The 50 most-cited articles in F1000Research, 2018

DNA sequencing analysis typically involves mapping reads to just one reference genome. Mapping against multiple genomes is necessary, however, when the genome of origin requires confirmation. Mapping against multiple genomes is also advisable for detecting contamination or for identifying sample swaps which, if left undetected, may lead to incorrect experimental conclusions. Consequently, we present FastQ Screen, a tool to validate the origin of DNA samples by quantifying the proportion of reads that map to a panel of reference genomes. FastQ Screen is intended to be used routinely as a quality control measure and for analysing samples in which the origin of the DNA is uncertain or has multiple sources.

Alzheimer's disease is the most common cause of dementia worldwide, with the prevalence continuing to grow in part because of the aging world population. This neurodegenerative disease process is characterized classically by two hallmark pathologies: β-amyloid plaque deposition and neurofibrillary tangles of hyperphosphorylated tau. Diagnosis is based upon clinical presentation fulfilling several criteria as well as fluid and imaging biomarkers. Treatment is currently targeted toward symptomatic therapy, although trials are underway that aim to reduce the production and overall burden of pathology within the brain. Here, we discuss recent advances in our understanding of the clinical evaluation and treatment of Alzheimer's disease, with updates regarding clinical trials still in progress.

The ability to easily and efficiently analyse RNA-sequencing data is a key strength of the Bioconductor project. Starting with counts summarised at the gene-level, a typical analysis involves pre-processing, exploratory data analysis, differential expression testing and pathway analysis with the results obtained informing future experiments and validation studies. In this workflow article, we analyse RNA-sequencing data from the mouse mammary gland, demonstrating use of the popular edgeR package to import, organise, filter and normalise the data, followed by the limma package with its voom method, linear modelling and empirical Bayes moderation to assess differential expression and perform gene set testing. This pipeline is further enhanced by the Glimma package which enables interactive exploration of the results so that individual samples and genes can be examined by the user. The complete analysis offered by these three packages highlights the ease with which researchers can turn the raw counts from an RNA-sequencing experiment into biological insights using Bioconductor.

Review, promotion, and tenure (RPT) processes significantly affect how faculty direct their own career and scholarly progression. Although RPT practices vary between and within institutions, and affect various disciplines, ranks, institution types, genders, and ethnicity in different ways, some consistent themes emerge when investigating what faculty would like to change about RPT. For instance, over the last few decades, RPT processes have generally increased the value placed on research, at the expense of teaching and service, which often results in an incongruity between how faculty actually spend their time vs. what is considered in their evaluation. Another issue relates to publication practices: most agree RPT requirements should encourage peer-reviewed works of high quality, but in practice, the value of publications is often assessed using shortcuts such as the prestige of the publication venue, rather than on the quality and rigor of peer review of each individual item. Open access and online publishing have made these issues even murkier due to misconceptions about peer…

Subpopulation identification, usually via some form of unsupervised clustering, is a fundamental step in the analysis of many single-cell RNA-seq data sets. This has motivated the development and application of a broad range of clustering methods, based on various underlying algorithms. Here, we provide a systematic and extensible performance evaluation of 14 clustering algorithms implemented in R, including both methods developed explicitly for scRNA-seq data and more general-purpose methods. The methods were evaluated using nine publicly available scRNA-seq data sets as well as three simulations with varying degree of cluster separability. The same feature selection approaches were used for all methods, allowing us to focus on the investigation of the performance of the clustering algorithms themselves. We evaluated the ability of recovering known subpopulations, the stability and the run time and scalability of the methods. Additionally, we investigated whether the performance could be improved by generating consensus partitions from multiple individual clustering methods. We…

Over the last 40 years, our understanding of the pathogenesis of myocardial infarction has evolved and allowed new treatment strategies that have greatly improved survival. Over the years, there has been a radical shift in therapy from passive healing of the infarction through weeks of bed rest to early discharge usually within 2 to 3 days as a result of immediate reperfusion strategies and other guideline-directed medical therapies. Nevertheless, challenges remain. Patients who develop cardiogenic shock still face a high 30-day mortality of at least 40%. Perhaps even more important is how do we identify and prevent patients from developing myocardial infarction in the first place? This article discusses these milestones of therapy and considers important issues for progress in the future.

The vimentin gene ( VIM ) encodes one of the 71 human intermediate filament (IF) proteins, which are the building blocks of highly ordered, dynamic, and cell type-specific fiber networks. Vimentin is a multi-functional 466 amino acid protein with a high degree of evolutionary conservation among vertebrates. Vim −/− mice, though viable, exhibit systemic defects related to development and wound repair, which may have implications for understanding human disease pathogenesis. Vimentin IFs are required for the plasticity of mesenchymal cells under normal physiological conditions and for the migration of cancer cells that have undergone epithelial–mesenchymal transition. Although it was observed years ago that vimentin promotes cell migration, the molecular mechanisms were not completely understood. Recent advances in microscopic techniques, combined with computational image analysis, have helped illuminate vimentin dynamics and function in migrating cells on a precise scale. This review includes a brief historical account of early studies that unveiled vimentin as a unique component of…

The internally transcribed spacer (ITS) region between the small subunit ribosomal RNA gene and large subunit ribosomal RNA gene is a widely used phylogenetic marker for fungi and other taxa. The eukaryotic ITS contains the conserved 5.8S rRNA and is divided into the ITS1 and ITS2 hypervariable regions. These regions are variable in length and are amplified using primers complementary to the conserved regions of their flanking genes. Previous work has shown that removing the conserved regions results in more accurate taxonomic classification. An existing software program, ITSx, is capable of trimming FASTA sequences by matching hidden Markov model profiles to the ends of the conserved genes using the software suite HMMER. ITSxpress was developed to extend this technique from marker gene studies using Operational Taxonomic Units (OTU's) to studies using exact sequence variants; a method used by the software packages Dada2, Deblur, QIIME 2, and Unoise. The sequence variant approach uses the quality scores of each read to identify sequences that are statistically likely to represent…

Rosacea is a common chronic inflammatory skin disease of the central facial skin and is of unknown origin. Currently, two classifications of rosacea exist that are based on either “preformed” clinical subtypes (erythematotelangiectatic, papulopustular, phymatous, and ocular) or patient-tailored analysis of the presented rosacea phenotype. Rosacea etiology and pathophysiology are poorly understood. However, recent findings indicate that genetic and environmental components can trigger rosacea initiation and aggravation by dysregulation of the innate and adaptive immune system. Trigger factors also lead to the release of various mediators such as keratinocytes (for example, cathelicidin, vascular endothelial growth factor, and endothelin-1), endothelial cells (nitric oxide), mast cells (cathelicidin and matrix metalloproteinases), macrophages (interferon-gamma, tumor necrosis factor, matrix metalloproteinases, and interleukin-26), and T helper type 1 (T H 1) and T H 17 cells. Additionally, trigger factors can directly communicate to the cutaneous nervous system and, by neurovascular…

Abstract The commercially available 10X Genomics protocol to generate droplet-based single cell RNA-seq (scRNA-seq) data is enjoying growing popularity among researchers. Fundamental to the analysis of such scRNA-seq data is the ability to cluster similar or same cells into non-overlapping groups. Many competing methods have been proposed for this task, but there is currently little guidance with regards to which method offers most accuracy. Answering this question is complicated by the fact that 10X Genomics data lack cell labels that would allow a direct performance evaluation. Thus in this review, we focused on comparing clustering solutions of a dozen methods for three datasets on human peripheral mononuclear cells generated with the 10X Genomics technology. While clustering solutions appeared robust, we found that solutions produced by different methods have little in common with each other. They also failed to replicate cell type assignment generated with supervised labeling approaches. Furthermore, we demonstrate that all clustering methods tested clustered cells to a large…

Neuronal networks consist of different types of neurons that all play their own role in order to maintain proper network function. The two main types of neurons segregate in excitatory and inhibitory neurons, which together regulate the flow of information through the network. It has been proposed that changes in the relative strength in these two opposing forces underlie the symptoms observed in psychiatric disorders, including autism and schizophrenia. Here, we review the role of alterations to the function of the inhibitory system as a cause of psychiatric disorders. First, we explore both patient and post-mortem evidence of inhibitory deficiency. We then discuss the function of different interneuron subtypes in the network and focus on the central role of a specific class of inhibitory neurons, parvalbumin-positive interneurons. Finally, we discuss genes known to be affected in different disorders and the effects that mutations in these genes have on the inhibitory system in cortex and hippocampus. We conclude that alterations to the inhibitory system are consistently identified…

Allergic rhinitis affects 20 to 30% of adults in both the United States and Europe and perhaps a somewhat higher percentage of children. In addition to nasal and ocular symptoms directly related to the allergic process, interference of these symptoms with sleep leads to daytime sleepiness and impaired quality of life. Patients miss work because of symptoms but an even greater problem is interference with work productivity, or presenteeism, which has been reported to be the biggest contributor to the total economic cost of allergic rhinitis. There has been increasing awareness that many patients with either seasonal or perennial symptoms but negative skin and in vitro tests for allergen sensitivity have local nasal allergy, diagnosable by the presence of allergen-specific IgE in their nasal secretions or a positive nasal allergen challenge or both. The pharmaceutical management of allergic rhinitis rests on symptomatic treatment with antihistamines that perhaps are more effectively administered intranasally than orally and intranasal corticosteroids. Allergen immunotherapy is very…

Environmental DNA (eDNA) metabarcoding is becoming a core tool in ecology and conservation biology, and is being used in a growing number of education, biodiversity monitoring, and public outreach programs in which professional research scientists engage community partners in primary research. Results from eDNA analyses can engage and educate natural resource managers, students, community scientists, and naturalists, but without significant training in bioinformatics, it can be difficult for this diverse audience to interact with eDNA results. Here we present the R package ranacapa, at the core of which is a Shiny web app that helps perform exploratory biodiversity analyses and visualizations of eDNA results. The app requires a taxonomy-by-sample matrix and a simple metadata file with descriptive information about each sample. The app enables users to explore the data with interactive figures and presents results from simple community ecology analyses. We demonstrate the value of ranacapa to two groups of community partners engaging with eDNA metabarcoding results.

International government guidance recommends patient and public involvement (PPI) to improve the relevance and quality of research. PPI is defined as research being carried out 'with' or 'by' patients and members of the public rather than 'to', 'about' or 'for' them ( http://www.invo.org.uk/). Patient involvement is different from collecting data from patients as participants. Ethical considerations also differ. PPI is about patients actively contributing through discussion to decisions about research design, acceptability, relevance, conduct and governance from study conception to dissemination. Occasionally patients lead or do research. The research methods of PPI range from informal discussions to partnership research approaches such as action research, co-production and co-learning. This article discusses how researchers can involve patients when they are applying for research funding and considers some opportunities and pitfalls. It reviews research funder requirements, draws on the literature and our collective experiences as clinicians, patients, academics and members of UK…

Platelet granules are unique among secretory vesicles in both their content and their life cycle. Platelets contain three major granule types—dense granules, α-granules, and lysosomes—although other granule types have been reported. Dense granules and α-granules are the most well-studied and the most physiologically important. Platelet granules are formed in large, multilobulated cells, termed megakaryocytes, prior to transport into platelets. The biogenesis of dense granules and α-granules involves common but also distinct pathways. Both are formed from the trans -Golgi network and early endosomes and mature in multivesicular bodies, but the formation of dense granules requires trafficking machinery different from that of α-granules. Following formation in the megakaryocyte body, both granule types are transported through and mature in long proplatelet extensions prior to the release of nascent platelets into the bloodstream. Granules remain stored in circulating platelets until platelet activation triggers the exocytosis of their contents. Soluble N -ethylmaleimide-sensitive…

Therapeutic medications for the treatment of depression have serious limitations, particularly delayed onset and low rates of efficacy. However, the discovery that a single subanesthetic dose of ketamine, a glutamate NMDA receptor channel blocker, can produce a rapid (within hours) antidepressant response that is sustained (about 1 week), even in patients considered treatment-resistant, has invigorated the field. In addition to these remarkable actions, ketamine has proven effective for the treatment of suicidal ideation. Efforts are under way to develop ketamine-like drugs with fewer side effects as well as agents that act at other sites within the glutamate neurotransmitter system. This includes ketamine metabolites and stereoisomers, drugs that act as NMDA allosteric modulators or that block mGluR2/3 autoreceptors. In addition, targets that enhance glutamate neurotransmission or synaptic function (or both), which are essential for the rapid and sustained antidepressant actions of ketamine in rodent models, are being investigated; examples are the muscarinic cholinergic antagonist…

The skin commensal Propionibacterium acnes, recently renamed Cutibacterium acnes, along with the other major pathophysiological factors of increased seborrhea, hyperkeratinization of the pilosebaceous unit, and inflammation, has long been implicated in the pathogenesis of acne. Recent advances have contributed to our understanding of the role of P. acnes in acne. Although there are no quantitative differences in P. acnes of the skin of patients with acne compared with controls, the P. acnes phylogenic groups display distinct genetic and phenotypic characteristics, P. acnes biofilms are more frequent in acne, and different phylotypes may induce distinct immune responses in acne. P. acnes plays a further important role in the homeostasis of the skin’s microbiome, interacting with other cutaneous commensal or pathogenic microorganisms such as Staphylococcus epidermidis, Streptococcus pyogenes, and Pseudomonas species. In the era of increasing antimicrobial resistance, the selection of acne treatment targeting P. acnes and the prevention of antibiotic resistance play a key role in…

Background: Massive high-throughput sequencing of short, hypervariable segments of the 16S ribosomal RNA (rRNA) gene has transformed the methodological landscape describing microbial diversity within and across complex biomes. However, several studies have shown that the methodology rather than the biological variation is responsible for the observed sample composition and distribution. This compromises meta-analyses, although this fact is often disregarded. Results: To facilitate true meta-analysis of microbiome studies, we developed NG-Tax, a pipeline for 16S rRNA gene amplicon sequence analysis that was validated with different mock communities and benchmarked against QIIME as a frequently used pipeline. The microbial composition of 49 independently amplified mock samples was characterized by sequencing two variable 16S rRNA gene regions, V4 and V5-V6, in three separate sequencing runs on Illumina’s HiSeq2000 platform. This allowed for the evaluation of important causes of technical bias in taxonomic classification: 1) run-to-run sequencing variation, 2) PCR–error, and 3)…

Nuclear factor of activated T cells (NFAT) was first described almost three decades ago as a Ca 2+ /calcineurin-regulated transcription factor in T cells. Since then, a large body of research uncovered the regulation and physiological function of different NFAT homologues in the immune system and many other tissues. In this review, we will discuss novel roles of NFAT in T cells, focusing mainly on its function in humoral immune responses, immunological tolerance, and the regulation of immune metabolism.

Human metapneumovirus (HMPV) is a leading cause of acute respiratory infection, particularly in children, immunocompromised patients, and the elderly. HMPV, which is closely related to avian metapneumovirus subtype C, has circulated for at least 65 years, and nearly every child will be infected with HMPV by the age of 5. However, immunity is incomplete, and re-infections occur throughout adult life. Symptoms are similar to those of other respiratory viral infections, ranging from mild (cough, rhinorrhea, and fever) to more severe (bronchiolitis and pneumonia). The preferred method for diagnosis is reverse transcription-polymerase chain reaction as HMPV is difficult to culture. Although there have been many advances made in the past 16 years since its discovery, there are still no US Food and Drug Administration-approved antivirals or vaccines available to treat HMPV. Both small animal and non-human primate models have been established for the study of HMPV. This review will focus on the epidemiology, transmission, and clinical manifestations in humans as well as the animal models of…

In this mini-review, I summarize and interpret the current status of sex/gender differences in terms of brain anatomy, brain function, behavior, and cognition. Based on this review and the reported findings, I conclude that most of these sex/gender differences are not large enough to support the assumption of sexual dimorphism in terms of brain anatomy, brain function, cognition, and behavior. Instead, I suggest that many brain and cognitive features are modulated by environment, culture, and practice (and several other influences). These influences interact with the menstrual cycle, the general hormone level, and current gender stereotypes in a way that has not yet been fully understood.

Infection with herpes simplex virus (HSV) types 1 and 2 is ubiquitous in the human population. Most commonly, virus replication is limited to the epithelia and establishes latency in enervating sensory neurons, reactivating periodically to produce localized recurrent lesions. However, these viruses can also cause severe disease such as recurrent keratitis leading potentially to blindness, as well as encephalitis, and systemic disease in neonates and immunocompromised patients. Although antiviral therapy has allowed continual and substantial improvement in the management of both primary and recurrent infections, resistance to currently available drugs and long-term toxicity pose a current and future threat that should be addressed through the development of new antiviral compounds directed against new targets. The development of several promising HSV vaccines has been terminated recently because of modest or controversial therapeutic effects in humans. Nevertheless, several exciting vaccine candidates remain in the pipeline and are effective in animal models; these must also be…

Nicotinamide adenine dinucleotide (NAD+) biosynthesis and its regulation have recently been attracting markedly increasing interest. Aging is marked by a systemic decrease in NAD+ across multiple tissues. The dysfunction of NAD+ biosynthesis plays a critical role in the pathophysiologies of multiple diseases, including age-associated metabolic disorders, neurodegenerative diseases, and mental disorders. As downstream effectors, NAD+-dependent enzymes, such as sirtuins, are involved in the progression of such disorders. These recent studies implicate NAD+ biosynthesis as a potential target for preventing and treating age-associated diseases. Indeed, new studies have demonstrated the therapeutic potential of supplementing NAD+ intermediates, such as nicotinamide mononucleotide and nicotinamide riboside, providing a proof of concept for the development of an effective anti-aging intervention.

Changes in cell adhesion and motility are considered key elements in determining the development of invasive and metastatic tumors. Co-opting the epithelial-to-mesenchymal transition (EMT) process, which is known to occur during embryonic development, and the associated changes in cell adhesion properties in cancer cells are considered major routes for tumor progression. More recent in vivo studies in tumor tissues and circulating tumor cell clusters suggest a stepwise EMT process rather than an “all-or-none” transition during tumor progression. In this commentary, we addressed the molecular mechanisms underlying the changes in cell adhesion and motility and adhesion-mediated signaling and their relationships to the partial EMT states and the acquisition of stemness traits by cancer cells.

Displaying data onto anatomical structures is a convenient technique to quickly observe tissue related information. However, drawing tissues is a complex task that requires both expertise in anatomy and the arts. While web based applications exist for displaying gene expression on anatograms, other non-genetic disciplines lack similar tools. Moreover, web based tools often lack the modularity associated with packages in programming languages, such as R. Here I present gganatogram, an R package used to plot modular species anatograms based on a combination of the graphical grammar of ggplot2 and the publicly available anatograms from the Expression Atlas. This combination allows for quick and easy, modular, and reproducible generation of anatograms. Using only one command and a data frame with tissue name, group, colour, and value, this tool enables the user to visualise specific human and mouse tissues with desired colours, grouped by a variable, or displaying a desired value, such as gene-expression, pharmacokinetics, or bacterial load across selected tissues. gganatogram consists…

Helminth parasites are complex metazoans that belong to different taxonomic families but that collectively share the capacity to downregulate the host immune response directed toward themselves (parasite-specific immunoregulation). During long-standing chronic infection, these helminths appear able to suppress immune responses to bystander pathogens/antigens and atopic, autoimmune, and metabolic disorders. Helminth-induced immunoregulation occurs through the induction of regulatory T cells or Th2-type cells (or both). However, secreted or excreted parasite metabolites, proteins, or extracellular vesicles (or a combination of these) may also directly induce signaling pathways in host cells. Therefore, the focus of this review will be to highlight recent advances in understanding the immune responses to helminth infection, emphasizing the strategies/molecules and some of the mechanisms used by helminth parasites to modulate the immune response of their hosts.

JAK inhibitors have been developed following the discovery of the JAK2 V617F in 2005 as the driver mutation of the majority of non- BCR-ABL1 myeloproliferative neoplasms (MPNs). Subsequently, the search for JAK2 inhibitors continued with the discovery that the other driver mutations ( CALR and MPL ) also exhibited persistent JAK2 activation. Several type I ATP-competitive JAK inhibitors with different specificities were assessed in clinical trials and exhibited minimal hematologic toxicity. Interestingly, these JAK inhibitors display potent anti-inflammatory activity. Thus, JAK inhibitors targeting preferentially JAK1 and JAK3 have been developed to treat inflammation, autoimmune diseases, and graft-versus-host disease. Ten years after the beginning of clinical trials, only two drugs have been approved by the US Food and Drug Administration: one JAK2/JAK1 inhibitor (ruxolitinib) in intermediate-2 and high-risk myelofibrosis and hydroxyurea-resistant or -intolerant polycythemia vera and one JAK1/JAK3 inhibitor (tofacitinib) in methotrexate-resistant rheumatoid arthritis. The…

Over the past decade, our understanding of the biology and pathophysiology of renal cell carcinoma (RCC) has improved significantly. Insight into the disease process has helped us in developing newer therapeutic approaches toward RCC. In this article, we review the various genetic and immune-related mechanisms involved in the pathogenesis and development of this cancer and how that knowledge is being used to develop therapeutic targeted drugs for the treatment of RCC. The main emphasis of this review article is on the most common genetic alterations found in clear cell RCC and how various drugs are currently targeting such pathways. This article also looks at the role of the immune system in allowing the growth of RCC and how the immune system can be manipulated to reactivate cytotoxic immunity against RCC.

Protein homeostasis (proteostasis) is an essential pillar for correct cellular function. Impairments in proteostasis are encountered both in aging and in several human disease conditions. Molecular chaperones are important players for proteostasis; in particular, heat shock protein 70 (Hsp70) has an essential role in protein folding, disaggregation, and degradation. We have recently proposed a model for Hsp70 functioning as a "multiple socket". In the model, Hsp70 provides a physical platform for the binding of client proteins, other chaperones, and cochaperones. The final fate of the client protein is dictated by the set of Hsp70 interactions that occur in a given cellular context. Obtaining structural information of the different Hsp70-based protein complexes will provide valuable knowledge to understand the functional mechanisms behind the master role of Hsp70 in proteostasis. We additionally evaluate some of the challenges for attaining high-resolution structures of such complexes.

The pdb-tools are a collection of Python scripts for working with molecular structure data in the Protein Data Bank (PDB) format. They allow users to edit, convert, and validate PDB files, from the command-line, in a simple but efficient manner. The pdb-tools are implemented in Python, without any external dependencies, and are freely available under the open-source Apache License at https://github.com/haddocking/pdb-tools/ and on PyPI.

Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders encountered in clinical practice. It is a heterogeneous disorder with a multifactorial pathogenesis. Recent studies have demonstrated that an imbalance in gut bacterial communities, or "dysbiosis", may be a contributor to the pathophysiology of IBS. There is evidence to suggest that gut dysbiosis may lead to activation of the gut immune system with downstream effects on a variety of other factors of potential relevance to the pathophysiology of IBS. This review will highlight the data addressing the emerging role of the gut microbiome in the pathogenesis of IBS and review the evidence for current and future microbiome based treatments.

Chondrosarcomas constitute a heterogeneous group of primary bone cancers characterized by hyaline cartilaginous neoplastic tissue. They are the second most common primary bone malignancy. The vast majority of chondrosarcomas are conventional chondrosarcomas, and most conventional chondrosarcomas are low- to intermediate-grade tumors (grade 1 or 2) which have indolent clinical behavior and low metastatic potential. Recurrence augurs a poor prognosis, as conventional chondrosarcomas are both radiation and chemotherapy resistant. Recent discoveries in the biology, genetics, and epigenetics of conventional chondrosarcomas have significantly advanced our understanding of the pathobiology of these tumors and offer insight into potential therapeutic targets.

Chronic pancreatitis is a syndrome involving inflammation, fibrosis, and loss of acinar and islet cells which can manifest in unrelenting abdominal pain, malnutrition, and exocrine and endocrine insufficiency. The Toxic-Metabolic, Idiopathic, Genetic, Autoimmune, Recurrent and Severe Acute Pancreatitis, Obstructive (TIGAR-O) classification system categorizes known causes and factors that contribute to chronic pancreatitis. Although determining disease etiology provides a framework for focused and specific treatments, chronic pancreatitis remains a challenging condition to treat owing to the often refractory, centrally mediated pain and the lack of consensus regarding when endoscopic therapy and surgery are indicated. Further complications incurred include both exocrine and endocrine pancreatic insufficiency, pseudocyst formation, bile duct obstruction, and pancreatic cancer. Medical treatment of chronic pancreatitis involves controlling pain, addressing malnutrition via the treatment of vitamin and mineral deficiencies and recognizing the risk of osteoporosis, and administering…

Background: There is no standardized definition of what a predatory journal is, nor have the characteristics of these journals been delineated or agreed upon. In order to study the phenomenon precisely a definition of predatory journals is needed. The objective of this scoping review is to summarize the literature on predatory journals, describe its epidemiological characteristics, and to extract empirical descriptions of potential characteristics of predatory journals. Methods: We searched five bibliographic databases: Ovid MEDLINE, Embase Classic + Embase, ERIC, and PsycINFO, and Web of Science on January 2 nd , 2018. A related grey literature search was conducted March 27 th , 2018. Eligible studies were those published in English after 2012 that discuss predatory journals. Titles and abstracts of records obtained were screened. We extracted epidemiological characteristics from all search records discussing predatory journals. Subsequently, we extracted statements from the empirical studies describing empirically derived characteristics of predatory journals. These…

Background: Single-cell RNASeq is a powerful tool for measuring gene expression at the resolution of individual cells. A significant challenge in the analysis of this data is the large amount of zero values, representing either missing data or no expression. Several imputation approaches have been proposed to deal with this issue, but since these methods generally rely on structure inherent to the dataset under consideration they may not provide any additional information. Methods: We evaluated the risk of generating false positive or irreproducible results when imputing data with five different methods. We applied each method to a variety of simulated datasets as well as to permuted real single-cell RNASeq datasets and consider the number of false positive gene-gene correlations and differentially expressed genes. Using matched 10X Chromium and Smartseq2 data from the Tabula Muris database we examined the reproducibility of markers before and after imputation. Results: The extent of false-positive signals introduced by imputation varied considerably by method. Data smoothing based…

The term spondyloarthritis refers to a group of immune-mediated diseases characterised by inflammation of the axial skeleton, peripheral joints, and entheses. Ankylosing spondylitis (AS) is the most common and characteristic of these entities and even though it was first described over two centuries ago, the understanding of the underlying disease mechanism remains incomplete. It is known that around 40% of patients with AS have subclinical bowel inflammation, suggesting that the origin of the disease could be in the gut. Also, more genes and new molecules have demonstrated a role in the pathogenesis of AS. In this review, we analyse the latest therapies for spondyloarthritis and the most relevant discoveries over the last three years, together with their implications for different aspects of the disease.

Background: There is no standardized definition of what a predatory journal is, nor have the characteristics of these journals been delineated or agreed upon. In order to study the phenomenon precisely a definition of predatory journals is needed. The objective of this scoping review is to summarize the literature on predatory journals, describe its epidemiological characteristics, and to extract empirical descriptions of potential characteristics of predatory journals. Methods: We searched five bibliographic databases: Ovid MEDLINE, Embase Classic + Embase, ERIC, and PsycINFO, and Web of Science on January 2 nd , 2018. A related grey literature search was conducted March 27 th , 2018. Eligible studies were those published in English after 2012 that discuss predatory journals. Titles and abstracts of records obtained were screened. We extracted epidemiological characteristics from all search records discussing predatory journals. Subsequently, we extracted statements from the empirical studies describing empirically derived characteristics of predatory journals. These…

Nanotechnology is an emerging, cross-disciplinary technology designed to create and synthesize new materials at the nanoscale (generally defined as a particle size range of ≤10-9 meters) to generate innovative or altered material properties. The particle properties can be modified to promote different and more flexible applications, resulting in consumer benefits, particularly in medical, cosmetic, and industrial applications. As this applied science matures and flourishes, concerns have arisen regarding potential health effects of exposures to untested materials, as many newly developed products have not been adequately evaluated. Indeed, it is necessary to ensure that societal and commercial advantages are not outweighed by potential human health or environmental disadvantages. Therefore, a variety of international planning activities or research efforts have been proposed or implemented, particularly in the European Union and United States, with the expectation that significant advances will be made in understanding potential hazards related to exposures in the occupational…

Clinical trial consent for protocols and their revisions should be transparent for patients and traceable for stakeholders. Our goal is to implement a process allowing for collection of patients' informed consent, which is bound to protocol revisions, storing and tracking the consent in a secure, unfalsifiable and publicly verifiable way, and enabling the sharing of this information in real time. For that, we build a consent workflow using a trending technology called Blockchain. This is a distributed technology that brings a built-in layer of transparency and traceability. From a more general and prospective point of view, we believe Blockchain technology brings a paradigmatical shift to the entire clinical research field. We designed a Proof-of-Concept protocol consisting of time-stamping each step of the patient's consent collection using Blockchain, thus archiving and historicising the consent through cryptographic validation in a securely unfalsifiable and transparent way. For each protocol revision, consent was sought again. We obtained a single document, in an open format,…

Female fertility decreases with increasing age, a reflection of declining oocyte quantity and quality. The menopausal transition occurs when the oocyte quantity falls below a threshold level. The pattern of follicular depletion as well as the factors, timing and mechanisms surrounding both declining oocyte number and oocyte quality remain incompletely understood. Further studies are needed to examine the factors involved and develop predictive models and biomarkers to assist in the management of age-related subfertility. This review summarises the current knowledge addressing the ageing ovary and its impact on fertility.

Over the last few years, certain areas in the management nasopharyngeal carcinoma (NPC) that have an impact on the care of these patients have evolved, particularly with regard to liquid biopsies, minimally invasive surgery, and advances in chemotherapy and immunotherapy. Beyond its proven role in the diagnostics, surveillance, and treatment of NPC, liquid biopsy with plasma Epstein-Barr virus DNA in the screening of high-risk populations for NPC is strongly supported by recent evidence. Surgery of the nasopharynx is reserved for locally recurrent NPC, and in recent years there have been great strides in minimally invasive techniques with survival rates similar to those of open techniques in treating NPC. Induction chemotherapy in a recent pooled analysis was shown to be superior to concurrent chemotherapy alone for locoregionally advanced NPC. Finally, immunotherapy with a PD-1 inhibitor in NPC has been shown to have 1-year overall survival rates comparable to those of other patients with heavily pre-treated metastatic or recurrent NPC. In this commentary, we discuss these recent…

Data exploration is critical to the comprehension of large biological data sets generated by high-throughput assays such as sequencing. However, most existing tools for interactive visualisation are limited to specific assays or analyses. Here, we present the iSEE (Interactive SummarizedExperiment Explorer) software package, which provides a general visual interface for exploring data in a SummarizedExperiment object. iSEE is directly compatible with many existing R/Bioconductor packages for analysing high-throughput biological data, and provides useful features such as simultaneous examination of (meta)data and analysis results, dynamic linking between plots and code tracking for reproducibility. We demonstrate the utility and flexibility of iSEE by applying it to explore a range of real transcriptomics and proteomics data sets.

Detection of differential transcript usage (DTU) from RNA-seq data is an important bioinformatic analysis that complements differential gene expression analysis. Here we present a simple workflow using a set of existing R/Bioconductor packages for analysis of DTU. We show how these packages can be used downstream of RNA-seq quantification using the Salmon software package. The entire pipeline is fast, benefiting from inference steps by Salmon to quantify expression at the transcript level. The workflow includes live, runnable code chunks for analysis using DRIMSeq and DEXSeq, as well as for performing two-stage testing of DTU using the stageR package, a statistical framework to screen at the gene level and then confirm which transcripts within the significant genes show evidence of DTU. We evaluate these packages and other related packages on a simulated dataset with parameters estimated from real data.

Studies of rare and common illnesses have led to remarkable progress in the understanding of the role of telomeres (nucleoprotein complexes at chromosome ends essential for chromosomal integrity) in human disease. Telomere biology disorders encompass a growing spectrum of conditions caused by rare pathogenic germline variants in genes encoding essential aspects of telomere function. Dyskeratosis congenita, a disorder at the severe end of this spectrum, typically presents in childhood with the classic triad of abnormal skin pigmentation, nail dystrophy, and oral leukoplakia, accompanied by a very high risk of bone marrow failure, cancer, pulmonary fibrosis, and other medical problems. In contrast, the less severe end of the telomere biology disorder spectrum consists of middle-age or older adults with just one feature typically seen in dyskeratosis congenita, such as pulmonary fibrosis or bone marrow failure. In the common disease realm, large-scale molecular epidemiology studies have discovered novel associations between illnesses, such as cancer, heart disease, and mental health,…

As a part of the ELIXIR-EXCELERATE efforts in capacity building, we present here 10 steps to facilitate researchers getting started in genome assembly and genome annotation. The guidelines given are broadly applicable, intended to be stable over time, and cover all aspects from start to finish of a general assembly and annotation project. Intrinsic properties of genomes are discussed, as is the importance of using high quality DNA. Different sequencing technologies and generally applicable workflows for genome assembly are also detailed. We cover structural and functional annotation and encourage readers to also annotate transposable elements, something that is often omitted from annotation workflows. The importance of data management is stressed, and we give advice on where to submit data and how to make your results Findable, Accessible, Interoperable, and Reusable (FAIR).

Crimean-Congo hemorrhagic fever virus (CCHFV) is a widely distributed hemorrhagic fever virus and the cause of hemorrhagic disease in Africa, Southern and Eastern Europe, the Middle East, India and Asia. Recent emergence of CCHFV into Spain indicates that the geographic range of this virus is expanding and the presence of its tick vector in several countries without reported disease suggest that CCHFV will continue to spread. Research into CCHFV was historically limited by a lack of suitable animal models and tools to study viral pathogenesis. However, in the past few years the toolset for studying CCHFV has expanded with small animal and non-human primate models for CCHFV being developed along with a reverse genetics system that allows for investigation of viral determinants of disease. These tools have been utilized to understand how CCHFV antagonizes host restriction factors and to develop novel vaccine candidates that may help limit the substantial morbidity and mortality in humans caused by CCHFV.

Antibiotic therapy is not necessary for acute diarrhea in children, as rehydration is the key treatment and symptoms resolve generally without specific therapy. Searching for the etiology of gastroenteritis is not usually needed; however, it may be necessary if antimicrobial treatment is considered. The latter is left to the physician evaluation in the absence of clear indications. Antimicrobial treatment should be considered in severely sick children, in those who have chronic conditions or specific risk factors or in specific settings. Traveler's diarrhea, prolonged diarrhea, and antibiotic-associated diarrhea may also require antibiotic therapy. Depending on the severity of symptoms or based on risk of spreading, empiric therapy may be started while awaiting the results of microbiological investigations. The choice of antibiotic depends on suspected agents, host conditions, and local epidemiology. In most cases, empiric therapy should be started while awaiting such results. Empiric therapy may be started with oral co-trimoxazole or metronidazole, but in severe cases parenteral…

Stakeholders in healthcare are increasingly turning to real world evidence (RWE) to inform their decisions, alongside evidence from randomized controlled trials. RWE is generated by analysing data gathered from routine clinical practice, and can be used across the product lifecycle, providing insights into areas including disease epidemiology, treatment effectiveness and safety, and health economic value and impact. Recently, the US Food and Drug Administration and the European Medicines Agency have stated their ambition for greater use of RWE to support applications for new indications, and are now consulting with their stakeholders to formalize standards and expected methods for generating RWE. Pharmaceutical companies are responding to the increasing demands for RWE by developing standards and processes for each stage of the evidence generation pathway. Some conventions are already in place for assuring quality, whereas other processes are specific to the research question and data sources available. As evidence generation increasingly becomes a core role of medical affairs…

Background: The predominant species in clinical Enterobacter isolates is E. hormaechei . Many articles, clinicians, and GenBank submissions misname these strains as E. cloacae . The lack of sequenced type strains or named species/subspecies for some clades in the E. cloacae complex complicate the issue. Methods: The genomes of the type strains for Enterobacter hormaechei subsp. oharae , E . hormaechei subsp. steigerwaltii , and E. xiangfangensis , and two strains from Hoffmann clusters III and IV of the E. cloacae complex were sequenced. These genomes, the E . hormaechei subsp. hormaechei type strain, and other available Enterobacter type strains were analysed in conjunction with all extant Enterobacter genomes in NCBI’s RefSeq using Average Nucleotide Identity (ANI). Results: There were five recognizable subspecies of E. hormaechei : E. hormaechei subsp. hoffmannii subsp. nov., E. hormaechei subsp. xiangfangensis comb. nov., and the three previously known subspecies. One of the strains sequenced from the E. cloacae complex was not a novel E. hormaechei subspecies but rather a…

Short tandem repeats (STRs), also known as microsatellites, are commonly defined as consisting of tandemly repeated nucleotide motifs of 2-6 base pairs in length. STRs appear throughout the human genome, and about 239,000 are documented in the Simple Repeats Track available from the UCSC (University of California, Santa Cruz) genome browser. STRs vary in size, producing highly polymorphic markers commonly used as genetic markers. A small fraction of STRs (about 30 loci) have been associated with human disease whereby one or both alleles exceed an STR-specific threshold in size, leading to disease. Detection of repeat expansions is currently performed with polymerase chain reaction-based assays or with Southern blots for large expansions. The tests are expensive and time-consuming and are not always conclusive, leading to lengthy diagnostic journeys for patients, potentially including missed diagnoses. The advent of whole exome and whole genome sequencing has identified the genetic cause of many genetic disorders; however, analysis pipelines are focused primarily on the detection of…