Showing papers by "University of Zurich published in 2021"
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 results of a collaborative multistakeholder consensus project on advanced bladder cancer (BC) have been incorporated in the 2020 guidelines, addressing those areas where it is unlikely that prospective comparative studies will be conducted.
946 citations
TL;DR: In this review, the scientific evidence on the risk factors of severity of COVID‐19 are highlighted and socioeconomic status, diet, lifestyle, geographical differences, ethnicity, exposed viral load, day of initiation of treatment, and quality of health care have been reported to influence individual outcomes.
Abstract: The pandemic of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused an unprecedented global social and economic impact, and high numbers of deaths. Many risk factors have been identified in the progression of COVID-19 into a severe and critical stage, including old age, male gender, underlying comorbidities such as hypertension, diabetes, obesity, chronic lung diseases, heart, liver and kidney diseases, tumors, clinically apparent immunodeficiencies, local immunodeficiencies, such as early type I interferon secretion capacity, and pregnancy. Possible complications include acute kidney injury, coagulation disorders, thoromboembolism. The development of lymphopenia and eosinopenia are laboratory indicators of COVID-19. Laboratory parameters to monitor disease progression include lactate dehydrogenase, procalcitonin, high-sensitivity C-reactive protein, proinflammatory cytokines such as interleukin (IL)-6, IL-1β, Krebs von den Lungen-6 (KL-6), and ferritin. The development of a cytokine storm and extensive chest computed tomography imaging patterns are indicators of a severe disease. In addition, socioeconomic status, diet, lifestyle, geographical differences, ethnicity, exposed viral load, day of initiation of treatment, and quality of health care have been reported to influence individual outcomes. In this review, we highlight the scientific evidence on the risk factors of severity of COVID-19.
703 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
University of Texas MD Anderson Cancer Center1, Cornell University2, Roswell Park Cancer Institute3, University of Adelaide4, Sarah Cannon Research Institute5, University of Cologne6, German Cancer Research Center7, University of Duisburg-Essen8, Fox Chase Cancer Center9, Institut Gustave Roussy10, University of Zurich11, Princess Margaret Cancer Centre12, Johns Hopkins University13, Emory University14, Amgen15, New York University16, Washington University in St. Louis17
TL;DR: Sotorasib showed anticancer activity in patients with KRAS p.G12C-mutated advanced solid tumors in a phase 1 study as discussed by the authors, and particularly promising anti-cancer activity was observed i...
Abstract: Background Sotorasib showed anticancer activity in patients with KRAS p.G12C–mutated advanced solid tumors in a phase 1 study, and particularly promising anticancer activity was observed i...
571 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, Cornell University24, Memorial Sloan Kettering Cancer Center25, 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
University of Glasgow1, University of London2, University of Edinburgh3, Lawrence Berkeley National Laboratory4, Cornell University5, Memorial Sloan Kettering Cancer Center6, University of Cambridge7, University of Zurich8, University of Lugano9, Maynooth University10, University of New South Wales11, ETH Zurich12, University of Liverpool13, Boston Children's Hospital14, National Institutes of Health15, Washington University in St. Louis16
TL;DR: In this paper, the authors demonstrate that the immunodominant SARS-CoV-2 spike (S) receptor binding motif (RBM) is a highly variable region of S and provide epidemiological, clinical, and molecular characterization of a prevalent, sentinel RBM mutation, N439K.
483 citations
TL;DR: In this article, the population of 47 compact binary mergers detected with a false-alarm rate of 0.614 were dynamically assembled, and the authors found that the BBH rate likely increases with redshift, but not faster than the star formation rate.
Abstract: We report on the population of 47 compact binary mergers detected with a false-alarm rate of 0.01 are dynamically assembled. Third, we estimate merger rates, finding RBBH = 23.9-+8.614.3 Gpc-3 yr-1 for BBHs and RBNS = 320-+240490 Gpc-3 yr-1 for binary neutron stars. We find that the BBH rate likely increases with redshift (85% credibility) but not faster than the star formation rate (86% credibility). Additionally, we examine recent exceptional events in the context of our population models, finding that the asymmetric masses of GW190412 and the high component masses of GW190521 are consistent with our models, but the low secondary mass of GW190814 makes it an outlier.
468 citations
TL;DR: In this paper, the authors show that during 2000-2019, glaciers lost a mass of 267 −±−16 gigatonnes per year, equivalent to 21 −−3 per cent of the observed sea-level rise.
Abstract: Glaciers distinct from the Greenland and Antarctic ice sheets are shrinking rapidly, altering regional hydrology1, raising global sea level2 and elevating natural hazards3. Yet, owing to the scarcity of constrained mass loss observations, glacier evolution during the satellite era is known only partially, as a geographic and temporal patchwork4,5. Here we reveal the accelerated, albeit contrasting, patterns of glacier mass loss during the early twenty-first century. Using largely untapped satellite archives, we chart surface elevation changes at a high spatiotemporal resolution over all of Earth’s glaciers. We extensively validate our estimates against independent, high-precision measurements and present a globally complete and consistent estimate of glacier mass change. We show that during 2000–2019, glaciers lost a mass of 267 ± 16 gigatonnes per year, equivalent to 21 ± 3 per cent of the observed sea-level rise6. We identify a mass loss acceleration of 48 ± 16 gigatonnes per year per decade, explaining 6 to 19 per cent of the observed acceleration of sea-level rise. Particularly, thinning rates of glaciers outside ice sheet peripheries doubled over the past two decades. Glaciers currently lose more mass, and at similar or larger acceleration rates, than the Greenland or Antarctic ice sheets taken separately7–9. By uncovering the patterns of mass change in many regions, we find contrasting glacier fluctuations that agree with the decadal variability in precipitation and temperature. These include a North Atlantic anomaly of decelerated mass loss, a strongly accelerated loss from northwestern American glaciers, and the apparent end of the Karakoram anomaly of mass gain10. We anticipate our highly resolved estimates to advance the understanding of drivers that govern the distribution of glacier change, and to extend our capabilities of predicting these changes at all scales. Predictions robustly benchmarked against observations are critically needed to design adaptive policies for the local- and regional-scale management of water resources and cryospheric risks, as well as for the global-scale mitigation of sea-level rise. Analysis of satellite stereo imagery uncovers two decades of mass change for all of Earth’s glaciers, revealing accelerated glacier shrinkage and regionally contrasting changes consistent with decadal climate variability.
380 citations
TL;DR: In this article, the authors reported the observation of gravitational waves from two compact binary coalescences in LIGO's and Virgo's third observing run with properties consistent with neutron star-black hole (NSBH) binaries.
Abstract: We report the observation of gravitational waves from two compact binary coalescences in LIGO’s and Virgo’s third observing run with properties consistent with neutron star–black hole (NSBH) binaries. The two events are named GW200105_162426 and GW200115_042309, abbreviated as GW200105 and GW200115; the first was observed by LIGO Livingston and Virgo and the second by all three LIGO–Virgo detectors. The source of GW200105 has component masses 8.9−1.5+1.2 and 1.9−0.2+0.3M⊙ , whereas the source of GW200115 has component masses 5.7−2.1+1.8 and 1.5−0.3+0.7M⊙ (all measurements quoted at the 90% credible level). The probability that the secondary’s mass is below the maximal mass of a neutron star is 89%–96% and 87%–98%, respectively, for GW200105 and GW200115, with the ranges arising from different astrophysical assumptions. The source luminosity distances are 280−110+110 and 300−100+150Mpc , respectively. The magnitude of the primary spin of GW200105 is less than 0.23 at the 90% credible level, and its orientation is unconstrained. For GW200115, the primary spin has a negative spin projection onto the orbital angular momentum at 88% probability. We are unable to constrain the spin or tidal deformation of the secondary component for either event. We infer an NSBH merger rate density of 45−33+75Gpc−3yr−1 when assuming that GW200105 and GW200115 are representative of the NSBH population or 130−69+112Gpc−3yr−1 under the assumption of a broader distribution of component masses.
374 citations
University of Michigan1, Cornell University2, University of Pennsylvania3, University of Massachusetts Medical School4, University of Naples Federico II5, Baylor College of Medicine6, Spanish National Research Council7, Complutense University of Madrid8, New York University9, Boston Children's Hospital10, University of Rome Tor Vergata11, NewYork–Presbyterian Hospital12, University of Pittsburgh13, University of Paris14, French Institute of Health and Medical Research15, National University of Cuyo16, Albert Einstein College of Medicine17, University of New Mexico18, Goethe University Frankfurt19, Weizmann Institute of Science20, University of Turku21, Sapienza University of Rome22, Virginia Commonwealth University23, St. Jude Children's Research Hospital24, Discovery Institute25, University of Copenhagen26, University of Tromsø27, Eötvös Loránd University28, Merck & Co.29, University of Freiburg30, Babraham Institute31, University of Adelaide32, University of South Australia33, University of Oviedo34, University of Chicago35, University of Graz36, National Institutes of Health37, Queens College38, City University of New York39, University of Tokyo40, University of Zurich41, University of British Columbia42, Austrian Academy of Sciences43, University of California, San Francisco44, Russian Academy of Sciences45, University Medical Center Groningen46, University of Cambridge47, University of Glasgow48, Rutgers University49, University of Padua50, Kazan Federal University51, University of Bern52, University of Oxford53, University of Oslo54, Oslo University Hospital55, Foundation for Research & Technology – Hellas56, University of Crete57, Francis Crick Institute58, Osaka University59, Chinese Academy of Sciences60, Harvard University61, Icahn School of Medicine at Mount Sinai62, Shanghai Jiao Tong University63, Karolinska Institutet64
TL;DR: In this paper, preclinical data linking autophagy dysfunction to the pathogenesis of major human disorders including cancer as well as cardiovascular, neurodegenerative, metabolic, pulmonary, renal, infectious, musculoskeletal, and ocular disorders.
Abstract: Autophagy is a core molecular pathway for the preservation of cellular and organismal homeostasis. Pharmacological and genetic interventions impairing autophagy responses promote or aggravate disease in a plethora of experimental models. Consistently, mutations in autophagy-related processes cause severe human pathologies. Here, we review and discuss preclinical data linking autophagy dysfunction to the pathogenesis of major human disorders including cancer as well as cardiovascular, neurodegenerative, metabolic, pulmonary, renal, infectious, musculoskeletal, and ocular disorders.
TL;DR: In this paper, the authors leveraged a prospective-longitudinal cohort study with data before and during the pandemic to describe patterns of noncompliance with COVID-19 related public health measures in young adults and to identify which characteristics increase the risk of non-compliance.
TL;DR: The data recorded by these instruments during their first and second observing runs are described, including the gravitational-wave strain arrays, released as time series sampled at 16384 Hz.
University of California, San Diego1, Northwestern University2, University of Zurich3, University of Amsterdam4, Washington University in St. Louis5, Claude Bernard University Lyon 16, University of Colorado Denver7, United States Department of Veterans Affairs8, Katholieke Universiteit Leuven9, University of Padua10, Queen Mary University of London11, Vanderbilt University12, University of Bordeaux13, Ege University14, University of Michigan15, Universidad del Desarrollo16, Flinders University17, University of Pisa18, University of Chile19, Case Western Reserve University20, Sanjay Gandhi Post Graduate Institute of Medical Sciences21, Chulalongkorn University22, University of Melbourne23, University of Ulsan24, Cornell University25, Mayo Clinic26, New York University27, Monash University28, University of Alberta29, University of Bern30, Kosin University31, University of Milan32, University of South Florida33, Autonomous University of Barcelona34, University College Hospital35, University of Washington36, National University of Singapore37, The Chinese University of Hong Kong38, Sun Yat-sen University39
TL;DR: The Chicago Classification v4.4.0 as discussed by the authors is the most recent version of the Chicago Classification, which uses high-resolution manometry (HRM) for motility disorders.
Abstract: Chicago Classification v4.0 (CCv4.0) is the updated classification scheme for esophageal motility disorders using metrics from high-resolution manometry (HRM). Fifty-two diverse international experts separated into seven working subgroups utilized formal validated methodologies over two-years to develop CCv4.0. Key updates in CCv.4.0 consist of a more rigorous and expansive HRM protocol that incorporates supine and upright test positions as well as provocative testing, a refined definition of esophagogastric junction (EGJ) outflow obstruction (EGJOO), more stringent diagnostic criteria for ineffective esophageal motility and description of baseline EGJ metrics. Further, the CCv4.0 sought to define motility disorder diagnoses as conclusive and inconclusive based on associated symptoms, and findings on provocative testing as well as supportive testing with barium esophagram with tablet and/or functional lumen imaging probe. These changes attempt to minimize ambiguity in prior iterations of Chicago Classification and provide more standardized and rigorous criteria for patterns of disorders of peristalsis and obstruction at the EGJ.
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, San Francisco28, University of California, Berkeley29, 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, Johns Hopkins University62, University of Turin63, 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: Systemic antibody production against SARS-CoV-2 develops mainly in severe COVID-19, with very high IgA titers seen in patients with severe ARDS, whereas mild disease may be associated with transient production of SARS-Cov-2-specific antibodies but stimulate mucosal SARs- coV- 2-specific IgA secretion.
Abstract: Background Whereas severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibody tests are increasingly being used to estimate the prevalence of SARS-CoV-2 infection, the determinants of these antibody responses remain unclear. Objectives Our aim was to evaluate systemic and mucosal antibody responses toward SARS-CoV-2 in mild versus severe coronavirus disease 2019 (COVID-19) cases. Methods Using immunoassays specific for SARS-CoV-2 spike proteins, we determined SARS-CoV-2–specific IgA and IgG in sera and mucosal fluids of 2 cohorts, including SARS-CoV-2 PCR-positive patients (n = 64) and PCR-positive and PCR-negtive health care workers (n = 109). Results SARS-CoV-2–specific serum IgA titers in patients with mild COVID-19 were often transiently positive, whereas serum IgG titers remained negative or became positive 12 to 14 days after symptom onset. Conversely, patients with severe COVID-19 showed a highly significant increase of SARS-CoV-2–specific serum IgA and IgG titers after symptom onset. Very high titers of SARS-CoV-2–specific serum IgA were correlated with severe acute respiratory distress syndrome. Interestingly, some health care workers with negative SARS-CoV-2–specific serum antibody titers showed SARS-CoV-2–specific IgA in mucosal fluids with virus-neutralizing capacity in some cases. SARS-CoV-2–specific IgA titers in nasal fluids were inversely correlated with age. Conclusions Systemic antibody production against SARS-CoV-2 develops mainly in patients with severe COVID-19, with very high IgA titers seen in patients with severe acute respiratory distress syndrome, whereas mild disease may be associated with transient production of SARS-CoV-2–specific antibodies but may stimulate mucosal SARS-CoV-2–specific IgA secretion.
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
TL;DR: In this paper, the authors used high-resolution scanning tunnelling microscopy to discover an unconventional chiral charge order in a kagome material, KV3Sb5, with both a topological band structure and a superconducting ground state.
Abstract: Intertwining quantum order and non-trivial topology is at the frontier of condensed matter physics1–4. A charge-density-wave-like order with orbital currents has been proposed for achieving the quantum anomalous Hall effect5,6 in topological materials and for the hidden phase in cuprate high-temperature superconductors7,8. However, the experimental realization of such an order is challenging. Here we use high-resolution scanning tunnelling microscopy to discover an unconventional chiral charge order in a kagome material, KV3Sb5, with both a topological band structure and a superconducting ground state. Through both topography and spectroscopic imaging, we observe a robust 2 × 2 superlattice. Spectroscopically, an energy gap opens at the Fermi level, across which the 2 × 2 charge modulation exhibits an intensity reversal in real space, signalling charge ordering. At the impurity-pinning-free region, the strength of intrinsic charge modulations further exhibits chiral anisotropy with unusual magnetic field response. Theoretical analysis of our experiments suggests a tantalizing unconventional chiral charge density wave in the frustrated kagome lattice, which can not only lead to a large anomalous Hall effect with orbital magnetism, but also be a precursor of unconventional superconductivity. An unconventional chiral charge order is observed in a kagome superconductor by scanning tunnelling microscopy. This charge order has unusual magnetic tunability and intertwines with electronic topology.
TL;DR: In this article, the authors report on initial follow-up 4 months after mild/moderate or severe/critical COVID-19 according to the WHO severity classification, patients after severe or critical CoV-19 had a 20.9 (95% CI 12.4-29.4, p=0.01) lower diffusing capacity (DLCO %-predicted, reduced 6MWD, and exerciseinduced oxygen desaturation.
Abstract: Background The coronavirus infectious disease (COVID-19) pandemic is an ongoing global health care challenge. Up to one third of hospitalised patients develop severe pulmonary complications and ARDS. Pulmonary outcomes following COVID-19 are unknown. Methods The Swiss COVID-19 lung study is a multicentre prospective cohort investigating pulmonary sequela of COVID-19. We report on initial follow-up 4 months after mild/moderate or severe/critical COVID-19 according to the WHO severity classification. Results 113 COVID-19 survivors were included (mild/moderate 47, severe/critical 66). We confirmed several comorbidities as risk factors for severe/critical disease. Severe/critical disease was associated with impaired pulmonary function, i.e. diffusing capacity (DLCO) %-predicted, reduced 6-MWD, and exercise-induced oxygen desaturation. After adjustment for potential confounding by age, sex, and BMI, patients after severe/critical COVID-19 had a 20.9 (95% CI 12.4-29.4, p=0.01) lower DLCO %-predicted at follow up. DLCO %-predicted was the strongest independent factor associated with previous severe/critical disease when age, sex, BMI, 6MWD, and minimal SpO2 at exercise, were included in the multivariable model (adjusted odds ratio [OR] per 10%-predicted 0.59 [95% CI 0. 37-0.87], p=0.01). Mosaic hypoattenuation on chest computed tomography at follow-up was significantly associated with previous severe/critical COVID-19 including adjustment for age and sex (adjusted OR 11.7 [95%CI 1.7-239), p=0.03). Conclusions Four months after SARS CoV-2 infection, severe/critical COVID-19 was associated with significant functional and radiological abnormalities, potentially due to small airway and lung parenchymal disease. A systematic follow-up for survivors needs to be evaluated to optimise care for patients recovering from COVID-19.
Queen Mary University of London1, Harvard University2, University of Auckland3, St. Michael's Hospital4, Winthrop-University Hospital5, Karolinska Institutet6, University of Zurich7, Pontifical Catholic University of Chile8, University of Copenhagen9, Boston Children's Hospital10, University of Parma11, University of London12, University of Colorado Denver13, Ben-Gurion University of the Negev14, McMaster University15, Case Western Reserve University16, Katholieke Universiteit Leuven17, University of Tampere18, Columbia University Medical Center19, Medical University of Łódź20, Pennsylvania State University21, University of Birmingham22, University of Otago23, Jikei University School of Medicine24, QIMR Berghofer Medical Research Institute25, Dartmouth College26, University of Helsinki27, University College of Medical Sciences28, Menzies Research Institute29, University of Melbourne30, University of Delhi31
TL;DR: A 2017 meta-analysis of data from 25 randomised controlled trials (RCTs) of vitamin D supplementation for the prevention of acute respiratory infections (ARIs) revealed a protective effect of this intervention as discussed by the authors.
TL;DR: Dsuite facilitates the assessment of evidence for gene flow, especially across larger genomic data sets, by allowing genome scale calculations of the D and f4‐ratio statistics across all combinations of tens or hundreds of populations or species directly from a variant call format (VCF) file.
Abstract: Patterson's D, also known as the ABBA-BABA statistic, and related statistics such as the f4 -ratio, are commonly used to assess evidence of gene flow between populations or closely related species. Currently available implementations often require custom file formats, implement only small subsets of the available statistics, and are impractical to evaluate all gene flow hypotheses across data sets with many populations or species due to computational inefficiencies. Here, we present a new software package Dsuite, an efficient implementation allowing genome scale calculations of the D and f4 -ratio statistics across all combinations of tens or hundreds of populations or species directly from a variant call format (VCF) file. Our program also implements statistics suited for application to genomic windows, providing evidence of whether introgression is confined to specific loci, and it can also aid in interpretation of a system of f4 -ratio results with the use of the "f-branch" method. Dsuite is available at https://github.com/millanek/Dsuite, is straightforward to use, substantially more computationally efficient than comparable programs, and provides a convenient suite of tools and statistics, including some not previously available in any software package. Thus, Dsuite facilitates the assessment of evidence for gene flow, especially across larger genomic data sets.
TL;DR: The potential outcomes of this exclusion of older adults from a society based on physical social contact are discussed and recommendations for rectifying the situation are provided, with a particular focus on older adults in long-term care facilities.
Abstract: The COVID-19 pandemic has excluded older adults from a society based on physical social contact. Vulnerable populations like older adults also tend to be excluded from digital services because they opt not to use the internet, lack necessary devices and network connectivity, or inexperience using the technology. Older adults who are frail and are not online, many of whom are in long-term care facilities, struggle with the double burden of social and digital exclusion. This paper discusses the potential outcomes of this exclusion and provides recommendations for rectifying the situation, with a particular focus on older adults in long-term care facilities.
Free University of Berlin1, Hospital Kuala Lumpur2, Cleveland Clinic3, Mater Dei Hospital4, University of Zurich5, Kantonsspital St. Gallen6, Medical University of Vienna7, Montreal Children's Hospital8, University of Cincinnati9, University of Southern Denmark10, Technische Universität München11, Opole University12, Federal University of Paraná13, University of Southampton14, Federal University of São Paulo15, New York University16, University of Debrecen17, Istanbul University18, Pompeu Fabra University19, University of Coimbra20, Vrije Universiteit Brussel21, Bethel University22, Laval University23, Hiroshima University24, Medical University of South Carolina25, Hannover Medical School26, Rappaport Faculty of Medicine27, Koç University28, Mahidol University29, University of Helsinki30, Royal Free Hospital31, Fraunhofer Society32, National and Kapodistrian University of Athens33, University of Groningen34, Nippon Medical School35, University of Milan36, Universidad Nacional de Asunción37, Johns Hopkins University38, Hacettepe University39, University of Paris40, University of Mainz41, University of Perugia42, University of Toronto43, University of Copenhagen44, Aarhus University Hospital45, Peking University46
TL;DR: This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS) on 3 December 2020 as mentioned in this paper, with the participation of 64 delegates of 50 national and international societies and from 31 countries.
Abstract: This update and revision of the international guideline for urticaria was developed following the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. It is a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the Global Allergy and Asthma European Network (GA²LEN) and its Urticaria and Angioedema Centers of Reference and Excellence (UCAREs and ACAREs), the European Dermatology Forum (EDF; EuroGuiDerm), and the Asia Pacific Association of Allergy, Asthma and Clinical Immunology with the participation of 64 delegates of 50 national and international societies and from 31 countries. The consensus conference was held on 3 December 2020. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). Urticaria is a frequent, mast cell-driven disease that presents with wheals, angioedema, or both. The lifetime prevalence for acute urticaria is approximately 20%. Chronic spontaneous or inducible urticaria is disabling, impairs quality of life, and affects performance at work and school. This updated version of the international guideline for urticaria covers the definition and classification of urticaria and outlines expert-guided and evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria.
01 Mar 2021
TL;DR: In this article, the authors search governmental and non-governmental databases to identify 222 devices approved in the USA and 240 devices in Europe and recommend more transparency on how devices are regulated and approved to enable and improve public trust, efficacy, safety, and quality of AI/ML-based medical devices.
Abstract: Summary There has been a surge of interest in artificial intelligence and machine learning (AI/ML)-based medical devices. However, it is poorly understood how and which AI/ML-based medical devices have been approved in the USA and Europe. We searched governmental and non-governmental databases to identify 222 devices approved in the USA and 240 devices in Europe. The number of approved AI/ML-based devices has increased substantially since 2015, with many being approved for use in radiology. However, few were qualified as high-risk devices. Of the 124 AI/ML-based devices commonly approved in the USA and Europe, 80 were first approved in Europe. One possible reason for approval in Europe before the USA might be the potentially relatively less rigorous evaluation of medical devices in Europe. The substantial number of approved devices highlight the need to ensure rigorous regulation of these devices. Currently, there is no specific regulatory pathway for AI/ML-based medical devices in the USA or Europe. We recommend more transparency on how devices are regulated and approved to enable and improve public trust, efficacy, safety, and quality of AI/ML-based medical devices. A comprehensive, publicly accessible database with device details for Conformite Europeene (CE)-marked medical devices in Europe and US Food and Drug Administration approved devices is needed.
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 Natural Resources and Life Sciences, Vienna10, University of Graz11, 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, University of Dundee26, UNESCO27, 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, International Centre for Integrated Mountain Development36, Utrecht University37, 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: A review of recent, emerging, and anticipated trends in probiotic and prebiotic science, and a vision for broad areas of developing influence in the field can be found in this article.
TL;DR: A framework to define the scope of future implementation research on lung cancer screening programmes referred to as Screening Planning and Implementation RAtionale for Lung cancer (SPIRAL) is presented.
Abstract: In the past decade, the introduction of molecularly targeted agents and immune-checkpoint inhibitors has led to improved survival outcomes for patients with advanced-stage lung cancer; however, this disease remains the leading cause of cancer-related mortality worldwide. Two large randomized controlled trials of low-dose CT (LDCT)-based lung cancer screening in high-risk populations - the US National Lung Screening Trial (NLST) and NELSON - have provided evidence of a statistically significant mortality reduction in patients. LDCT-based screening programmes for individuals at a high risk of lung cancer have already been implemented in the USA. Furthermore, implementation programmes are currently underway in the UK following the success of the UK Lung Cancer Screening (UKLS) trial, which included the Liverpool Health Lung Project, Manchester Lung Health Check, the Lung Screen Uptake Trial, the West London Lung Cancer Screening pilot and the Yorkshire Lung Screening trial. In this Review, we focus on the current evidence on LDCT-based lung cancer screening and discuss the clinical developments in high-risk populations worldwide; additionally, we address aspects such as cost-effectiveness. We present a framework to define the scope of future implementation research on lung cancer screening programmes referred to as Screening Planning and Implementation RAtionale for Lung cancer (SPIRAL).
TL;DR: In this article, the authors describe five monoclonal antibodies cross-reacting with the stem helix of multiple β-coronavirus spike glycoproteins isolated from COVID-19 convalescent individuals.
Abstract: The spillovers of β-coronaviruses in humans and the emergence of SARS-CoV-2 variants highlight the need for broad coronavirus countermeasures. We describe five monoclonal antibodies (mAbs) cross-reacting with the stem helix of multiple β-coronavirus spike glycoproteins isolated from COVID-19 convalescent individuals. Using structural and functional studies we show that the mAb with the greatest breadth (S2P6) neutralizes pseudotyped viruses from three different subgenera through inhibition of membrane fusion and delineate the molecular basis for its cross-reactivity. S2P6 reduces viral burden in hamsters challenged with SARS-CoV-2 through viral neutralization and Fc-mediated effector functions. Stem helix antibodies are rare, oftentimes of narrow specificity and can acquire neutralization breadth through somatic mutations. These data provide a framework for structure-guided design of pan-β-coronavirus vaccines eliciting broad protection.
TL;DR: In this article, the first and second observing runs of the Advanced LIGO and Virgo detector network were used to obtain the first standard-siren measurement of the Hubble constant (H 0).
Abstract: This paper presents the gravitational-wave measurement of the Hubble constant (H 0) using the detections from the first and second observing runs of the Advanced LIGO and Virgo detector network. The presence of the transient electromagnetic counterpart of the binary neutron star GW170817 led to the first standard-siren measurement of H 0. Here we additionally use binary black hole detections in conjunction with galaxy catalogs and report a joint measurement. Our updated measurement is H 0 = km s−1 Mpc−1 (68.3% of the highest density posterior interval with a flat-in-log prior) which is an improvement by a factor of 1.04 (about 4%) over the GW170817-only value of km s−1 Mpc−1. A significant additional contribution currently comes from GW170814, a loud and well-localized detection from a part of the sky thoroughly covered by the Dark Energy Survey. With numerous detections anticipated over the upcoming years, an exhaustive understanding of other systematic effects are also going to become increasingly important. These results establish the path to cosmology using gravitational-wave observations with and without transient electromagnetic counterparts.
TL;DR: The updated taxonomy of Negarnaviricota is presented, as now accepted by the ICTV, after the phylum was amended and emended in March 2020.
Abstract: In March 2020, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. At the genus rank, 20 new genera were added, two were deleted, one was moved, and three were renamed. At the species rank, 160 species were added, four were deleted, ten were moved and renamed, and 30 species were renamed. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV.