Showing papers by "Northwestern University 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 Quality assurance efforts have been ramped up to address potentially out-of-date or inaccurate annotations.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
University of Oklahoma1, University of Vermont2, University of Missouri–Kansas City3, Children's Mercy Hospital4, Boston Children's Hospital5, Harvard University6, University of North Carolina at Chapel Hill7, Ohio University8, American Academy of Pediatrics9, University of Cincinnati10, Cincinnati Children's Hospital Medical Center11, American Academy of Family Physicians12, Centers for Disease Control and Prevention13, Vanderbilt University14, American Academy of Child and Adolescent Psychiatry15, Northwestern University16
TL;DR: Attention-deficit/hyperactivity disorder (ADHD) is the most common neurobehavioral disorder of childhood and can profoundly affect the academic achievement, well-being, and social interactions of children.
Abstract: Attention-deficit/hyperactivity disorder (ADHD) is the most common neurobehavioral disorder of childhood and can profoundly affect the academic achievement, well-being, and social interactions of children; the American Academy of Pediatrics first published clinical recommendations for the diagnosis and evaluation of ADHD in children in 2000; recommendations for treatment followed in 2001.
1,657 citations
Harvard University1, University of Glasgow2, University of Minnesota3, Fudan University4, National University of Cordoba5, Baylor University Medical Center6, University Medical Center Groningen7, Université de Montréal8, Medical University of South Carolina9, University of Lorraine10, University of Barcelona11, Northwestern University12, Charité13, University of Groningen14, Cardiovascular Institute of the South15, University of São Paulo16, Semmelweis University17, Novartis18
TL;DR: Sacubitril-valsartan did not result in a significantly lower rate of total hospitalizations for heart failure and death from cardiovascular causes among patients with heart failureand an ejection fraction of 45% or higher, and among 12 prespecified subgroups, there was suggestion of heterogeneity with possible benefit in patients with lower ejection fractions and in women.
Abstract: Background The angiotensin receptor–neprilysin inhibitor sacubitril–valsartan led to a reduced risk of hospitalization for heart failure or death from cardiovascular causes among patients ...
1,306 citations
Roswell Park Cancer Institute1, Johns Hopkins University2, Duke University3, Brigham and Women's Hospital4, Mayo Clinic5, City of Hope National Medical Center6, Memorial Sloan Kettering Cancer Center7, Fred Hutchinson Cancer Research Center8, Fox Chase Cancer Center9, Yale Cancer Center10, Washington University in St. Louis11, University of California, San Diego12, University of Wisconsin-Madison13, University Hospitals of Cleveland14, University of Alabama at Birmingham15, Vanderbilt University16, Moffitt Cancer Center17, University of Colorado Boulder18, University of Tennessee Health Science Center19, University of California, San Francisco20, Northwestern University21, Ohio State University22, University of Michigan23, Stanford University24, University of Utah25, National Comprehensive Cancer Network26
TL;DR: The NCCN Guidelines for Prostate Cancer include recommendations regarding diagnosis, risk stratification and workup, treatment options for localized disease, and management of recurrent and advanced disease for clinicians who treat patients with prostate cancer.
Abstract: The NCCN Guidelines for Prostate Cancer include recommendations regarding diagnosis, risk stratification and workup, treatment options for localized disease, and management of recurrent and advanced disease for clinicians who treat patients with prostate cancer. The portions of the guidelines included herein focus on the roles of germline and somatic genetic testing, risk stratification with nomograms and tumor multigene molecular testing, androgen deprivation therapy, secondary hormonal therapy, chemotherapy, and immunotherapy in patients with prostate cancer.
1,218 citations
17 Jul 2019
TL;DR: Zhang et al. as discussed by the authors proposed a Text Graph Convolutional Network (Text GCN) for text classification, which jointly learns the embeddings for both words and documents, as supervised by the known class labels for documents.
Abstract: Text classification is an important and classical problem in natural language processing. There have been a number of studies that applied convolutional neural networks (convolution on regular grid, e.g., sequence) to classification. However, only a limited number of studies have explored the more flexible graph convolutional neural networks (convolution on non-grid, e.g., arbitrary graph) for the task. In this work, we propose to use graph convolutional networks for text classification. We build a single text graph for a corpus based on word co-occurrence and document word relations, then learn a Text Graph Convolutional Network (Text GCN) for the corpus. Our Text GCN is initialized with one-hot representation for word and document, it then jointly learns the embeddings for both words and documents, as supervised by the known class labels for documents. Our experimental results on multiple benchmark datasets demonstrate that a vanilla Text GCN without any external word embeddings or knowledge outperforms state-of-the-art methods for text classification. On the other hand, Text GCN also learns predictive word and document embeddings. In addition, experimental results show that the improvement of Text GCN over state-of-the-art comparison methods become more prominent as we lower the percentage of training data, suggesting the robustness of Text GCN to less training data in text classification.
1,215 citations
University of Texas MD Anderson Cancer Center1, Johns Hopkins University2, City of Hope National Medical Center3, University of California, Davis4, Emory University5, University of Washington6, Fred Hutchinson Cancer Research Center7, Northwestern University8, Monash University9, AbbVie10, Genentech11, University of Colorado Denver12, Harvard University13
TL;DR: The novel combination of venetoclax with decitabine or azacitidine was effective and well tolerated in elderly patients with AML and achieved complete remission (CR) + CR with incomplete count recovery (CRi).
1,153 citations
Dresden University of Technology1, Brigham and Women's Hospital2, University of California, San Francisco3, University of Düsseldorf4, University of Pisa5, Northwestern University6, Medical University of Vienna7, National and Kapodistrian University of Athens8, Medical University of South Carolina9, University of Cambridge10, University of Barcelona11, The Feinstein Institute for Medical Research12, Toronto Western Hospital13, University of California, Los Angeles14, Humboldt University of Berlin15, Copenhagen University Hospital16, University of Michigan17, University of the Basque Country18, University Health Network19, University of Crete20, University of Zagreb21, University of Paris-Sud22, University of Hong Kong23, University of Calgary24, Hospital for Special Surgery25, University of Pécs26, University of Padua27, Medical University of Graz28, National Institutes of Health29, New York University30, Université Paris-Saclay31, University Hospital Complex Of Vigo32, University of Occupational and Environmental Health Japan33, University of Porto34, Leeds Teaching Hospitals NHS Trust35, Cedars-Sinai Medical Center36, Istanbul Bilim University37, McMaster University38
TL;DR: To develop new classification criteria for systemic lupus erythematosus (SLE) jointly supported by the European League Against Rheumatism and the American College of Rheumatology (ACR).
Abstract: Objective To develop new classification criteria for systemic lupus erythematosus (SLE) jointly supported by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). Methods This international initiative had four phases. 1) Evaluation of antinuclear antibody (ANA) as an entry criterion through systematic review and meta-regression of the literature and criteria generation through an international Delphi exercise, an early patient cohort, and a patient survey. 2) Criteria reduction by Delphi and nominal group technique exercises. 3) Criteria definition and weighting based on criterion performance and on results of a multi-criteria decision analysis. 4) Refinement of weights and threshold scores in a new derivation cohort of 1,001 subjects and validation compared with previous criteria in a new validation cohort of 1,270 subjects. Results The 2019 EULAR/ACR classification criteria for SLE include positive ANA at least once as obligatory entry criterion; followed by additive weighted criteria grouped in 7 clinical (constitutional, hematologic, neuropsychiatric, mucocutaneous, serosal, musculoskeletal, renal) and 3 immunologic (antiphospholipid antibodies, complement proteins, SLE-specific antibodies) domains, and weighted from 2 to 10. Patients accumulating ≥10 points are classified. In the validation cohort, the new criteria had a sensitivity of 96.1% and specificity of 93.4%, compared with 82.8% sensitivity and 93.4% specificity of the ACR 1997 and 96.7% sensitivity and 83.7% specificity of the Systemic Lupus International Collaborating Clinics 2012 criteria. Conclusion These new classification criteria were developed using rigorous methodology with multidisciplinary and international input, and have excellent sensitivity and specificity. Use of ANA entry criterion, hierarchically clustered, and weighted criteria reflects current thinking about SLE and provides an improved foundation for SLE research.
1,018 citations
University of Washington1, California Institute of Technology2, Stockholm University3, University of Maryland, College Park4, Humboldt University of Berlin5, Goddard Space Flight Center6, National Central University7, Weizmann Institute of Science8, Macau University of Science and Technology9, Tel Aviv University10, University of California, Santa Barbara11, University of Michigan12, Adler Planetarium13, Northwestern University14, Lawrence Berkeley National Laboratory15, University of California, Berkeley16, Soka University of America17, Centre national de la recherche scientifique18, Radboud University Nijmegen19, University of Wisconsin–Milwaukee20, Los Alamos National Laboratory21
TL;DR: The Zwicky Transient Facility (ZTF) as mentioned in this paper is a new optical time-domain survey that uses the Palomar 48 inch Schmidt telescope, which provides a 47 deg^2 field of view and 8 s readout time, yielding more than an order of magnitude improvement in survey speed relative to its predecessor survey.
Abstract: The Zwicky Transient Facility (ZTF) is a new optical time-domain survey that uses the Palomar 48 inch Schmidt telescope. A custom-built wide-field camera provides a 47 deg^2 field of view and 8 s readout time, yielding more than an order of magnitude improvement in survey speed relative to its predecessor survey, the Palomar Transient Factory. We describe the design and implementation of the camera and observing system. The ZTF data system at the Infrared Processing and Analysis Center provides near-real-time reduction to identify moving and varying objects. We outline the analysis pipelines, data products, and associated archive. Finally, we present on-sky performance analysis and first scientific results from commissioning and the early survey. ZTF's public alert stream will serve as a useful precursor for that of the Large Synoptic Survey Telescope.
1,009 citations
TL;DR: The major risk factors for hepatocellular carcinoma (HCC) in contemporary clinical practice are becoming increasingly related to sustained virological response after hepatitis C, suppressed hepatitis B virus during treatment, and alcoholic and nonalcoholic fatty liver disease.
958 citations
University of California, Los Angeles1, University of Mississippi Medical Center2, Fred Hutchinson Cancer Research Center3, Rutgers University4, Public Health England5, Northwestern University6, Columbia University7, University of North Carolina at Chapel Hill8, Stanford University9, National Institutes of Health10
TL;DR: Using large scale validation data from thousands of individuals, it is demonstrated that DNAm GrimAge stands out among existing epigenetic clocks in terms of its predictive ability for time-to-death, and a novel measure of epigenetic age acceleration, AgeAccelGrim.
Abstract: It was unknown whether plasma protein levels can be estimated based on DNA methylation (DNAm) levels, and if so, how the resulting surrogates can be consolidated into a powerful predictor of lifespan. We present here, seven DNAm-based estimators of plasma proteins including those of plasminogen activator inhibitor 1 (PAI-1) and growth differentiation factor 15. The resulting predictor of lifespan, DNAm GrimAge (in units of years), is a composite biomarker based on the seven DNAm surrogates and a DNAm-based estimator of smoking pack-years. Adjusting DNAm GrimAge for chronological age generated novel measure of epigenetic age acceleration, AgeAccelGrim.Using large scale validation data from thousands of individuals, we demonstrate that DNAm GrimAge stands out among existing epigenetic clocks in terms of its predictive ability for time-to-death (Cox regression P=2.0E-75), time-to-coronary heart disease (Cox P=6.2E-24), time-to-cancer (P= 1.3E-12), its strong relationship with computed tomography data for fatty liver/excess visceral fat, and age-at-menopause (P=1.6E-12). AgeAccelGrim is strongly associated with a host of age-related conditions including comorbidity count (P=3.45E-17). Similarly, age-adjusted DNAm PAI-1 levels are associated with lifespan (P=5.4E-28), comorbidity count (P= 7.3E-56) and type 2 diabetes (P=2.0E-26). These DNAm-based biomarkers show the expected relationship with lifestyle factors including healthy diet and educational attainment.Overall, these epigenetic biomarkers are expected to find many applications including human anti-aging studies.
903 citations
TL;DR: This Perspective begins with a historical flashback to early reports before the "perovskite fever", and follows this original work to its fruition in the present day, where 2D halide perovskites are in the spotlight of current research, offering characteristics desirable in high-performance optoelectronics.
Abstract: Hybrid halide perovskites have become the “next big thing” in emerging semiconductor materials, as the past decade witnessed their successful application in high-performance photovoltaics. This resurgence has encompassed enormous and widespread development of the three-dimensional (3D) perovskites, spearheaded by CH3NH3PbI3. The next generation of halide perovskites, however, is characterized by reduced dimensionality perovskites, emphasizing the two-dimensional (2D) perovskite derivatives which expand the field into a more diverse subgroup of semiconducting hybrids that possesses even higher tunability and excellent photophysical properties. In this Perspective, we begin with a historical flashback to early reports before the “perovskite fever”, and we follow this original work to its fruition in the present day, where 2D halide perovskites are in the spotlight of current research, offering characteristics desirable in high-performance optoelectronics. We approach the evolution of 2D halide perovskites f...
TL;DR: It is argued that systematic reviews are a key methodology for clarifying whether and how research findings replicate and for explaining possible inconsistencies, and it is called for researchers to conduct systematic reviews to help elucidate whether there is a replication crisis.
Abstract: Systematic reviews are characterized by a methodical and replicable methodology and presentation. They involve a comprehensive search to locate all relevant published and unpublished work on a subject; a systematic integration of search results; and a critique of the extent, nature, and quality of evidence in relation to a particular research question. The best reviews synthesize studies to draw broad theoretical conclusions about what a literature means, linking theory to evidence and evidence to theory. This guide describes how to plan, conduct, organize, and present a systematic review of quantitative (meta-analysis) or qualitative (narrative review, meta-synthesis) information. We outline core standards and principles and describe commonly encountered problems. Although this guide targets psychological scientists, its high level of abstraction makes it potentially relevant to any subject area or discipline. We argue that systematic reviews are a key methodology for clarifying whether and how research findings replicate and for explaining possible inconsistencies, and we call for researchers to conduct systematic reviews to help elucidate whether there is a replication crisis.
TL;DR: The results support the feasibility of discovery-based approaches using next-generation sequencing technologies to identify signaling pathways for targeting in the development of personalized therapies for patients with pulmonary fibrosis.
Abstract: Rationale: The contributions of diverse cell populations in the human lung to pulmonary fibrosis pathogenesis are poorly understood. Single-cell RNA sequencing can reveal changes within individual cell populations during pulmonary fibrosis that are important for disease pathogenesis. Objectives: To determine whether single-cell RNA sequencing can reveal disease-related heterogeneity within alveolar macrophages, epithelial cells, or other cell types in lung tissue from subjects with pulmonary fibrosis compared with control subjects. Methods: We performed single-cell RNA sequencing on lung tissue obtained from eight transplant donors and eight recipients with pulmonary fibrosis and on one bronchoscopic cryobiospy sample from a patient with idiopathic pulmonary fibrosis. We validated these data using in situ RNA hybridization, immunohistochemistry, and bulk RNA-sequencing on flow-sorted cells from 22 additional subjects. Measurements and Main Results: We identified a distinct, novel population of profibrotic alveolar macrophages exclusively in patients with fibrosis. Within epithelial cells, the expression of genes involved in Wnt secretion and response was restricted to nonoverlapping cells. We identified rare cell populations including airway stem cells and senescent cells emerging during pulmonary fibrosis. We developed a web-based tool to explore these data. Conclusions: We generated a single-cell atlas of pulmonary fibrosis. Using this atlas, we demonstrated heterogeneity within alveolar macrophages and epithelial cells from subjects with pulmonary fibrosis. These results support the feasibility of discovery-based approaches using next-generation sequencing technologies to identify signaling pathways for targeting in the development of personalized therapies for patients with pulmonary fibrosis.
TL;DR: This review summarizes the latest advances in this emerging field of "bio-integrated" technologies in a comprehensive manner that connects fundamental developments in chemistry, material science, and engineering with sensing technologies that have the potential for widespread deployment and societal benefit in human health care.
Abstract: Bio-integrated wearable systems can measure a broad range of biophysical, biochemical, and environmental signals to provide critical insights into overall health status and to quantify human performance. Recent advances in material science, chemical analysis techniques, device designs, and assembly methods form the foundations for a uniquely differentiated type of wearable technology, characterized by noninvasive, intimate integration with the soft, curved, time-dynamic surfaces of the body. This review summarizes the latest advances in this emerging field of “bio-integrated” technologies in a comprehensive manner that connects fundamental developments in chemistry, material science, and engineering with sensing technologies that have the potential for widespread deployment and societal benefit in human health care. An introduction to the chemistries and materials for the active components of these systems contextualizes essential design considerations for sensors and associated platforms that appear in f...
TL;DR: In this paper, the authors improved initial estimates of the binary's properties, including component masses, spins, and tidal parameters, using the known source location, improved modeling, and recalibrated Virgo data.
Abstract: On August 17, 2017, the Advanced LIGO and Advanced Virgo gravitational-wave detectors observed a low-mass compact binary inspiral. The initial sky localization of the source of the gravitational-wave signal, GW170817, allowed electromagnetic observatories to identify NGC 4993 as the host galaxy. In this work, we improve initial estimates of the binary's properties, including component masses, spins, and tidal parameters, using the known source location, improved modeling, and recalibrated Virgo data. We extend the range of gravitational-wave frequencies considered down to 23 Hz, compared to 30 Hz in the initial analysis. We also compare results inferred using several signal models, which are more accurate and incorporate additional physical effects as compared to the initial analysis. We improve the localization of the gravitational-wave source to a 90% credible region of 16 deg2. We find tighter constraints on the masses, spins, and tidal parameters, and continue to find no evidence for nonzero component spins. The component masses are inferred to lie between 1.00 and 1.89 M when allowing for large component spins, and to lie between 1.16 and 1.60 M (with a total mass 2.73-0.01+0.04 M) when the spins are restricted to be within the range observed in Galactic binary neutron stars. Using a precessing model and allowing for large component spins, we constrain the dimensionless spins of the components to be less than 0.50 for the primary and 0.61 for the secondary. Under minimal assumptions about the nature of the compact objects, our constraints for the tidal deformability parameter Λ are (0,630) when we allow for large component spins, and 300-230+420 (using a 90% highest posterior density interval) when restricting the magnitude of the component spins, ruling out several equation-of-state models at the 90% credible level. Finally, with LIGO and GEO600 data, we use a Bayesian analysis to place upper limits on the amplitude and spectral energy density of a possible postmerger signal.
University of Texas MD Anderson Cancer Center1, Duke University2, Northwestern University3, City of Hope National Medical Center4, University of California, San Francisco5, Fox Chase Cancer Center6, Brigham and Women's Hospital7, University of California, San Diego8, Fred Hutchinson Cancer Research Center9, Memorial Sloan Kettering Cancer Center10, Vanderbilt University11, University of Utah12, University of Michigan13, Roswell Park Cancer Institute14, Mayo Clinic15, Yale Cancer Center16, Johns Hopkins University17, University of Colorado Boulder18, University of Wisconsin-Madison19, University Hospitals of Cleveland20, Washington University in St. Louis21, Ohio State University22, University of South Florida23, Stanford University24, University of Pennsylvania25, Harvard University26, National Comprehensive Cancer Network27
TL;DR: This selection from the NCCN Guidelines for Esophageal and Esophagogastric Junction Cancers focuses on recommendations for the management of locally advanced and metastatic adenocarcinoma of the esophagus and EGJ.
Abstract: Esophageal cancer is the sixth leading cause of cancer-related deaths worldwide. Squamous cell carcinoma is the most common histology in Eastern Europe and Asia, and adenocarcinoma is most common in North America and Western Europe. Surgery is a major component of treatment of locally advanced resectable esophageal and esophagogastric junction (EGJ) cancer, and randomized trials have shown that the addition of preoperative chemoradiation or perioperative chemotherapy to surgery significantly improves survival. Targeted therapies including trastuzumab, ramucirumab, and pembrolizumab have produced encouraging results in the treatment of patients with advanced or metastatic disease. Multidisciplinary team management is essential for all patients with esophageal and EGJ cancers. This selection from the NCCN Guidelines for Esophageal and Esophagogastric Junction Cancers focuses on recommendations for the management of locally advanced and metastatic adenocarcinoma of the esophagus and EGJ.
TL;DR: These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community providing the theory and key practical aspects offlow cytometry enabling immunologists to avoid the common errors that often undermine immunological data.
Abstract: These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells. The latest flow cytometry techniques and applications are also described, featuring examples of the data that can be generated and, importantly, how the data can be analysed. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid, all written and peer-reviewed by leading experts in the field, making this an essential research companion.
Seattle Cancer Care Alliance1, Memorial Sloan Kettering Cancer Center2, Duke University3, University of Wisconsin-Madison4, Brigham and Women's Hospital5, University of Michigan6, University of South Florida7, Fox Chase Cancer Center8, Harvard University9, Ohio State University10, Vanderbilt University11, Yale Cancer Center12, Stanford University13, University of Texas MD Anderson Cancer Center14, University of Colorado Boulder15, Roswell Park Cancer Institute16, University of Utah17, City of Hope National Medical Center18, University of Alabama at Birmingham19, Northwestern University20, Mayo Clinic21, Washington University in St. Louis22, Case Western Reserve University23, Johns Hopkins University24, University of Nebraska Medical Center25, University of Tennessee Health Science Center26, University of California, San Francisco27, University of California, San Diego28, National Comprehensive Cancer Network29
TL;DR: This manuscript discusses guiding principles for the workup, staging, and treatment of early stage and locally advanced cervical cancer, as well as evidence for these recommendations.
Abstract: Cervical cancer is a malignant epithelial tumor that forms in the uterine cervix. Most cases of cervical cancer are preventable through human papilloma virus (HPV) vaccination, routine screening, and treatment of precancerous lesions. However, due to inadequate screening protocols in many regions of the world, cervical cancer remains the fourth-most common cancer in women globally. The complete NCCN Guidelines for Cervical Cancer provide recommendations for the diagnosis, evaluation, and treatment of cervical cancer. This manuscript discusses guiding principles for the workup, staging, and treatment of early stage and locally advanced cervical cancer, as well as evidence for these recommendations. For recommendations regarding treatment of recurrent or metastatic disease, please see the full guidelines on NCCN.org.
Brigham and Women's Hospital1, Barts Health NHS Trust2, Hospital for Special Surgery3, Cornell University4, University of Rochester Medical Center5, University of Alabama at Birmingham6, University of Massachusetts Medical School7, Broad Institute8, University of California, San Diego9, Northwestern University10, The Feinstein Institute for Medical Research11, University of Pittsburgh12, Queen Mary University of London13, University Hospitals Birmingham NHS Foundation Trust14, University of Colorado Denver15
TL;DR: Several single-cell -omics approaches are used to define the cellular processes and pathways in the human RA joint and attributed IL6 expression to THY1+HLA-DRAhi fibroblasts and IL1B production to pro-inflammatory monocytes, potentially key mediators of RA pathogenesis.
Abstract: To define the cell populations that drive joint inflammation in rheumatoid arthritis (RA), we applied single-cell RNA sequencing (scRNA-seq), mass cytometry, bulk RNA sequencing (RNA-seq) and flow cytometry to T cells, B cells, monocytes, and fibroblasts from 51 samples of synovial tissue from patients with RA or osteoarthritis (OA). Utilizing an integrated strategy based on canonical correlation analysis of 5,265 scRNA-seq profiles, we identified 18 unique cell populations. Combining mass cytometry and transcriptomics revealed cell states expanded in RA synovia: THY1(CD90)+HLA-DRAhi sublining fibroblasts, IL1B+ pro-inflammatory monocytes, ITGAX+TBX21+ autoimmune-associated B cells and PDCD1+ peripheral helper T (TPH) cells and follicular helper T (TFH) cells. We defined distinct subsets of CD8+ T cells characterized by GZMK+, GZMB+, and GNLY+ phenotypes. We mapped inflammatory mediators to their source cell populations; for example, we attributed IL6 expression to THY1+HLA-DRAhi fibroblasts and IL1B production to pro-inflammatory monocytes. These populations are potentially key mediators of RA pathogenesis.
Dresden University of Technology1, Brigham and Women's Hospital2, University of California, San Francisco3, University of Düsseldorf4, University of Pisa5, Northwestern University6, Medical University of Vienna7, National and Kapodistrian University of Athens8, University of Cyprus9, Medical University of South Carolina10, University of Cambridge11, University of Barcelona12, University Health Network13, The Feinstein Institute for Medical Research14, Toronto Western Hospital15, University of California, Los Angeles16, Humboldt University of Berlin17, Copenhagen University Hospital18, University of Michigan19, Harvard University20, University of the Basque Country21, University of Crete22, University of Kiel23, University Hospital Centre Zagreb24, University of Paris-Sud25, University of Hong Kong26, University of Calgary27, Hospital for Special Surgery28, University of Pécs29, University of Padua30, Medical University of Graz31, National Institutes of Health32, New York University33, Université Paris-Saclay34, University Hospital Complex Of Vigo35, University of Occupational and Environmental Health Japan36, University of Porto37, Leeds Teaching Hospitals NHS Trust38, University of Leeds39, Cedars-Sinai Medical Center40, Istanbul Bilim University41, McMaster University42, University of Paris43, University of Toronto44
TL;DR: These new classification criteria for systemic lupus erythematosus have excellent sensitivity and specificity, and were developed using rigorous methodology with multidisciplinary and international input.
Abstract: Objective To develop new classification criteria for systemic lupus erythematosus (SLE) jointly supported by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). Methods This international initiative had four phases. (1) Evaluation of antinuclear antibody (ANA) as an entry criterion through systematic review and meta-regression of the literature and criteria generation through an international Delphi exercise, an early patient cohort and a patient survey. (2) Criteria reduction by Delphi and nominal group technique exercises. (3) Criteria definition and weighting based on criterion performance and on results of a multi-criteria decision analysis. (4) Refinement of weights and threshold scores in a new derivation cohort of 1001 subjects and validation compared with previous criteria in a new validation cohort of 1270 subjects. Results The 2019 EULAR/ACR classification criteria for SLE include positive ANA at least once as obligatory entry criterion; followed by additive weighted criteria grouped in seven clinical (constitutional, haematological, neuropsychiatric, mucocutaneous, serosal, musculoskeletal, renal) and three immunological (antiphospholipid antibodies, complement proteins, SLE-specific antibodies) domains, and weighted from 2 to 10. Patients accumulating ≥10 points are classified. In the validation cohort, the new criteria had a sensitivity of 96.1% and specificity of 93.4%, compared with 82.8% sensitivity and 93.4% specificity of the ACR 1997 and 96.7% sensitivity and 83.7% specificity of the Systemic Lupus International Collaborating Clinics 2012 criteria. Conclusion These new classification criteria were developed using rigorous methodology with multidisciplinary and international input, and have excellent sensitivity and specificity. Use of ANA entry criterion, hierarchically clustered and weighted criteria reflect current thinking about SLE and provide an improved foundation for SLE research.
Kavli Institute for Theoretical Physics1, Polish Academy of Sciences2, University of California, Santa Cruz3, University of California, Santa Barbara4, Princeton University5, York University6, Harvard University7, University of Amsterdam8, State University of New York at Oswego9, Northwestern University10, University of Liège11, University of Wisconsin-Madison12, Arizona State University13, University of Wisconsin–Eau Claire14, California Institute of Technology15
TL;DR: In this paper, the capabilities of the open-knowledge software instrument Modules for Experiments in Stellar Astrophysics (MESA) have been updated to improve numerical energy conservation capabilities, including during mass changes.
Abstract: We update the capabilities of the open-knowledge software instrument Modules for Experiments in Stellar Astrophysics (MESA). RSP is a new functionality in MESAstar that models the nonlinear radial stellar pulsations that characterize RR Lyrae, Cepheids, and other classes of variable stars. We significantly enhance numerical energy conservation capabilities, including during mass changes. For example, this enables calculations through the He flash that conserve energy to better than 0.001%. To improve the modeling of rotating stars in MESA, we introduce a new approach to modifying the pressure and temperature equations of stellar structure, as well as a formulation of the projection effects of gravity darkening. A new scheme for tracking convective boundaries yields reliable values of the convective core mass and allows the natural emergence of adiabatic semiconvection regions during both core hydrogen- and helium-burning phases. We quantify the parallel performance of MESA on current-generation multicore architectures and demonstrate improvements in the computational efficiency of radiative levitation. We report updates to the equation of state and nuclear reaction physics modules. We briefly discuss the current treatment of fallback in core-collapse supernova models and the thermodynamic evolution of supernova explosions. We close by discussing the new MESA Testhub software infrastructure to enhance source code development.
TL;DR: The community is paying significant attention to Pb-free materials and has achieved promising results albeit not yet approaching the spectacular performance of APbI3 materials.
Abstract: Since the 2012 breakthroughs1–3, it is now very much accepted that halide perovskite solar cells may have a strong practical impact in next-generation solar cells. The most efficient solar cells are using Pb-based halide perovskites. The presence of Pb in these devices, however, has caused some concerns due to the high perceived toxicity of Pb, which may slow down or even hinder the pace of commercialization. Therefore, the science community has been searching for lower-toxicity perovskite-type materials as a back-up strategy. The community is paying significant attention to Pb-free materials and has achieved promising results albeit not yet approaching the spectacular performance of APbI3 materials. In this comment, we summarize the present status and future prospects for Pb-free perovskite materials and their devices.
Max Planck Society1, Heidelberg University2, Heidelberg Institute for Theoretical Studies3, National Autonomous University of Mexico4, Massachusetts Institute of Technology5, University of Florida6, York University7, University of Bologna8, Smithsonian Institution9, Northwestern University10, Durham University11, University of Iceland12
TL;DR: The full public release of all data from the TNG100 and TNG300 simulations of the IllustrisTNG project is presented in this article, which includes a comprehensive model for galaxy formation physics, and each TNG simulation selfconsistently solves for the coupled evolution of dark matter, cosmic gas, luminous stars, and supermassive black holes from early time to the present day.
Abstract: We present the full public release of all data from the TNG100 and TNG300 simulations of the IllustrisTNG project. IllustrisTNG is a suite of large volume, cosmological, gravo-magnetohydrodynamical simulations run with the moving-mesh code Arepo. TNG includes a comprehensive model for galaxy formation physics, and each TNG simulation self-consistently solves for the coupled evolution of dark matter, cosmic gas, luminous stars, and supermassive black holes from early time to the present day, $z=0$
. Each of the flagship runs—TNG50, TNG100, and TNG300—are accompanied by halo/subhalo catalogs, merger trees, lower-resolution and dark-matter only counterparts, all available with 100 snapshots. We discuss scientific and numerical cautions and caveats relevant when using TNG. The data volume now directly accessible online is ∼750 TB, including 1200 full volume snapshots and ∼80,000 high time-resolution subbox snapshots. This will increase to ∼1.1 PB with the future release of TNG50. Data access and analysis examples are available in IDL, Python, and Matlab. We describe improvements and new functionality in the web-based API, including on-demand visualization and analysis of galaxies and halos, exploratory plotting of scaling relations and other relationships between galactic and halo properties, and a new JupyterLab interface. This provides an online, browser-based, near-native data analysis platform enabling user computation with local access to TNG data, alleviating the need to download large datasets.
University of Texas at Austin1, University of California, Irvine2, Stanford University3, Northwestern University4, Michigan State University5, University of Virginia6, University of Chicago7, Paradigm8, ICF International9, Arizona State University10, Pennsylvania State University11, Harvard University12, University of Pennsylvania13
TL;DR: A US national experiment showed that a short, online, self-administered growth mindset intervention can increase adolescents’ grades and advanced course-taking, and identified the types of school that were poised to benefit the most.
Abstract: A global priority for the behavioural sciences is to develop cost-effective, scalable interventions that could improve the academic outcomes of adolescents at a population level, but no such interventions have so far been evaluated in a population-generalizable sample. Here we show that a short (less than one hour), online growth mindset intervention-which teaches that intellectual abilities can be developed-improved grades among lower-achieving students and increased overall enrolment to advanced mathematics courses in a nationally representative sample of students in secondary education in the United States. Notably, the study identified school contexts that sustained the effects of the growth mindset intervention: the intervention changed grades when peer norms aligned with the messages of the intervention. Confidence in the conclusions of this study comes from independent data collection and processing, pre-registration of analyses, and corroboration of results by a blinded Bayesian analysis.
TL;DR: This work recommends dropping the NHST paradigm—and the p-value thresholds intrinsic to it—as the default statistical paradigm for research, publication, and discovery in the biomedical and social sciences and argues that it seldom makes sense to calibrate evidence as a function of p-values or other purely statistical measures.
Abstract: We discuss problems the null hypothesis significance testing (NHST) paradigm poses for replication and more broadly in the biomedical and social sciences as well as how these problems remain unreso
TL;DR: The results demonstrate that hierarchical metal sulfides can serve as highly efficient all-pH (pH = 0-14) electrocatalysts for overall water splitting.
Abstract: The design of low-cost yet high-efficiency electrocatalysts for hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) over a wide pH range is highly challenging. We now report a hierarchical co-assembly of interacting MoS2 and Co9S8 nanosheets attached on Ni3S2 nanorod arrays which are supported on nickel foam (NF). This tiered structure endows high performance toward HER and OER over a very broad pH range. By adjusting the molar ratio of the Co:Mo precursors, we have created CoMoNiS-NF- xy composites ( x: y means Co:Mo molar ratios ranging from 5:1 to 1:3) with controllable morphology and composition. The three-dimensional composites have an abundance of active sites capable of universal pH catalytic HER and OER activity. The CoMoNiS-NF-31 demonstrates the best electrocatalytic activity, giving ultralow overpotentials (113, 103, and 117 mV for HER and 166, 228, and 405 mV for OER) to achieve a current density of 10 mA cm-2 in alkaline, acidic, and neutral electrolytes, respectively. It also shows a remarkable balance between electrocatalytic activity and stability. Based on the distinguished catalytic performance of CoMoNiS-NF-31 toward HER and OER, we demonstrate a two-electrode electrolyzer performing water electrolysis over a wide pH range, with low cell voltages of 1.54, 1.45, and 1.80 V at 10 mA cm-2 in alkaline, acidic, and neutral media, respectively. First-principles calculations suggest that the high OER activity arises from electron transfer from Co9S8 to MoS2 at the interface, which alters the binding energies of adsorbed species and decreases overpotentials. Our results demonstrate that hierarchical metal sulfides can serve as highly efficient all-pH (pH = 0-14) electrocatalysts for overall water splitting.
University of Virginia1, Cornell University2, University of Texas Health Science Center at San Antonio3, University of Illinois at Chicago4, University of Pennsylvania5, Stanford University6, Colorado State University7, Providence Portland Medical Center8, Johns Hopkins University9, University of California, San Diego10, Brown University11, Northwestern University12, University of California, Davis13, Harvard University14, International University, Cambodia15, University of Bonn16, University of Washington17, Mayo Clinic18, Rush University Medical Center19, Keio University20, University of Texas Medical Branch21, Baylor College of Medicine22
TL;DR: Given that the majority of the biological and human health variables remained stable, or returned to baseline, after a 340-day space mission, these data suggest that human health can be mostly sustained over this duration of spaceflight.
Abstract: INTRODUCTION To date, 559 humans have been flown into space, but long-duration (>300 days) missions are rare (n = 8 total). Long-duration missions that will take humans to Mars and beyond are planned by public and private entities for the 2020s and 2030s; therefore, comprehensive studies are needed now to assess the impact of long-duration spaceflight on the human body, brain, and overall physiology. The space environment is made harsh and challenging by multiple factors, including confinement, isolation, and exposure to environmental stressors such as microgravity, radiation, and noise. The selection of one of a pair of monozygotic (identical) twin astronauts for NASA’s first 1-year mission enabled us to compare the impact of the spaceflight environment on one twin to the simultaneous impact of the Earth environment on a genetically matched subject. RATIONALE The known impacts of the spaceflight environment on human health and performance, physiology, and cellular and molecular processes are numerous and include bone density loss, effects on cognitive performance, microbial shifts, and alterations in gene regulation. However, previous studies collected very limited data, did not integrate simultaneous effects on multiple systems and data types in the same subject, or were restricted to 6-month missions. Measurement of the same variables in an astronaut on a year-long mission and in his Earth-bound twin indicated the biological measures that might be used to determine the effects of spaceflight. Presented here is an integrated longitudinal, multidimensional description of the effects of a 340-day mission onboard the International Space Station. RESULTS Physiological, telomeric, transcriptomic, epigenetic, proteomic, metabolomic, immune, microbiomic, cardiovascular, vision-related, and cognitive data were collected over 25 months. Some biological functions were not significantly affected by spaceflight, including the immune response (T cell receptor repertoire) to the first test of a vaccination in flight. However, significant changes in multiple data types were observed in association with the spaceflight period; the majority of these eventually returned to a preflight state within the time period of the study. These included changes in telomere length, gene regulation measured in both epigenetic and transcriptional data, gut microbiome composition, body weight, carotid artery dimensions, subfoveal choroidal thickness and peripapillary total retinal thickness, and serum metabolites. In addition, some factors were significantly affected by the stress of returning to Earth, including inflammation cytokines and immune response gene networks, as well as cognitive performance. For a few measures, persistent changes were observed even after 6 months on Earth, including some genes’ expression levels, increased DNA damage from chromosomal inversions, increased numbers of short telomeres, and attenuated cognitive function. CONCLUSION Given that the majority of the biological and human health variables remained stable, or returned to baseline, after a 340-day space mission, these data suggest that human health can be mostly sustained over this duration of spaceflight. The persistence of the molecular changes (e.g., gene expression) and the extrapolation of the identified risk factors for longer missions (>1 year) remain estimates and should be demonstrated with these measures in future astronauts. Finally, changes described in this study highlight pathways and mechanisms that may be vulnerable to spaceflight and may require safeguards for longer space missions; thus, they serve as a guide for targeted countermeasures or monitoring during future missions.
04 Jan 2019
TL;DR: This survey study provides nationally representative estimates of the distribution, severity, and factors associated with adult food allergy in the United States.
Abstract: Importance Food allergy is a costly, potentially life-threatening condition. Although studies have examined the prevalence of childhood food allergy, little is known about prevalence, severity, or health care utilization related to food allergies among US adults. Objective To provide nationally representative estimates of the distribution, severity, and factors associated with adult food allergies. Design, Setting, and Participants In this cross-sectional survey study of US adults, surveys were administered via the internet and telephone from October 9, 2015, to September 18, 2016. Participants were first recruited from NORC at the University of Chicago’s probability-based AmeriSpeak panel, and additional participants were recruited from the non–probability-based Survey Sampling International (SSI) panel. Exposures Demographic and allergic participant characteristics. Main Outcomes and Measures Self-reported food allergies were the main outcome and were considered convincing if reported symptoms to specific allergens were consistent with IgE-mediated reactions. Diagnosis history to specific allergens and food allergy–related health care use were also primary outcomes. Estimates were based on this nationally representative sample using small-area estimation and iterative proportional fitting methods. To increase precision, AmeriSpeak data were augmented by calibration-weighted, non–probability-based responses from SSI. Results Surveys were completed by 40 443 adults (mean [SD] age, 46.6 [20.2] years), with a survey completion rate of 51.2% observed among AmeriSpeak panelists (n = 7210) and 5.5% among SSI panelists (n = 33 233). Estimated convincing food allergy prevalence among US adults was 10.8% (95% CI, 10.4%-11.1%), although 19.0% (95% CI, 18.5%-19.5%) of adults self-reported a food allergy. The most common allergies were shellfish (2.9%; 95% CI, 2.7%-3.1%), milk (1.9%; 95% CI, 1.8%-2.1%), peanut (1.8%; 95% CI, 1.7%-1.9%), tree nut (1.2%; 95% CI, 1.1%-1.3%), and fin fish (0.9%; 95% CI, 0.8%-1.0%). Among food-allergic adults, 51.1% (95% CI, 49.3%-52.9%) experienced a severe food allergy reaction, 45.3% (95% CI, 43.6%-47.1%) were allergic to multiple foods, and 48.0% (95% CI, 46.2%-49.7%) developed food allergies as an adult. Regarding health care utilization, 24.0% (95% CI, 22.6%-25.4%) reported a current epinephrine prescription, and 38.3% (95% CI, 36.7%-40.0%) reported at least 1 food allergy–related lifetime emergency department visit. Conclusions and Relevance These data suggest that at least 10.8% (>26 million) of US adults are food allergic, whereas nearly 19% of adults believe that they have a food allergy. Consequently, these findings suggest that it is crucial that adults with suspected food allergy receive appropriate confirmatory testing and counseling to ensure food is not unnecessarily avoided and quality of life is not unduly impaired.
A. Abada1, Marcello Abbrescia2, Marcello Abbrescia3, Shehu S. AbdusSalam4 +1491 more•Institutions (239)
TL;DR: In this article, the authors present the second volume of the Future Circular Collider Conceptual Design Report, devoted to the electron-positron collider FCC-ee, and present the accelerator design, performance reach, a staged operation scenario, the underlying technologies, civil engineering, technical infrastructure, and an implementation plan.
Abstract: In response to the 2013 Update of the European Strategy for Particle Physics, the Future Circular Collider (FCC) study was launched, as an international collaboration hosted by CERN. This study covers a highest-luminosity high-energy lepton collider (FCC-ee) and an energy-frontier hadron collider (FCC-hh), which could, successively, be installed in the same 100 km tunnel. The scientific capabilities of the integrated FCC programme would serve the worldwide community throughout the 21st century. The FCC study also investigates an LHC energy upgrade, using FCC-hh technology. This document constitutes the second volume of the FCC Conceptual Design Report, devoted to the electron-positron collider FCC-ee. After summarizing the physics discovery opportunities, it presents the accelerator design, performance reach, a staged operation scenario, the underlying technologies, civil engineering, technical infrastructure, and an implementation plan. FCC-ee can be built with today’s technology. Most of the FCC-ee infrastructure could be reused for FCC-hh. Combining concepts from past and present lepton colliders and adding a few novel elements, the FCC-ee design promises outstandingly high luminosity. This will make the FCC-ee a unique precision instrument to study the heaviest known particles (Z, W and H bosons and the top quark), offering great direct and indirect sensitivity to new physics.
TL;DR: The findings indicate that PD-L1 expression as a predictive biomarker has limitations and that the decision to pursue testing must be carefully implemented for clinical decision-making.
Abstract: The development of immune checkpoint inhibitors has changed the treatment paradigm for advanced cancers across many tumor types. Despite encouraging and sometimes durable responses in a subset of patients, most patients do not respond. Tumors have adopted the PD-1/PD-L1 axis for immune escape to facilitate tumor growth, which can be leveraged as a potential target for immune checkpoint inhibitors. On this basis, PD-L1 protein expression on tumor or immune cells emerged as the first potential predictive biomarker for sensitivity to immune checkpoint blockade. The goal of our study was to evaluate PD-L1 as a predictive biomarker based on all US Food and Drug Administration (FDA) drug approvals of immune checkpoint inhibitors. We evaluated the primary studies associated with 45 FDA drug approvals from 2011 until April 2019. In total, there were approvals across 15 tumor types. Across all approvals, PD-L1 was predictive in only 28.9% of cases, and was either not predictive (53.3%) or not tested (17.8%) in the remaining cases. There were 9 FDA approvals linked to a specific PD-L1 threshold and companion diagnostic: bladder cancer (N = 3), non-small cell lung cancer (N = 3), triple-negative breast cancer (N = 1), cervical cancer (N = 1), and gastric/gastroesophageal junction cancer (N = 1) with 8 of 9 (88.9%) with immune checkpoint inhibitor monotherapy. The PD-L1 thresholds were variable both within and across tumor types using several different assays, including approvals at the following PD-L1 thresholds: 1, 5, and 50%. PD-L1 expression was also measured in a variable fashion either on tumor cells, tumor-infiltrating immune cells, or both. In conclusion, our findings indicate that PD-L1 expression as a predictive biomarker has limitations and that the decision to pursue testing must be carefully implemented for clinical decision-making.