Showing papers by "Johns Hopkins University published in 2021"
Monash University1, University of Amsterdam2, University of Paris3, Bond University4, University of Texas Health Science Center at San Antonio5, University of Ottawa6, American University of Beirut7, Oregon Health & Science University8, University of York9, Ottawa Hospital Research Institute10, University of Southern Denmark11, Johns Hopkins University12, Brigham and Women's Hospital13, Indiana University14, University of Bristol15, University College London16, University of Toronto17
TL;DR: The preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement as discussed by the authors was designed to help systematic reviewers transparently report why the review was done, what the authors did, and what they found.
Abstract: The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement, published in 2009, was designed to help systematic reviewers transparently report why the review was done, what the authors did, and what they found. Over the past decade, advances in systematic review methodology and terminology have necessitated an update to the guideline. The PRISMA 2020 statement replaces the 2009 statement and includes new reporting guidance that reflects advances in methods to identify, select, appraise, and synthesise studies. The structure and presentation of the items have been modified to facilitate implementation. In this article, we present the PRISMA 2020 27-item checklist, an expanded checklist that details reporting recommendations for each item, the PRISMA 2020 abstract checklist, and the revised flow diagrams for original and updated reviews.
16,613 citations
Monash University1, University of Ottawa2, University of Amsterdam3, University of Paris4, Bond University5, University of Texas Health Science Center at San Antonio6, American University of Beirut7, Oregon Health & Science University8, University of York9, Ottawa Hospital Research Institute10, University of Southern Denmark11, Johns Hopkins University12, Brigham and Women's Hospital13, Indiana University14, University of Bristol15, University College London16, University of Toronto17
TL;DR: The preferred reporting items for systematic reviews and meta-analyses (PRISMA 2020) as mentioned in this paper was developed to facilitate transparent and complete reporting of systematic reviews, and has been updated to reflect recent advances in systematic review methodology and terminology.
Abstract: The methods and results of systematic reviews should be reported in sufficient detail to allow users to assess the trustworthiness and applicability of the review findings. The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement was developed to facilitate transparent and complete reporting of systematic reviews and has been updated (to PRISMA 2020) to reflect recent advances in systematic review methodology and terminology. Here, we present the explanation and elaboration paper for PRISMA 2020, where we explain why reporting of each item is recommended, present bullet points that detail the reporting recommendations, and present examples from published reviews. We hope that changes to the content and structure of PRISMA 2020 will facilitate uptake of the guideline and lead to more transparent, complete, and accurate reporting of systematic reviews.
2,217 citations
Monash University1, University of Amsterdam2, University of Paris3, Bond University4, University of Texas Health Science Center at San Antonio5, University of Ottawa6, American University of Beirut7, Oregon Health & Science University8, University of York9, Ottawa Hospital Research Institute10, University of Southern Denmark11, Johns Hopkins University12, Brigham and Women's Hospital13, Indiana University14, University of Bristol15, University College London16, University of Toronto17
TL;DR: The preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement as discussed by the authors was designed to help systematic reviewers transparently report why the review was done, what the authors did, and what they found.
Abstract: The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement, published in 2009, was designed to help systematic reviewers transparently report why the review was done, what the authors did, and what they found. Over the past decade, advances in systematic review methodology and terminology have necessitated an update to the guideline. The PRISMA 2020 statement replaces the 2009 statement and includes new reporting guidance that reflects advances in methods to identify, select, appraise, and synthesise studies. The structure and presentation of the items have been modified to facilitate implementation. In this article, we present the PRISMA 2020 27-item checklist, an expanded checklist that details reporting recommendations for each item, the PRISMA 2020 abstract checklist, and the revised flow diagrams for original and updated reviews.
2,192 citations
Monash University1, University of Amsterdam2, University of Paris3, Bond University4, University of Texas Health Science Center at San Antonio5, University of Ottawa6, American University of Beirut7, Oregon Health & Science University8, University of York9, Ottawa Hospital Research Institute10, University of Southern Denmark11, Johns Hopkins University12, Brigham and Women's Hospital13, Indiana University14, University of Bristol15, University College London16, University of Toronto17
TL;DR: The preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement as discussed by the authors was designed to help systematic reviewers transparently report why the review was done, what the authors did, and what they found.
1,725 citations
Daniel J. Klionsky1, Amal Kamal Abdel-Aziz2, Sara Abdelfatah3, Mahmoud Abdellatif4 +2980 more•Institutions (777)
TL;DR: In this article, the authors present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes.
Abstract: In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
1,129 citations
01 Jun 2021
TL;DR: Some of the prevailing trends in embedding physics into machine learning are reviewed, some of the current capabilities and limitations are presented and diverse applications of physics-informed learning both for forward and inverse problems, including discovering hidden physics and tackling high-dimensional problems are discussed.
Abstract: Despite great progress in simulating multiphysics problems using the numerical discretization of partial differential equations (PDEs), one still cannot seamlessly incorporate noisy data into existing algorithms, mesh generation remains complex, and high-dimensional problems governed by parameterized PDEs cannot be tackled. Moreover, solving inverse problems with hidden physics is often prohibitively expensive and requires different formulations and elaborate computer codes. Machine learning has emerged as a promising alternative, but training deep neural networks requires big data, not always available for scientific problems. Instead, such networks can be trained from additional information obtained by enforcing the physical laws (for example, at random points in the continuous space-time domain). Such physics-informed learning integrates (noisy) data and mathematical models, and implements them through neural networks or other kernel-based regression networks. Moreover, it may be possible to design specialized network architectures that automatically satisfy some of the physical invariants for better accuracy, faster training and improved generalization. Here, we review some of the prevailing trends in embedding physics into machine learning, present some of the current capabilities and limitations and discuss diverse applications of physics-informed learning both for forward and inverse problems, including discovering hidden physics and tackling high-dimensional problems. The rapidly developing field of physics-informed learning integrates data and mathematical models seamlessly, enabling accurate inference of realistic and high-dimensional multiphysics problems. This Review discusses the methodology and provides diverse examples and an outlook for further developments.
1,114 citations
Monash University1, University of Amsterdam2, University of Paris3, Bond University4, University of Texas Health Science Center at San Antonio5, University of Ottawa6, American University of Beirut7, Oregon Health & Science University8, University of York9, Ottawa Hospital Research Institute10, University of Southern Denmark11, Johns Hopkins University12, Brigham and Women's Hospital13, Indiana University14, University of Bristol15, University College London16, University of Toronto17
TL;DR: The PRISMA 2020, an updated reporting guideline for systematic reviews and meta-analyses, was proposed by Page and colleagues as discussed by the authors, who describe the guidelines as "an updated reporting guidelines for systematic review and meta analysis".
Abstract: Matthew Page and co-authors describe PRISMA 2020, an updated reporting guideline for systematic reviews and meta-analyses.
824 citations
Daniel Taliun1, Daniel N. Harris2, Michael D. Kessler2, Jedidiah Carlson1 +202 more•Institutions (61)
TL;DR: The Trans-Omics for Precision Medicine (TOPMed) project as discussed by the authors aims to elucidate the genetic architecture and biology of heart, lung, blood and sleep disorders, with the ultimate goal of improving diagnosis, treatment and prevention of these diseases.
Abstract: The Trans-Omics for Precision Medicine (TOPMed) programme seeks to elucidate the genetic architecture and biology of heart, lung, blood and sleep disorders, with the ultimate goal of improving diagnosis, treatment and prevention of these diseases The initial phases of the programme focused on whole-genome sequencing of individuals with rich phenotypic data and diverse backgrounds Here we describe the TOPMed goals and design as well as the available resources and early insights obtained from the sequence data The resources include a variant browser, a genotype imputation server, and genomic and phenotypic data that are available through dbGaP (Database of Genotypes and Phenotypes)1 In the first 53,831 TOPMed samples, we detected more than 400 million single-nucleotide and insertion or deletion variants after alignment with the reference genome Additional previously undescribed variants were detected through assembly of unmapped reads and customized analysis in highly variable loci Among the more than 400 million detected variants, 97% have frequencies of less than 1% and 46% are singletons that are present in only one individual (53% among unrelated individuals) These rare variants provide insights into mutational processes and recent human evolutionary history The extensive catalogue of genetic variation in TOPMed studies provides unique opportunities for exploring the contributions of rare and noncoding sequence variants to phenotypic variation Furthermore, combining TOPMed haplotypes with modern imputation methods improves the power and reach of genome-wide association studies to include variants down to a frequency of approximately 001% The goals, resources and design of the NHLBI Trans-Omics for Precision Medicine (TOPMed) programme are described, and analyses of rare variants detected in the first 53,831 samples provide insights into mutational processes and recent human evolutionary history
801 citations
Université Paris-Saclay1, Autonomous University of Barcelona2, University of Cambridge3, National Institute for Occupational Safety and Health4, German Center for Neurodegenerative Diseases5, University of Bonn6, Harvard University7, University of Lausanne8, National Research Council9, University of Padua10, Heidelberg University11, Salk Institute for Biological Studies12, University of Minnesota13, Pasteur Institute14, Tel Aviv University15, Johns Hopkins University16, University of Portsmouth17, Katholieke Universiteit Leuven18, PSL Research University19, Trinity College, Dublin20, Baylor College of Medicine21, University College London22, University of Edinburgh23, Oregon Health & Science University24, National Institutes of Health25, Columbia University26, University of Copenhagen27, University of Rochester28, Ludwig Maximilian University of Munich29, University of Málaga30, Tufts University31, University of Freiburg32, Utrecht University33, Nihon University34, Max Delbrück Center for Molecular Medicine35, University of California, Los Angeles36, University of Yamanashi37, New York University38, University of British Columbia39, King Abdullah University of Science and Technology40, University of Wisconsin-Madison41, University of California, San Francisco42, McGill University43, University of Kentucky44, Kyushu University45, University of Bordeaux46, Polytechnic Institute of Cávado and Ave47, University of Minho48, University of Alabama at Birmingham49, University of Gothenburg50, University of Poitiers51, Cajal Institute52, King's College London53, University of Strasbourg54, Virginia Tech55, University of Düsseldorf56, I.M. Sechenov First Moscow State Medical University57, Russian Academy of Sciences58, University of Seville59, Georgia Institute of Technology60, University of Texas Health Science Center at Houston61, University of California, San Diego62, Universidade Federal do Rio Grande do Sul63, University of Ljubljana64, University of Manchester65, Ikerbasque66
TL;DR: In this article, the authors point out the shortcomings of binary divisions of reactive astrocytes into good-vs-bad, neurotoxic vs-neuroprotective or A1-vs.A2.
Abstract: Reactive astrocytes are astrocytes undergoing morphological, molecular, and functional remodeling in response to injury, disease, or infection of the CNS. Although this remodeling was first described over a century ago, uncertainties and controversies remain regarding the contribution of reactive astrocytes to CNS diseases, repair, and aging. It is also unclear whether fixed categories of reactive astrocytes exist and, if so, how to identify them. We point out the shortcomings of binary divisions of reactive astrocytes into good-vs-bad, neurotoxic-vs-neuroprotective or A1-vs-A2. We advocate, instead, that research on reactive astrocytes include assessment of multiple molecular and functional parameters-preferably in vivo-plus multivariate statistics and determination of impact on pathological hallmarks in relevant models. These guidelines may spur the discovery of astrocyte-based biomarkers as well as astrocyte-targeting therapies that abrogate detrimental actions of reactive astrocytes, potentiate their neuro- and glioprotective actions, and restore or augment their homeostatic, modulatory, and defensive functions.
797 citations
TL;DR: The relative risk of COVID-19-associated death for younger individuals (under 65) is consistent across countries and can be used to robustly compare the underlying number of infections in each country, and the age distribution of deaths in younger age groups is very consistent across different settings.
Abstract: Estimating the size of the coronavirus disease 2019 (COVID-19) pandemic and the infection severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is made challenging by inconsistencies in the available data. The number of deaths associated with COVID-19 is often used as a key indicator for the size of the epidemic, but the observed number of deaths represents only a minority of all infections1,2. In addition, the heterogeneous burdens in nursing homes and the variable reporting of deaths of older individuals can hinder direct comparisons of mortality rates and the underlying levels of transmission across countries3. Here we use age-specific COVID-19-associated death data from 45 countries and the results of 22 seroprevalence studies to investigate the consistency of infection and fatality patterns across multiple countries. We find that the age distribution of deaths in younger age groups (less than 65 years of age) is very consistent across different settings and demonstrate how these data can provide robust estimates of the share of the population that has been infected. We estimate that the infection fatality ratio is lowest among 5-9-year-old children, with a log-linear increase by age among individuals older than 30 years. Population age structures and heterogeneous burdens in nursing homes explain some but not all of the heterogeneity between countries in infection fatality ratios. Among the 45 countries included in our analysis, we estimate that approximately 5% of these populations had been infected by 1 September 2020, and that much higher transmission rates have probably occurred in a number of Latin American countries. This simple modelling framework can help countries to assess the progression of the pandemic and can be applied in any scenario for which reliable age-specific death data are available.
762 citations
TL;DR: In this article, the antibody response following the second dose of SARS-CoV2 mRNA vaccine in recipients of solid organ transplants was measured using a follow-up study.
Abstract: This follow-up study measures the antibody response following the second dose of SARS-CoV-2 mRNA vaccine in recipients of solid organ transplants.
TL;DR: In this paper, the authors present a thorough review of recent Hubble constant estimates and a summary of the proposed theoretical solutions, including early or dynamical dark energy, neutrino interactions, interacting cosmologies, primordial magnetic fields, and modified gravity.
Abstract: The $\Lambda$CDM model provides a good fit to a large span of cosmological data but harbors areas of phenomenology. With the improvement of the number and the accuracy of observations, discrepancies among key cosmological parameters of the model have emerged. The most statistically significant tension is the $4-6\sigma$ disagreement between predictions of the Hubble constant $H_0$ by early time probes with $\Lambda$CDM model, and a number of late time, model-independent determinations of $H_0$ from local measurements of distances and redshifts. The high precision and consistency of the data at both ends present strong challenges to the possible solution space and demand a hypothesis with enough rigor to explain multiple observations--whether these invoke new physics, unexpected large-scale structures or multiple, unrelated errors. We present a thorough review of the problem, including a discussion of recent Hubble constant estimates and a summary of the proposed theoretical solutions. Some of the models presented are formally successful, improving the fit to the data in light of their additional degrees of freedom, restoring agreement within $1-2\sigma$ between {\it Planck} 2018, using CMB power spectra data, BAO, Pantheon SN data, and R20, the latest SH0ES Team measurement of the Hubble constant ($H_0 = 73.2 \pm 1.3{\rm\,km\,s^{-1}\,Mpc^{-1}}$ at 68\% confidence level). Reduced tension might not simply come from a change in $H_0$ but also from an increase in its uncertainty due to degeneracy with additional physics, pointing to the need for additional probes. While no specific proposal makes a strong case for being highly likely or far better than all others, solutions involving early or dynamical dark energy, neutrino interactions, interacting cosmologies, primordial magnetic fields, and modified gravity provide the best options until a better alternative comes along.[Abridged]
Baylor University Medical Center1, University of Texas MD Anderson Cancer Center2, Jagiellonian University Medical College3, University of Cologne4, Katholieke Universiteit Leuven5, Lille University of Science and Technology6, Fundación Favaloro7, Johns Hopkins University8, Akita University9, Duke University10, Princess Margaret Cancer Centre11, Ghent University12, University of California, San Francisco13, Bristol-Myers Squibb14, Harvard University15, University of Mainz16
TL;DR: In this paper, no adjuvant treatment has been established for patients who remain at high risk for recurrence after neoadjuvant chemoradiotherapy and surgery for esophageal or gastroesophageaal...
Abstract: Background No adjuvant treatment has been established for patients who remain at high risk for recurrence after neoadjuvant chemoradiotherapy and surgery for esophageal or gastroesophageal...
Northwestern University1, University of California, San Francisco2, University of Michigan3, City of Hope National Medical Center4, Vanderbilt University5, Seattle Cancer Care Alliance6, Fox Chase Cancer Center7, University of Wisconsin-Madison8, University of Texas Southwestern Medical Center9, University of Utah10, University of Nebraska Medical Center11, University of Alabama at Birmingham12, University of California, Los Angeles13, University of South Florida14, Mayo Clinic15, Washington University in St. Louis16, Yale Cancer Center17, Stanford University18, Case Western Reserve University19, University of Colorado Boulder20, Brigham and Women's Hospital21, Ohio State University22, Roswell Park Cancer Institute23, University of Texas MD Anderson Cancer Center24, Harvard University25, University of California, San Diego26, Memorial Sloan Kettering Cancer Center27, University of Pennsylvania28, University of Tennessee29, Johns Hopkins University30, Duke University31, National Comprehensive Cancer Network32
TL;DR: The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Colon Cancer focuses on systemic therapy options for the treatment of metastatic colorectal cancer (mCRC), because important updates have recently been made to this section as discussed by the authors.
Abstract: This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Colon Cancer focuses on systemic therapy options for the treatment of metastatic colorectal cancer (mCRC), because important updates have recently been made to this section. These updates include recommendations for first-line use of checkpoint inhibitors for mCRC, that is deficient mismatch repair/microsatellite instability-high, recommendations related to the use of biosimilars, and expanded recommendations for biomarker testing. The systemic therapy recommendations now include targeted therapy options for patients with mCRC that is HER2-amplified, or BRAF V600E mutation-positive. Treatment and management of nonmetastatic or resectable/ablatable metastatic disease are discussed in the complete version of the NCCN Guidelines for Colon Cancer available at NCCN.org. Additional topics covered in the complete version include risk assessment, staging, pathology, posttreatment surveillance, and survivorship.
University of Texas MD Anderson Cancer Center1, Cornell University2, Roswell Park Cancer Institute3, University of Adelaide4, Sarah Cannon Research Institute5, University of Cologne6, University of Duisburg-Essen7, German Cancer Research Center8, Fox Chase Cancer Center9, Institut Gustave Roussy10, University of Zurich11, Princess Margaret Cancer Centre12, Johns Hopkins University13, Emory University14, Amgen15, New York University16, Washington University in St. Louis17
TL;DR: Sotorasib showed anticancer activity in patients with KRAS p.G12C-mutated advanced solid tumors in a phase 1 study as discussed by the authors, and particularly promising anti-cancer activity was observed i...
Abstract: Background Sotorasib showed anticancer activity in patients with KRAS p.G12C–mutated advanced solid tumors in a phase 1 study, and particularly promising anticancer activity was observed i...
European Bioinformatics Institute1, Newcastle upon Tyne Hospitals NHS Foundation Trust2, Newcastle University3, Oregon Health & Science University4, University of Genoa5, Istituto Giannina Gaslini6, University of Western Australia7, King Edward Memorial Hospital8, American College of Medical Genetics9, Anschutz Medical Campus10, Johns Hopkins University11, Ludwig Maximilian University of Munich12, Children's Hospital of Philadelphia13, Austrian Academy of Sciences14, University of Connecticut15, French Institute of Health and Medical Research16, Lawrence Berkeley National Laboratory17, University of Michigan18, University of Freiburg19, University of Luxembourg20, Oregon State University21, Chestnut Hill College22, Medical University of Graz23, Queen Mary University of London24, Hebrew University of Jerusalem25, University of Pennsylvania26
TL;DR: Recent major extensions of the Human Phenotype Ontology for neurology, nephrology, immunology, pulmonology, newborn screening, and other areas are presented and new efforts to harmonize computational definitions of phenotypic abnormalities across the HPO and multiple phenotype ontologies used for animal models of disease are presented.
Abstract: The Human Phenotype Ontology (HPO, https://hpo.jax.org) was launched in 2008 to provide a comprehensive logical standard to describe and computationally analyze phenotypic abnormalities found in human disease. The HPO is now a worldwide standard for phenotype exchange. The HPO has grown steadily since its inception due to considerable contributions from clinical experts and researchers from a diverse range of disciplines. Here, we present recent major extensions of the HPO for neurology, nephrology, immunology, pulmonology, newborn screening, and other areas. For example, the seizure subontology now reflects the International League Against Epilepsy (ILAE) guidelines and these enhancements have already shown clinical validity. We present new efforts to harmonize computational definitions of phenotypic abnormalities across the HPO and multiple phenotype ontologies used for animal models of disease. These efforts will benefit software such as Exomiser by improving the accuracy and scope of cross-species phenotype matching. The computational modeling strategy used by the HPO to define disease entities and phenotypic features and distinguish between them is explained in detail.We also report on recent efforts to translate the HPO into indigenous languages. Finally, we summarize recent advances in the use of HPO in electronic health record systems.
Mayo Clinic1, Johns Hopkins University2, Seattle Cancer Care Alliance3, University of Colorado Boulder4, University of Utah5, Fox Chase Cancer Center6, Northwestern University7, Case Western Reserve University8, University of Texas MD Anderson Cancer Center9, Brigham and Women's Hospital10, Duke University11, University of South Florida12, University of Texas Southwestern Medical Center13, Yale Cancer Center14, University of California, San Francisco15, Roswell Park Cancer Institute16, Harvard University17, University of Wisconsin-Madison18, University of Michigan19, Stanford University20, Vanderbilt University21, City of Hope National Medical Center22, Washington University in St. Louis23, University of Tennessee Health Science Center24, Ohio State University25, University of California, San Diego26, Memorial Sloan Kettering Cancer Center27, University of Pennsylvania28, University of California, Los Angeles29, National Comprehensive Cancer Network30
TL;DR: The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer (NSCLC) address all aspects of management for NSCLC as mentioned in this paper.
Abstract: The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer (NSCLC) address all aspects of management for NSCLC. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines regarding targeted therapies, immunotherapies, and their respective biomarkers.
TL;DR: It is hypothesized that age-related decline and dysregulation of immune function, i.e., immunosenescence and inflammaging play a major role in contributing to heightened vulnerability to severe COVID-19 outcomes in older adults and partitioning all immunological outcome data by age to better understand disease heterogeneity and aging.
Centers for Disease Control and Prevention1, United States Public Health Service2, Harvard University3, New York University4, University of Colorado Denver5, University of Texas at Dallas6, Nationwide Children's Hospital7, Johns Hopkins University8, Yale University9, Westchester Medical Center10, Rutgers University11, University of Alabama at Birmingham12, Children's Mercy Hospital13, University of Miami14, University of North Carolina at Chapel Hill15, Baylor College of Medicine16, University of Mississippi17, Vanderbilt University18, SUNY Downstate Medical Center19, California State University, Long Beach20, University of Minnesota21, Saint Barnabas Medical Center22, University of Arkansas for Medical Sciences23, Children's Hospital Oakland Research Institute24, Boston Children's Hospital25, University of Washington26, Central Michigan University27, Icahn School of Medicine at Mount Sinai28, University of Iowa29, Indiana University30, Emory University31, Medical University of South Carolina32, University of Pennsylvania33, Northwestern University34
TL;DR: In this article, the authors compared clinical characteristics and outcomes of children and adolescents with MIS-C vs those with severe coronavirus disease 2019 (COVID-19) at 66 US hospitals in 31 states.
Abstract: Importance Refinement of criteria for multisystem inflammatory syndrome in children (MIS-C) may inform efforts to improve health outcomes. Objective To compare clinical characteristics and outcomes of children and adolescents with MIS-C vs those with severe coronavirus disease 2019 (COVID-19). Setting, Design, and Participants Case series of 1116 patients aged younger than 21 years hospitalized between March 15 and October 31, 2020, at 66 US hospitals in 31 states. Final date of follow-up was January 5, 2021. Patients with MIS-C had fever, inflammation, multisystem involvement, and positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcriptase–polymerase chain reaction (RT-PCR) or antibody test results or recent exposure with no alternate diagnosis. Patients with COVID-19 had positive RT-PCR test results and severe organ system involvement. Exposure SARS-CoV-2. Main Outcomes and Measures Presenting symptoms, organ system complications, laboratory biomarkers, interventions, and clinical outcomes. Multivariable regression was used to compute adjusted risk ratios (aRRs) of factors associated with MIS-C vs COVID-19. Results Of 1116 patients (median age, 9.7 years; 45% female), 539 (48%) were diagnosed with MIS-C and 577 (52%) with COVID-19. Compared with patients with COVID-19, patients with MIS-C were more likely to be 6 to 12 years old (40.8% vs 19.4%; absolute risk difference [RD], 21.4% [95% CI, 16.1%-26.7%]; aRR, 1.51 [95% CI, 1.33-1.72] vs 0-5 years) and non-Hispanic Black (32.3% vs 21.5%; RD, 10.8% [95% CI, 5.6%-16.0%]; aRR, 1.43 [95% CI, 1.17-1.76] vs White). Compared with patients with COVID-19, patients with MIS-C were more likely to have cardiorespiratory involvement (56.0% vs 8.8%; RD, 47.2% [95% CI, 42.4%-52.0%]; aRR, 2.99 [95% CI, 2.55-3.50] vs respiratory involvement), cardiovascular without respiratory involvement (10.6% vs 2.9%; RD, 7.7% [95% CI, 4.7%-10.6%]; aRR, 2.49 [95% CI, 2.05-3.02] vs respiratory involvement), and mucocutaneous without cardiorespiratory involvement (7.1% vs 2.3%; RD, 4.8% [95% CI, 2.3%-7.3%]; aRR, 2.29 [95% CI, 1.84-2.85] vs respiratory involvement). Patients with MIS-C had higher neutrophil to lymphocyte ratio (median, 6.4 vs 2.7,P Conclusions and Relevance This case series of patients with MIS-C and with COVID-19 identified patterns of clinical presentation and organ system involvement. These patterns may help differentiate between MIS-C and COVID-19.
TL;DR: This randomized clinical trial examines the efficacy of psilocybin as an adjunct to psychotherapy and other treatments for major depressive disorder.
Abstract: Importance Major depressive disorder (MDD) is a substantial public health burden, but current treatments have limited effectiveness and adherence. Recent evidence suggests that 1 or 2 administrations of psilocybin with psychological support produces antidepressant effects in patients with cancer and in those with treatment-resistant depression. Objective To investigate the effect of psilocybin therapy in patients with MDD. Design, Setting, and Participants This randomized, waiting list–controlled clinical trial was conducted at the Center for Psychedelic and Consciousness Research at Johns Hopkins Bayview Medical Center in Baltimore, Maryland. Adults aged 21 to 75 years with an MDD diagnosis, not currently using antidepressant medications, and without histories of psychotic disorder, serious suicide attempt, or hospitalization were eligible to participate. Enrollment occurred between August 2017 and April 2019, and the 4-week primary outcome assessments were completed in July 2019. A total of 27 participants were randomized to an immediate treatment condition group (n = 15) or delayed treatment condition group (waiting list control condition; n = 12). Data analysis was conducted from July 1, 2019, to July 31, 2020, and included participants who completed the intervention (evaluable population). Interventions Two psilocybin sessions (session 1: 20 mg/70 kg; session 2: 30 mg/70 kg) were given (administered in opaque gelatin capsules with approximately 100 mL of water) in the context of supportive psychotherapy (approximately 11 hours). Participants were randomized to begin treatment immediately or after an 8-week delay. Main Outcomes and Measures The primary outcome, depression severity was assessed with the GRID-Hamilton Depression Rating Scale (GRID-HAMD) scores at baseline (score of ≥17 required for enrollment) and weeks 5 and 8 after enrollment for the delayed treatment group, which corresponded to weeks 1 and 4 after the intervention for the immediate treatment group. Secondary outcomes included the Quick Inventory of Depressive Symptomatology-Self Rated (QIDS-SR). Results Of the randomized participants, 24 of 27 (89%) completed the intervention and the week 1 and week 4 postsession assessments. This population had a mean (SD) age of 39.8 (12.2) years, was composed of 16 women (67%), and had a mean (SD) baseline GRID-HAMD score of 22.8 (3.9). The mean (SD) GRID-HAMD scores at weeks 1 and 4 (8.0 [7.1] and 8.5 [5.7]) in the immediate treatment group were statistically significantly lower than the scores at the comparable time points of weeks 5 and 8 (23.8 [5.4] and 23.5 [6.0]) in the delayed treatment group. The effect sizes were large at week 5 (Cohend = 2.5; 95% CI, 1.4-3.5;P Conclusions and Relevance Findings suggest that psilocybin with therapy is efficacious in treating MDD, thus extending the results of previous studies of this intervention in patients with cancer and depression and of a nonrandomized study in patients with treatment-resistant depression. Trial Registration ClinicalTrials.gov Identifier:NCT03181529
27 Sep 2021
TL;DR: Jeon et al. as discussed by the authors proposed a gated axial-attention model which extends the existing transformer-based architectures by introducing an additional control mechanism in the selfattention module.
Abstract: Over the past decade, deep convolutional neural networks have been widely adopted for medical image segmentation and shown to achieve adequate performance. However, due to inherent inductive biases present in convolutional architectures, they lack understanding of long-range dependencies in the image. Recently proposed transformer-based architectures that leverage self-attention mechanism encode long-range dependencies and learn representations that are highly expressive. This motivates us to explore transformer-based solutions and study the feasibility of using transformer-based network architectures for medical image segmentation tasks. Majority of existing transformer-based network architectures proposed for vision applications require large-scale datasets to train properly. However, compared to the datasets for vision applications, in medical imaging the number of data samples is relatively low, making it difficult to efficiently train transformers for medical imaging applications. To this end, we propose a gated axial-attention model which extends the existing architectures by introducing an additional control mechanism in the self-attention module. Furthermore, to train the model effectively on medical images, we propose a Local-Global training strategy (LoGo) which further improves the performance. Specifically, we operate on the whole image and patches to learn global and local features, respectively. The proposed Medical Transformer (MedT) is evaluated on three different medical image segmentation datasets and it is shown that it achieves better performance than the convolutional and other related transformer-based architectures. Code: https://github.com/jeya-maria-jose/Medical-Transformer
TL;DR: The biopsychosocial model of chronic pain this paper presents physical symptoms as the denouement of a dynamic interaction between biological, psychological, and social factors, which can be classified as nociceptive (from tissue injury), neuropathic (from nerve injury), or nociplastic (from a sensitised nervous system).
Fox Chase Cancer Center1, Vanderbilt University2, University of Tennessee Health Science Center3, University of Utah4, Washington University in St. Louis5, University of Pennsylvania6, University of Alabama at Birmingham7, Johns Hopkins University8, Roswell Park Cancer Institute9, University of California, Los Angeles10, Northwestern University11, University of Colorado Boulder12, Stanford University13, University of South Florida14, University of Texas MD Anderson Cancer Center15, University of California, San Francisco16, Duke University17, University of Michigan18, Seattle Cancer Care Alliance19, Memorial Sloan Kettering Cancer Center20, Case Western Reserve University21, University of Nebraska Medical Center22, Ohio State University23, Harvard University24, University of California, San Diego25, City of Hope National Medical Center26, Mayo Clinic27, University of Wisconsin-Madison28, Brigham and Women's Hospital29, National Comprehensive Cancer Network30
TL;DR: The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic focus primarily on assessment of pathogenic or likely pathogenic variants associated with increased risk of breast, ovarian, and pancreatic cancer and recommended approaches to genetic testing/counseling and management strategies as mentioned in this paper.
Abstract: The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic focus primarily on assessment of pathogenic or likely pathogenic variants associated with increased risk of breast, ovarian, and pancreatic cancer and recommended approaches to genetic testing/counseling and management strategies in individuals with these pathogenic or likely pathogenic variants. This manuscript focuses on cancer risk and risk management for BRCA-related breast/ovarian cancer syndrome and Li-Fraumeni syndrome. Carriers of a BRCA1/2 pathogenic or likely pathogenic variant have an excessive risk for both breast and ovarian cancer that warrants consideration of more intensive screening and preventive strategies. There is also evidence that risks of prostate cancer and pancreatic cancer are elevated in these carriers. Li-Fraumeni syndrome is a highly penetrant cancer syndrome associated with a high lifetime risk for cancer, including soft tissue sarcomas, osteosarcomas, premenopausal breast cancer, colon cancer, gastric cancer, adrenocortical carcinoma, and brain tumors.
TL;DR: In this article, an expanded sample of 75 Milky Way Cepheids with Hubble Space Telescope (HST) photometry and Gaia EDR3 parallaxes were used to recalibrate the extragalactic distance ladder and refine the determination of the Hubble constant.
Abstract: We present an expanded sample of 75 Milky Way Cepheids with Hubble Space Telescope (HST) photometry and Gaia EDR3 parallaxes which we use to recalibrate the extragalactic distance ladder and refine the determination of the Hubble constant All HST observations were obtained with the same instrument (WFC3) and filters (F555W, F814W, F160W) used for imaging of extragalactic Cepheids in Type Ia supernova (SN Ia) hosts The HST observations used the WFC3 spatial scanning mode to mitigate saturation and reduce pixel-to-pixel calibration errors, reaching a mean photometric error of 5 millimags per observation We use new Gaia EDR3 parallaxes, vastly improved since DR2, and the Period-Luminosity (PL) relation of these Cepheids to simultaneously calibrate the extragalactic distance ladder and to refine the determination of the Gaia EDR3 parallax offset The resulting geometric calibration of Cepheid luminosities has 10% precision, better than any alternative geometric anchor Applied to the calibration of SNe~Ia, it results in a measurement of the Hubble constant of 730 +/- 14 km/sec/Mpc, in good agreement with conclusions based on earlier Gaia data releases We also find the slope of the Cepheid PL relation in the Milky Way, and the metallicity dependence of its zeropoint, to be in good agreement with the mean values derived from other galaxies In combination with the best complementary sources of Cepheid calibration, we reach 18% precision and find H_0=732 +/- 13 km/sec/Mpc, a 42 sigma difference with the prediction from Planck CMB observations under LambdaCDM We expect to reach ~13% precision in the near term from an expanded sample of ~40 SNe Ia in Cepheid hosts
TL;DR: The literature review focuses primarily on U.S.-based studies of adults with diabetes and on key definitions and SDOH frameworks, and concludes with recommendations for linkages across health care and community sectors from national advisory committees, recommendations for diabetes research, and recommendations for research to inform practice.
Abstract: Decades of research have demonstrated that diabetes affects racial and ethnic minority and low-income adult populations in the U.S. disproportionately, with relatively intractable patterns seen in these populations’ higher risk of diabetes and rates of diabetes complications and mortality (1). With a health care shift toward greater emphasis on population health outcomes and value-based care, social determinants of health (SDOH) have risen to the forefront as essential intervention targets to achieve health equity (2–4). Most recently, the COVID-19 pandemic has highlighted unequal vulnerabilities borne by racial and ethnic minority groups and by disadvantaged communities. In the wake of concurrent pandemic and racial injustice events in the U.S., the American College of Physicians, American Academy of Pediatrics, Society of General Internal Medicine, National Academy of Medicine, and other professional organizations have published statements on SDOH (5–8), and calls to action focus on amelioration of these determinants at individual, organizational, and policy levels (9–11).
In diabetes, understanding and mitigating the impact of SDOH are priorities due to disease prevalence, economic costs, and disproportionate population burden (12–14). In 2013, the American Diabetes Association (ADA) published a scientific statement on socioecological determinants of prediabetes and type 2 diabetes (15). Toward the goal ofunderstanding and advancing opportunities for health improvement among the population with diabetes through addressing SDOH, ADA convened the current SDOH and diabetes writing committee, prepandemic, to review the literature on 1 ) associations of SDOH with diabetes risk and outcomes and 2 ) impact of interventions targeting amelioration of SDOH on diabetes outcomes. This article begins with an overview of key definitions and SDOH frameworks. The literature review focuses primarily on U.S.-based studies of adults with diabetes and on five SDOH: socioeconomic status (education, income, occupation); neighborhood and physical environment (housing, built environment, toxic environmental …
University of London1, National Institute for Health Research2, University of Auckland3, University of Cambridge4, Anglia Ruskin University5, Sun Yat-sen University6, Queen's University Belfast7, The Fred Hollows Foundation8, Mbarara University of Science and Technology9, Ministry of Health and Family Welfare10, University of Geneva11, St Thomas' Hospital12, Leeds Teaching Hospitals NHS Trust13, Southwest University of Visual Arts14, Orbis International15, International Agency for the Prevention of Blindness16, University of Cape Town17, University Hospitals Birmingham NHS Foundation Trust18, University of Michigan19, Emory University20, Johns Hopkins University21, Massachusetts Eye and Ear Infirmary22, University of São Paulo23, University of Nairobi24, Seva Foundation25, Tilganga Institute of Ophthalmology26, Heidelberg University27, The George Institute for Global Health28, University of New South Wales29, L V Prasad Eye Institute30, College of Health Sciences, Bahrain31, Muhimbili University of Health and Allied Sciences32, International Institute of Minnesota33, University of the West Indies34, University of Melbourne35, Kenya Medical Training College36, Federal University of São Paulo37, Capital Medical University38, Singapore National Eye Center39, National University of Singapore40, Pan American Health Organization41, Brien Holden Vision Institute42, University of Calabar43
TL;DR: In this paper, the authors defined eye health as maximised vision, ocular health, and functional ability, thereby contributing to overall health and wellbeing, social inclusion, and quality of life.
Centre for Mental Health1, Swansea University2, University of Sydney3, University of Manchester4, Griffith University5, University College Cork6, Stellenbosch University7, Sao Paulo State University8, University of Zagreb9, University of Rochester Medical Center10, University of Udine11, National Taiwan University12, Innsbruck Medical University13, Yale University14, Australian National University15, Johns Hopkins University16, Brigham and Women's Hospital17, University of Auckland18, Hobart Corporation19, Columbia University Medical Center20, University of Oxford21, National Institute for Health Research22, Aga Khan University23, Katholieke Universiteit Leuven24, University of Peradeniya25, University of Bristol26, World Health Organization27, Karolinska Institutet28, First Pavlov State Medical University of St. Peterburg29, Medical University of Vienna30, University of Nottingham31, University of Glasgow32, University of Edinburgh33, Columbia University34, Shanghai Jiao Tong University35, University of Ulm36, University of Oslo37, Goethe University Frankfurt38, Saint Petersburg State University39, University of Toronto40, Sunnybrook Health Sciences Centre41, Waseda University42, Rajarata University of Sri Lanka43, Tel Aviv University44, University Hospitals Bristol NHS Foundation Trust45
TL;DR: In this article, the early effect of the COVID-19 pandemic on suicide rates around the world was assessed using real-time suicide data from countries or areas within countries through a systematic internet search and recourse to our networks and the published literature.
TL;DR: In this article, the authors quantified antispike protein antibody responses to first-dose messenger RNA (mRNA) COVID-19 vaccines in solid organ transplant recipients to better understand the immunogenicity of the vaccines in immunocompromised individuals.
Abstract: This study quantifies antispike protein antibody responses to first-dose messenger RNA (mRNA) COVID-19 vaccines in solid organ transplant recipients to better understand the immunogenicity of the vaccines in immunocompromised individuals.
University of California, San Francisco1, University of South Florida2, University of Michigan3, University of Tennessee Health Science Center4, Northwestern University5, Vanderbilt University6, Seattle Cancer Care Alliance7, City of Hope National Medical Center8, Duke University9, University of Colorado Boulder10, Ohio State University11, University of California, Los Angeles12, Fox Chase Cancer Center13, Harvard University14, Roswell Park Cancer Institute15, Case Western Reserve University16, Washington University in St. Louis17, University of Nebraska Medical Center18, Yale Cancer Center19, University of Wisconsin-Madison20, University of California, San Diego21, Pancreatic Cancer Action Network22, Johns Hopkins University23, University of Texas Southwestern Medical Center24, University of Alabama at Birmingham25, Memorial Sloan Kettering Cancer Center26, University of Utah27, Stanford University28, University of Pennsylvania29, University of Texas MD Anderson Cancer Center30, Brigham and Women's Hospital31, National Comprehensive Cancer Network32
Abstract: Pancreatic cancer is the fourth leading cause of cancer-related death among men and women in the United States. A major challenge in treatment remains patients' advanced disease at diagnosis. The NCCN Guidelines for Pancreatic Adenocarcinoma provides recommendations for the diagnosis, evaluation, treatment, and follow-up for patients with pancreatic cancer. Although survival rates remain relatively unchanged, newer modalities of treatment, including targeted therapies, provide hope for improving patient outcomes. Sections of the manuscript have been updated to be concordant with the most recent update to the guidelines. This manuscript focuses on the available systemic therapy approaches, specifically the treatment options for locally advanced and metastatic disease.