Showing papers by "University of Maryland, Baltimore published in 2019"
TL;DR: GO-CAM, a new framework for representing gene function that is more expressive than standard GO annotations, has been released, and users can now explore the growing repository of these models.
Abstract: The Gene Ontology resource (GO; http://geneontology.org) provides structured, computable knowledge regarding the functions of genes and gene products. Founded in 1998, GO has become widely adopted in the life sciences, and its contents are under continual improvement, both in quantity and in quality. Here, we report the major developments of the GO resource during the past two years. Each monthly release of the GO resource is now packaged and given a unique identifier (DOI), enabling GO-based analyses on a specific release to be reproduced in the future. The molecular function ontology has been refactored to better represent the overall activities of gene products, with a focus on transcription regulator activities. Quality assurance efforts have been ramped up to address potentially out-of-date or inaccurate annotations. New evidence codes for high-throughput experiments now enable users to filter out annotations obtained from these sources. GO-CAM, a new framework for representing gene function that is more expressive than standard GO annotations, has been released, and users can now explore the growing repository of these models. We also provide the ‘GO ribbon’ widget for visualizing GO annotations to a gene; the widget can be easily embedded in any web page.
2,138 citations
TL;DR: Among patients with elevated triglyceride levels despite the use of statins, the risk of ischemic events, including cardiovascular death, was significantly lower among those who received 2 g of icosapent ethyl twice daily than amongThose who received placebo.
Abstract: Background Patients with elevated triglyceride levels are at increased risk for ischemic events. Icosapent ethyl, a highly purified eicosapentaenoic acid ethyl ester, lowers triglyceride levels, but data are needed to determine its effects on ischemic events. Methods We performed a multicenter, randomized, double-blind, placebo-controlled trial involving patients with established cardiovascular disease or with diabetes and other risk factors, who had been receiving statin therapy and who had a fasting triglyceride level of 135 to 499 mg per deciliter (1.52 to 5.63 mmol per liter) and a low-density lipoprotein cholesterol level of 41 to 100 mg per deciliter (1.06 to 2.59 mmol per liter). The patients were randomly assigned to receive 2 g of icosapent ethyl twice daily (total daily dose, 4 g) or placebo. The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina. The key secondary end point was a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Results A total of 8179 patients were enrolled (70.7% for secondary prevention of cardiovascular events) and were followed for a median of 4.9 years. A primary end-point event occurred in 17.2% of the patients in the icosapent ethyl group, as compared with 22.0% of the patients in the placebo group (hazard ratio, 0.75; 95% confidence interval [CI], 0.68 to 0.83; P Conclusions Among patients with elevated triglyceride levels despite the use of statins, the risk of ischemic events, including cardiovascular death, was significantly lower among those who received 2 g of icosapent ethyl twice daily than among those who received placebo. (Funded by Amarin Pharma; REDUCE-IT ClinicalTrials.gov number, NCT01492361 .).
1,915 citations
Mike A. Nalls1, Cornelis Blauwendraat1, Costanza L. Vallerga2, Karl Heilbron +245 more•Institutions (23)
TL;DR: These data provide the most comprehensive survey of genetic risk within Parkinson's disease to date, providing a biological context for these risk factors, and showing that a considerable genetic component of this disease remains unidentified.
Abstract: Summary Background Genome-wide association studies (GWAS) in Parkinson's disease have increased the scope of biological knowledge about the disease over the past decade. We aimed to use the largest aggregate of GWAS data to identify novel risk loci and gain further insight into the causes of Parkinson's disease. Methods We did a meta-analysis of 17 datasets from Parkinson's disease GWAS available from European ancestry samples to nominate novel loci for disease risk. These datasets incorporated all available data. We then used these data to estimate heritable risk and develop predictive models of this heritability. We also used large gene expression and methylation resources to examine possible functional consequences as well as tissue, cell type, and biological pathway enrichments for the identified risk factors. Additionally, we examined shared genetic risk between Parkinson's disease and other phenotypes of interest via genetic correlations followed by Mendelian randomisation. Findings Between Oct 1, 2017, and Aug 9, 2018, we analysed 7·8 million single nucleotide polymorphisms in 37 688 cases, 18 618 UK Biobank proxy-cases (ie, individuals who do not have Parkinson's disease but have a first degree relative that does), and 1·4 million controls. We identified 90 independent genome-wide significant risk signals across 78 genomic regions, including 38 novel independent risk signals in 37 loci. These 90 variants explained 16–36% of the heritable risk of Parkinson's disease depending on prevalence. Integrating methylation and expression data within a Mendelian randomisation framework identified putatively associated genes at 70 risk signals underlying GWAS loci for follow-up functional studies. Tissue-specific expression enrichment analyses suggested Parkinson's disease loci were heavily brain-enriched, with specific neuronal cell types being implicated from single cell data. We found significant genetic correlations with brain volumes (false discovery rate-adjusted p=0·0035 for intracranial volume, p=0·024 for putamen volume), smoking status (p=0·024), and educational attainment (p=0·038). Mendelian randomisation between cognitive performance and Parkinson's disease risk showed a robust association (p=8·00 × 10−7). Interpretation These data provide the most comprehensive survey of genetic risk within Parkinson's disease to date, to the best of our knowledge, by revealing many additional Parkinson's disease risk loci, providing a biological context for these risk factors, and showing that a considerable genetic component of this disease remains unidentified. These associations derived from European ancestry datasets will need to be followed-up with more diverse data. Funding The National Institute on Aging at the National Institutes of Health (USA), The Michael J Fox Foundation, and The Parkinson's Foundation (see appendix for full list of funding sources).
1,152 citations
TL;DR: The expansive and growing field of MSC research is teaching us basic human cell biology as well as how to use this type of cell for cellular therapy in a variety of clinical settings, and while much promise is evident, careful new work is still needed.
Abstract: The terms MSC and MSCs have become the preferred acronym to describe a cell and a cell population of multipotential stem/progenitor cells commonly referred to as mesenchymal stem cells, multipotential stromal cells, mesenchymal stromal cells, and mesenchymal progenitor cells. The MSCs can differentiate to important lineages under defined conditions in vitro and in limited situations after implantation in vivo. MSCs were isolated and described about 30 years ago and now there are over 55,000 publications on MSCs readily available. Here, we have focused on human MSCs whenever possible. The MSCs have broad anti-inflammatory and immune-modulatory properties. At present, these provide the greatest focus of human MSCs in clinical testing; however, the properties of cultured MSCs in vitro suggest they can have broader applications. The medical utility of MSCs continues to be investigated in over 950 clinical trials. There has been much progress in understanding MSCs over the years, and there is a strong foundation for future scientific research and clinical applications, but also some important questions remain to be answered. Developing further methods to understand and unlock MSC potential through intracellular and intercellular signaling, biomedical engineering, delivery methods and patient selection should all provide substantial advancements in the coming years and greater clinical opportunities. The expansive and growing field of MSC research is teaching us basic human cell biology as well as how to use this type of cell for cellular therapy in a variety of clinical settings, and while much promise is evident, careful new work is still needed.
975 citations
University of Pennsylvania1, University of Texas MD Anderson Cancer Center2, University of Marburg3, Memorial Sloan Kettering Cancer Center4, University of Bologna5, Carlos III Health Institute6, University of Maryland, Baltimore7, University of Chicago8, University of Minnesota9, University of Alabama at Birmingham10, Medical University of South Carolina11, University of California, San Francisco12, Thomas Jefferson University13, National Taiwan University14, Yale University15, Centre Hospitalier Universitaire de Toulouse16, University of Fukui17, Seoul National University18, University of Ulsan19, Wake Forest University20, Harvard University21, Astellas Pharma22, Johns Hopkins University23
TL;DR: Gilteritinib resulted in significantly longer survival and higher percentages of patients with remission than salvage chemotherapy among patients with relapsed or refractory FLT3-mutated AML.
Abstract: Background Patients with relapsed or refractory acute myeloid leukemia (AML) with mutations in the FMS-like tyrosine kinase 3 gene (FLT3) infrequently have a response to salvage chemothera...
687 citations
Daniel Taliun1, Daniel N. Harris2, Michael D. Kessler2, Jedidiah Carlson3 +191 more•Institutions (61)
TL;DR: The nearly complete catalog of genetic variation in TOPMed studies provides unique opportunities for exploring the contributions of rare and non-coding sequence variants to phenotypic variation as well as resources and early insights from the sequence data.
Abstract: Summary paragraph The Trans-Omics for Precision Medicine (TOPMed) program seeks to elucidate the genetic architecture and disease biology of heart, lung, blood, and sleep disorders, with the ultimate goal of improving diagnosis, treatment, and prevention. The initial phases of the program focus on whole genome sequencing of individuals with rich phenotypic data and diverse backgrounds. Here, we describe TOPMed goals and design as well as resources and early insights from the sequence data. The resources include a variant browser, a genotype imputation panel, and sharing of genomic and phenotypic data via dbGaP. In 53,581 TOPMed samples, >400 million single-nucleotide and insertion/deletion variants were detected by alignment with the reference genome. Additional novel variants are detectable through assembly of unmapped reads and customized analysis in highly variable loci. Among the >400 million variants detected, 97% have frequency
662 citations
University of Washington1, University of Southern California2, University of Michigan3, Harvard University4, Max Planck Society5, University of Groningen6, University of Maryland, Baltimore7, Icahn School of Medicine at Mount Sinai8, Xi'an Jiaotong University9, University of Texas MD Anderson Cancer Center10, University of North Carolina at Charlotte11, Broad Institute12, European Bioinformatics Institute13, Yale University14, University of California, Davis15, University of Utah16, Pacific Biosciences17, University of California, San Diego18, Illumina19, Ludwig Institute for Cancer Research20, Ewha Womans University21, Drexel University22, University of Texas Health Science Center at Houston23, Washington University in St. Louis24, University of Malaya25, University of California, San Francisco26, University of British Columbia27, BC Cancer Agency28
TL;DR: A suite of long-read, short- read, strand-specific sequencing technologies, optical mapping, and variant discovery algorithms are applied to comprehensively analyze three trios to define the full spectrum of human genetic variation in a haplotype-resolved manner.
Abstract: The incomplete identification of structural variants (SVs) from whole-genome sequencing data limits studies of human genetic diversity and disease association. Here, we apply a suite of long-read, short-read, strand-specific sequencing technologies, optical mapping, and variant discovery algorithms to comprehensively analyze three trios to define the full spectrum of human genetic variation in a haplotype-resolved manner. We identify 818,054 indel variants (<50 bp) and 27,622 SVs (≥50 bp) per genome. We also discover 156 inversions per genome and 58 of the inversions intersect with the critical regions of recurrent microdeletion and microduplication syndromes. Taken together, our SV callsets represent a three to sevenfold increase in SV detection compared to most standard high-throughput sequencing studies, including those from the 1000 Genomes Project. The methods and the dataset presented serve as a gold standard for the scientific community allowing us to make recommendations for maximizing structural variation sensitivity for future genome sequencing studies.
606 citations
University of Wisconsin-Madison1, Philippines National Collegiate Athletic Association2, Western University of Health Sciences3, George Washington University4, International Olympic Committee5, University of São Paulo6, McGill University7, Stanford University8, University of Portsmouth9, University of Amsterdam10, University of Arizona11, Chung-Ang University12, University of Maryland, Baltimore13, McMaster University14, Kocaeli University15, Rutgers University16, Princeton University17, Vanderbilt University Medical Center18, University of Nebraska–Lincoln19, Stellenbosch University20
TL;DR: To advance a more standardised, evidence based approach to mental health symptoms and disorders in elite athletes, an International Olympic Committee Consensus Work Group critically evaluated the current state of science and provided recommendations.
Abstract: Mental health symptoms and disorders are common among elite athletes, may have sport related manifestations within this population and impair performance. Mental health cannot be separated from physical health, as evidenced by mental health symptoms and disorders increasing the risk of physical injury and delaying subsequent recovery. There are no evidence or consensus based guidelines for diagnosis and management of mental health symptoms and disorders in elite athletes. Diagnosis must differentiate character traits particular to elite athletes from psychosocial maladaptations.Management strategies should address all contributors to mental health symptoms and consider biopsychosocial factors relevant to athletes to maximise benefit and minimise harm. Management must involve both treatment of affected individual athletes and optimising environments in which all elite athletes train and compete. To advance a more standardised, evidence based approach to mental health symptoms and disorders in elite athletes, an International Olympic Committee Consensus Work Group critically evaluated the current state of science and provided recommendations.
513 citations
National Center for Immunization and Respiratory Diseases1, University of California, San Diego2, Boston Children's Hospital3, University of Washington4, Northeast Ohio Medical University5, Brown University6, University of Virginia Health System7, Centers for Disease Control and Prevention8, University of Maryland, Baltimore9, Northwestern University10, Nova Scotia Health Authority11, University of Toronto12, Harvard University13, Duke University14, McMaster University15, Infectious Diseases Society of America16, University of Utah17
TL;DR: These clinical practice guidelines are an update of the guidelines published by the Infectious Diseases Society of America in 2009 and address new information regarding diagnostic testing, treatment and chemoprophylaxis with antiviral medications, and issues related to institutional outbreak management for seasonal influenza.
Abstract: These clinical practice guidelines are an update of the guidelines published by the Infectious Diseases Society of America (IDSA) in 2009, prior to the 2009 H1N1 influenza pandemic. This document addresses new information regarding diagnostic testing, treatment and chemoprophylaxis with antiviral medications, and issues related to institutional outbreak management for seasonal influenza. It is intended for use by primary care clinicians, obstetricians, emergency medicine providers, hospitalists, laboratorians, and infectious disease specialists, as well as other clinicians managing patients with suspected or laboratory-confirmed influenza. The guidelines consider the care of children and adults, including special populations such as pregnant and postpartum women and immunocompromised patients.
496 citations
TL;DR: There is moderate-to-strong support that PA benefits cognitive functioning during early and late periods of the life span and in certain populations characterized by cognitive deficits.
Abstract: PurposePhysical activity (PA) is known to improve cognitive and brain function, but debate continues regarding the consistency and magnitude of its effects, populations and cognitive domains most affected, and parameters necessary to achieve the greatest improvements (e.g., dose).MethodsIn t
440 citations
University of California, San Diego1, McGill University2, Oregon Health & Science University3, Florida International University4, Yale University5, Washington University in St. Louis6, Virginia Commonwealth University7, University of Vermont8, University of Michigan9, Medical University of South Carolina10, National Institutes of Health11, SRI International12, University of Southern California13, McGovern Institute for Brain Research14, Harvard University15, Medical College of Wisconsin16, University of California, Irvine17, University of California, Los Angeles18, University of California, San Francisco19, University of Colorado Boulder20, University of Florida21, University of Maryland, Baltimore22, University of Massachusetts Boston23, University of Minnesota24, University of Pittsburgh25, University of Rochester26, University of Tennessee27, University of Utah28, University of Wisconsin–Milwaukee29, Boston University30, United States Department of Veterans Affairs31
TL;DR: The baseline neuroimaging processing and subject-level analysis methods used by the Adolescent Brain Cognitive Development Study are described to be a resource of unprecedented scale and depth for studying typical and atypical development.
University of Manitoba1, Boston University2, University of Michigan3, University of Maryland, Baltimore4, University of Wisconsin-Madison5, University of Minnesota6, University of Washington7, University of Amsterdam8, University of Miami9, Yale University10, Northwestern University11, Baylor College of Medicine12, Lund University13, McMaster University14
TL;DR: The current guideline updates the recommendations of the 2005 guideline, includes new recommendations for populations not previously addressed, and, where relevant, addresses the interpretation of nonlocalizing clinical symptoms in populations with a high prevalence of ASB.
Abstract: Asymptomatic bacteriuria (ASB) is a common finding in many populations, including healthy women and persons with underlying urologic abnormalities. The 2005 guideline from the Infectious Diseases Society of America recommended that ASB should be screened for and treated only in pregnant women or in an individual prior to undergoing invasive urologic procedures. Treatment was not recommended for healthy women; older women or men; or persons with diabetes, indwelling catheters, or spinal cord injury. The guideline did not address children and some adult populations, including patients with neutropenia, solid organ transplants, and nonurologic surgery. In the years since the publication of the guideline, further information relevant to ASB has become available. In addition, antimicrobial treatment of ASB has been recognized as an important contributor to inappropriate antimicrobial use, which promotes emergence of antimicrobial resistance. The current guideline updates the recommendations of the 2005 guideline, includes new recommendations for populations not previously addressed, and, where relevant, addresses the interpretation of nonlocalizing clinical symptoms in populations with a high prevalence of ASB.
Laboratory of Molecular Biology1, University of Victoria2, University of Colorado Boulder3, National University of Singapore4, Pasteur Institute5, Biogen Idec6, Northeastern University7, University of Pennsylvania8, Novo Nordisk9, Scripps Research Institute10, Washington University in St. Louis11, University of Washington12, Johnson & Johnson13, Utrecht University14, University of Southern Denmark15, University of Massachusetts Amherst16, University of California, Berkeley17, University of Western Ontario18, Academy of Sciences of the Czech Republic19, Hebrew University of Jerusalem20, Iowa State University21, Hoffmann-La Roche22, Genentech23, University of Kansas24, York University25, University of Maryland, Baltimore26, Amgen27, University of Calgary28, University of Copenhagen29
TL;DR: Recommendations arising from community discussions emerging out of the first International Conference on Hydrogen-Exchange Mass Spectrometry (IC-HDX; 2017) are provided, meant to represent both a consensus viewpoint and an opportunity to stimulate further additions and refinements as the field advances.
Abstract: Hydrogen deuterium exchange mass spectrometry (HDX-MS) is a powerful biophysical technique being increasingly applied to a wide variety of problems. As the HDX-MS community continues to grow, adoption of best practices in data collection, analysis, presentation and interpretation will greatly enhance the accessibility of this technique to nonspecialists. Here we provide recommendations arising from community discussions emerging out of the first International Conference on Hydrogen-Exchange Mass Spectrometry (IC-HDX; 2017). It is meant to represent both a consensus viewpoint and an opportunity to stimulate further additions and refinements as the field advances.
TL;DR: This guideline update is intended for all clinicians who diagnose or manage adult patients who present with sudden hearing loss and should improve diagnostic accuracy, facilitate prompt intervention, decrease variations in management, reduce unnecessary tests and imaging procedures, and improve hearing and rehabilitative outcomes for affected patients.
Abstract: ObjectiveSudden hearing loss is a frightening symptom that often prompts an urgent or emergent visit to a health care provider. It is frequently but not universally accompanied by tinnitus and/or v...
Baker IDI Heart and Diabetes Institute1, Saint Louis University2, University of Alberta3, Columbia University4, The Chinese University of Hong Kong5, Memorial Hospital of South Bend6, King's College London7, Heidelberg University8, National Institutes of Health9, National University of Singapore10, Sichuan University11, University of Amsterdam12, Kyung Hee University13, Uppsala University14, University of Helsinki15, University of Oulu16, University of Western Australia17, Harvard University18, Université du Québec à Montréal19, University of Zurich20, University of Maryland, Baltimore21, Queen's University22, University of Florida23, University of Miami24, McMaster University25, King Saud University26, University of Otago27, French Institute of Health and Medical Research28
TL;DR: The task force of the International Conference of Frailty and Sarcopenia Research developed these clinical practice guidelines to overview the current evidence-base and provide recommendations for the identification and management of frailty in older adults using the GRADE approach.
Abstract: Objective: The task force of the International Conference of Frailty and Sarcopenia Research (ICFSR) developed these clinical practice guidelines to overview the current evidence-base and to provide recommendations for the identification and management of frailty in older adults. Methods: These recommendations were formed using the GRADE approach, which ranked the strength and certainty (quality) of the supporting evidence behind each recommendation. Where the evidence-base was limited or of low quality, Consensus Based Recommendations (CBRs) were formulated. The recommendations focus on the clinical and practical aspects of care for older people with frailty, and promote person-centred care. Recommendations for Screening and Assessment: The task force recommends that health practitioners case identify/screen all older adults for frailty using a validated instrument suitable for the specific setting or context (strong recommendation). Ideally, the screening instrument should exclude disability as part of the screening process. For individuals screened as positive for frailty, a more comprehensive clinical assessment should be performed to identify signs and underlying mechanisms of frailty (strong recommendation). Recommendations for Management: A comprehensive care plan for frailty should address polypharmacy (whether rational or nonrational), the management of sarcopenia, the treatable causes of weight loss, and the causes of exhaustion (depression, anaemia, hypotension, hypothyroidism, and B12 deficiency) (strong recommendation). All persons with frailty should receive social support as needed to address unmet needs and encourage adherence to a comprehensive care plan (strong recommendation). First-line therapy for the management of frailty should include a multi-component physical activity programme with a resistance-based training component (strong recommendation). Protein/caloric supplementation is recommended when weight loss or undernutrition are present (conditional recommendation). No recommendation was given for systematic additional therapies such as cognitive therapy, problem-solving therapy, vitamin D supplementation, and hormone-based treatment. Pharmacological treatment as presently available is not recommended therapy for the treatment of frailty.
TL;DR: This review follows the CoV outbreaks that are speculated to have originated in bats and reviews studies that have allowed researchers to identify unique adaptation in bats that may allow them to harbor CoVs without severe disease.
Abstract: Bats are speculated to be reservoirs of several emerging viruses including coronaviruses (CoVs) that cause serious disease in humans and agricultural animals. These include CoVs that cause severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), porcine epidemic diarrhea (PED) and severe acute diarrhea syndrome (SADS). Bats that are naturally infected or experimentally infected do not demonstrate clinical signs of disease. These observations have allowed researchers to speculate that bats are the likely reservoirs or ancestral hosts for several CoVs. In this review, we follow the CoV outbreaks that are speculated to have originated in bats. We review studies that have allowed researchers to identify unique adaptation in bats that may allow them to harbor CoVs without severe disease. We speculate about future studies that are critical to identify how bats can harbor multiple strains of CoVs and factors that enable these viruses to “jump” from bats to other mammals. We hope that this review will enable readers to identify gaps in knowledge that currently exist and initiate a dialogue amongst bat researchers to share resources to overcome present limitations.
Fred Hutchinson Cancer Research Center1, Alberta Health Services2, Pennington Biomedical Research Center3, Centers for Disease Control and Prevention4, University of Maryland, Baltimore5, University of Illinois at Urbana–Champaign6, University of Connecticut7, United States Department of Health and Human Services8
TL;DR: Levels of physical activity recommended in the 2018 Guidelines are associated with reduced risk and improved survival for several cancers, and more research is needed to determine the associations between physical activity and incidence for less common cancers and associations with survival for other cancers.
Abstract: PurposeThis article reviews and updates the evidence on the associations between physical activity and risk for cancer, and for mortality in persons with cancer, as presented in the 2018 Physical Activity Guidelines Advisory Committee Scientific Report.MethodsSystematic reviews of meta-analy
TL;DR: The DO’s continual integration of human disease knowledge, evidenced by the more than 200 SVN/GitHub releases/revisions, includes the addition of 2650 new disease terms, a 30% increase of textual definitions, and an expanding suite of disease classification hierarchies constructed through defined logical axioms.
Abstract: The Human Disease Ontology (DO) (http://www.disease-ontology.org), database has undergone significant expansion in the past three years. The DO disease classification includes specific formal semantic rules to express meaningful disease models and has expanded from a single asserted classification to include multiple-inferred mechanistic disease classifications, thus providing novel perspectives on related diseases. Expansion of disease terms, alternative anatomy, cell type and genetic disease classifications and workflow automation highlight the updates for the DO since 2015. The enhanced breadth and depth of the DO’s knowledgebase has expanded the DO’s utility for exploring the multi-etiology of human disease, thus improving the capture and communication of health-related data across biomedical databases, bioinformatics tools, genomic and cancer resources and demonstrated by a 6.6× growth in DO’s user community since 2015. The DO’s continual integration of human disease knowledge, evidenced by the more than 200 SVN/GitHub releases/revisions, since previously reported in our DO 2015 NAR paper, includes the addition of 2650 new disease terms, a 30% increase of textual definitions, and an expanding suite of disease classification hierarchies constructed through defined logical axioms.
Hartford Hospital1, University of Michigan2, Nanjing Medical University3, Duke University4, Beth Israel Deaconess Medical Center5, University of Pennsylvania6, Cleveland Clinic7, Washington University in St. Louis8, Northwestern University9, Vita-Salute San Raffaele University10, University of Maryland, Baltimore11, University of Queensland12, University of Alabama at Birmingham13, Indiana University14, University of Tsukuba15, University of California, San Francisco16, Australian National University17, Queen Elizabeth II Health Sciences Centre18, University of Antwerp19, Kyorin University20, Vanderbilt University21, Brigham and Women's Hospital22, University of Colorado Denver23, Leiden University Medical Center24
TL;DR: This document is to help electrophysiologists around the world to appropriately select patients for catheter ablation, to perform procedures in a safe and efficacious manner, and to provide follow-up and adjunctive care in order to obtain the best possible outcomes for patients with ventricular arrhythmias.
Abstract: Ventricular arrhythmias are an important cause of morbidity and mortality and come in a variety of forms, from single premature ventricular complexes to sustained ventricular tachycardia and fibrillation. Rapid developments have taken place over the past decade in our understanding of these arrhythmias and in our ability to diagnose and treat them. The field of catheter ablation has progressed with the development of new methods and tools, and with the publication of large clinical trials. Therefore, global cardiac electrophysiology professional societies undertook to outline recommendations and best practices for these procedures in a document that will update and replace the 2009 EHRA/HRS Expert Consensus on Catheter Ablation of Ventricular Arrhythmias. An expert writing group, after reviewing and discussing the literature, including a systematic review and meta-analysis published in conjunction with this document, and drawing on their own experience, drafted and voted on recommendations and summarized current knowledge and practice in the field. Each recommendation is presented in knowledge byte format and is accompanied by supportive text and references. Further sections provide a practical synopsis of the various techniques and of the specific ventricular arrhythmia sites and substrates encountered in the electrophysiology lab. The purpose of this document is to help electrophysiologists around the world to appropriately select patients for catheter ablation, to perform procedures in a safe and efficacious manner, and to provide follow-up and adjunctive care in order to obtain the best possible outcomes for patients with ventricular arrhythmias.
Joint Genome Institute1, University of Liverpool2, Radboud University Nijmegen3, University of Guelph4, Catholic University of Leuven5, University of Cape Town6, Arizona State University7, European Bioinformatics Institute8, Cairo University9, Vanderbilt University10, University of South Florida11, Colorado State University12, University of Michigan13, University of California, Davis14, University of Auvergne15, University of Southern California16, University of Queensland17, University of Arizona18, Texas A&M University19, National Institute of Genetics20, University of Alicante21, Kyoto University22, Université Paris-Saclay23, University of Chicago24, University of Los Andes25, Universidad Miguel Hernández de Elche26, University of Maryland, Baltimore27, University of Hawaii at Manoa28, Ohio State University29, École Polytechnique Fédérale de Lausanne30, University of British Columbia31, University of Exeter32, Oregon State University33, Australian Institute of Marine Science34, University of California, Irvine35, University of Tennessee36, University of Delaware37, Max Planck Society38, Montana State University39, J. Craig Venter Institute40, University of California, San Diego41
TL;DR: The MIUViG (Minimum Information about an Uncultivated Virus Genome) as mentioned in this paper standard was developed within the Genomic Standards Consortium framework and includes virus origin, genome quality, genome annotation, taxonomic classification, biogeographic distribution and in silico host prediction.
Abstract: We present an extension of the Minimum Information about any (x) Sequence (MIxS) standard for reporting sequences of uncultivated virus genomes. Minimum Information about an Uncultivated Virus Genome (MIUViG) standards were developed within the Genomic Standards Consortium framework and include virus origin, genome quality, genome annotation, taxonomic classification, biogeographic distribution and in silico host prediction. Community-wide adoption of MIUViG standards, which complement the Minimum Information about a Single Amplified Genome (MISAG) and Metagenome-Assembled Genome (MIMAG) standards for uncultivated bacteria and archaea, will improve the reporting of uncultivated virus genomes in public databases. In turn, this should enable more robust comparative studies and a systematic exploration of the global virosphere.
University of Alabama at Birmingham1, McMaster University2, University of Pennsylvania3, Toronto Western Hospital4, Cleveland Clinic5, Oregon Health & Science University6, Boston Medical Center7, Stanford University8, University of Washington9, Brigham and Women's Hospital10, University of Rochester Medical Center11, University of Maryland, Baltimore12, Florida State University13, Eastern Virginia Medical School14, American College of Rheumatology15, ECRI Institute16, University of Oxford17, New York Medical College18, Case Western Reserve University19, Johns Hopkins University20, New York University21, University of Utah22
TL;DR: The 2018 ACR/NPF guideline as mentioned in this paper provides evidence-based guidelines for the pharmacologic and non-pharmacologic treatment of psoriatic arthritis (PsA) using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology.
Abstract: Objective To develop an evidence-based guideline for the pharmacologic and nonpharmacologic treatment of psoriatic arthritis (PsA), as a collaboration between the American College of Rheumatology (ACR) and the National Psoriasis Foundation (NPF). Methods We identified critical outcomes in PsA and clinically relevant PICO (population/intervention/comparator/outcomes) questions. A Literature Review Team performed a systematic literature review to summarize evidence supporting the benefits and harms of available pharmacologic and nonpharmacologic therapies for PsA. GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology was used to rate the quality of the evidence. A voting panel, including rheumatologists, dermatologists, other health professionals, and patients, achieved consensus on the direction and the strength of the recommendations. Results The guideline covers the management of active PsA in patients who are treatment-naive and those who continue to have active PsA despite treatment, and addresses the use of oral small molecules, tumor necrosis factor inhibitors, interleukin-12/23 inhibitors (IL-12/23i), IL-17 inhibitors, CTLA4-Ig (abatacept), and a JAK inhibitor (tofacitinib). We also developed recommendations for psoriatic spondylitis, predominant enthesitis, and treatment in the presence of concomitant inflammatory bowel disease, diabetes, or serious infections. We formulated recommendations for a treat-to-target strategy, vaccinations, and nonpharmacologic therapies. Six percent of the recommendations were strong and 94% conditional, indicating the importance of active discussion between the health care provider and the patient to choose the optimal treatment. Conclusion The 2018 ACR/NPF PsA guideline serves as a tool for health care providers and patients in the selection of appropriate therapy in common clinical scenarios. Best treatment decisions consider each individual patient situation. The guideline is not meant to be proscriptive and should not be used to limit treatment options for patients with PsA.
University of Maryland, Baltimore1, University of Texas Health Science Center at San Antonio2, Universidade Luterana do Brasil3, University of Hong Kong4, Thammasat University5, King's College London6, University of Queensland7, Sofia Medical University8, Suranaree University of Technology9, University of Copenhagen10
TL;DR: A global perspective on ECC epidemiology, aetiology, risk factors, risk assessment, global impact, and management is aimed to foster improved worldwide understanding and management of ECC.
Abstract: Background: This paper is a summary of the proceedings of the International Association of Paediatric Dentistry Bangkok Conference on early childhood caries (ECC) held in 3-4 November 2018. Aim: The paper aims to convey a global perspective of ECC definitions, aetiology, risk factors, societal costs, management, educational curriculum, and policy. Design: This global perspective on ECC is the compilation of the state of science, current concepts, and literature regarding ECC from worldwide experts on ECC. Results: Early childhood caries is related to frequent sugar consumption in an environment of enamel adherent, acid-producing bacteria in a complex biofilm, as well as developmental defects of enamel. The seriousness, societal costs, and impact on quality of life of dental caries in pre-school children are enormous. Worldwide data show that ECC continues to be highly prevalent, yet infrequently treated. Approaches to reduce the prevalence include interventions that start in the first year of a child's life, evidence-based and risk-based management, and reimbursement systems that foster preventive care. Conclusions: This global perspective on ECC epidemiology, aetiology, risk assessment, global impact, and management is aimed to foster improved worldwide understanding and management of ECC.
University of Alabama at Birmingham1, McMaster University2, University of Pennsylvania3, Toronto Western Hospital4, Cleveland Clinic5, Oregon Health & Science University6, Boston Medical Center7, Stanford University8, University of Washington9, Brigham and Women's Hospital10, University of Rochester Medical Center11, University of Maryland, Baltimore12, Florida State University13, Eastern Virginia Medical School14, American College of Rheumatology15, ECRI Institute16, University of Oxford17, New York Medical College18, Case Western Reserve University19, Johns Hopkins University20, New York University21, University of Utah22
TL;DR: To develop an evidence‐based guideline for the pharmacologic and nonpharmacologic treatment of psoriatic arthritis (PsA), as a collaboration between the American College of Rheumatology and the National Psoriasis Foundation (NPF).
Abstract: Objective:To develop an evidence-based guideline for the pharmacologic and nonpharmacologic treatment of psoriatic arthritis (PsA), as a collaboration between the American College of Rheumatology (...
Stanford University1, University of Illinois at Urbana–Champaign2, Purdue University3, George Washington University4, University of Pittsburgh5, Northeastern University6, University of Iowa7, Pennington Biomedical Research Center8, Duke University9, University of Maryland, Baltimore10, University of Illinois at Chicago11, Fred Hutchinson Cancer Research Center12, University of South Carolina13, University of Connecticut14, Winston-Salem State University15
TL;DR: New described benefits of physical activity include reduced risk of excessive weight gain in children and adults, incidence of 6 types of cancer, and fall-related injuries in older people.
Abstract: Background: The 2018 Physical Activity Guidelines Advisory Committee Scientific Report provides the evidence base for the Physical Activity Guidelines for Americans, 2nd Edition. Methods: The 2018 ...
TL;DR: The data suggest that the increased disease severity observed in individuals with MERS and comorbid type 2 diabetes is likely due to a dysregulated immune response which results in more severe and prolonged lung pathology.
Abstract: Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012 in Saudi Arabia and has caused over 2400 cases and more than 800 deaths. Epidemiological studies identified diabetes as the primary comorbidity associated with severe or lethal MERS-CoV infection. Understanding how diabetes affects MERS is important because of the global burden of diabetes and pandemic potential of MERS-CoV. We used a model in which mice were made susceptible to MERS-CoV by expressing human DPP4, and type 2 diabetes was induced by administering a high-fat diet. Upon infection with MERS-CoV, diabetic mice had a prolonged phase of severe disease and delayed recovery that was independent of virus titers. Histological analysis revealed that diabetic mice had delayed inflammation, which was then prolonged through 21 days after infection. Diabetic mice had fewer inflammatory monocyte/macrophages and CD4+ T cells, which correlated with lower levels of Ccl2 and Cxcl10 expression. Diabetic mice also had lower levels of Tnfa, Il6, Il12b, and Arg1 expression and higher levels of Il17a expression. These data suggest that the increased disease severity observed in individuals with MERS and comorbid type 2 diabetes is likely due to a dysregulated immune response, which results in more severe and prolonged lung pathology.
TL;DR: This work describes FDA-ARGOS, a reference database for high-quality microbial reference genomes, and demonstrates its utility on the example of two use cases and provides quality control metrics for the FDA- ARGOS genomic database resource and outlines the need for genome quality gap filling in the public domain.
Abstract: FDA proactively invests in tools to support innovation of emerging technologies, such as infectious disease next generation sequencing (ID-NGS). Here, we introduce FDA-ARGOS quality-controlled reference genomes as a public database for diagnostic purposes and demonstrate its utility on the example of two use cases. We provide quality control metrics for the FDA-ARGOS genomic database resource and outline the need for genome quality gap filling in the public domain. In the first use case, we show more accurate microbial identification of Enterococcus avium from metagenomic samples with FDA-ARGOS reference genomes compared to non-curated GenBank genomes. In the second use case, we demonstrate the utility of FDA-ARGOS reference genomes for Ebola virus target sequence comparison as part of a composite validation strategy for ID-NGS diagnostic tests. The use of FDA-ARGOS as an in silico target sequence comparator tool combined with representative clinical testing could reduce the burden for completing ID-NGS clinical trials. To be able to use infectious disease next generation sequencing as a diagnostic tool, appropriate reference datasets are required. Here, Sichtig et al. describe FDA-ARGOS, a reference database for high-quality microbial reference genomes, and demonstrate its utility on the example of two use cases.
TL;DR: Increased potassium secretion and angiogenic signaling represent early kidney responses in human diabetic nephropathy, and are suggested to be important for ion transport, angiogenesis, and immune cell activation.
Abstract: Diabetic nephropathy is characterized by damage to both the glomerulus and tubulointerstitium, but relatively little is known about accompanying cell-specific changes in gene expression. We performed unbiased single-nucleus RNA sequencing (snRNA-seq) on cryopreserved human diabetic kidney samples to generate 23,980 single-nucleus transcriptomes from 3 control and 3 early diabetic nephropathy samples. All major cell types of the kidney were represented in the final dataset. Side-by-side comparison demonstrated cell-type–specific changes in gene expression that are important for ion transport, angiogenesis, and immune cell activation. In particular, we show that the diabetic thick ascending limb, late distal convoluted tubule, and principal cells all adopt a gene expression signature consistent with increased potassium secretion, including alterations in Na+/K+-ATPase, WNK1, mineralocorticoid receptor, and NEDD4L expression, as well as decreased paracellular calcium and magnesium reabsorption. We also identify strong angiogenic signatures in glomerular cell types, proximal convoluted tubule, distal convoluted tubule, and principal cells. Taken together, these results suggest that increased potassium secretion and angiogenic signaling represent early kidney responses in human diabetic nephropathy.
Centers for Disease Control and Prevention1, United States Department of Agriculture2, University of Naples Federico II3, University of Ljubljana4, Mississippi State University5, University of Texas Medical Branch6, Friedrich Loeffler Institute7, Colorado State University8, Columbia University9, University of California, Irvine10, University of the Free State11, Xinjiang University12, Aix-Marseille University13, International Rice Research Institute14, Scripps Research Institute15, Public Health Agency of Canada16, Mayo Clinic17, Hacettepe University18, United States Army Medical Research Institute of Infectious Diseases19, Chinese Center for Disease Control and Prevention20, Kansas State University21, Bernhard Nocht Institute for Tropical Medicine22, Paris Diderot University23, University of Queensland24, University of Helsinki25, University of Zurich26, Public Health England27, Seoul National University28, Charité29, Slovak Academy of Sciences30, Karolinska Institutet31, Katholieke Universiteit Leuven32, University of Washington33, Wuhan University of Science and Technology34, University of Louisville35, University of São Paulo36, University of Bari37, Hokkaido University38, University of Hamburg39, Public Health Agency of Sweden40, Washington State University41, Aristotle University of Thessaloniki42, Oswaldo Cruz Foundation43, University of Brasília44, National University of La Plata45, Pasteur Institute46, University of Maryland, Baltimore47, National Agriculture and Food Research Organization48, University of Glasgow49, University of Tokyo50, University of Oxford51, Korea University52, National Research Council53, Fujian Agriculture and Forestry University54, North Carolina State University55, Universidade Federal de Viçosa56, Fudan University57, National Institutes of Health58
TL;DR: The updated taxonomy of the order Bunyavirales now accepted by the International Committee on Taxonomy of Viruses (ICTV) is presented.
Abstract: In February 2019, following the annual taxon ratification vote, the order Bunyavirales was amended by creation of two new families, four new subfamilies, 11 new genera and 77 new species, merging of two species, and deletion of one species. This article presents the updated taxonomy of the order Bunyavirales now accepted by the International Committee on Taxonomy of Viruses (ICTV).
TL;DR: Antibiotics are frequently supplied without a prescription in many countries and this overuse of antibiotics could facilitate the development and spread of antibiotic resistance.
National Institutes of Health1, University of Queensland2, University of Maryland, Baltimore3, Oslo University Hospital4, German Center for Neurodegenerative Diseases5, University of Tübingen6, Montreal Neurological Institute and Hospital7, McGill University8, University of Oulu9, Oulu University Hospital10, Michael J. Fox Foundation11, Queen Mary University of London12, UCL Institute of Neurology13, Baylor College of Medicine14, University of Paris15, Leiden University Medical Center16, University of Helsinki17, University of Oslo18, University of Glasgow19, Boston Children's Hospital20, Translational Research Institute21
TL;DR: The genetic determinants of PD age at onset are largely unknown and increasing evidence supports an extensive and complex genetic contribution to PD.
Abstract: Background: Increasing evidence supports an extensive and complex genetic contribution to PD. Previous genome-wide association studies (GWAS) have shed light on the genetic basis of risk for this disease. However, the genetic determinants of PD age at onset are largely unknown. Objectives: To identify the genetic determinants of PD age at onset. Methods: Using genetic data of 28,568 PD cases, we performed a genome-wide association study based on PD age at onset. Results: We estimated that the heritability of PD age at onset attributed to common genetic variation was ∼0.11, lower than the overall heritability of risk for PD (∼0.27), likely, in part, because of the subjective nature of this measure. We found two genome-wide significant association signals, one at SNCA and the other a protein-coding variant in TMEM175, both of which are known PD risk loci and a Bonferroni-corrected significant effect at other known PD risk loci, GBA, INPP5F/BAG3, FAM47E/SCARB2, and MCCC1. Notably, SNCA, TMEM175, SCARB2, BAG3, and GBA have all been shown to be implicated in α-synuclein aggregation pathways. Remarkably, other well-established PD risk loci, such as GCH1 and MAPT, did not show a significant effect on age at onset of PD. Conclusions: Overall, we have performed the largest age at onset of PD genome-wide association studies to date, and our results show that not all PD risk loci influence age at onset with significant differences between risk alleles for age at onset. This provides a compelling picture, both within the context of functional characterization of disease-linked genetic variability and in defining differences between risk alleles for age at onset, or frank risk for disease.