles* mosquitoes that act as vectors for both diseases, how the species interact, overlap or differ across the country [@pone.0028347-WHO1], [@pone.0028347-WHO2]. Knowledge of the geographical distribution of the different species, their ecological parameters, role in transmission, and susceptibility to insecticide-based interventions is critical if malaria and LF are to be controlled and eliminated in the next decade [@pone.0028347-WHO3].\n\nThe World Health Organization\\'s (WHO) Position Statement on Integrated Vector Management to control malaria and lymphatic filariasis promotes integrated vector management (IVM) to improve the cost effectiveness of vector-control operations, and to strengthen the capacity of programmes, partnerships and intersectoral collaboration in their efforts to control vector-borne diseases [@pone.0028347-WHO3]. There is overlapping geographical distribution of malaria and LF in large areas of Africa, and where *Anopheles* mosquitoes transmit both the malarial and lymphatic filariasis parasites, scaling up vector-control methods such of insecticide-treated mosquito nets (ITNs) and implementing indoor residual"
-"1. Introduction {#sec1-animals-10-00214}\n===============\n\nThe maternal capacity of the doe determines the growth of kits and their mortality in the pre-weaning period \\[[@B1-animals-10-00214],[@B2-animals-10-00214]\\]. The growth of rabbit kits in the pre-weaning period is also affected by the litter size at birth \\[[@B3-animals-10-00214],[@B4-animals-10-00214]\\] and by crossbreeding pure breeds \\[[@B5-animals-10-00214]\\]. The most popular rabbits in the big scale production of rabbit broilers are not pure breeds but crosses of synthetic rabbit lines, such as Hycole, Hyla, Hyplus, or Martini. Rabbit maternal lines are selected for high fertility, high prolificacy, and high milk yield. The development of rabbit synthetic lines is a very dynamic process, and the maternal lines are subjected to continuous improvement of maternal capacity. The lines are characterized by aligned reproductive traits: the mean number of live kits at kindling is 10.7, the mean number of weaned kits per insemination is 8.2, the length of lactation is about 28 days, and the milk yield is about 5.5--7.0 kg per lactation \\[[@B6-animals-10-00214],[@B7-animals-10-00214],[@B8-animals-10-00214]\\]. According to the literature, the highest milk yield of the nursing does occurs about 18--20 days post-partum, but in multiparous does subjected to intensive reproduction rhythms, this peak appears even 2--3 days earlier \\[[@B2-animals-10-00214],[@B9-animals-10-00214]\\]. On the commercial rabbit farms,"
-"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 Asian cockroach, *Blattella asahinai* Mizukubo, is a relatively new invasive species from South Asia and a peridomestic pest around residences and in crop fields in the southeastern United States ([@CIT0035], [@CIT0048], [@CIT0006]). Since its likely initial introduction into Florida, *B. asahinai* has expanded its range and has been confirmed in Alabama, Georgia, Texas, North Carolina, and South Carolina ([@CIT0006], [@CIT0056], [@CIT0002], [@CIT0059], [@CIT0032]). This range expansion is likely facilitated by human transportation along major highways ([@CIT0059]). The closest relative of *B. asahinai* is one of the most prevalent cockroach pests worldwide, *Blattella germanica* (L.) (Blattodea: Ectobiidae), the German cockroach ([@CIT0039]). The two species are morphologically similar but can be positively identified using the morphology of the adult male tergal glands and cuticular hydrocarbon profiles ([@CIT0048], [@CIT0008]). The outdoor habitat and capability of sustained flight are the most striking differences between *B. asahinai* and *B. germanica*, an entirely domestic species that cannot fly ([@CIT0048], [@CIT0006], [@CIT0005]).\n\nInformation on the life history and biology of pest insects is critical to develop control methods based on predictions of pest population dynamics. Different instars may have different tolerances to temperature, tolerances to insect growth regulators, and relative food consumption rates ([@CIT0014], [@CIT0063], [@CIT0003],"
-"INTRODUCTION\n============\n\nPlantar fasciitis (PF) is the most common cause of heel pain, yet its etiology is not well understood \\[[@B1][@B2]\\]. Recently, several studies proposed that PF is inflammation of the plantar fascia \\[[@B3]\\]. It is characterized by pain and stiffness in the heel, the medial arch of the foot, and can affect daily activities \\[[@B3][@B4]\\].\n\nThe symptoms vary in intensity and the foot pain usually occurs on the first step in the morning \\[[@B5]\\]. Sometimes the pain may improve after a few steps or within a few hours, but it often increases as the day progresses \\[[@B1]\\]. Typically, the prognosis of PF is quite good \\[[@B1]\\]. In more than 80% of patients, foot pain will disappear within a year \\[[@B3]\\].\n\nThe diagnosis of PF is clinical and based on a history of foot pain and pain upon palpation of the fascia \\[[@B6]\\]. Diagnostic imaging may be used to exclude other causes of pain. Radiographic examinations may help to identify heel spurs (found in 27% of cases), and ultrasound examinations of symptomatic patients may reveal thickened fascia and inflammation \\[[@B7][@B8]\\].\n\nConservative treatments, such as stretching of the plantar fascia or Achilles tendon, icing, heating, applying electrical modalities, using anti-inflammatory medications,"
-"Patterns on networks\n====================\n\nPatterns are found throughout nature and much of science is dedicated to identifying and understanding the origin and growth of such patterns. Alan Turing first developed a mathematical theory of pattern formation for spatial media in an attempt to explain cellular differentiation and morphogenesis[@b1]. His analysis looked at a symmetry breaking bifurcation in reaction-diffusion systems of partial differential equations (PDEs) in continuous media and subsequent research by Othmer and Scriven[@b2] generalised this to discrete lattices in a framework that can be applied to other, potentially complex, network topologies.\n\nMany natural and human systems can be represented as networks[@b3][@b4], where individual elements are represented by nodes on a graph and interactions between them as edges. There is also growing interest in using models of reaction-diffusion systems organised on complex network topologies, particularly in systems with activator-inhibitor dynamics on the nodes, to explain interesting biological applications such as pattern development arising in networks of activating and suppressing genes involved in embryonic development[@b5] or the evolution of complex structures (*autocatalytic sets*) in systems of competing proteins, such as could lead to the origin of life from a random starting condition[@b6]. However, the networks connecting such species, genes or individuals"
-"World Heart Day will be observed September 29, 2014. The focus of World Heart Day this year is creating heart-healthy environments in which persons are able to make heart-healthy choices wherever they live, learn, work, and play. Heart disease and stroke are the world's leading causes of death, claiming an estimated 17.3 million lives in 2008, and representing 30% of all deaths worldwide ([@b1-843]). A heart-healthy environment can help persons make healthy choices to reduce their risk for heart disease. World Heart Day 2014 encourages persons to reduce their risk for cardiovascular disease by promoting smoke-free environments, environments that encourage physical activity, access to healthy food choices, and a heart-healthy planet for all.\n\nCDC is working to help create heart-healthy environments in multiple ways, including community-based approaches, such as the Sodium Reduction in Communities Program (SRCP), and community-clinical linkages, such as the Million Hearts Initiative. SRCP aims to increase access to and accessibility of lower-sodium food options while building the evidence base on population approaches to reduce sodium consumption at the community level. Million Hearts aims to prevent 1 million heart attacks and strokes by 2017 by bringing together communities, health systems, nonprofit organizations, federal agencies, and private-sector partners from"
-"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"
-"1. Introduction {#sec1}\n===============\n\nTriple-negative breast cancer (TNBC) constituting 10--20% in breast cancer is highly metastasizing and recurrent with poorer prognoses \\[[@B1]--[@B3]\\]. Although TNBC is sensitive to chemotherapies, TNBC metastases frequently occur and shorten 5-year survival rates of patients \\[[@B1], [@B3]\\]. Furthermore, target therapies for TNBC remain yet to be clearly elucidated in clinical trials. Recent studies in cancer therapeutics revisit a traditional herbal medicine, since herbal extracts or mixtures based on the traditional medicines have shown anticancer effects with no or less side effects compared to other anticancer therapeutics including chemical compounds and targeting antibodies \\[[@B4]--[@B6]\\]. Anticancer effects of herbal extracts from*Astragalus membranaceus* (Am),*Angelica gigas* (Ag), or*Trichosanthes Kirilowii*Maximowicz (Tk) have been revealed in different cancer cell types such as leukemia, hepatocellular carcinoma, colon cancer, non-small-cell lung cancer, and gastric cancer cells \\[[@B7]--[@B13]\\]. Furthermore, extracts from a mixture of Am and Ag have been shown to affect various diseases including hematologic diseases or endocrine disorders \\[[@B14]--[@B16]\\].\n\nInflammation is a risk factor in cancer disease \\[[@B17]--[@B22]\\], which is tightly linked to cancer progression including tumorigenesis and metastasis \\[[@B23], [@B24]\\]. Cancer inflammation is activated by several inflammatory cytokines such as TNF-*\u03b1*, IL-1, IL-6, IL-8, and IL-18 \\[[@B25]\\]. Particularly, IL-6 as a poor"
-"Background {#Sec1}\n==========\n\nGRAS proteins are a family of plant-specific transcription factors whose names are derived from the first three members: GIBBERELLIN ACID INSENSITIVE (GAI), [R]{.ul}EPRESSOR of G[A]{.ul}1 (RGA) and [S]{.ul}CARECROW (SCR) \\[[@CR1]\\]. Typically, GRAS proteins consist of 400--770 amino acids residues with a variable N-terminal and a highly conserved C-terminal region \\[[@CR2], [@CR3]\\]. The highly conserved carboxyl terminal region is composed of several ordered motifs, including leucine rich region I, VHIID, leucine-rich region II, PFYRE and SAW, which are crucial for the interactions between GRAS and other proteins \\[[@CR1], [@CR4]\\]. According to the report in *Arabidopsis thaliana*, the GRAS family is classed into eight well-known subfamilies, including LISCL, PAT1, SCL3, DELLA, SCR, SHR, LAS and HAM \\[[@CR5]\\]. However, Liu et al. (2014) classified the *GRAS* family into 13 branches. The subfamily identification of *GRAS* genes has a slight difference among diverse species.\n\nIn the recent 10\u2009years, with increasing species having complete genome sequence, the genome-wide analyses of *GRAS* gene family were carried out in more than 30 species belonging to more than 20 genera, such as in *A. thaliana* \\[[@CR4]\\], rice \\[[@CR4]\\], maize \\[[@CR6]\\], Chinese cabbage \\[[@CR7]\\], tomato \\[[@CR8]\\], *Prunus mume* \\[[@CR9]\\] and *Poplar* \\[[@CR10]\\]. GRAS proteins play"
-"Introduction {#s1}\n============\n\nCoronary fractional flow reserve (FFR) is the gold standard in evaluating the hemodynamic significance of intermediate coronary lesions \\[[@r1]\\]. In many clinical studies FFR-guided percutaneous coronary intervention (PCI) has proven a positive effect on patient long-term outcomes \\[[@r2], [@r3]\\]. Maximal hyperemia is essential to ensure FFR measurements; therefore intravenous (*i.v.*) adenosine infusion is accepted as a gold standard method \\[[@r4]\\]. However, the search for a different hyperemic agent began due to the fact that *i.v.* adenosine is expensive and has potential side effects. Intracoronary (*i.c.*) adenosine, papaverine, sodium nitroprusside and nicorandil have been tested as alternatives \\[[@r5]\\]. Intracoronary adenosine was accepted as an alternative method to *i.v.* adenosine \\[[@r6], [@r7]\\]. Recently, coronary hemodynamic assessment methods without a hyperemic agent, such as the instantaneous wave free ratio, have been studied widely. However, there is still controversy about the use of this method \\[[@r1], [@r4]\\]. Non-ionic contrast media are routinely used in coronary angiography. Hyperemic effects of these agents have long been known. Two encouraging studies demonstrated that measurement of the significance of intermediate stenoses was feasible by using contrast medium instead of adenosine \\[[@r8], [@r9]\\].\n\nAim {#s2}\n===\n\nOur study aimed to compare contrast medium induced Pd/Pa ratio"
-"Introduction {#Sec1}\n============\n\nHypertension is a common co-morbidity of type 2 diabetes mellitus, affecting nearly 80% of patients.\\[[@CR1]\\] The coexistence of these two conditions is particularly detrimental because of their demonstrated association with cardiovascular and renal disease. Each 5 mmHg increase in seated cuff systolic blood pressure (SeSBP) or seated cuff diastolic blood pressure (SeDBP) increases the risk of cardiovascular disease by 20--30%.\\[[@CR2]\\] Moreover, data from observational studies have shown that patients with both hypertension and diabetes have an approximately 2-fold greater risk of developing cardiovascular disease than patients with hypertension and no diabetes.\\[[@CR3]\\] The United Kingdom Prospective Diabetes Study (UKPDS) was the first large-scale study to demonstrate a direct relationship between systolic blood pressure (SBP) and the complications of diabetes over time, and that intensive blood pressure (BP) lowering was associated with clinically important reductions in both diabetes-related, and cardiovascular morbidity and mortality in patients with type 2 diabetes.\\[[@CR4]\\] Consequently, BP reduction was suggested to be at least as important as blood glucose control in patients with both hypertension and diabetes.\n\nThe assessment of BP control typically employs the seated cuff BP (SeBP) method, which has demonstrated both good practicality and clinical utility. The American Diabetes Association (ADA), the"
-"1. Introduction {#sec1}\n===============\n\nThe goal to achieve ideal pediatric drug therapy is a worldwide challenge for regulatory bodies and clinicians. Children are treated with medicines not tested for safety and efficacy and are frequently supported by the low quality of evidence \\[[@B1]\\]. In the absence of standard prescribing information, clinicians prescribe drugs in an off-label manner. Off-label use means use of medicine which is outside the terms of product license with respect to dose, route of administration, indication, or age \\[[@B2]\\]. Off-label medicine use among children represents an important health issue as the effects and health risks may be unexpected. Various national and international studies have been published about the amount of and problems associated with off-label medicines in children. The magnitude of off-label prescribing is accounted to be between 18% and 60% in infants but it may be up to 90% in neonates \\[[@B3]--[@B9]\\].\n\nMost of these studies have been conducted outside India and may not be applicable as hospitalization and prescribing patterns differ based on culture, healthcare infrastructure, and health policies. There is a distinct lack of research on off-label prescribing in India. Only one previous study has been conducted in India which reported 50.62% of off-label"
-"Introduction\n============\n\nTraditional prevention programs for eating disorders (ED), which are mainly based on providing information about risk factors, have so far proved largely unsuccessful.[@b1-ijgm-3-263],[@b2-ijgm-3-263] Although certain changes in content[@b3-ijgm-3-263] have improved these programs, research has yet to demonstrate any clear effects in terms of a change in subjects' knowledge, attitudes, and behavior, especially in the case of children and adolescents.[@b4-ijgm-3-263] Therefore, in order to address these aspects, it is necessary to devise programs that include interactive components, which implies active participation in workshops rather than the passive receipt of information.[@b5-ijgm-3-263]\n\nIn this context, it has been argued that at the level of primary prevention it is best not to make ED the specific focus of any intervention.[@b6-ijgm-3-263] It is also considered that the best place in which to promote the mental health of children and adolescents is the school. Indeed, schools are an ideal place to run prevention programs in that they offer access to the majority of adolescents.[@b7-ijgm-3-263],[@b8-ijgm-3-263] A further issue is that parents, alongside teachers, coaches, and other school staff, play a key role in the social environment of young people and, as such, may be included in any interventions.[@b9-ijgm-3-263] Finally, it appears that a positive psychology"
-"Background {#Sec1}\n==========\n\nPolycythemia vera (PV; MIM 263330) is a clonal progressive myeloproliferative disorder primarily characterized by elevation in red blood cells, often with increased myeloid elements. The major pathogenic event in PV is the acquisition of a somatic gain-of-function mutation in the *Janus Kinase 2* gene (*JAK2*; MIM 147796), resulting in erythropoietin independent proliferation of erythroid progenitor cells. Approximately 96\u00a0% of PV cases involve the p.V617F mutation in exon 14 of *JAK2* \\[[@CR1]\\], while 3\u00a0% involve exon 12, with 37 different mutations described to date \\[[@CR2]--[@CR5]\\]. Transformation into myelofibrosis and acute leukemia occurs in 10 and \\<3\u00a0% of the patients, respectively, during a 10-year disease course \\[[@CR1]\\].\n\nThe Mediterranean fever gene (*MEFV*; MIM 608107) is highly expressed in myeloid cells, particularly in mature granulocytes. This gene codes for pyrin, a cytoplasmatic protein that regulates the maturation and secretion of the proinflammatory cytokines IL-1b and IL-18 in the inflammasome complex \\[[@CR6]--[@CR9]\\]. Missense mutations in *MEFV* associate with familial Mediterranean fever (FMF; MIM 249100), an autoinflammatory and inherited disorder prevalent in Mediterranean descendants. FMF is characterized by 2--3\u00a0days long self-limited attacks of fever, abdominal pain, arthritis and /or pleuritis \\[[@CR10]\\]. The attacks are accompanied by leukocytosis and"
-"Introduction {#sec1-1}\n============\n\nThe classical paradigm in the radiobiology field states that the biological effects of radiation are due to the deposition of energy and associated DNA damage in the cell nucleus.\\[[@ref1]\\] However, in the early 1990s, significant evidence emerged to challenge classical target theory and highlighted the potential role of nontargeted effects.\\[[@ref1][@ref2]\\] These nontargeted effects, including radiation-induced genomic instability (RIGI) which is observed in the progeny of cells exposed to ionizing radiation, can be manifested in different ways such as gene mutations, chromosomal instability, micronucleus (MN) formation, and an enhanced death rate.\\[[@ref2][@ref3]\\] In addition, there is considerable overlap between RIGI and the genomic instability commonly observed in tumors, which is a well-known enabling characteristic assisting the transition of cells from normal to oncogenic by the acquisition of the various hallmarks of cancer.\\[[@ref4]\\] RIGI is a high-frequency event that occurs at a higher frequency and then can be explained by specific gene mutations. For example, MN formation was used to measure the DNA damage after 7 days in both high-dose rate (HDR) and low-dose rate (LDR)-irradiated mouse lymphocytes cells. The frequency of MN induction in the HDR population cells was higher compared to the equivalent LDR population cells following *in"
-"1. Introduction {#sec1-sensors-19-02300}\n===============\n\nIn indoor environments, global navigation satellite systems (GNSS) can be affected by unfavorable factors, such as signal blocking and multipath propagation, which make it unable to achieve a satisfactory positioning performance \\[[@B1-sensors-19-02300]\\]. According to the report of the US Environmental Protection Agency, people spend nearly 70--90% of their time indoors \\[[@B2-sensors-19-02300]\\]. Therefore, it is important to establish an accurate, reliable, and real-time indoor positioning system to satisfy the public demand for indoor positioning. With the rapid development of intelligent terminals, smartphones have more sensors and have become excellent tools for indoor positioning. Additionally, WiFi signal receiving modules have been widely embedded in smartphones, and hotspots have also been covered in many public places, such as office buildings, airports, and shopping malls. Therefore, WiFi fingerprint positioning has become one of the most popular indoor positioning schemes and has been widely used in recent years \\[[@B3-sensors-19-02300]\\]. The WiFi fingerprint positioning can be divided into the offline stage and the online stage. In the offline stage, the user collects the received signal strength (RSS) from the wireless access points (APs) on each reference point (RP) whose position is known, the coordinates and RSS are stored in a fingerprint database."
-"Introduction {#Sec1}\n============\n\nInflammation plays a central role in the development of cardiovascular disease (CVD). Immune and inflammatory cells mediate atherogenesis and plaque destabilization, and the circulating levels of inflammatory mediators have been linked with disease progression and prognosis^[@CR1]^. The S100 proteins A8 and A9 are alarmins belonging to the S100 calcium-binding protein family. They are expressed in neutrophils, monocytes, thrombocytes and dendritic cells but also in activated macrophages, vascular endothelial cells and fibroblasts^[@CR2],[@CR3]^. S100A8 and S100A9 exist as homodimers, but preferably form the heterodimer S100A8/A9, also known as calprotectin. S100A8/A9 constitutes approximately 45% of all cytosolic proteins in neutrophils and about 1% in monocytes^[@CR4]^.\n\nS100A8/A9 is an endogenous ligand of toll-like receptor 4 (TLR4)^[@CR5],[@CR6]^ and of the receptor for advanced glycation end-products (RAGE)^[@CR7]--[@CR9]^, present on various cell types. S100A8/A9 binding to these receptors promotes the synthesis of pro-inflammatory mediators and has been shown to be involved in the pathogenesis of acute coronary syndrome (ACS)^[@CR2]^. Systemic levels of S100A8/A9 correlate with established markers of systemic inflammation in patients with stable coronary artery disease (CAD)^[@CR10]^, and with the severity of CAD in type 1 and type 2 diabetic patients^[@CR2]^. Further, S100A8/A9 is elevated in vulnerable human carotid plaques^[@CR11]^ and systemic levels"
-"1. Introduction {#sec1-ijms-17-01559}\n===============\n\nNanotechnology is a multidisciplinary field that employs proficiencies and tools from diverse disciplines \\[[@B1-ijms-17-01559]\\]. The technology has offered tremendous advancement in the field of therapeutics by means of designing various drug delivery systems, thereby increasing the possibilities of controlling infections at the molecular level \\[[@B2-ijms-17-01559]\\]. The nanoparticle-based systems exhibit significant potential for treatment and prevention of tuberculosis due to their ability to intersect biological barriers and targeting the cellular reservoirs of *Mycobacterium tuberculosis* (MTB) \\[[@B2-ijms-17-01559]\\]. Appreciable interest in the search for potential biomedical applications of biomaterials, such as exosomes, liposomes and chitosan, as carriers of therapeutic agents has been reported \\[[@B1-ijms-17-01559],[@B3-ijms-17-01559]\\]. Over the years, interest in chitosan has dramatically grown due to its novel properties, such as biocompatibility, biodegradability, affordability, stability, low toxicity, as well as its simple and moderate preparation procedures. Moreover, chitosan offers various administration routes, such as oral, nasal and ocular mucosa, making it one of the most significantly attractive materials for drug delivery \\[[@B4-ijms-17-01559],[@B5-ijms-17-01559]\\]. Chitosan has been investigated as a carrier of bioactive molecules to various target cells, such as cancer cells \\[[@B6-ijms-17-01559]\\]. However, scanty information is available on the application of chitosan in the delivery of potential anti-TB drugs. The treatment"
-"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"
-"Introduction {#sec1-1}\n============\n\nTwo distinct trends are easily detectable in Europe regarding privacy and public health research. On the one hand, we have a European data protection regulation that, after an amendment voted in October 2013, will introduce restrictive rules concerning the use of personal data for scientific research;^[@ref1],[@ref2]^ on the other hand, Europe is challenging a huge effort to develop as quickly as possible large networks of individual medical information (often linked to biological materials) for epidemiological and biomedical research (*e.g*: BBMRI, *Biobanking and Biomolecular Resources Infrastructure*; EPIC Project, *The European Prospective Investigation into Cancer and Nutrition*). The use of health data, in particular information retrieved from medical records, is crucial to public health research and policy. Follow-up, record-linkage and quality control procedures require data to be re-identifiable, and it may not be always feasible to implement informed consent procedures every time data is used for research purposes. Concerns about the European Union's forthcoming regulation of access to medical records seem to be widespread in the international scientific community.^[@ref1]^ It is noticeable that a general balance between privacy protection and public health interests remains an urgent priority both at national level, where the protection of personal data is strictly"
-"###### Strengths and limitations of this study\n\n-   There is a lack of information on the most appropriate MCH care models for refugee populations.\n\n-   The use of consensus-based methodologies will ensure the research is relevant and responds to the specific needs and priorities of refugee women.\n\n-   Consensus methodologies can be limited by the time required to collect data and the small number of participants may not represent all stakeholder views.\n\n-   The Delphi method promotes structured communication with a panel of experts using a series of iterative questionnaires among the policy and stakeholder participants.\n\n-   The nominal group method ensures that women's voices will be heard, further building confidence in the results, strategies and decision-making process.\n\nIntroduction {#s1}\n============\n\nIn the last 10 years wars, civil conflicts and natural disasters have led to the largest number of people who have been forcibly displaced since World War II.[@R1] In 2018, 70.8 million people globally were displaced by war and violent conflict.[@R2] Of these, 25.9\u2009million were refugees, with the vast majority coming from middle-income and low-income countries. Many have sought refuge in high-income countries, including Germany (1.1\u2009million), the UK (126 600), the USA (313 200) and Canada (114"
-"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"
-"The vertebrate gut contains numerous bacteria interacting with each other as well as with their host. The commensal gut microbiota contributes to the \"energy harvest\" from the diet by breaking down complex carbohydrates into monomers for further microbial fermentation. The end products of this fermentation process, short chain fatty acids (SCFA), are released into the gut and adsorbed by host cells[@b1][@b2][@b3]. Dietary carbohydrates are less nutritionally significant for carnivorous/planktivorous fish such as cod and killifish, where the main energy yield comes from ingested fats and protein[@b4][@b5]. However, the gut microbiota may also have an effect on digestion of lipids and fat, as germ-free zebrafish show reduced differentiation of gut epithelia and reduced lipid uptake compared to conventional controls[@b6][@b7].\n\nIn accordance with the idea of microbes increasing the yield of ingested food, specific members of gut microbiota appear to be positively correlated with obesity in humans and mice[@b2][@b8]. Obese mice and humans have altered ratios of bacteria belonging to Firmicutes/Bacteroidetes (F/B) compared to their lean counterparts, as well as lower microbial diversity. In a recent paper by Zhao *et al.*[@b9], the F/B ratio and causality of obesity is reviewed. Zhao suggests that the F/B ratio is too simple, and that a"
-"1. Introduction {#sec1-ijms-21-04914}\n===============\n\nMany data presented in scientific publications report that the administration of carcinogenic substances during embryo organogenesis does not cause tumors in offspring \\[[@B1-ijms-21-04914],[@B2-ijms-21-04914]\\], while it is possible to induce tumors in offspring after the end of the cell differentiation process \\[[@B3-ijms-21-04914],[@B4-ijms-21-04914],[@B5-ijms-21-04914],[@B6-ijms-21-04914]\\]. Such data seem to indicate that cancer can be considered a reversible process, which can be controlled by the factors present during organogenesis. Taking that into account, it was decided that a systematic study of the cellular differentiation process should be conducted. Many experiments were carried out in our laboratories using the Zebrafish embryo as a model to study the cell differentiation process for the following reasons: first, that it is easy to establish the exact time of zebrafish egg fertilization. This is important for standardizing all the experiments, with the goal of obtaining repeatable results over time in different research studies; second, notwithstanding their size and relative simplicity, the proteins extracted from Zebrafish might have been overall evolutionarily conserved in humans. In fact, all the different protein types taken from Zebrafish embryos after the beginning of stem cell differentiation were identified in our research using liquid chromatography mass spectrometry testing \\[[@B7-ijms-21-04914]\\]. It was demonstrated"
-"1.. INTRODUCTION {#sec1}\n================\n\nCurrently, the healthcare system faces various challenges ranging from excessive costs that could be avoided and information management issues to unnecessary Electronic Health Record (EHR) duplications and omission or unavailability of critical data ( [@ref1] ). Such difficulties lie in the fact that providers are not able to exchange information and in most cases, they are still using obsolete formats. According to the IEEE ( [@ref2] ) definition, interoperability is the \"ability of a system or a product to work with other systems or products without special effort on the part of the customer\" made possible by the implementation of standards. The Semantic Health study ( [@ref3] ) classifies the semantic interoperability of systems into those with local interoperability (within, e.g., hospitals or hospital networks) and those with regional, national and cross-border interoperability. Rector et al. ( [@ref4] ) state that EHRs are \"information models\" and that \"ontology\" is the conceptualization of healthcare information (clinical, demographics, etc.). CrowdHEALTH project aims at processing datasets with structured and unstructured information coming from different Use Cases ( [@ref5] - [@ref9] ). Thus, there is a need to identify or map the entities and attributes from a proprietary source to"
-"Introduction {#s1}\n============\n\nThe maladaptive cardiac remodeling that often develops after myocardial infarction (MI) triggers adverse cardiovascular events that often lead to the ultimate heart failure if not properly treated ([@B6]). Unfortunately, the pathological remodeling of the infarcted myocardium still develops in many MI patients, even those treated, with coronary angioplasty--reperfusion and standard drugs ([@B35]). Therefore, post-MI remodeling represents an attractive target for new pharmacological approaches aimed at the improvement of morbidity and mortality in patients following MI.\n\nResults of previously published analyses of the post-MI myocardium strongly suggested that a rapid autophagy of the dead cells remnants constitutes an essential step in cardiac recovery both in human clinic and in experimental conditions ([@B8]). Meaningfully, the upregulation of autophagy observed in rapidly recovered MI patients associated with inhibition of their left ventricular (LV) dilatation during the evolution of LV hypertrophy decreased the rate of the heart failure following MI ([@B9]). Moreover, it has been shown that pharmacologic inhibition of the mechanistic target of rapamycin (mTOR) pathway, known to be centrally involved in pathological remodeling of the heart (with rapamycin), prevented the LV remodeling and limited the size of the experimental infarct ([@B30]; [@B2]). In contrast, it has been also established"
-"Serpiginous choroiditis (SC) is characterized by a geographic pattern of inflammation involving the peripapillary area and overlying retinal pigment epithelium (RPE), causing irreversible damage to the photoreceptors.\\[[@ref1]\\] It can present either as classic SC or serpiginous-like choroiditis (SLC) and the recent terminology described for it is multifocal serpiginoid choroiditis (MSC). Identification of the spectrum of tuberculosis (TB)-SLC is of great concern as it is more common in TB-endemic areas, with a unilateral presentation.\\[[@ref2][@ref3]\\] TB association with SC was described by Hutchinson and later by others.\\[[@ref4][@ref5][@ref6]\\] The TB-associated disease was re-labeled as MSC in a large series of 105 patients.\\[[@ref5]\\]\n\nGenitourinary TB (GUTB) occurring in the kidney, ureter, testis, and epididymis can spread through blood-borne infection and accounts for \\<0.5% of all patients with extrapulmonary TB and 1.5% of all patients with pulmonary TB.\\[[@ref3]\\] The association of GUTB with SC is barely reported.\\[[@ref3]\\] We herein report a case of MSC proven with real-time polymerase chain reaction (PCR) and biopsy of testicular tissue in an immunocompetent patient suggestive of tubercular etiology.\n\nCase Report {#sec1-2}\n===========\n\nA 47-year-old, Asian Indian male presented with blurring of vision in the left eye for the past 4 months. The best-corrected visual activity was 6/6, N6 in"
-"Background\n==========\n\nAnkle sprain is one of the most common sports injuries. The incidence of ankle sprain can be as high as 20% out of all sports-related injuries \\[[@b1-medscimonit-26-e922925]\\]. Although most ankle sprains respond well to conservative measures with rehabilitation training and physical therapies, the incidence of chronic ankle instability after acute ankle sprains is 20--40% \\[[@b2-medscimonit-26-e922925]\\]. Although certain improvements in ankle function can be achieved using conservative methods, it is difficult to avoid lateral collateral ligament (LCL) reconstruction due to persistent ankle pain and instability \\[[@b3-medscimonit-26-e922925]\\].\n\nThe aim of surgical treatments is to provide ligament repair or reconstruction. Although the lateral ligament can be repaired in most cases, ligament reconstruction is needed in certain conditions, such as when the ligament cannot be repaired or needs to be strengthened, when the Brostrom-Gould repair fails, and when the ankle is under abnormal pressure. Ligament reconstruction consists of anatomical and non-anatomical reconstructions. Non-anatomical reconstruction, such as Chrisman-Snook \\[[@b4-medscimonit-26-e922925]\\], Evans \\[[@b5-medscimonit-26-e922925]\\], and related modified procedures, involve a certain degree of donor-area injury. For example, the valgus strength is reduced due to the loss of fibular tendon function and the effect of some surgical methods on the subtalar joint. Furthermore, long-term outcomes of non-anatomical"
-"Introduction {#s1}\n============\n\nDuring the development of the nervous system, synapses are eliminated on a broad scale (Thompson, [@B33]; Bourgeois and Rakic, [@B3]). This allows connectivity to be refined on the basis of Hebbian activity-dependent axonal competition (Jansen and Fladby, [@B12]; Sanes and Lichtman, [@B23]). In newborn animals, the skeletal muscle fibers are polyinnervated in the neuromuscular junction area (NMJ; Redfern, [@B21]; Brown et al., [@B4]; Ribchester and Barry, [@B22]), but at the end of the axonal competition, endplates are innervated by a single axon (Benoit and Changeux, [@B2]; O'Brien et al., [@B20]; Jansen and Fladby, [@B12]; Sanes and Lichtman, [@B23]). This peripheral synapse has been studied extensively as a model for synapse development (Liu et al., [@B16]; Nguyen and Lichtman, [@B19]; Chang and Balice-Gordon, [@B8]; Sanes and Lichtman, [@B23]; Lanuza et al., [@B14]; Santaf\u00e9 et al., [@B26]; Herrera and Zeng, [@B11]; Wyatt and Balice-Gordon, [@B37]; Buffelli et al., [@B5]; Garcia et al., [@B10]). Several signaling molecules and presynaptic receptors play a role in the axonal competition, which means that the various nerve endings influence one another (Santaf\u00e9 et al., [@B25]; Garcia et al., [@B10]; Nadal et al., [@B17]). Postsynaptic-derived trophic substances (Nadal et al., [@B17]) and the participation of"
-"INTRODUCTION {#s1}\n============\n\nIrritable bowel syndrome (IBS) is a common functional gastrointestinal disorder, appearing as complex symptoms such as abdominal pain/discomfort \\[[@R1]\\]. As a chronic biopsychological disorder, IBS is characterized by altered bowel habits excluding organic disorders. Except for the astrointestinal motility abnormality and distorted visceral perception of sensation, IBS is also connected with several gastrointestinal and extraintestinal manifestations \\[[@R2]\\]. Although IBS is one of the most common disease, the etiology of the disease remains unknown. Several physical and psychological factors, such as stress, anxiety, and abnormal attitudes towards illness, are known to contribute to IBS\\'s pathogenesis \\[[@R3]\\]. Nowadays the worldwide prevalence of IBS ranges from 3% to 22% of the population \\[[@R4]\\] and in America, IBS affects 15% of the population \\[[@R5]\\]. Current evidence figures out that the diagnosis of IBS is still according to Rome IV and the actual quantity of the presence of such underlying cause of IBS, however, IBS\\'s pathogenesis remains unknown. Therefore, the objective of our research was to find novel pathogenesis so as to contribute to the treatment of IBS.\n\nIn the human body, aquaporins (AQPs) are considered play important roles in the water transport system \\[[@R6]\\]. There are currently 13 types of AQP,"
-"Introduction {#sec1-1}\n============\n\nEarly onset bipolar disorder, usually becomes chronic, does not have specified periods and reveals a high level of the mixed mania.\\[[@ref1]\\] Early onset bipolar disorder can affect the development and function of the individual\\'s psychosocial characteristics and increase the risk of suicide and substance abuse, as well as academic and social behavior problems. The average onset of symptoms to diagnosis and therapy lasts 10 years which arises the need for early diagnosis and prompt treatment of symptoms.\\[[@ref2]\\] Bipolar disorder type one with early onset has a slow response to treatment, sustaining mood swings, high relapse rate, high suicide risk, and severe social and psychological destruction.\\[[@ref3]\\]\n\nSymptoms of mania include uncontrolled and risky behaviors in early onset bipolar disorder differ from adults' symptoms.\\[[@ref2]\\]\n\nWhen mania has been recognized based on the Diagnostic and Statistical Manual of Mental Disorders (DSM), there must be decrease of executive function which has a separate definition in youth patients. The performance of children and adolescents is specified according to chronological age and intellectual ability mentioned in the definition of psychosocial development. Due to the lack of insight associated with the symptoms of mania in children and adolescents, much of information should be obtained"
-"Data are available from the CSIRO Data Access Portal at: <https://doi.org/10.25919/5dbba9661087a>.\n\nIntroduction {#sec001}\n============\n\nClimate change is rapidly emerging as one of the most significant threats to biodiversity and ecosystems worldwide \\[[@pone.0224625.ref001], [@pone.0224625.ref002]\\]. Global temperatures now average nearly 1\u00b0C greater than in the pre-industrial era, and climate variability and extreme events are increasing \\[[@pone.0224625.ref003], [@pone.0224625.ref004]\\]. Researchers have already documented widespread climate-associated ecological change, including mass mortality events, shifting species distributions, altered phenology, and changing ecosystem productivity \\[[@pone.0224625.ref002], [@pone.0224625.ref004]--[@pone.0224625.ref006]\\], with subsequent effects on societies and economies predicted around the world \\[[@pone.0224625.ref007]\\].\n\nObserving and documenting effects of climate change on biodiversity and ecosystems is an important step towards achieving effective responses through climate change mitigation and adaptation activity. In particular, understanding impacts can directly guide choice of adaptation options \\[[@pone.0224625.ref008]\\], as well as influence willingness to take action \\[[@pone.0224625.ref009], [@pone.0224625.ref010]\\]. While ecological effects of climate change have been widely documented for a broad range of taxonomic groups and ecosystem types, large geographic gaps in documentation remain \\[[@pone.0224625.ref005]\\]. Most empirical studies of ecological impact originate from northern Europe, North America and Russia, facilitated by the availability of long-term observational records. Data from the Southern Hemisphere, including Africa, South America and Australia, are limited"
-"Background {#Sec1}\n==========\n\nFraming the question {#Sec2}\n--------------------\n\nHospitals are hard organizations to change. Publicly owned and operated hospitals even more so. In many countries, both managers and staff anticipate, despite constant calls for improvements in efficiency, quality, and responsiveness, that little will be different tomorrow or next year. Similarly, politicians, seeking to outflank these intra-institutional expectations, have learned to introduce major reforms early in their term to maximize what leverage they have over public hospital managers and staff.\n\nThis creates a narrow window for organizational change in public hospitals which, combined with the standard political hazards \\[[@CR1]\\], still has only a relatively low probability of success, and thus further reinforces the view of hospital management and staff that 'this too shall pass'.\n\nConversely, while public hospitals remain broadly insulated from major policy-driven change, there continues to be rapid successful change in the practice of medicine. This can be seen in clinical treatments, diagnostic technology, in reduced lengths of stay and increased ambulatory treatment, all in spite of a shift to patients being older, more complex and with increasing amounts of chronic disease.\n\nTaken together, these conflicting trends result in most public hospital change being technical and functional rather than"
-"Introduction {#s1}\n============\n\nEvolutionary processes and genetic attributes of invasive populations may underpin their success in becoming established in a new range [@pone.0077083-Lee1]--[@pone.0077083-Dlugosch1]. Life-history traits associated with reproductive strategy are potentially good candidates for rapid evolutionary shifts during invasions [@pone.0077083-Phillips1], because reproductive strategy affects population dynamics and genetic parameters that can, in turn, have feedback effects on evolutionary processes [@pone.0077083-Lambrinos1]--[@pone.0077083-Burton1]. Indeed, when species shift their range, they encounter a suite of new selective pressures that may affect their reproductive strategy. For instance, the lower population density at an expanding front would be expected to select for higher fecundity, lower age at first reproduction, or even a switch from outcrossing to selfing, all of which increase the individual\\'s rate of reproduction [@pone.0077083-Barrett1], [@pone.0077083-Bufford1], [@pone.0077083-MacArthur1]. Rapid evolution towards higher levels of reproduction following invasions may also result from a relaxation of selection for defence against enemies in the invaded range [@pone.0077083-Blossey1], [@pone.0077083-Crawley1]. In accordance with these expectations, a number of studies have shown that invasive populations can display increased reproductive efforts, have higher levels of reproductive investment, shorter generation times or higher selfing rates than native populations [@pone.0077083-Barrett1], [@pone.0077083-Blossey1], [@pone.0077083-Buckley1]--[@pone.0077083-Amundsen1]. Reproductive strategy can also influence the adaptive potential of invasive populations. The"
-"Background\n==========\n\nMigraine is a multifactorial disorder in which genetic factors play a relevant role in both predisposing and determining underlying mechanisms. Approaches to identified genes for monogenic subtypes migraine (e.g. Familial Hemiplegic Migraine - FHM) has been successful (*CACNA1A*, *ATP1A2*, *SCN1A*genes causing FMH 1, 2 and 3 respectively) \\[[@B1]-[@B4]\\]. Conversely, finding genes for the most frequent types of migraine (with and without aura) and defining their pathogenic role has proven much more difficult \\[[@B5]\\]. However, synaptic hyper-excitability has been invocated as one major pathogenic mechanism in both common and monogenic forms of migraine, and data from animal (experimental cortical spreading depression; c-fos protein expression at the trigeminal nucleus caudalis, plasma protein extravasations at level of dura-mater circulation, electrophysiological studies) \\[[@B6],[@B7]\\] and human (assessment of glutamate concentration in plasma, platelets and cerebrospinal fluid in migraneurs vs. control, glutamate and migraine symptoms; glutamate and sensitization) \\[[@B8]\\] studies suggest that glutamate is one of the principal factors involved.\n\nGlutamate is the major excitatory neurotransmitter in the central nervous system which exerts this action mainly through its interaction with its ionotropic or metabotropic receptors.\n\nIn this study we investigated the association of *GRIA1, GRIA2, GRIA3*and *GRIA4*genes that encode for the four subunits (GluR1-GluR4)"
-"Introduction {#Sec1}\n============\n\nIn contrast to both conventional T lymphocytes and other types of Tregs, invariant natural killer T (iNKT) cells comprise a unique subgroup of immunoregulatory T lymphocytes that are restricted by the non-classical MHC class I molecule CD1d and expression of the invariant V\u03b124--J\u03b118 T cell receptor (TCR) preferably paired with V\u03b211 \\[[@CR1]-[@CR6]\\]. Furthermore, iNKT cells can either upregulate or downregulate cell-mediated immunity and thus these cells could have diverse influences in various disease models \\[[@CR5]-[@CR8]\\].\n\nSarcoidosis is the most common interstitial lung disease in the western world. It frequently involves organs other than the lungs. This multisystem disorder features the presence of CD4^+^ T cells that differentiate into Th1-like cells and amplify the local immune response \\[[@CR9]-[@CR11]\\]. Despite much research over the past decade, the cause of the Th1-biased hyperactive response remains unknown. Ho et al. \\[[@CR12]\\] first hypothesized that the loss of immunoregulation by iNKT cells could explain amplified and persistent T cell activity. This hypothesis was based on NOD mice that are deficient for iNKT cells. These mice are generally healthy, but they are predisposed to disorders with increased Th1 responses \\[[@CR13]\\]. Ho reported a significant decrease in iNKT cell frequency in the peripheral blood"
-"Introduction\n============\n\nChild malnutrition and anemia are both global public health problems with monumental consequences at adulthood. The prevalence of stunting is declining and according to UNICEF, 40% (257 million) of the world\\'s children in 1990 suffered from stunting whereas in 2013, the proportion had decreased to 25% (161 million)[@R1]. The prevalence of wasting has also significantly declined, from 19% (122 million) in 1990 to 8% (51 million) in 2013. In 2008, over 1 billion people worldwide were said to be malnourished[@R2] and 2 billion people are globally affected with anemia[@R3]. Recent reports have shown that Africa and Asia accounted for more than 85% of the absolute anemia burden in high-risk groups and a quarter of the global population, including 293 million (47%) children younger than 5 years, and women of reproductive age, 42% in pregnant women, and 468 million (30%) non-pregnant women[@R4].\n\nMalnutrition is a condition that arises as a result of consuming a diet that contains insufficient or too many nutrients or as a result of faulty or under-utilization of foods. Anthropometric indices are commonly used in order to classify individuals as malnourished or of normal nutritional status. Stunting (short height- for- age) is an indicator of linear"
-"Introduction {#s1}\n============\n\nBurst suppression is an EEG pattern characterized by quasiperiodic high amplitude activity (bursts) and relativity low amplitude activity (suppressions; Amzica, [@B4]; Brown et al., [@B11]). The phenomenon was first observed while recording EEG from the motor cortex of cats under tribromoethanol and pentobarbital-induced general anesthesia (Derbyshire et al., [@B22]). Investigations into the effects of ether and pentobarbital anesthesia on the EEG of canines led to the creation of the term \"burst suppression\" (Swank and Watson, [@B90]). Although early work on burst suppression focused on general anesthesia, burst suppression can be induced by several different etiologies (Martin et al., [@B57]).\n\nIn the first part of this article, algorithms employed to quantify burst suppression, different causes of burst suppression, and theories about the mechanisms underlying burst suppression are reviewed. We also describe clinical applications of burst suppression induced by general anesthetics. In the second part of this article, we present original research findings from our laboratory that demonstrate the distinct electrophysiological characteristics of burst suppression induced by the inhaled anesthetic sevoflurane and the intravenous anesthetic propofol.\n\nQuantification of burst suppression {#s1-1}\n-----------------------------------\n\nA widely used method for quantifying burst suppression is the burst suppression ratio (BSR; Rampil et al.,"
-"CASE REPORT\n===========\n\nA 53-year-old Caucasian male was referred to our Department due to an asymptomatic erythematous plaque on the left buttock evolving for 5 months and with progressive increase. On physical examination, an erythematous-brownish plaque was observed with a raised erythematous-red border and areas of erosion ([Figure 1](#f01){ref-type=\"fig\"}). There were no other signs or symptoms. A biopsy showed hyperkeratosis, acanthosis and spongiosis, as well as epidermotropism of isolated and grouped large-sized atypical lymphocytes with pale halos, also present in the upper dermis. Immunohistochemistry revealed positive staining of these cells for CD3 and CD8 ([Figure 2](#f02){ref-type=\"fig\"}) without staining for CD4, CD30 and CD56, consistent with the diagnosis of pagetoid reticulosis (PR) - Woringer-Kolopp disease (WKD). The microbiological examinations of the skin were negative. Three weeks later the patient developed several nummular erythematous lesions with a scaling border scattered on the legs ([Figure 3](#f03){ref-type=\"fig\"}). We repeated the biopsy, which revealed identical findings plus positive staining for CD45 and a proliferative index of 90% (Ki67). Subsequently, these lesions increased in size, assuming the shape of the original plaque and a diagnosis of Ketron-Goodman disease (KGD) was established. The patient started treatment once daily with betamethasone dipropionate ointment and, simultaneously, was referred to"
-"Introduction {#Sec1}\n============\n\nOne potential barrier to extending nuclear light water reactor lifetimes to 80 years is embrittlement of their massive reactor pressure vessel (RPV)^[@CR1]^. Embrittlement is primarily due to the formation of nm-scale precipitates, which cause hardening and a corresponding increase in the ductile-to-brittle transition temperature^[@CR2],[@CR3]^. A major effect of irradiation is radiation enhanced solute diffusion (RED) associated with excess vacancy and self-interstitial concentrations. RED leads to hardening by Cu-rich precipitates (CRP) at low to intermediate neutron fluence (*\u03d5t*) in steels with more than \u22480.07\u2009at.% Cu^[@CR2],[@CR4]^. Cu is highly insoluble at typical RPV service temperatures (*T*~*i*~) of \u2248290\u2009\u00b0C and quickly precipitates as coherent bcc clusters that are also enriched in Mn, Ni and Si. Solute-defect cluster complexes, known as stable matrix features, which form in displacement cascades, also cause modest hardening, initially increasing roughly with the square root of *\u03d5t* in both low Cu and Cu bearing steels^[@CR3]^. These features are thought to be precursors to formation of well-formed Mn-Ni-Si precipitates at higher *\u03d5t*, as discussed below.\n\nA main challenge for RPV life extension is predicting embrittlement at low service-flux (*\u03d5*) and high *\u03d5t*, where new embrittlement mechanisms may emerge. Notably, large mole fractions (*f*) of what"
-"Background\n==========\n\nBesides Hong Kong, Macao is the other special administrative region (SAR) belongs to the People's Republic of China. As the only government hospital in Macao, Centro Hospitalar Conde de S\u00e3o Janu\u00e1rio is responsible for all of the peritoneal dialysis (PD) patients. Benefitting from the superior end-stage renal disease (ESRD) funding system provided by Macao SAR, almost all the resident patients on chronic dialysis can get free treatment including dialysis and medication. Different from Hong Kong, there is no PD-first policy in Macao. Nevertheless, PD has been rapidly developed during the past decade in Macao with about 40% of the PD penetration rate in chronic dialysis patients \\[[@B1]\\].\n\nCardiovascular disease (CVD) is the leading cause of mortality and morbidity among patients with ESRD on chronic dialysis \\[[@B2]\\]. According to U.S. Renal Data System and Hong Kong Renal Registry reports, CVD accounts for approximately 40% mortality in dialysis patients and also is the main cause of hospitalization \\[[@B3],[@B4]\\]. In keeping with these facts, data from the Macao Renal Registry show that 36.2% of the mortality in PD patients is attributable to CVD. Currently, many available studies have shown that increased arterial stiffness, which can be examined by pulse wave velocity"
-"Background {#Sec1}\n==========\n\nCurrent prompt revascularization by primary percutaneous coronary intervention and optimized medical therapy for ST-elevation myocardial infarction (STEMI) have resulted in dramatic improvement of patient mortality \\[[@CR1]\\]. This improvement provided by serial medical interventions, beginning with first medical contact, has increased in recent years. On the other hand, since short-term mortality in STEMI caused by left main trunk (LMT) lesions remains high, faster diagnosis and medical intervention is required to improve patient survival \\[[@CR2], [@CR3]\\].\n\nConventional electrocardiography remains the gold standard modality for early diagnosis of STEMI, even in the current advanced diagnostic modality era. The Electrocardiogram (ECG) plays an important role in diagnosis and identification of the location of the culprit infarct artery, and its diagnostic accuracy is reported to be high \\[[@CR4]\\].\n\nHowever, it is not always easy to confirm that the culprit lesion is an LMT lesion, based only on initial ECG findings; it is especially difficult to distinguish an LMT lesion from a left anterior descending artery (LAD) lesion (Fig.\u00a0[1](#Fig1){ref-type=\"fig\"}). Definition of differences in respective ECG findings of these two lesions may help choose a more appropriate medical intervention strategy and thus improve short term-mortality \\[[@CR5]\\].Fig. 1Representative electrocardiograms. **a** STEMI due to LMT"
-"Introduction {#Sec1}\n============\n\nCoronaviruses (CoVs) are single-stranded positive sense RNA viruses that belong to the *Coronaviridae* family. The family comprises four genera: *Alphacoronavirus* (*\u03b1-CoV*), *Betacoronavirus* (*\u03b2-CoV*), *Gammacoronavirus* (*\u03b3-CoV*), and *Deltacoronavirus* (*\u03b4-CoV*) \\[[@CR1]\\]. These viruses infect several species of animals and can cause hepatic, enteric, neurological, and acute and chronic respiratory infection \\[[@CR2]\\]. In humans, they generally cause mild upper respiratory tract disease with low mortality \\[[@CR3]\\]. In 2003 and 2012 respectively, the emergence of highly pathogenic *\u03b2-CoV* SARS-CoV (severe acute respiratory syndrome) and MERS-CoV (Middle East respiratory syndrome) revealed that this group of viruses can also cause severe respiratory illness in humans \\[[@CR4], [@CR5]\\].\n\nBats are widespread flying mammals that are distributed worldwide. About 1150 bat species have been described and 179 were reported in Brazil \\[[@CR6]--[@CR8]\\]. Numerous viruses have been reported to infect bats, and these animals are being studied as potential reservoir for several zoonotic diseases, including Coronaviruses \\[[@CR3], [@CR9], [@CR10]\\]. The majority of Bat Coronavirus (BtCoV) have been identified in bats from Asia, Africa, and Europe \\[[@CR11]--[@CR19]\\]; however, CoV has also been reported in bats from South American countries including Brazil, Trinidad, Costa Rica, Ecuador, Panama, and Mexico \\[[@CR20]--[@CR25]\\].\n\nAlthough there is no report of CoV pathogenesis"
-"Every compound can be identified by a unique arrangement of the atoms in the crystal structure, which determines the inter--atomic distances and the compositional ratios and thus helps understanding specific material properties. For this reason, crystal structure determination and analysis are essential not only from a mere crystallographic viewpoint, but also for numerous fields of materials research, chemistry, physics and life sciences.\n\nThe evaluation of crystal structures can be facilitated by various tools and indicators. For instance, Goldschmidt tolerance factor (*T*\u2009) of perovskite compounds ABX~3~ (A and B: metal cations, X: chalcogen or halogen group) is widely used to assess the geometric stability and distortion of crystal structures in terms of the constituent ionic packing. The *T* is defined by ratios of constituent ionic radii of A, B and X as *T*\u2009=\u2009(*R*~A~\u2009+\u2009*R*~X~)/\u221a2(*R*~B~\u2009+\u2009*R*~X~), where *R*~A~, *R*~B~ and *R*~X~ are the ionic radii of A, B and X, respectively (c.f. [Fig. 1a](#f1){ref-type=\"fig\"}). The ideal perovskite compounds adopt a cubic close packed structure with *T*\u2009=\u20091. When the ratio of the ionic radii deviates from the ideal value (*T\u2009*\u2260\u20091), a geometric strain and crystal distortions arise. As the deviation from *T*\u2009=\u20091"
-"Introduction\n============\n\nHerpes simplex virus (HSV) is one of the most common viral diseases in humans. HSV exists as two types, herpes simplex virus 1 (HSV-1) and herpes simplex virus 2 (HSV-2) which have been distinguished by clinical manifestations, biological and serological criteria. A characteristic property of herpes viruses is their ability to establish and maintain latent infections that can be frequently reactivated by several different stimuli such as stress, ultraviolet light, hormones, transient hyperthermia, and immunosuppression. Infections of these viruses can cause a wide range of signs and symptoms varying from mucocutaneous lesions to life-threatening encephalitis ([@b21-ijn-2-419]; [@b17-ijn-2-419]).\n\nSeveral drugs have proven to be useful in the treatment of many specific infections, but viral strains resistant to these drugs have been increasingly identified and several cases of toxicity have been encountered, particularly in immunocompromised patients ([@b13-ijn-2-419]). According to the type and severity of the infection, antiviral agents may be administered *via* several routes: orally for the treatment of primary oral or genital infections, parenterally for serious infections such as neonatal herpes and herpes infections of the central nervous system, in drops for ocular herpetic infections and topically on lips and mucosae for mild recurrent orolabial lesions ([@b2-ijn-2-419]).\n\nIn order"
-"INTRODUCTION {#s5}\n============\n\nInflammatory bowel disease (IBD) is a chronic, relapsing inflammatory disorder in the gastrointestinal tract that affects up to 0.5% of the population of the Western world.^[@CIT0001]^ The 2 major forms of IBD, ulcerative colitis (UC) and Crohn's disease (CD), are characterized by a dysregulated mucosal immune response triggered by intestinal commensal flora.^[@CIT0002]^ The onset of IBD symptoms appears to be caused by an imbalance between pro- and anti-inflammatory molecules.^[@CIT0003]^ However, several factors might be involved in the chronic inflammatory state observed in IBD. These include cytokines, interleukins (ILs), nitric oxide (NO), free radicals, activated Toll-like receptors, oxylipins, and microbiota.^[@CIT0003]^ Furthermore, it has previously been shown that colitis is associated with a disruption in the lipid metabolism.^[@CIT0004]^\n\nOxylipins are bioactive derivatives mainly from omega 3 and omega 6 polyunsaturated fatty acids (\u03c9-3 and \u03c9-6 PUFAs) such as \u03c9-6 arachidonic acid (AA), \u03c9-6 linoleic acid (LA), \u03c9-3 eicosapentaenoic acid (EPA), and \u03c9-3 docosahexaenoic acid (DHA).^[@CIT0005]^ Oxylipins are synthetized through 3 main enzymatic pathways, namely cyclooxygenase (*COX*), lipoxygenase (*LOX*), and cytochrome P450 (*CYP450*), resulting in more than 100 active mediators. The AA-derived oxylipins, also known as eicosanoids, are involved in chemotaxis and promoting the recruitment of neutrophils to the site"
-"The epidemic of severe acute respiratory syndrome (SARS), an emerging infectious respiratory disease caused by a novel coronavirus,[@bib1] started in Guangdong Province, China in November 2002 and swept over 31 countries and regions worldwide, accounting for a cumulative number of 8,098 infected cases and 774 deaths (case fatality, 9.56% as reported on January 24, 2004).[@bib2] With regards to the treatment of SARS, no specific approaches so far are available. Glucocorticosteroid administration for acute lung injury (ALI) or ARDS arising from critical SARS remains controversial, as does for ALI or ARDS arising from other etiologies. Many studies have looked into the use of corticosteroids in SARS management in terms of efficacy, duration, dose, and severe adverse events; however, further investigations are needed to characterize the treatment efficacy and safety profiles of steroids in this condition.[@bib3] Some authors[@bib4], [@bib5], [@bib6] implied that large-dose steroids were indicated during the early phase once a diagnosis was made, to prevent further deterioration, while some others[@bib7], [@bib8], [@bib9] thought that large-dose therapy was not advisable although steroids could help. Open clinical trials[@bib6], [@bib9], [@bib10], [@bib11], [@bib12], [@bib13], [@bib14] also demonstrated that pulse steroid therapy could reduce mortality without associating an increased rate of life-threatening complications. Unfortunately,"
-"Introduction {#Sec1}\n============\n\n*Clostridium difficile* is one of the prominent causes of infectious nosocomial diarrhea and is responsible for \\~25% of human antibiotic-associated diarrhea^[@CR1]^. Although patients with *C. difficile* infection (CDI) may acquire the organism from the environment^[@CR2]^, potential sources of CDI in humans may include domestic and farm animals since an overlap between isolates from humans and animals has been demonstrated^[@CR3],\\ [@CR4]^. CDI causes diseases ranging from mild diarrhea to life-threatening pseudomembranous colitis. The number of incidence and the level of severity of CDI has markedly increased across the continents^[@CR5],\\ [@CR6]^. Antimicrobial treatment plays an important role in the progression of CDI. It has been postulated that the antibiotic therapy disrupts normal gut microbiota, allowing *C. difficile* colonization and growth because it is naturally resistant to many drugs used to treat other infections, thereby enabling its toxin production^[@CR7]^. The first-line therapy for CDI includes metronidazole and vancomycin, however, the resistance to these drugs has been reported, rendering the treatment ineffective^[@CR8]^. In recent years, the antimicrobial therapy for CDI tends to be more difficult due to the development of multidrug resistant (MDR) strains including the hypervirulent drug resistant strain, BI/NAP1/027^[@CR9]^. A number of highly virulent MDR strains belonging to other"
-"Introduction {#S1}\n============\n\nThe health status of older adults is highly variable, with some individuals experiencing few age-related limitations and others facing with multiple comorbidities, social isolation, and reduced socioeconomic resources. Additionally, men and women might face distinct challenges and stressors in late life, and they might experience different and specific physical and mental health problems. Indeed, sex has been recognized as a variable that influences behavioral and lifestyle choices and, consequently, may play an important role in the development and progression of age-related chronic diseases. Importantly, the known universal women advantage in life expectancy does not necessarily mean that they present better health status than men. In fact, higher prevalence of functional limitations, physical disability, and poor self-rated health has been reported among women compared with age-matched men in previous studies ([@B54]; [@B42]; [@B9]). In general, sex differences in health status in late life have been explained attending to psychosocial factors, such as differential vulnerability, and/or exposure to social and biological factors among women and men. However, sex differences in general health status have not been previously explored in an older community-dwelling Galician population, and there is still much to be done in order to further understand why men"
-"Epilepsy is a neurological disorder characterized by recurrent seizures, which are sudden, unprovoked, and transitory episodes of abnormal hypersynchronous neuronal discharge. It is estimated that more than 50 million people worldwide are epileptic (1--2% of the world\\'s population), out of whom 40 million are believed to be living in the developing countries.\\[[@ref1]\\] The currently available antiepileptic drugs have several limitations as they provide only symptomatic relief and their use is often plagued by significant adverse effects such as rash, blood dyscrasias, vitamin K and folate deficiencies, loss of libido, hormonal dysfunction, and bone marrow hypoplasia and fetal abnormalities such cleft palate, cleft lip, congenital heart disease, slowed growth rate, and mental deficiency. Moreover, a significant proportion of patients (up to 40%) do not respond to these agents and this proportion is quite high in the developing countries.\\[[@ref2][@ref3]\\] Additionally, the high cost of newer and more effective antiepileptic drugs have led to a greater proportion of patients in Ghana and possibly other third world countries, resorting to the use of traditional medicine. There is therefore a universal and local need for continued research into the development of newer and cost effective agents for the management of this disorder.\\[[@ref4]--[@ref6]\\] Plant sources of"
-"INTRODUCTION {#s1}\n============\n\nRecently, with the development of genetic engineering technology, rapidly increasing researches focus on gene edited rats as an optimal model for human disease studies, including cancer, because rats are physiologically more similar to human than mice \\[[@R1]--[@R3]\\]. However, because of the high cost and technical demanding, production of genetically engineered rats has been severely hampered. Fortunately, several promising novel methods of efficient, targeted genome editing technology have emerged, including zinc finger nucleases (ZFN) \\[[@R4]\\], transcription activator-like effector nucleases (TALENs) \\[[@R5]\\] and the recently developed clustered regularly interspaced short palindromic repeat (CRISPR) \\[[@R6]\\], all useful to efficiently modify the genome DNA sequence. TALENs are customizable, DNA binding nucleases that can be targeted to bind almost any sequence in the genome. Every TALEN is consisted of two domains, one is composed by repeating units to form DNA binding domain, and the other is FoK I endonuclease, which has the unspecificity activity of endonuclease. Each repeating unit is composed by 33--35 amino acids, and the adjacent amino acids of 12 and 13 can specifically recognize DNA nucleotide sequences, such as the amino acids of NI, NN, NG, HD can identification A, G, T, C bases, respectively. Therefore, TALEN can edit"
-"Introduction {#s0001}\n============\n\nThe concept of tracer drugs (TDs) as essential medicines (EMs) was pioneered by the World Health Organization (WHO) in 1977. At inception, EMs was defined as medicines that are of utmost importance, and are basic, indispensable, and necessary for the health needs of the population.[@cit0001] They are selected with due regard to public health relevance, evidence of efficacy, and safety as well as cost-effectiveness.[@cit0002]\n\nEthiopian-integrated pharmaceutical logistics system was aimed to integrate all vertical programs into one supply chain and deliver pharmaceuticals directly to health facilities every other month from pharmaceutical supply agency.[@cit0003] It used pharmaceutical logistics management information system (LMIS) as a system of records and reports of pharmaceuticals data to ensure the continuous availability of all pharmaceuticals that are required for patient care. At the same time, responding to sudden increases in drug demand and ensuring that adequate supplies should always be in place to deal with any emergencies that arise.[@cit0004],[@cit0005]\n\nAn effective LMIS collects essential data about stock status and consumption so that it ensures accountability and cost-effectiveness for all products in the supply chain.[@cit0004] Lack of effective LMIS not only affects the availability of EMs but also significantly affects the efficiency of the"
-"1. Introduction\n===============\n\nQuercetin is a category in the class of flavonoids, and a sub class of flavonol. Flavonoids are plant polyphenolics found as pigments in fruits, vegetables, seeds, nuts, flowers, barks and leaves. It is also found in medicinal botanicals, such as Ginkgo biloba, Hypericum perforatum (St. John's Wort), and Sambucum canadensis (El-der) \\[[@B001]\\]. The International Union of Pure and Applied Chemistry's (IUPAC's) name for quercetin is 3, 3', 4', 5, 7-pentahydroxyflavone (or its synonym 3, 3', 4', 5, 7-pentahydroxy-2-phenylchromen-4-one). Fig.1 shows the chemical structure of quercetin. The hydroxyl (-OH) groups attached at positions 3, 5, 7, 3', and 4' and the catechol B-ring produce the antioxidant properties of quercetin \\[[@B002], [@B003]\\]. The antioxidant and the free radical scavenging properties of quercetin have been reported to contribute to anti carcinogenic and anti inflammatory effects, and haves been extensively studied by researchers around the world \\[[@B002]\\].\n\nExtensive amounts of *in vitro* and *in vivo* animal research on quercetin's pharmacological activities have been carried out, suggesting that quercetin might be used as a new therapeutic approach to decrease blood pressure \\[[@B004]\\], to inhibit fibronectin production by keloid derived fibroblasts \\[[@B005]\\], to inhibit neointimal hyperplasia in the abdominal aorta of rats \\[[@B006]\\],"
-"Background {#Sec1}\n==========\n\nMedicinal plants are considered as potential source for drug development and many novel products have reached clinical trials. Scientists are investigating properties of medicinal plants in order to develop novel drugs against disease like cancer, from natural products. Medicinal herbs have profound scope and have been used to find potential anticancer compounds in them \\[[@CR1]\\]. Use of phytochemicals from the medicinal plants in cancer treatment, may reduce adverse side effects and help to treat cancer and they have in recent years, shown promising anticancer efficiency against different cancers like human mouth epidermal carcinoma (KB cell line), murine leukemia (P388 cell line), human colorectal cancer (BE cell line) and prostate cancer (PC3 cell line) by various mechanisms like up-regulation of p16INK4A, preventing inhibition of MRCK-kinase targeting multiple gene products and targeting mitotic processes \\[[@CR2]--[@CR8]\\]. Many medicinal plants found in Nepal are also found to have cytotoxic effects against different cancer cell lines. For example, Cell viability assay of plant extracts from *Berberis aristata*; showed a significant cytotoxicity to MDA-MB-231 and U-87 MG human cancer cell line; Withanone from *Withania somnifera* (Ashwagandha) has been identified to have p53-activating tumor-inhibiting property. Ashwagandha leaf powder was non-toxic and anti-tumorigenic in mice"
-"1. Introduction\n===============\n\nX-linked hyper-IgM syndrome (XHIGM) caused by the CD40 ligand (CD40L) mutation is a rare primary immunodeficiency condition that decreases immunity to opportunistic infections because there are defects in neutrophils, complement proteins, macrophages, and lymphocyte subsets.^\\[[@R1],[@R2]\\]^ A missed or delayed diagnosis of XHIGM is widespread and concerning, especially in patients without a relevant family or medical history. Distinct clinical infectious complications could occur in those with XHIGM syndrome based on the genetic characteristics and the exact type of the syndrome, which makes it a challenge for researchers and clinicians. The respiratory tract was the most commonly involved organ in XHIGM patients, which also included the gastrointestinal tract, skin, central nervous system, and septicemia. The most common opportunistic pathogens include *Pneumo-cystis pneumonia* (PCP), fungal infection, *Cryptosporidium* infection, and infections by members of the herpesvirus family.^\\[[@R1],[@R3]--[@R5]\\]^\n\nHere, we report a male infant with a novel mutation of CD40L who developed severe interstitial pneumonia and respiratory failure with PCP, cytomegalovirus (CMV) and fungal infection.\n\n1.1. Case presentation\n----------------------\n\nA 10-month-old boy with recurrent fever, cough, tachypnea and cyanosis for 8 days with a history of antibiotic therapy was admitted to our emergency department with suspected pneumonia. This infant was the only"
-"Introduction\n============\n\nCoronary artery disease (CAD) is the leading cause of death in the world and is responsible for 7.4 million deaths in 2012.[@b1-mder-8-359] Major advances in treatment and technology have led to a reduction in age-related cardiovascular deaths over the past 25--30 years.[@b2-mder-8-359] Paradoxically, however, the prevalence of CAD is expected to further increase as a result of the continuously growing epidemic of obesity and its consequences, including hypertension, dyslipidemia, and diabetes.[@b2-mder-8-359]\n\nThe introduction of percutaneous coronary catheter interventions has revolutionized the field of coronary revascularization, and key developments in percutaneous coronary intervention (PCI) have significantly contributed to improve outcomes in patients with CAD: coronary bare-metal stents (BMSs) provided an answer to acute vessel closure, caused by dissection or elastic recoil after balloon angioplasty.[@b3-mder-8-359] While BMS prevented late lumen narrowing owing to vascular remodeling, they simultaneously triggered neointimal proliferation, ultimately leading to in-stent restenosis.[@b3-mder-8-359] Drug-eluting stents (DESs) virtually eliminated restenosis, providing controlled antiproliferative drug release from BMS carriers.[@b4-mder-8-359] While the latest revolution in interventional cardiology introduced fully resorbable scaffolds with a promise of vessel restoration, lumen enlargement, and regained vasomotion,[@b5-mder-8-359] versatile engineering of permanent metallic implants represents a unique opportunity to improve stent delivery, conformability and radial strength, both"
-"1. Introduction {#sec1-pharmacy-06-00121}\n===============\n\nAsthma is a significant public health problem all over the world and an everyday reality for the 2.4 million Canadians living with asthma \\[[@B1-pharmacy-06-00121]\\]. Asthma control can be achieved with effective and safe medications and treatment guidelines \\[[@B2-pharmacy-06-00121]\\]. However, level of asthma control has not improved over the last decade and currently 9 out of 10 Canadians with asthma are out of control \\[[@B3-pharmacy-06-00121]\\]. Poor asthma control is burdensome to patients and increases emergency room visits, hospitalizations, and absence from work or school \\[[@B4-pharmacy-06-00121]\\].\n\nThe reasons for poor asthma management are multifaceted including the disease itself, presence of comorbidities, patients' self-management, healthcare professionals' care, or the interaction among these factors \\[[@B5-pharmacy-06-00121],[@B6-pharmacy-06-00121]\\]. Medication therapy is the primary intervention used in asthma highlighting asthma patients have needs that pharmacists can address \\[[@B7-pharmacy-06-00121],[@B8-pharmacy-06-00121]\\]. Pharmacists frequently encounter asthma patients and are not only well placed to identify patients with poorly controlled asthma but also resolve medication problems, educate patients on inhaler technique, monitor therapy, and develop personalised asthma action plans \\[[@B8-pharmacy-06-00121],[@B9-pharmacy-06-00121],[@B10-pharmacy-06-00121]\\].\n\nPharmacist-delivered interventions in asthma management have improved patient outcomes \\[[@B11-pharmacy-06-00121],[@B12-pharmacy-06-00121],[@B13-pharmacy-06-00121],[@B14-pharmacy-06-00121],[@B15-pharmacy-06-00121]\\] but only few have explored the patient experience of pharmacist care as one of the factors contributing to positive"
-"Introduction\n============\n\nRegular physical activity is associated with lower morbidity and mortality rates from cardiovascular disease \\[[@ref1]-[@ref4]\\], diabetes mellitus \\[[@ref5]\\], cancer \\[[@ref6]\\], and osteoporosis \\[[@ref7]\\]. Despite these proven health benefits, the majority of the adult population in Western nations does not meet the public health recommendations for physical activity \\[[@ref8]-[@ref12]\\]. Therefore, there is a need for the delivery of effective interventions aimed at positively influencing physical activity behavior.\n\nTraditionally, most physical activity interventions use face-to-face modes of delivery (eg, individual consultations or group meetings). Their mainly short-term effectiveness has been extensively documented in a number of systematic reviews \\[[@ref13]-[@ref18]\\]. In addition, these reviews demonstrated that many of the physical activity studies suffer from several methodological weaknesses. The main methodological shortcomings identified by these reviews included use of physical activity measures without validity/reliability data, exclusive reliance on self-report measures, inadequate control of confounding factors, small sample sizes, lack of data on follow-up, and low follow-up rates.\n\nWith the number of people having access to and using the Internet rapidly increasing \\[[@ref19]\\], the Internet is more and more used as a mode of delivery for physical activity programs. The strength of Internet-based physical activity interventions lies in the fact that with this"
-"All relevant data are within the paper and its Supporting Information files.\n\nIntroduction {#sec001}\n============\n\nThe involvement of endothelial, hormonal and neural factors in the regulation of vascular function is well established \\[[@pone.0168841.ref001], [@pone.0168841.ref002]\\], although the contribution of these factors depends on the type of the vessel. In response to different stimuli the endothelium can release different factors, such as nitric oxide (NO), prostanoids, reactive oxygen species (ROS), among others \\[[@pone.0168841.ref001]\\]. NO is a signaling molecule formed by the enzyme nitric oxide synthase (NOS) that plays a crucial role in vascular homeostasis regulating the vascular tone, and therefore also influences blood pressure. This molecule exerts vasodilation in smooth muscle cells by stimulating the protein kinase G (PKG) trough soluble guanylate cyclase (sGC) in the smooth muscle of the arterial wall \\[[@pone.0168841.ref003]\\]. Also, NO has anti-inflammatory, antithrombotic, antiproliferative, and antioxidant effects. A decrease in NO synthesis and/or bioavailability leads to the development of vascular dysfunction \\[[@pone.0168841.ref004]\\].\n\nThe endothelium is also a source of ROS generated through the activation of xanthine oxidase, cyclooxygenase, and cytochrome P-450 \\[[@pone.0168841.ref005], [@pone.0168841.ref006]\\]. Excessive production of ROS, causes vascular dysfunction by outstripping endogenous antioxidant defense mechanisms, and it has been implicated in the pathogenesis of many cardiovascular"
-"INTRODUCTION {#sec0010}\n============\n\nHigh risk (high grade, cTa, cT1, and cTis), non-muscle invasive bladder cancer (NMIBC) is principally managed with transurethral resections (TUR) and adjuvant intravesical bacillus Calmette-Guerin (BCG) therapy. However, disease recurs or progresses in approximately 40%--50% of patients \\[[@r1]\\]. Available management options for patients with recurrent or progressive high grade NMIBC include radical cystectomy (RC), additional intravesical therapy typically with chemotherapy, and clinical trial entry \\[[@r2]\\]. Some advocate RC in lieu of additional intravesical therapy as BCG failure portends poor oncologic outcomes when treated with bladder preservation and long-term survival in patients undergoing cystectomy with cTa/T1/Tis disease ranges from 80%--88% \\[[@r3]\\]. Furthermore, cystectomy may be more cost-effective than intravesical therapy when used as first line treatment in certain high risk settings of NMIBC \\[[@r5]\\].\n\nMitomycin C (MMC) is predominantly utilized as treatment for patients with intermediate and high risk NMIBC as well as for patients who recur or progress despite intravesical BCG therapy \\[[@r6]\\]. There have been no randomized controlled trials (RCTs) evaluating the clinical or economic benefit of mitomycin C intravesical therapy over radical cystectomy in high risk NMIBC populations largely due to the expected challenges in patient accrual, real ethical concerns, expected costs of such a"
-"Background\n==========\n\nThe developing cerebral cortex and other brain regions undergo substantial cell suicide during the period of neurogenesis and early differentiation \\[[@B1]-[@B10]\\], to generate a mature brain. Mechanisms that control the survival or death of neuroblasts and neurons in the developing cerebral cortex are likely to have profound effects on the organization of cognition, affect and sensori-motor integration in the adult. One generally accepted mechanism that is invoked to explain developmental apoptosis is the competition among neurons for limited supplies of trophic molecules within the environment (reviewed in \\[[@B11]\\]). According to this model, a neuron\\'s inability to find growth factor support within its environment precedes the initiation of apoptosis. However, the presence of cell-surface suicide receptors, like the Fas/Apo \\[Apoptosis\\]-1/CD95 receptor, and their trans-membrane ligands (e.g., FasL) in the developing brain \\[[@B9]\\] suggests that neural cells may actively communicate apoptosis signals to each other. In addition to competing for a limited supply of trophic factors, developing neural progenitors and differentiating neurons may engage in an active killing process whereby \\'killer cells\\' induce apoptosis in \\'suicide-receptive\\' cells, to limit cell number in the brain. It is therefore important to understand the signaling mechanisms and circumstances that regulate cell-suicide receptor expression"
-"1. Background {#sec31049}\n=============\n\nTransposition of the Great Arteries (TGA) is one of the most common congenital heart diseases, accounting for 5% to 7% of all congenital cardiac lesions resulting in cyanosis. In the past three decades, the Arterial Switch Operation (ASO) has become the preferred surgical procedure for TGA. After the first successful ASO by Jatene in 1975 and its modification by Lecompte et al., a considerable number of series have been reported ([@A12212R1]).\n\nA limited number of long-term studies revealed an excellent outcome and freedom from reoperation in the patients undergoing ASO ([@A12212R1], [@A12212R2]).However, in the ASO, the coronary arteries are translocated, the pulmonary valve becomes the systemic outflow valve, and the pulmonary arteries may be distorted because of the atypical relation between the great vessels. Also, concerns exist regarding the fate of coronary arteries ([@A12212R3]), the function of neo-aortic valve ([@A12212R2], [@A12212R3]) , and the development of pulmonary artery stenosis ([@A12212R2]). However, during the past 10 years, some clues have been gathered over the long and midterm problem of neonatal ASO, especially about the problem related to the neo-aortic valve ([@A12212R4]), neo-aortic root enlargement, and the patency as well as function of the reimplanted coronary arteries ([@A12212R5],"
-"INTRODUCTION {#sec1-1}\n============\n\nPromotion of physical activity levels is one of the most three important and effective strategies for reducing the risk of noncommunicable diseases. Few studies have shown more than 80% of the Iranians physically inactive, and other local studies also report similar patterns in Iranian youth.\\[[@ref1]\\]\n\nPhysical activity can be estimated objectively or subjectively.\\[[@ref2]\\] Various criterion measures, such as doubly labeled water (DLW), motion sensors, heart rate monitors, accelerometer, and activity records have been used to determine the relative validity of physical activity questionnaires.\\[[@ref3]\\] The DLW method is the most suitable approach for this task.\\[[@ref3]\\] Questionnaires are common subjective forms of measuring physical activity in epidemiological researches. Those are relatively feasible, fast, and cheap to produce and administer.\\[[@ref4]\\] Intensity, frequency, and duration, together define the total volume of an activity.\\[[@ref5]\\] A self-report questionnaire is the only practical method of collecting a broad range of data from a large number of children and adolescents, but it is still important that the questionnaire items provide acceptably accurate data.\\[[@ref6]\\]\n\nThe Modifiable Activity Questionnaire (MAQ), developed originally by Kriska *et al*., is a self-reported questionnaire\\[[@ref7]\\] that records frequency and duration of different levels of physical activity and has been modified to measure"
-"Introduction\n============\n\nNew climatic conditions induced by global warming can lead to alterations of different biological processes in both plant and animal species ([@B62]). These changes include temporal, spatial or behavioral adjustments of species, such as changes in distribution range, phenological or physiological characteristics ([@B5]). In this context, it is expected that many species will not be able to adapt to the new conditions, leading to a generalized increase of the extinction rate ([@B77]). In contrast, species with specific life-history traits that confer them high capacity to adapt to environmental changes, such as invasive species, are likely to be promoted in the new climatic scenario ([@B32]; [@B81]).\n\nBiological invasions and their drastic alteration of natural ecosystems are widespread and have long been recognized as a significant component of global environmental change ([@B82], [@B83]). Understanding how environmental change factors are influencing fundamental biological processes is imperative for conservation and management of natural ecosystems. The continued spread of non-native plant species, synergistic with accelerating global environmental changes, poses significant challenges for understanding how natural ecosystems and the native plant communities will be altered ([@B31]). Once introduced, one way by which invasive species displace or exclude native species is through hybridization and introgression"
-"1. Background {#sec1-ijms-18-02618}\n=============\n\nCharacterizing the organization of an organism into autonomous genetic and phenotypic modules has gained strong theoretical and empirical interest \\[[@B1-ijms-18-02618],[@B2-ijms-18-02618],[@B3-ijms-18-02618],[@B4-ijms-18-02618]\\]. Such modular organization helps to understand the evolutionary dynamics of complex organisms given that the compartmentalization of a function (or of a set of functions) will permit this functional aspect to evolve independently of how selection acts on other functional aspects of the organisms (i.e., it alleviates the so-called \"cost of complexity\" or \"cost of pleiotropy\" \\[[@B5-ijms-18-02618],[@B6-ijms-18-02618],[@B7-ijms-18-02618]\\]). However, understanding the evolution of such functional modules requires a characterization of the interactions between the different elements within a module and how these interactions determine their joint evolution \\[[@B1-ijms-18-02618],[@B2-ijms-18-02618]\\]. Recently-developed computational tools can complement our understanding of molecular evolution within a genetic system or network by estimating the probability that a nucleotide site coevolved with a site in another gene across a phylogenetic tree \\[[@B8-ijms-18-02618],[@B9-ijms-18-02618]\\]. The use of such tools is a major difference in relation to previous studies, where only the coevolution within a protein or gene sequence (e.g., due to structural constraints) could be considered \\[[@B10-ijms-18-02618]\\].\n\nThe melanocortin system is a key hormonal pathway that exhibits the features of a module. It is composed of a"
-"Background {#Sec1}\n==========\n\nWorldwide prevalence of obesity almost doubled between 1980 and 2008 \\[[@CR1]\\] and a similar trend has been observed in Switzerland \\[[@CR2]\\]. Several socio-demographic and behavioural factors have been shown to influence weight gain. A consistent positive association between marital status \\[[@CR3]\\], occupational position \\[[@CR4]\\], low educational level, economic difficulties \\[[@CR5]\\] and weight gain has been reported. Still, the impact of SES on weight gain might differ according to gender \\[[@CR6]\\] or to the country's level of socioeconomic development -- while in high income countries a high socioeconomic status (SES) is generally related to a lower prevalence of obesity, the opposite association is found in low income countries \\[[@CR7]\\].\n\nIn Switzerland, several cross-sectional studies have shown an inverse association between obesity and socio-demographic and behavioural factors \\[[@CR8],[@CR9]\\], but whether socio-demographic and behavioural factors have an impact on weight gain has never been investigated prospectively. Indeed, one of the main objectives of the Swiss national programme on healthy eating and physical activity (PNAAP) is achieving a health weight \\[[@CR10]\\] and such data are important for adequately designing health promotion policies and to evaluate their impact in the target population.\n\nThus, we aimed to assess the socio-demographic and behavioural determinants"
-"Introduction {#Sec1}\n============\n\nThe timing of the Middle Pleistocene glacial-interglacial cycles and the feedback mechanisms between climatic shifts and earth-surface processes are still poorly understood. This is largely due to a lack of dating results of sediments representing the advance and retreat of Middle Pleistocene ice sheets, as well as periglacial, interglacial or interstadial environments.\n\nOne key issue is the onset of the Elsterian glaciation, which was the first and southern-most ice advance of Fennoscandian ice sheets into the European continent^[@CR1]^, and its relationship with the Middle Pleistocene Revolution (hereafter MPR). The MPR describes the shift from 41 ka--100 ka climate cycles that occurred \\~1.5\u2009Ma--0.5\u2009Ma ago^[@CR2]^. That significant change in climate cyclicity occurred without any change in external isolation forcing^[@CR3]^, and huge ice sheets might have played a key role in this^[@CR4],[@CR5]^, as they balanced insolation maxima^[@CR3]^. To understand the feedback between earth ice sheets and the MPR, it is crucial to understand when this southern-most advance of Fennoscandian glaciers occurred. The timing of this important event is still a matter of debate^[@CR1],[@CR6]--[@CR9]^.\n\nSeveral Early- and Middle-Pleistocene expansions of the British and Scandinavian ice are documented from the North Sea Basin^[@CR8]--[@CR12]^. The first basin-wide ice sheet expansion corresponds"
-"Intrauterine growth retardation (IUGR) is defined as a fetal or birth weight of less than the 10^th^ percentile in a given population or less than 2 SD of the mean body weight at the same gestational age \\[[@r1], [@r2]\\], and it is closely associated with inhibition of embryonic/fetal development, smaller organs, and higher perinatal morbidity and mortality \\[[@r3], [@r4]\\]. In America, more than 8% of infants have IUGR, which is caused by many factors, including maternal undernutrition, genetics, environmental stress, and dysfunction of the placenta or uterus. The rate of IUGR in pigs is 5--10% \\[[@r5],[@r6],[@r7]\\]. IUGR is thought to be a prevalent, severe problem both in humans and in animals used for production, especially multiparous animals.\n\nThe small intestine is an important organ for both immunity and nutrient absorption, and IUGR is closely associated with intestinal injuries, such as necrotizing enterocolitis \\[[@r8], [@r9]\\]. Because of ethical restrictions, studies on infant pathologies are commonly dependent on the use of appropriate animal models, such as pig and rat. Our previous studies revealed that IUGR affects intestinal growth and morphology in neonatal piglets and alters the gene expression of growth-related proteins \\[[@r10], [@r11]\\]. D\\'Inca *et al*. \\[[@r12]\\] showed that IUGR reduced the"
-"On behalf of the International Union of Pure and Applied Chemistry (IUPAC), and in particular its Commission on Atomic Weights and Isotopic Abundances, I should like to inform the readers of the *Journal of Research of the National Institute of Standards and Technology* of the following, based on Refs. \\[[@b1-j13cop]\\] and \\[[@b2-j13cop]\\].\n\nTo eliminate possible confusion in the reporting of isotopic abundances on noncorresponding scales, the Commission on Atomic Weights and Isotopic Abundances of the International Union of Pure and Applied Chemistry (IUPAC) recommended at the IUPAC 37th General Assembly in August 1993 at Lisbon, Portugal, that (i) ^2^H/^1^H relative ratios of all substances be expressed relative to VSMOW (Vienna Standard Mean Ocean Water) on a scale such that ^2^H/^1^H of SLAP (Standard Light Antarctic Precipitation) is 0.572 times that of VSMOW; (ii) ^13^C/^12^C relative ratios of all substances be expressed relative to VPDB (Vienna Peedee belemnite) on a scale such that ^13^C/^12^C of NBS19-limestone (RM 8544) is 1.00195 times that of VPDB; and (iii) ^18^O/^16^O ratios of all substances be expressed relative to either VSMOW or VPDB on scales such that ^18^O/^16^O of SLAP is 0.9445 times that of VSMOW.\n\nAs a consequence, the Commission recommends that researchers should:"
-"1. Introduction\n===============\n\nThe measurement of absorption and scattering in a turbid environment is an important problem. Such measurements are used to characterize impurities in water \\[[@b1-v114.n02.a01]\\] and to characterize aquatic particles \\[[@b2-v114.n02.a01]\\]. In these applications, a spectrometer with an integrating sphere detector (IS) is ideal since the IS can reduce the effect of scattering and enhance the effect due to molecular absorption. Description of the use of IS with a cuvette holder inside the IS was given by Nelson \\[[@b3-v114.n02.a01]\\]. A description of the IS with an internal sample is given by Labsphere \\[[@b4-v114.n02.a01]\\]. An approach that places samples outside the IS was also described \\[[@b5-v114.n02.a01]\\]. Although the IS with an internal sample seems to provide the least sensitivity to scattering, this arrangement results in an non-ideal IS \\[[@b6-v114.n02.a01]\\] and has problems with stirring and temperature control. An IS with the sample filling the complete volume of the IS have been described in the literature \\[[@b7-v114.n02.a01],[@b8-v114.n02.a01]\\]. This later technique is not practical for biological samples with requirements for small sample volume. Microalgae cultivation is an important area where absorption measurements will gain in importance. The absorption spectra of chlorophyll in plants is a rich source of information about the"
-"Introduction {#S1}\n============\n\nHeart failure (HF) is a clinical syndrome characterized by structural and/or functional impairment of ventricular filling or ejection of blood resulting in insufficient perfusion to meet metabolic demands. There is no single diagnostic test for HF, it is a clinical diagnosis based on history, physical examination, laboratory and imaging parameters \\[[@R1]\\]. Thyroid hormones (TH) have numerous effects on body systems, especially the heart and cardiovascular system including effects on the relaxation and contractile properties of the heart and are critical in preserving cardiac structure \\[[@R2]\\]. In recent years, studies have shown that alterations in TH are associated with a wide spectrum of cardiovascular diseases - specifically, hypothyroidism and subclinical hypothyroidism have been reported to be associated with increased incidence and worsening of HF, with and without underlying heart disease \\[[@R3],[@R4]\\]. The aim of this review is to evaluate the effects of hypothyroidism and subclinical hypothyroidism. We will also discuss the postulated mechanisms that may induce and/or exacerbate HF and highlight the appropriate management strategies.\n\nPrevalence of Decrease T3/HF/Subclinical and Associations (Prevalence of Hypothyroidism/Subclinical Hypothyroidism in HF) {#S2}\n=========================================================================================================================\n\nNearly 10 million people (4.6%) in the United States have hypothyroidism. Most of them are asymptomatic, i.e. with subclinical"
-"Introduction {#sec1}\n============\n\nInterleukin-18 (IL-18), a pro-inflammatory cytokine produced by macrophages, is involved in both adaptive and innate immune responses [@bib1]. IL-18 stimulates interferon-\u03b3 production in T-lymphocytes and natural killer cells, both of which play a role in atherosclerotic progression [@bib2]. IL-18 expression is up-regulated in atherosclerotic plaques and associated with the presence of pathological signs of plaque instability [@bib3]. IL-18 levels have since been confirmed as an independent predictor of coronary events in healthy middle aged men [@bib4].\n\nMore recently IL-18 has been suggested to be an adipogenic cytokine [@bib5], associated with excess adiposity [@bib6]. Adipocytes from obese individuals produce higher levels of IL-18 compared to lean individuals [@bib7] and higher circulating IL-18 levels were observed in obese individuals [@bib8], and those with Type 2 Diabetes (T2D) and the metabolic syndrome [@bib9]. Several studies have suggested that muscle is the major source of circulating IL-18 in humans, and not adipocytes [@bib10; @bib11]. Nevertheless, IL-18 levels have been have been consistently associated with insulin resistance measured by the homeostasis model assessment (HOMA) [@bib12] and studies in humans [@bib13] and *il18* ^\u2212/\u2212^ mice [@bib14] suggest a possible role for IL-18 in insulin sensitivity and energy homeostasis.\n\nVariation in *IL18* has been"
-"One-lung ventilation (OLV) is a challenging anesthetic technique used in thoracic surgery, including minimally invasive transthoracic esophagectomy. Single-lumen tubes (SLT) with endobronchial blockers (EB), or double-lumen tubes (DLT), are routinely used for the selective blockage of one lung to facilitate OLV. The first DLT was introduced in 1949, and has for a long time been the most commonly used device for this technique \\[[@b1-kja-d-18-00237]\\]. It consists of an endotracheal lumen terminating in the trachea and an endobronchial lumen positioned in the mainstem bronchus, allowing independent OLV ([Fig. 1](#f1-kja-d-18-00237){ref-type=\"fig\"}). An alternative device for lung isolation is a endobronchial blocker, a balloon-tipped semi-rigid catheter that is inserted through a standard SLT. Numerous types of EB have been developed during the last few decades, among which is the EZ-Blocker^TM^ (Rusch^\u24c7^, Anaesthet-IQ, the Netherlands), a new type of EB with a Y-shaped distal end that mirrors the carina, and contains a cuff on each side that can be inflated for selective bronchus blocking ([Fig. 2](#f2-kja-d-18-00237){ref-type=\"fig\"}). The EZ-Blocker^TM^ is advanced through the trachea and placed in the carina under direct bronchoscopic guidance \\[[@b2-kja-d-18-00237]--[@b4-kja-d-18-00237]\\]. Common complaints with the use of both techniques are hoarseness and sore throat; major complications like airway rupture are very rare, but"
-"Introduction {#s1}\n============\n\nOne of the hallmark features of legumes (Fabaceae) is their ability to form beneficial symbioses with nitrogen-fixing soil bacteria collectively known as rhizobia. The establishment of such symbioses is a very complex process that involves many genes, as it requires proper recognition of the symbiotic partners, with subsequent development of novel symbiotic organs and partial integration of metabolic pathways in organisms belonging to different domains (Oldroyd et al., [@B55]; Suzaki et al., [@B69]; Zipfel and Oldroyd, [@B83]). The main function of these symbioses is the fixation of atmospheric nitrogen, making it a significant evolutionary advantage for legumes (Wheatley and Sprent, [@B75]; Werner et al., [@B74]).\n\nThe establishment of the legume--rhizobial symbiosis begins with mutual recognition of the partners. During this initial step, a bacterial lipo-chitooligosaccharide signaling molecule known as the Nod factor (nodulation factor; Denarie et al., [@B20]) is recognized by plant receptors in the LysM-RLK protein family (Limpens et al., [@B44]; Madsen et al., [@B48]; Broghammer et al., [@B10]). LysM-RLKs are receptor-like kinases (RLKs) with three lysin motifs (LysMs) in the ligand-binding extracellular region (Nakagawa et al., [@B51]; Mesnage et al., [@B50]). Although LysMs are widespread among prokaryotes and eukaryotes (with the exception of the Archaea),"
-"Introduction\n============\n\nCardiac resynchronization therapy (CRT) is an effective treatment in patients with medically refractory heart failure, severe left ventricular (LV) dysfunction, and prolonged QRS duration \\[[@R1]\\]. The response to CRT depends on several factors, including device settings. Optimally programmed atrio-ventricular delay (AVD) can affect the acute haemodynamic response and may influence the magnitude of clinical improvement under chronic pacing \\[[@R2]\\]. There are scarce data regarding the AVD optimization in CRT patients during atrial-paced compared with atrial-sensed biventricular pacing. The present case report shows how to determine the optimal AVD during echocardiographic examination and underlines possible marked differences between atrial-sensed and atrial-paced rhythms in CRT patients.\n\nCase report\n===========\n\nA 55-year-old white male had an artificial mitral valve implanted due to severe mitral insufficiency in the course of the degenerative process, and a dual chamber pacemaker because of perioperative third degree atrio-ventricular block. One year later he was admitted to our hospital because of chronic heart failure exacerbation (NYHA III). Before admission the patient was treated with bisoprolol 5 mg, perindopril 10 mg, spironolactone 25 mg and furosemide 80 mg. Intravenous furosemide (120 mg) and spironolactone (100 mg) were administered. The ECG showed permanent VAT pacing (atrially triggered ventricular pacing)"
-"Introduction {#s0001}\n============\n\nAlzheimer's disease (AD) is one of the most prevalent forms of late-life mental failure in humans. About 6% of the population aged over 65 is affected by this disease[@CIT0001], and it is estimated that 70 million people will suffer from AD by 2050[@CIT0002]. Therefore, discovery of efficient anti-AD agents is of great importance for drug developers[@CIT0003]^,^[@CIT0004]. So far, the mechanism for AD is still not clearly elucidated, but it is well-accepted that AD is a multifactorial syndrome deriving from a complex array of neurochemical factors[@CIT0005]. Several hypotheses about AD pathogenesis are presented, such as cholinergic dysfunction[@CIT0006], amyloid cascade[@CIT0007], hyperphosphorylation of \u03c4-protein[@CIT0008], cell cycle hypothesis[@CIT0009], and brain-derived neurotrophic factor hypothesis[@CIT0010], oxidative stress[@CIT0011], free radical formation[@CIT0012], metal dyshomeostasis[@CIT0013], and mitochondrial dysfunction[@CIT0014]. These findings not only inspire the design of new anti-AD agents with diverse mechanisms, but also depict a more complex AD scenario.\n\nSo far, designing drugs targeting the cholinergic system is still the most successful therapeutic strategy against AD. Many studies have shown that the decline of acetylcholine (ACh) level results in the cognitive and memory deficits[@CIT0015]. Therefore, recovering cholinergic function by inhibiting cholinesterases (ChEs), which are in charge of the hydrolysis of ACh, is beneficial for the"
-"A 55-year-old man sought outpatient treatment with a 6-year history of progressive dyspnea, which had worsened over the prior 4 months. A CT scan showed scattered small centrilobular nodules that were a few millimeters away from the pleural surface and fissures and did not touch them ([Figure 1](#f1){ref-type=\"fig\"}).\n\nFigure 1Axial CT scan at the level of the upper lobes, showing small soft-tissue density nodules that are distributed homogeneously throughout the lungs but do not touch the peripheral pleural surfaces (black arrows) or fissures (white arrows).\n\nThe patient had multiple, small interstitial nodules on CT. A nodular pattern refers to multiple, round pulmonary soft-tissue density opacities smaller than 3 cm. Small nodules (or micronodules) are those that are less than 1 cm in diameter. On the basis of their distribution in the lung parenchyma, they can be classified as perilymphatic, centrilobular, or random.[@B1]\n\nA perilymphatic pattern is characterized by small nodules located predominantly along the peribronchovascular interstitium, interlobular septa, and subpleural regions (which contain the pulmonary lymphatics). This pattern of distribution is frequently found in sarcoidosis, silicosis, and lymphangitic carcinomatosis. A centrilobular distribution is characterized by nodules that are a few millimeters away from the pleural surface and fissures but do"
-"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"
-"![](125_2018_4682_Figa_HTML){#MO1}\n\nIntroduction {#Sec1}\n============\n\nWith an ageing population and the growing prevalence of obesity due to increasingly sedentary lifestyles, the incidence of diabetes mellitus is rising at an alarming rate \\[[@CR1]\\]. One of the common complications associated with diabetes is diabetic retinopathy, which is the leading cause of vision loss in the working-age population \\[[@CR2]\\]. Diabetic retinopathy is a progressive disorder that results in alterations in the neuroretina, leading to retinal neurodegeneration and microangiopathy in its early stages \\[[@CR3]\\]. Non-proliferative diabetic retinopathy can lead to retinal non-perfusion, which ultimately drives pathological intraocular neovascularisation, known as proliferative diabetic retinopathy \\[[@CR4]\\]. How diabetes leads to diabetic retinopathy is still not fully understood; however, inflammation is known to play an important role in its development and progression \\[[@CR5]\\]. Other ocular complications associated with diabetes include cataract and corneal diseases \\[[@CR6]\\]. Cataract is the leading cause of blindness worldwide and one of the major factors responsible for vision impairment \\[[@CR7]\\].\n\nClinical studies have shown a clear link between diabetes and cataract formation \\[[@CR8]\\]. Diabetic individuals tend to develop cataracts prematurely and progression is more rapid compared with people without diabetes \\[[@CR9], [@CR10]\\]. Owing to the rising prevalence of diabetes, the incidence of diabetic cataracts"
-"Introduction {#Sec1}\n============\n\nUrothelial bladder cancer (UBC) results in approximately 165,000 deaths worldwide annually \\[[@CR1]\\]. In patients with metastatic UBC, median overall survival is approximately 9--15\u00a0months following first-line platinum-based chemotherapy and 7--9\u00a0months for patients relapsing after platinum-based treatment \\[[@CR2]--[@CR4]\\]. Cancer immunotherapy is a treatment modality addressing this high medical need in UBC. Immune checkpoints, such as the programmed death-ligand 1 (PD-L1)/programmed death-1 (PD-1) pathway, block the development of active antitumor immune responses \\[[@CR5]\\], and inhibition of this pathway has demonstrated excellent response and survival rates in locally advanced or metastatic UBC \\[[@CR6]--[@CR9]\\].\n\nEfforts to identify patients most likely to benefit from anti-PD-L1/PD-1 therapy suggest that expression of PD-L1 on tumor cells (TC) and/or tumor-infiltrating immune cells (IC) may correlate with efficacy of anti-PD-L1 therapy in UBC \\[[@CR7], [@CR8], [@CR10], [@CR11]\\], as may other potential biomarkers such as tumor mutational burden \\[[@CR12]\\].\n\nIn the USA, the anti-PD-L1 antibody atezolizumab is approved for the treatment of patients with locally advanced or metastatic UBC, ineligible for cisplatin-containing therapy, whose tumors have PD-L1-stained IC, covering \u2265\u20095% of the tumor area, or ineligible for any platinum-containing therapy regardless of PD-L1 expression \\[[@CR13]\\]. The anti-PD-1 antibody pembrolizumab is also approved in the USA"
-"1. Introduction {#sec1}\n===============\n\nResearch suggests that the number of one-time principal investigators of drug trials regulated by The U.S. Food and Drug Administration is on the rise \\[[@bib1]\\]. Attrition from clinical trials is not limited to first-time investigators, as scholars note that challenges facing the clinical research enterprise are also causing some veteran investigators to leave research \\[[@bib2]\\]. Publicly available data in the Bioresearch Monitoring Information System (BMIS) database show that annually, approximately 40% of unique investigators choose not to participate in another FDA-regulated trial \\[[@bib3]\\]. This exodus of experienced clinical investigators, as well as the time and resources required to initiate new investigators into the clinical trial process, are believed to be linked to inefficiency, instability, and increased costs associated with conducting clinical trials \\[[@bib1]\\].\n\nPrincipal investigators contend with many challenges related to trial implementation and conduct, including site infrastructure issues \\[[@bib2]\\], lack of institutional support \\[[@bib4],[@bib5]\\], competing priorities \\[[@bib4]\\], difficulties in making research financially viable for investigators \\[[@bib6]\\], and long timelines and administrative burden \\[[@bib7]\\]. In our own previous research \\[[@bib8]\\], we identified reasons why U.S.-based investigators who conducted only a single FDA-regulated drug trial (\"one-and-done\" investigators) chose not to continue with clinical research as a principal"
-"Introduction {#s1}\n============\n\nThe development and progression of hepatocellular carcinoma (HCC) is significantly correlated to the accumulation of genomic alterations [@pone.0028404-Coleman1]. Therefore, it is important to have a clear landscape of the genomic aberrations that occur during the multistep process of hepatocarcinogenesis. Previous studies have used high-resolution molecular karyotyping analyses to provide a comprehensive catalog of structural aberrations of the whole chromosomes in HCC [@pone.0028404-Wong1]. However, this method is highly specialized and time-consuming. As a consequence, only a very limited number of HCC cases have been evaluated in these studies. Moreover, the modest resolution of the karyotyping analysis made it difficult to fully define the overall genomic profiles of HCC in a more accurate manner. Comparative genomic hybridization (CGH) has been developed in recent years to monitor the DNA copy number changes at a global level [@pone.0028404-Kallioniemi1]. However, traditional CGH techniques still have the limitation of modest resolution (approximately 2 Mb for amplifications and 10--20 Mb for deletions) and thus could not detect changes in smaller chromosomal regions [@pone.0028404-Hermsen1]. In comparison, array-based CGH (array CGH) is a newly developed technology that allows for high-throughput and high-resolution (at 1 Mb) screening of genome-wide DNA copy number changes (either amplifications or deletions)"
-"Introduction\n============\n\nLarge-scale cooling water systems are widely used to remove heat from industrial equipment using a heat exchanger in chemical manufacturing facilities, power plants and petroleum refineries ([@B42]). Natural water from a river, lake or sea can be used ([@B36]). In some cooling water systems, the treated refinery wastewater was used ([@B27]). These water systems contain diverse species of microorganisms, organic matters and inorganic salts that enable microbial growth, leading to microbiologically influenced corrosion (MIC) and biofouling ([@B41]; [@B28]). Cooling tower systems typically have a water temperature between 25\u00b0C and 35\u00b0C that is ideal for microbes to grow ([@B29]). Microbes attach to the surfaces to form biofilms by secreting extra polymeric substances (EPS) ([@B12]). These biofilms can cause MIC and biofouling ([@B7]; [@B21]; [@B37]; [@B43]).\n\nMicrobiologically influenced corrosion is a major problem in various industrial sectors, such as water utilities, oil and gas, and power generation ([@B35]; [@B44]; [@B18]). MIC in recirculating cooling water systems causes deterioration of metallic surfaces and reduces the lifetime of the systems ([@B15]). Biofouling on the other hand reduces the heat exchanging efficiency and hinders pipe flows ([@B40]). Thus, these problematic biofilms reduce the reliability and increase the operating cost of the systems ([@B33])."
-"INTRODUCTION\n============\n\nReducing unintended variation in clinical practice improves value in health care delivery.^[@R1],[@R2]^ Noting significant practice variation within our organization, we recognized the need to develop a Clinical Effectiveness (CE) program to identify and reduce unnecessary variation, improve quality and outcomes, and sustain a change in culture toward value-based healthcare. Turning to the literature for guidance, we came across several Quality Improvement (QI) and CE programs aimed at targeting variation. However, their impact was variable, with particular challenges in reliability and sustainability.^[@R3]--[@R11]^ Programs struggled with lack of transparency in clinical practice guidelines and clinical pathways, leading to mistrust among providers.^[@R12]--[@R16]^ Inflexibility and inertness of guidelines limited relevance and applicability to dynamic clinical practice.^[@R12]--[@R15],[@R17]^ One program addressed some of these challenges by involving a multidisciplinary clinical team in guideline development and creating a dynamic system focused on gathering and analyzing data after implementation to continually improve the guideline.^[@R8],[@R9]^ However, this approach involves extensive data management and analysis burden potentially limiting scalability and sustainability. Other clinical pathway programs employed different strategies with varying success. The heterogeneity of these programs coupled with a limited description of interventions and contexts, made it challenging to extrapolate best practices.^[@R3]-[@R10]^\n\nGiven this lack of literature-based best"
-"The biological olfactory system is capable of solving problems related to the olfactory information processing such as odor discrimination. This system is composed of three main parts: the layer receptors of the nose, the bulb and the piriform cortex \\[[@B1]\\]. The sense of smell is a chemical neural process where odorant molecules stimulate the olfactory system. These molecules are inhaled through the nose, where they contact the olfactory receptor neurons. The olfactory neurons transduce receptor activation into electrical signals in neurons. The signals travel along the olfactory nerve which terminates in the olfactory bulb. Finally, the olfactory bulb, which is composed of different cell layers, sends the information to the piriform cortex where discrimination between odors is performed. Odors are represented as patterns of neuronal activity. This representation may be encoded by space, time or a combination of both \\[[@B2]\\]. In this research, we described an approach for modeling the olfactory system in order to perform an odor discrimination task by means of the neural activity produced by a network of spiking neurons (SNs).\n\nOur model is composed of three layers. The first layer contains a set of neurons acting as receptive fields, which normalized the input stimulus and sent"
-"Introduction {#s1}\n============\n\nThe sharing of data for verification purposes is not common practice in psychology [@pone.0103360-Wicherts1], [@pone.0103360-Wolins1] and other research fields [@pone.0103360-Firebaugh1]--[@pone.0103360-Vines1]. Wicherts et al. [@pone.0103360-Wicherts1] found that 73% of the contacted authors who had published a paper in one of four top journals published by the *American Psychological Association* (APA) failed to share their data, notwithstanding the fact that authors had signed a contract upon acceptance of their paper that they would make the data available to peers for reanalysis [@pone.0103360-American1]. Wicherts et al. [@pone.0103360-Wicherts2] subsequently showed that this sharing of data is related to the quality of the reporting of statistical results and the strength of evidence. In their study, they compared a subset of the articles used in Wicherts et al. [@pone.0103360-Wicherts1], and found that articles from which data were shared contained relatively fewer reporting errors. Reporting errors are discrepancies between the reported *p* value and the recalculated *p* value based on the reported test statistic and degrees of freedom (*df*). Earlier, we [@pone.0103360-Bakker1] documented that more than half of the articles in psychology that involved the use of null hypothesis significance testing contained at least one such reporting error (see also [@pone.0103360-Leggett1], [@pone.0103360-Caperos1]). Wicherts et"
-"Background {#s1}\n==========\n\nPlant transcription factors (TFs) are the regulatory gene families, which modulate the expression of innumerable downstream genes during several physiological processes, including growth and development, photosynthesis, reproduction, and resistance responses \\[[@R01]\\]. The TFs accomplish their regulatory roles by binding to specific DNA sequences on the promoter regions of their target genes \\[[@R02]\\]. Although, TFs are the common features shared in all the Eukaryotes, some of the TF families are exclusive to plants, including WRKYs, Auxin Response Factors (ARFs), No Apical Meristems (NAMs), and Squamosa Promoter-binding protein-like (SBPs or SPLs) \\[[@R03]\\]. The SPL TF family genes are characterized by the presence of a highly conserved SBP DNA binding domain \\[[@R04]\\]. Further, the association of the zinc finger motifs and a C-terminus nuclear localization signal (NLS) is known to be the key characteristic features of the SPL genes \\[[@R05]\\]. SPL genes were first discovered in Antirrhinum majus, where the identified genes AmSBP1 and AmSBP2 directly interacted with a sequence motif on the promoter of the SQUAMOSA floral meristem identity gene \\[[@R06]\\]. Since then, many studies have reported the identification and characterization of the SPL genes in the model plant Arabidopsis involved in numerous plant physiological processes, including development of"
-"INTRODUCTION {#s1}\n============\n\nSarcomas are a heterogeneous group of over 80 different tumors arising from mesenchymal or connective tissue. In 2018, soft tissue sarcomas will represent approximately 0.8% of all cancers in the United States (US)and are among the top five causes of cancer deaths for those under 20 years old \\[[@R1]\\]. It is estimated that approximately 13-16,000 new cases and 5-6,000 deaths will be attributable to sarcomas in the US \\[[@R1], [@R2]\\].\n\nThe variability of all subtypes of sarcomas are not well described due to the heterogeneity of the disease, with subtypes varying in biology, behavior, and treatment responses \\[[@R3]--[@R6]\\]. The complexity and rarity of sarcomas make them challenging to study as well as medically manage. This has driven the development of many long-term institutional, multi-institutional, and national databases that collect epidemiological and clinical data on sarcomas to better understand the disease processes \\[[@R3]--[@R6]\\]. This study utilizes a nationally representative cancer database, the Surveillance, Epidemiology and End Results (SEER), to study sarcomas in the US over 12 recent years and evaluate trends in epidemiology, management, and survival.\n\nRESULTS {#s2}\n=======\n\nTrends of sarcomas over time {#s2_1}\n----------------------------\n\nA total of 78,527 patients with sarcomas were identified in SEER from"
-"Introduction {#s1}\n============\n\nAlthough meiosis is essential for the production of both eggs and sperm, it is highly sexually dimorphic. Indeed, it could be argued that the differences between male and female meiosis are more numerous than the similarities. Oocytes initiate meiosis in the fetal gonad, enter an extended arrest phase (dictyate), and do not resume meiosis until the time of ovulation, some 10-50 years later \\[[@B1]\\]. During the female reproductive lifespan, the number of mature eggs produced is limited to several hundred and, because sperm penetration triggers the completion of the second meiotic division, only eggs that are successfully fertilized complete meiosis. In contrast, in the male, the onset of meiosis coincides with sexual maturation, germline stem cells ensure that large numbers of sperm are produced continuously, and the meiotic phase is comparatively short -- approximately 3-4 weeks of the nine total weeks required to generate a mature sperm cell.\n\nIn addition to these obvious sex-specific temporal differences there is, particularly in humans, a striking difference in error rate between the sexes. An estimated 5-10% of clinically recognized human pregnancies are chromosomally abnormal, with the vast majority resulting in miscarriage or congenital birth defects \\[[@B2]\\]. The most common chromosome"
-"Introduction\n============\n\nAcross a variety of medical disciplines, longer-term measures of gait performance have the potential to benefit both patients and practitioners. Gait speed remains an underutilized clinical measure, despite convincing data suggesting that decreases in gait speed are associated with greater mortality \\[[@ref1]\\], diminished cognition \\[[@ref2]\\], greater functional disability \\[[@ref3]\\], poorer quality of life, and increased healthcare spending \\[[@ref3],[@ref4]\\]. There is also evidence suggesting that improved gait speed may be a sensitive biomarker for improved overall functional status \\[[@ref5]\\]. Resistance to including gait speed in current clinical practice is multifactorial, with time and space constraints and provider unfamiliarity being major factors \\[[@ref6]\\]. Longitudinal clinical measures of gait speed are also challenging to obtain, since collecting these measures may be more subject to various biases than more easily obtained metrics such as pulse oximetry or body weight \\[[@ref7]\\].\n\nIn the past, gait speed studies have typically relied on measurements taken in the clinic. The standard method for determining gait speed involves timing an individual while walking a short, predetermined distance (eg, 4 to 6 meters). This approach is less than ideal because physical activity, including gait, is influenced by performance biases (eg, participants who know they are being observed try"