Showing papers by "Heidelberg University published in 2021"
Harvard University1, University of California, San Francisco2, University of Amsterdam3, Northwestern University4, International Agency for Research on Cancer5, Aix-Marseille University6, University of Toronto7, The Chinese University of Hong Kong8, German Cancer Research Center9, University of Düsseldorf10, University of Turin11, Heidelberg University12, St. Jude Children's Research Hospital13
TL;DR: The fifth edition of the WHO Classification of Tumors of the Central Nervous System (CNS), published in 2021, is the sixth version of the international standard for the classification of brain and spinal cord tumors as mentioned in this paper.
Abstract: The fifth edition of the WHO Classification of Tumors of the Central Nervous System (CNS), published in 2021, is the sixth version of the international standard for the classification of brain and spinal cord tumors. Building on the 2016 updated fourth edition and the work of the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy, the 2021 fifth edition introduces major changes that advance the role of molecular diagnostics in CNS tumor classification. At the same time, it remains wedded to other established approaches to tumor diagnosis such as histology and immunohistochemistry. In doing so, the fifth edition establishes some different approaches to both CNS tumor nomenclature and grading and it emphasizes the importance of integrated diagnoses and layered reports. New tumor types and subtypes are introduced, some based on novel diagnostic technologies such as DNA methylome profiling. The present review summarizes the major general changes in the 2021 fifth edition classification and the specific changes in each taxonomic category. It is hoped that this summary provides an overview to facilitate more in-depth exploration of the entire fifth edition of the WHO Classification of Tumors of the Central Nervous System.
2,908 citations
TL;DR: nnU-Net as mentioned in this paper is a deep learning-based segmentation method that automatically configures itself, including preprocessing, network architecture, training and post-processing for any new task.
Abstract: Biomedical imaging is a driver of scientific discovery and a core component of medical care and is being stimulated by the field of deep learning. While semantic segmentation algorithms enable image analysis and quantification in many applications, the design of respective specialized solutions is non-trivial and highly dependent on dataset properties and hardware conditions. We developed nnU-Net, a deep learning-based segmentation method that automatically configures itself, including preprocessing, network architecture, training and post-processing for any new task. The key design choices in this process are modeled as a set of fixed parameters, interdependent rules and empirical decisions. Without manual intervention, nnU-Net surpasses most existing approaches, including highly specialized solutions on 23 public datasets used in international biomedical segmentation competitions. We make nnU-Net publicly available as an out-of-the-box tool, rendering state-of-the-art segmentation accessible to a broad audience by requiring neither expert knowledge nor computing resources beyond standard network training.
2,040 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
TL;DR: The morphological changes associated with infection such as thromboembolic ischemic infarction of the CNS and evidence of SARS-CoV-2 neurotropism are described and presented.
Abstract: The newly identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19, a pandemic respiratory disease. Moreover, thromboembolic events throughout the body, including in the CNS, have been described. Given the neurological symptoms observed in a large majority of individuals with COVID-19, SARS-CoV-2 penetrance of the CNS is likely. By various means, we demonstrate the presence of SARS-CoV-2 RNA and protein in anatomically distinct regions of the nasopharynx and brain. Furthermore, we describe the morphological changes associated with infection such as thromboembolic ischemic infarction of the CNS and present evidence of SARS-CoV-2 neurotropism. SARS-CoV-2 can enter the nervous system by crossing the neural-mucosal interface in olfactory mucosa, exploiting the close vicinity of olfactory mucosal, endothelial and nervous tissue, including delicate olfactory and sensory nerve endings. Subsequently, SARS-CoV-2 appears to follow neuroanatomical structures, penetrating defined neuroanatomical areas including the primary respiratory and cardiovascular control center in the medulla oblongata.
888 citations
Université Paris-Saclay1, Autonomous University of Barcelona2, University of Cambridge3, National Institute for Occupational Safety and Health4, University of Bonn5, German Center for Neurodegenerative Diseases6, Harvard University7, University of Lausanne8, University of Padua9, National Research Council10, 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 Rochester27, University of Copenhagen28, 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, University of Minho47, Polytechnic Institute of Cávado and Ave48, 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, Russian Academy of Sciences57, I.M. Sechenov First Moscow State Medical University58, 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, Ikerbasque65, University of Manchester66
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
Harvard University1, university of lille2, University of California, San Francisco3, Icahn School of Medicine at Mount Sinai4, Sarah Cannon Research Institute5, Emory University6, Rutgers University7, Centre Hospitalier Universitaire de Nantes8, Lille University of Science and Technology9, Katholieke Universiteit Leuven10, University of Würzburg11, German Cancer Research Center12, Heidelberg University13, University of Hamburg14, University of Tübingen15, University of Milan16, Autonomous University of Barcelona17, Bristol-Myers Squibb18, University of Navarra19
TL;DR: In this article, a B-cell maturation antigen-directed chimeric antigen receptor (CAR) T-cell therapy, has shown clinical activity with expecable clinical outcomes with the use of idecabtagene vicleucel (ide-cel), also called bb2121.
Abstract: Background Idecabtagene vicleucel (ide-cel, also called bb2121), a B-cell maturation antigen–directed chimeric antigen receptor (CAR) T-cell therapy, has shown clinical activity with expec...
776 citations
University of Zurich1, Erasmus University Rotterdam2, Medical University of Vienna3, Ludwig Maximilian University of Munich4, University of Siena5, University Hospital Heidelberg6, Aix-Marseille University7, Leiden University Medical Center8, Sahlgrenska University Hospital9, German Cancer Research Center10, Heidelberg University11, St James's University Hospital12, University of Düsseldorf13
TL;DR: These evidence-based guidelines incorporate major changes in diagnostic algorithms based on the 2016 update of the WHO Classification of Tumors of the Central Nervous System as well as on evidence from recent large clinical trials.
Abstract: In response to major changes in diagnostic algorithms and the publication of mature results from various large clinical trials, the European Association of Neuro-Oncology (EANO) recognized the need to provide updated guidelines for the diagnosis and management of adult patients with diffuse gliomas. Through these evidence-based guidelines, a task force of EANO provides recommendations for the diagnosis, treatment and follow-up of adult patients with diffuse gliomas. The diagnostic component is based on the 2016 update of the WHO Classification of Tumors of the Central Nervous System and the subsequent recommendations of the Consortium to Inform Molecular and Practical Approaches to CNS Tumour Taxonomy - Not Officially WHO (cIMPACT-NOW). With regard to therapy, we formulated recommendations based on the results from the latest practice-changing clinical trials and also provide guidance for neuropathological and neuroradiological assessment. In these guidelines, we define the role of the major treatment modalities of surgery, radiotherapy and systemic pharmacotherapy, covering current advances and cognizant that unnecessary interventions and expenses should be avoided. This document is intended to be a source of reference for professionals involved in the management of adult patients with diffuse gliomas, for patients and caregivers, and for health-care providers.
629 citations
Novo Nordisk1, German Cancer Research Center2, University of Zurich3, University of Barcelona4, Newcastle University5, Medical University of Vienna6, University of Tübingen7, University Hospital Heidelberg8, Weizmann Institute of Science9, Max Planck Society10, Technische Universität München11, Heidelberg University12, Icahn School of Medicine at Mount Sinai13, National and Kapodistrian University of Athens14, University of Turin15, University of Cambridge16, University of Florence17, Paris Diderot University18, Humanitas University19, Hannover Medical School20, University of Hamburg21, University of Mainz22, University of Düsseldorf23, Memorial Sloan Kettering Cancer Center24, Cornell University25, Harvard University26, University of Cologne27, Leibniz Association28, University of Bern29, Mount Sinai Hospital30, University of Texas MD Anderson Cancer Center31, Kindai University32, Taipei Veterans General Hospital33, National Yang-Ming University34, University of Grenoble35, French Institute of Health and Medical Research36, Imperial College London37, Catalan Institution for Research and Advanced Studies38
TL;DR: The progressive accumulation of exhausted, unconventionally activated CD8+PD1+ T cells in NASH-affected livers provides a rationale for stratification of patients with HCC according to underlying aetiology in studies of immunotherapy as a primary or adjuvant treatment.
Abstract: Hepatocellular carcinoma (HCC) can have viral or non-viral causes1-5. Non-alcoholic steatohepatitis (NASH) is an important driver of HCC. Immunotherapy has been approved for treating HCC, but biomarker-based stratification of patients for optimal response to therapy is an unmet need6,7. Here we report the progressive accumulation of exhausted, unconventionally activated CD8+PD1+ T cells in NASH-affected livers. In preclinical models of NASH-induced HCC, therapeutic immunotherapy targeted at programmed death-1 (PD1) expanded activated CD8+PD1+ T cells within tumours but did not lead to tumour regression, which indicates that tumour immune surveillance was impaired. When given prophylactically, anti-PD1 treatment led to an increase in the incidence of NASH-HCC and in the number and size of tumour nodules, which correlated with increased hepatic CD8+PD1+CXCR6+, TOX+, and TNF+ T cells. The increase in HCC triggered by anti-PD1 treatment was prevented by depletion of CD8+ T cells or TNF neutralization, suggesting that CD8+ T cells help to induce NASH-HCC, rather than invigorating or executing immune surveillance. We found similar phenotypic and functional profiles in hepatic CD8+PD1+ T cells from humans with NAFLD or NASH. A meta-analysis of three randomized phase III clinical trials that tested inhibitors of PDL1 (programmed death-ligand 1) or PD1 in more than 1,600 patients with advanced HCC revealed that immune therapy did not improve survival in patients with non-viral HCC. In two additional cohorts, patients with NASH-driven HCC who received anti-PD1 or anti-PDL1 treatment showed reduced overall survival compared to patients with other aetiologies. Collectively, these data show that non-viral HCC, and particularly NASH-HCC, might be less responsive to immunotherapy, probably owing to NASH-related aberrant T cell activation causing tissue damage that leads to impaired immune surveillance. Our data provide a rationale for stratification of patients with HCC according to underlying aetiology in studies of immunotherapy as a primary or adjuvant treatment.
526 citations
Lund University1, Dresden University of Technology2, European Space Agency3, Heidelberg University4, University of Barcelona5, University of Edinburgh6, INAF7, University of Paris8, Max Planck Society9, Goddard Space Flight Center10, University of Maryland, Baltimore County11, Leiden University12, University of Turin13, Centre national de la recherche scientifique14, Leibniz Institute for Astrophysics Potsdam15, Netherlands Institute for Space Research16, Las Cumbres Observatory Global Telescope Network17, Liverpool John Moores University18, University of Leicester19, Princeton University20, Université de Namur21
TL;DR: Gaia Early Data Release 3 (Gaia EDR3) as mentioned in this paper contains results for 1.812 billion sources in the magnitude range G = 3-21 based on observations collected by the European Space Agency Gaia satellite during the first 34 months of its operational phase.
Abstract: Context. Gaia Early Data Release 3 (Gaia EDR3) contains results for 1.812 billion sources in the magnitude range G = 3–21 based on observations collected by the European Space Agency Gaia satellite during the first 34 months of its operational phase.Aims. We describe the input data, the models, and the processing used for the astrometric content of Gaia EDR3, as well as the validation of these results performed within the astrometry task.Methods. The processing broadly followed the same procedures as for Gaia DR2, but with significant improvements to the modelling of observations. For the first time in the Gaia data processing, colour-dependent calibrations of the line- and point-spread functions have been used for sources with well-determined colours from DR2. In the astrometric processing these sources obtained five-parameter solutions, whereas other sources were processed using a special calibration that allowed a pseudocolour to be estimated as the sixth astrometric parameter. Compared with DR2, the astrometric calibration models have been extended, and the spin-related distortion model includes a self-consistent determination of basic-angle variations, improving the global parallax zero point.Results. Gaia EDR3 gives full astrometric data (positions at epoch J2016.0, parallaxes, and proper motions) for 1.468 billion sources (585 millionwith five-parameter solutions, 882 million with six parameters), and mean positions at J2016.0 for an additional 344 million.Solutions with five parameters are generally more accurate than six-parameter solutions, and are available for 93% of the sources brighter than the 17th magnitude. The median uncertainty in parallax and annual proper motion is 0.02–0.03 mas at magnitude G = 9–14, and around 0.5 mas at G = 20. Extensive characterisation of the statistical properties of the solutions is provided, including the estimated angular power spectrum of parallax bias from the quasars.
475 citations
National Institute for Health Research1, University of London2, University of Auckland3, Anglia Ruskin University4, University of Cambridge5, 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, University of New South Wales28, The George Institute for Global Health29, 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.
435 citations
TL;DR: In this article, the parallax bias in EDR3 was investigated and the main dependences of the bias were mapped to the magnitude, colour, and ecliptic latitude of the source.
Abstract: Context. Gaia Early Data Release 3 (Gaia EDR3) gives trigonometric parallaxes for nearly 1.5 billion sources. Inspection of the EDR3 data for sources identified as quasars reveals that their parallaxes are biased, that is, they are systematically offset from the expected distribution around zero, by a few tens of microarcseconds.Aims. We attempt to map the main dependences of the parallax bias in EDR3. In principle, this could provide a recipe for correcting the EDR3 parallaxes.Methods. Quasars provide the most direct way for estimating the parallax bias for faint sources. In order to extend this to brighter sources and a broader range of colours, we used differential methods based on physical pairs (binaries) and sources in the Large Magellanic Cloud. The functional forms of the dependences were explored by mapping the systematic differences between EDR3 and DR2 parallaxes.Results. The parallax bias is found to depend in a non-trivial way on (at least) the magnitude, colour, and ecliptic latitude of the source. Different dependences apply to the five- and six-parameter solutions in EDR3. While it is not possible to derive a definitive recipe for the parallax correction, we give tentative expressions to be used at the researcher’s discretion and point out some possible paths towards future improvements.
Niamh Mullins1, Andreas J. Forstner2, Andreas J. Forstner3, Andreas J. Forstner4 +396 more•Institutions (119)
TL;DR: The authors performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci, including genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics.
Abstract: Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies.
TL;DR: In this article, the authors conducted a systematic review using PubMed, Medline, Web of Science, and Scopus for population-based studies published up to March 2020 to provide updated estimates on the global prevalence and number of people with diabetic retinopathy through 2045.
TL;DR: This paper aims to demonstrate the efforts towards in-situ applicability of EMMARM, which aims to provide real-time information about the physical and emotional impacts of age-related illness and disability on individuals and society.
Abstract: 1School of Social Work, Bar Ilan University, Ramat Gan, Israel. 2Department of Psychology, University of Toronto, Ontario, Canada. 3Department of Human Development and Family Studies, Colorado State University, Fort Collins. 4Social and Behavioral Sciences Department, Yale School of Public Health, New Haven, Connecticut. 5Department of Psychology, North Carolina State University, Raleigh. 6Department of Psychology, Friedrich-Schiller-University Jena, Germany. 7German Centre of Gerontology, Berlin, Germany. 8Network of Aging Research, Heidelberg University, Germany.
TL;DR: Aghanim et al. as mentioned in this paper used the same data set to derive a 95% upper bound of 0.020 using the principal component analysis (PCA) model and uniform priors on the PCA mode amplitudes.
Abstract: Author(s): Aghanim, N; Akrami, Y; Ashdown, M; Aumont, J; Baccigalupi, C; Ballardini, M; Banday, AJ; Barreiro, RB; Bartolo, N; Basak, S; Battye, R; Benabed, K; Bernard, JP; Bersanelli, M; Bielewicz, P; Bock, JJ; Bond, JR; Borrill, J; Bouchet, FR; Boulanger, F; Bucher, M; Burigana, C; Butler, RC; Calabrese, E; Cardoso, JF; Carron, J; Challinor, A; Chiang, HC; Chluba, J; Colombo, LPL; Combet, C; Contreras, D; Crill, BP; Cuttaia, F; De Bernardis, P; De Zotti, G; Delabrouille, J; Delouis, JM; DI Valentino, E; DIego, JM; Dore, O; Douspis, M; Ducout, A; Dupac, X; Dusini, S; Efstathiou, G; Elsner, F; Enslin, TA; Eriksen, HK; Fantaye, Y; Farhang, M; Fergusson, J; Fernandez-Cobos, R; Finelli, F; Forastieri, F; Frailis, M; Fraisse, AA; Franceschi, E; Frolov, A; Galeotta, S; Galli, S; Ganga, K; Genova-Santos, RT; Gerbino, M; Ghosh, T; Gonzalez-Nuevo, J; Gorski, KM; Gratton, S; Gruppuso, A; Gudmundsson, JE; Hamann, J; Handley, W; Hansen, FK; Herranz, D; Hildebrandt, SR; Hivon, E; Huang, Z; Jaffe, AH; Jones, WC; Karakci, A; Keihanen, E; Keskitalo, R; Kiiveri, K; Kim, J; Kisner, TS | Abstract: In the original version, the bounds given in Eqs. (87a) and (87b) on the contribution to the early-time optical depth, (15,30), contained a numerical error in deriving the 95th percentile from the Monte Carlo samples. The corrected 95% upper bounds are: τ(15,30) l 0:018 (lowE, flat τ(15, 30), FlexKnot), (1) τ(15, 30) l 0:023 (lowE, flat knot, FlexKnot): (2) These bounds are a factor of 3 larger than the originally reported results. Consequently, the new bounds do not significantly improve upon previous results from Planck data presented in Millea a Bouchet (2018) as was stated, but are instead comparable. Equations (1) and (2) give results that are now similar to those of Heinrich a Hu (2021), who used the same Planck 2018 data to derive a 95% upper bound of 0.020 using the principal component analysis (PCA) model and uniform priors on the PCA mode amplitudes.
University of Manchester1, City University of New York2, Istanbul Technical University3, New York University4, Heidelberg University5, Niels Bohr Institute6, University of Edinburgh7, University of Bologna8, Academy of Athens9, Sapienza University of Rome10, University of Naples Federico II11, Stanford University12, Institut d'Astrophysique de Paris13, University of Portsmouth14, Cardiff University15, Universidade Federal do Espírito Santo16, University of Michigan17, Asia Pacific Center for Theoretical Physics18, University of New Mexico19, University of Barcelona20, University of St. Thomas (Minnesota)21, Princeton University22, National Autonomous University of Mexico23, California Institute of Technology24, INAF25, University of Chicago26, Michigan Technological University27, Lawrence Berkeley National Laboratory28, University of Cambridge29, Imperial College London30, Ruhr University Bochum31, University of Oxford32, University of Waterloo33, Johns Hopkins University34, University of Pennsylvania35, University of California, Davis36, Birla Institute of Technology and Science37, RWTH Aachen University38, Université libre de Bruxelles39, University of Padua40, Indian Institute of Technology Kharagpur41, Spanish National Research Council42, University of North Carolina at Chapel Hill43, University of Arizona44, University of Oslo45, Jamia Millia Islamia46, University of Southern Denmark47, National Institute for Space Research48, Fermilab49, Presidency University, Kolkata50, Université Paris-Saclay51, University of Montpellier52, University of Szczecin53, Korea Astronomy and Space Science Institute54, University of California, Los Angeles55, University of Paris56, Leiden University57, Swarthmore College58, University of Sheffield59, University of Amsterdam60, United College, Winnipeg61, Liaoning Normal University62
TL;DR: In this article, the authors focus on the 4.4σ tension between the Planck estimate of the Hubble constant H0 and the SH0ES collaboration measurements and discuss how the next decade's experiments will be crucial.
03 Feb 2021
TL;DR: In this paper, the authors identify the human pancreas as a target of SARS-CoV-2 infection and suggest that β-cell infection could contribute to the metabolic dysregulation observed in patients with COVID-19.
Abstract: Infection-related diabetes can arise as a result of virus-associated β-cell destruction. Clinical data suggest that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing the coronavirus disease 2019 (COVID-19), impairs glucose homoeostasis, but experimental evidence that SARS-CoV-2 can infect pancreatic tissue has been lacking. In the present study, we show that SARS-CoV-2 infects cells of the human exocrine and endocrine pancreas ex vivo and in vivo. We demonstrate that human β-cells express viral entry proteins, and SARS-CoV-2 infects and replicates in cultured human islets. Infection is associated with morphological, transcriptional and functional changes, including reduced numbers of insulin-secretory granules in β-cells and impaired glucose-stimulated insulin secretion. In COVID-19 full-body postmortem examinations, we detected SARS-CoV-2 nucleocapsid protein in pancreatic exocrine cells, and in cells that stain positive for the β-cell marker NKX6.1 and are in close proximity to the islets of Langerhans in all four patients investigated. Our data identify the human pancreas as a target of SARS-CoV-2 infection and suggest that β-cell infection could contribute to the metabolic dysregulation observed in patients with COVID-19.
RWTH Aachen University1, Bayer HealthCare Pharmaceuticals2, Martin Luther University of Halle-Wittenberg3, Heidelberg University4, Radboud University Nijmegen5, Boston Children's Hospital6, University of Edinburgh7, University of Hamburg8, Monash University9, Erasmus University Rotterdam10, Molecular Medicine Partnership Unit11
TL;DR: Using single-cell RNA sequencing, the transcriptomes of cells from the proximal and non-proximal tubules of healthy and fibrotic human kidneys are profiled to map the entire human kidney and identify distinct subpopulations of pericytes and fibroblasts as the main cellular sources of scar-forming myofibro Blasts during human kidney fibrosis.
Abstract: Kidney fibrosis is the hallmark of chronic kidney disease progression; however, at present no antifibrotic therapies exist1-3. The origin, functional heterogeneity and regulation of scar-forming cells that occur during human kidney fibrosis remain poorly understood1,2,4. Here, using single-cell RNA sequencing, we profiled the transcriptomes of cells from the proximal and non-proximal tubules of healthy and fibrotic human kidneys to map the entire human kidney. This analysis enabled us to map all matrix-producing cells at high resolution, and to identify distinct subpopulations of pericytes and fibroblasts as the main cellular sources of scar-forming myofibroblasts during human kidney fibrosis. We used genetic fate-tracing, time-course single-cell RNA sequencing and ATAC-seq (assay for transposase-accessible chromatin using sequencing) experiments in mice, and spatial transcriptomics in human kidney fibrosis, to shed light on the cellular origins and differentiation of human kidney myofibroblasts and their precursors at high resolution. Finally, we used this strategy to detect potential therapeutic targets, and identified NKD2 as a myofibroblast-specific target in human kidney fibrosis.
State University of New York Upstate Medical University1, Heidelberg University2, University of Melbourne3, Capital Medical University4, Harvard University5, Monash University, Clayton campus6, Icahn School of Medicine at Mount Sinai7, Montreal Children's Hospital8, Universidade Federal do Rio Grande do Sul9, Peking University10, University of Southampton11, University of Toronto12, University of Washington13, King Khalid University14, King's College London15, Aga Khan University16, Karolinska Institutet17, Radboud University Nijmegen18, Vrije Universiteit Brussel19, University of Nottingham20, Aarhus University21, University of Cologne22, Trinity College, Dublin23, University of Würzburg24, University of Bergen25, University Medical Center Groningen26, University of Wyoming27, University of California, Berkeley28, University of California, San Francisco29, Nottinghamshire Healthcare NHS Foundation Trust30, Duke University31, University of Amsterdam32, Örebro University33, Chongqing Medical University34, Tel Aviv University35, Washington University in St. Louis36, Federal University of Rio de Janeiro37, University College Cork38, University of British Columbia39, University of Pittsburgh40, Oregon Health & Science University41, University of Montpellier42, University of Ibadan43, University of São Paulo44, Hebrew University of Jerusalem45, University of Sydney46, Jawaharlal Institute of Postgraduate Medical Education and Research47, University of Canterbury48, Autonomous University of Barcelona49, Stellenbosch University50, University of California, Davis51, National Medical College52, Hofstra University53, University of Texas Health Science Center at Houston54, University of Southern Denmark55, University of California, Irvine56, Cardiff University57, Okinawa Institute of Science and Technology58, HU University of Applied Sciences Utrecht59, Katholieke Universiteit Leuven60, University of the Free State61, University of Turin62, Johns Hopkins University63, University of Zurich64
TL;DR: In this article, the authors presented 208 empirically supported statements about ADHD using meta-analysis, which allow for firm statements about the nature, course, outcome causes and treatments for disorders that are useful for reducing misconceptions and stigma.
TL;DR: In the phase III IMpassion130 trial, combining atezolizumab with first-line nanoparticle albumin-bound-paclitaxel for advanced triple-negative breast cancer (aTNBC) showed a statistically significant progression-free survival (PFS) benefit in the intention-to-treat (ITT) and programmed death-ligand 1 (PD-L1)-positive populations, and a clinically meaningful overall survival (OS) effect in PD-L 1-positive aTNBC as discussed by the authors.
Universidad Francisco de Vitoria1, University of Ferrara2, Tel Aviv University3, University of Padua4, University of Zurich5, University College London6, Mayo Clinic7, Maastricht University8, Katholieke Universiteit Leuven9, Saarland University10, Heidelberg University11, NewYork–Presbyterian Hospital12, University of Pavia13, University of Marburg14, Martin Luther University of Halle-Wittenberg15, First Faculty of Medicine, Charles University in Prague16
TL;DR: In this paper, the Working Group on Myocardial and Pericardial Disease proposes an invasive and non-invasive definition of cardiac amyloidosis, addresses clinical scenarios and situations to suspect the condition and proposes a diagnostic algorithm to aid diagnosis.
Abstract: Cardiac amyloidosis is a serious and progressive infiltrative disease that is caused by the deposition of amyloid fibrils at the cardiac level It can be due to rare genetic variants in the hereditary forms or as a consequence of acquired conditions Thanks to advances in imaging techniques and the possibility of achieving a non-invasive diagnosis, we now know that cardiac amyloidosis is a more frequent disease than traditionally considered In this position paper the Working Group on Myocardial and Pericardial Disease proposes an invasive and non-invasive definition of cardiac amyloidosis, addresses clinical scenarios and situations to suspect the condition and proposes a diagnostic algorithm to aid diagnosis Furthermore, we also review how to monitor and treat cardiac amyloidosis, in an attempt to bridge the gap between the latest advances in the field and clinical practice
01 Jun 2021
TL;DR: In this paper, the authors demonstrate how combining the effectiveness of the inductive bias of CNNs with the expressivity of transformers enables them to model and thereby synthesize high-resolution images.
Abstract: Designed to learn long-range interactions on sequential data, transformers continue to show state-of-the-art results on a wide variety of tasks. In contrast to CNNs, they contain no inductive bias that prioritizes local interactions. This makes them expressive, but also computationally infeasible for long sequences, such as high-resolution images. We demonstrate how combining the effectiveness of the inductive bias of CNNs with the expressivity of transformers enables them to model and thereby synthesize high-resolution images. We show how to (i) use CNNs to learn a context-rich vocabulary of image constituents, and in turn (ii) utilize transformers to efficiently model their composition within high-resolution images. Our approach is readily applied to conditional synthesis tasks, where both non-spatial information, such as object classes, and spatial information, such as segmentations, can control the generated image. In particular, we present the first results on semantically-guided synthesis of megapixel images with transformers. Project page at https://git.io/JLlvY.
TL;DR: An absolute requirement for the VMP1, TMEM41, and TMEM64 domain-containing protein transmembrane protein 41B (TMEM41B) for infection by SARS-CoV-2 and three seasonal coronaviruses is identified.
TL;DR: The nonperturbative functional renormalization-group (FRG) approach as discussed by the authors is a modern implementation of Wilson's RG, which allows one to set up nonperturative approximation schemes that go beyond the standard perturbative RG approaches.
TL;DR: In this article, the authors reported that individuals with BAT had lower prevalences of cardiometabolic diseases, and the presence of BAT was independently correlated with lower odds of type 2 diabetes, dyslipidemia, coronary artery disease, cerebrovascular disease, congestive heart failure and hypertension.
Abstract: White fat stores excess energy, whereas brown and beige fat are thermogenic and dissipate energy as heat. Thermogenic adipose tissues markedly improve glucose and lipid homeostasis in mouse models, although the extent to which brown adipose tissue (BAT) influences metabolic and cardiovascular disease in humans is unclear1,2. Here we retrospectively categorized 134,529 18F-fluorodeoxyglucose positron emission tomography-computed tomography scans from 52,487 patients, by presence or absence of BAT, and used propensity score matching to assemble a study cohort. Scans in the study population were initially conducted for indications related to cancer diagnosis, treatment or surveillance, without previous stimulation. We report that individuals with BAT had lower prevalences of cardiometabolic diseases, and the presence of BAT was independently correlated with lower odds of type 2 diabetes, dyslipidemia, coronary artery disease, cerebrovascular disease, congestive heart failure and hypertension. These findings were supported by improved blood glucose, triglyceride and high-density lipoprotein values. The beneficial effects of BAT were more pronounced in individuals with overweight or obesity, indicating that BAT might play a role in mitigating the deleterious effects of obesity. Taken together, our findings highlight a potential role for BAT in promoting cardiometabolic health.
Institute for Health Metrics and Evaluation1, Auckland University of Technology2, University of Washington3, Mayo Clinic4, University of the Philippines Manila5, Johns Hopkins University6, Heidelberg University7, Harvard University8, Mario Negri Institute for Pharmacological Research9, New York University10, University at Buffalo11, University of California, San Diego12, Veterans Health Administration13, University of Peradeniya14, University of Rochester15, Tufts Medical Center16, Kaiser Permanente17, Rowan University18, Istituto Superiore di Sanità19, Tehran University of Medical Sciences20, University of Texas at Austin21, Florida State University College of Arts and Sciences22, Sheffield Hallam University23, Ball State University24, Northeastern University25, Duke University26, University of Michigan27, Nationwide Children's Hospital28, Ohio State University29, University of Bari30, University of Cape Town31, National Institutes of Health32, Pacific Institute33, Curtin University34, University of Mississippi35, Mizan–Tepi University36, Iran University of Medical Sciences37, Emory University38, Lund University39, University of Central Florida40, Charité41, University of Edinburgh42, Yonsei University43, University of Alabama at Birmingham44, United States Department of Veterans Affairs45, Norwegian University of Science and Technology46, Imperial College London47, University of Maryland, Baltimore48, George Washington University49, University of California, Berkeley50
TL;DR: A large and increasing number of people have various neurological disorders in the US, with significant variation in the burden of and trends in neurological disorders across the US states, and the reasons for these geographic variations need to be explored further.
Abstract: IMPORTANCE Accurate and up-to-date estimates on incidence, prevalence, mortality, and
disability-adjusted life-years (burden) of neurological disorders are the backbone of
evidence-based health care planning and resource allocation for these disorders. It appears
that no such estimates have been reported at the state level for the US.
OBJECTIVE To present burden estimates of major neurological disorders in the US states by
age and sex from 1990 to 2017.
DESIGN, SETTING, AND PARTICIPANTS This is a systematic analysis of the Global Burden of
Disease (GBD) 2017 study. Data on incidence, prevalence, mortality, and disability-adjusted
life-years (DALYs) of major neurological disorders were derived from the GBD 2017 study of
the 48 contiguous US states, Alaska, and Hawaii. Fourteen major neurological disorders were
analyzed: stroke, Alzheimer disease and other dementias, Parkinson disease, epilepsy,
multiple sclerosis, motor neuron disease, migraine, tension-type headache, traumatic brain
injury, spinal cord injuries, brain and other nervous system cancers, meningitis, encephalitis,
and tetanus.
EXPOSURES Any of the 14 listed neurological diseases.
MAIN OUTCOME AND MEASURE Absolute numbers in detail by age and sex and
age-standardized rates (with 95% uncertainty intervals) were calculated.
RESULTS The 3 most burdensome neurological disorders in the US in terms of absolute
number of DALYs were stroke (3.58 [95% uncertainty interval [UI], 3.25-3.92] million DALYs),
Alzheimer disease and other dementias (2.55 [95% UI, 2.43-2.68] million DALYs), and
migraine (2.40 [95% UI, 1.53-3.44] million DALYs). The burden of almost all neurological
disorders (in terms of absolute number of incident, prevalent, and fatal cases, as well as
DALYs) increased from 1990 to 2017, largely because of the aging of the population.
Exceptions for this trend included traumatic brain injury incidence (−29.1% [95% UI, −32.4%
to −25.8%]); spinal cord injury prevalence (−38.5% [95% UI, −43.1% to −34.0%]); meningitis
prevalence (−44.8% [95% UI, −47.3% to −42.3%]), deaths (−64.4% [95% UI, −67.7% to
−50.3%]), and DALYs (−66.9% [95% UI, −70.1% to −55.9%]); and encephalitis DALYs
(−25.8% [95% UI, −30.7% to −5.8%]). The different metrics of age-standardized rates varied
between the US states from a 1.2-fold difference for tension-type headache to 7.5-fold for
tetanus; southeastern states and Arkansas had a relatively higher burden for stroke, while
northern states had a relatively higher burden of multiple sclerosis and eastern states had
higher rates of Parkinson disease, idiopathic epilepsy, migraine and tension-type headache,
and meningitis, encephalitis, and tetanus.
CONCLUSIONS AND RELEVANCE There is a large and increasing burden of noncommunicable
neurological disorders in the US, with up to a 5-fold variation in the burden of and trends in
particular neurological disorders across the US states. The information reported in this article
can be used by health care professionals and policy makers at the national and state levels to
advance their health care planning and resource allocation to prevent and reduce the burden
of neurological disorders.
University of Calgary1, Swiss Federal Institute for Forest, Snow and Landscape Research2, Cooperative Institute for Research in Environmental Sciences3, ETH Zurich4, University of Washington5, University of Zurich6, University of Potsdam7, United States Geological Survey8, University of Minnesota9, University of Graz10, University of Natural Resources and Life Sciences, Vienna11, University of Toulouse12, University of Utah13, Heidelberg University14, University of Geneva15, University of Leeds16, Simon Fraser University17, Newcastle University18, University of Dayton19, University of Oslo20, Planetary Science Institute21, University of Alberta22, University of Grenoble23, University of Sheffield24, Indian Institute of Technology Indore25, UNESCO26, University of Dundee27, Jawaharlal Nehru University28, Stockholm International Water Institute29, University of British Columbia30, University of Exeter31, Kathmandu32, Wadia Institute of Himalayan Geology33, University of Kashmir34, University of Delhi35, Utrecht University36, International Centre for Integrated Mountain Development37, University of Chile38, Northumbria University39
TL;DR: In this paper, an analysis of satellite imagery, seismic records, numerical model results, and eyewitness videos reveals that ~27x106 m3 of rock and glacier ice collapsed from the steep north face of Ronti Peak.
Abstract: On 7 Feb 2021, a catastrophic mass flow descended the Ronti Gad, Rishiganga, and Dhauliganga valleys in Chamoli, Uttarakhand, India, causing widespread devastation and severely damaging two hydropower projects. Over 200 people were killed or are missing. Our analysis of satellite imagery, seismic records, numerical model results, and eyewitness videos reveals that ~27x106 m3 of rock and glacier ice collapsed from the steep north face of Ronti Peak. The rock and ice avalanche rapidly transformed into an extraordinarily large and mobile debris flow that transported boulders >20 m in diameter, and scoured the valley walls up to 220 m above the valley floor. The intersection of the hazard cascade with downvalley infrastructure resulted in a disaster, which highlights key questions about adequate monitoring and sustainable development in the Himalaya as well as other remote, high-mountain environments.
TL;DR: Increased digital screen time, near work and limited outdoor activities were found to be associated with the onset and progression of myopia, and could potentially be aggravated during and beyond the COVID-19 pandemic outbreak period.
TL;DR: This pathogen has the potential to become a pandemic and it is therefore vital to follow the personal care recommendations issued by the World Health Organisation.
Abstract: A new coronavirus outbreak emerged on the 31st of December 2019 in Wuhan, China, causing commotion among the medical community and the rest of the world. This new species of coronavirus has been termed 2019-nCoV and has caused a considerable number of cases of infection and deaths in China and, to a growing degree, beyond China, becoming a worldwide public health emergency. 2019-nCoV has high homology to other pathogenic coronaviruses, such as those originating from bat-related zoonosis (SARS-CoV), which caused approximately 646 deaths in China at the start of the decade. The mortality rate for 2019-nCoV is not as high (approximately 2-3%), but its rapid propagation has resulted in the activation of protocols to stop its spread. This pathogen has the potential to become a pandemic. It is therefore vital to follow the personal care recommendations issued by the World Health Organization.
Charité1, University of Mississippi2, National and Kapodistrian University of Athens3, RWTH Aachen University4, National University of Singapore5, Boehringer Ingelheim6, Heidelberg University7, Saarland University8, University of São Paulo9, Wrocław Medical University10, Harvard University11, University of Toronto12, University of London13, Baylor University Medical Center14, Imperial College London15
TL;DR: In EMPEROR-Reduced (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction), empaglif Lozin significantly improved cardiovascular and renal outcomes in patients with heart failure and a reduced ejection fraction, independent of baseline diabetes status and across the continuum of HbA1c.
Abstract: Background: Sodium-glucose cotransporter 2 inhibitors improve outcomes in patients with heart failure with reduced ejection fraction, but additional information is needed about whether glycemic sta...