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Showing papers by "Harvard University published in 2020"


Journal ArticleDOI
Theo Vos1, Theo Vos2, Theo Vos3, Stephen S Lim  +2416 moreInstitutions (246)
TL;DR: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates, and there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries.

5,802 citations


Journal ArticleDOI
27 May 2020-Nature
TL;DR: A catalogue of predicted loss-of-function variants in 125,748 whole-exome and 15,708 whole-genome sequencing datasets from the Genome Aggregation Database (gnomAD) reveals the spectrum of mutational constraints that affect these human protein-coding genes.
Abstract: Genetic variants that inactivate protein-coding genes are a powerful source of information about the phenotypic consequences of gene disruption: genes that are crucial for the function of an organism will be depleted of such variants in natural populations, whereas non-essential genes will tolerate their accumulation. However, predicted loss-of-function variants are enriched for annotation errors, and tend to be found at extremely low frequencies, so their analysis requires careful variant annotation and very large sample sizes1. Here we describe the aggregation of 125,748 exomes and 15,708 genomes from human sequencing studies into the Genome Aggregation Database (gnomAD). We identify 443,769 high-confidence predicted loss-of-function variants in this cohort after filtering for artefacts caused by sequencing and annotation errors. Using an improved model of human mutation rates, we classify human protein-coding genes along a spectrum that represents tolerance to inactivation, validate this classification using data from model organisms and engineered human cells, and show that it can be used to improve the power of gene discovery for both common and rare diseases. A catalogue of predicted loss-of-function variants in 125,748 whole-exome and 15,708 whole-genome sequencing datasets from the Genome Aggregation Database (gnomAD) reveals the spectrum of mutational constraints that affect these human protein-coding genes.

4,913 citations


Journal ArticleDOI
TL;DR: CVD burden continues its decades-long rise for almost all countries outside high-income countries, and alarmingly, the age-standardized rate of CVD has begun to rise in some locations where it was previously declining in high- income countries.

3,315 citations



Journal ArticleDOI
TL;DR: Evidence from a selection of research topics relevant to pandemics is discussed, including work on navigating threats, social and cultural influences on behaviour, science communication, moral decision-making, leadership, and stress and coping.
Abstract: The COVID-19 pandemic represents a massive global health crisis. Because the crisis requires large-scale behaviour change and places significant psychological burdens on individuals, insights from the social and behavioural sciences can be used to help align human behaviour with the recommendations of epidemiologists and public health experts. Here we discuss evidence from a selection of research topics relevant to pandemics, including work on navigating threats, social and cultural influences on behaviour, science communication, moral decision-making, leadership, and stress and coping. In each section, we note the nature and quality of prior research, including uncertainty and unsettled issues. We identify several insights for effective response to the COVID-19 pandemic and highlight important gaps researchers should move quickly to fill in the coming weeks and months.

3,223 citations


Book
Georges Aad1, E. Abat2, Jalal Abdallah3, Jalal Abdallah4  +3029 moreInstitutions (164)
23 Feb 2020
TL;DR: The ATLAS detector as installed in its experimental cavern at point 1 at CERN is described in this paper, where a brief overview of the expected performance of the detector when the Large Hadron Collider begins operation is also presented.
Abstract: The ATLAS detector as installed in its experimental cavern at point 1 at CERN is described in this paper. A brief overview of the expected performance of the detector when the Large Hadron Collider begins operation is also presented.

3,111 citations


Journal ArticleDOI
TL;DR: In patients with unresectable hepatocellular carcinoma, atezolIZumab combined with bevacizumab resulted in better overall and progression-free survival outcomes than sorafenib.
Abstract: Background The combination of atezolizumab and bevacizumab showed encouraging antitumor activity and safety in a phase 1b trial involving patients with unresectable hepatocellular carcinom...

3,085 citations


Journal ArticleDOI
TL;DR: The largest declines in risk exposure from 2010 to 2019 were among a set of risks that are strongly linked to social and economic development, including household air pollution; unsafe water, sanitation, and handwashing; and child growth failure.

3,059 citations


Posted ContentDOI
12 Oct 2020-bioRxiv
TL;DR: ‘weighted-nearest neighbor’ analysis is introduced, an unsupervised framework to learn the relative utility of each data type in each cell, enabling an integrative analysis of multiple modalities.
Abstract: The simultaneous measurement of multiple modalities, known as multimodal analysis, represents an exciting frontier for single-cell genomics and necessitates new computational methods that can define cellular states based on multiple data types. Here, we introduce ‘weighted-nearest neighbor’ analysis, an unsupervised framework to learn the relative utility of each data type in each cell, enabling an integrative analysis of multiple modalities. We apply our procedure to a CITE-seq dataset of hundreds of thousands of human white blood cells alongside a panel of 228 antibodies to construct a multimodal reference atlas of the circulating immune system. We demonstrate that integrative analysis substantially improves our ability to resolve cell states and validate the presence of previously unreported lymphoid subpopulations. Moreover, we demonstrate how to leverage this reference to rapidly map new datasets, and to interpret immune responses to vaccination and COVID-19. Our approach represents a broadly applicable strategy to analyze single-cell multimodal datasets, including paired measurements of RNA and chromatin state, and to look beyond the transcriptome towards a unified and multimodal definition of cellular identity. Availability Installation instructions, documentation, tutorials, and CITE-seq datasets are available at http://www.satijalab.org/seurat

2,924 citations


Journal ArticleDOI
01 May 2020-Science
TL;DR: Real-time mobility data from Wuhan and detailed case data including travel history are used to elucidate the role of case importation in transmission in cities across China and to ascertain the impact of control measures.
Abstract: The ongoing coronavirus disease 2019 (COVID-19) outbreak expanded rapidly throughout China. Major behavioral, clinical, and state interventions were undertaken to mitigate the epidemic and prevent the persistence of the virus in human populations in China and worldwide. It remains unclear how these unprecedented interventions, including travel restrictions, affected COVID-19 spread in China. We used real-time mobility data from Wuhan and detailed case data including travel history to elucidate the role of case importation in transmission in cities across China and to ascertain the impact of control measures. Early on, the spatial distribution of COVID-19 cases in China was explained well by human mobility data. After the implementation of control measures, this correlation dropped and growth rates became negative in most locations, although shifts in the demographics of reported cases were still indicative of local chains of transmission outside of Wuhan. This study shows that the drastic control measures implemented in China substantially mitigated the spread of COVID-19.

2,362 citations


Journal ArticleDOI
TL;DR: The current understanding of the pathogenesis, epidemiology, management and outcomes of patients with COVID-19 who develop venous or arterial thrombosis, and of those with preexistingThrombotic disease who develop CO VID-19 are reviewed.

Journal ArticleDOI
14 Apr 2020-Science
TL;DR: Using existing data to build a deterministic model of multiyear interactions between existing coronaviruses, with a focus on the United States, is used to project the potential epidemic dynamics and pressures on critical care capacity over the next 5 years and projected that recurrent wintertime outbreaks of SARS-CoV-2 will probably occur after the initial, most severe pandemic wave.
Abstract: It is urgent to understand the future of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) transmission. We used estimates of seasonality, immunity, and cross-immunity for human coronavirus OC43 (HCoV-OC43) and HCoV-HKU1 using time-series data from the United States to inform a model of SARS-CoV-2 transmission. We projected that recurrent wintertime outbreaks of SARS-CoV-2 will probably occur after the initial, most severe pandemic wave. Absent other interventions, a key metric for the success of social distancing is whether critical care capacities are exceeded. To avoid this, prolonged or intermittent social distancing may be necessary into 2022. Additional interventions, including expanded critical care capacity and an effective therapeutic, would improve the success of intermittent distancing and hasten the acquisition of herd immunity. Longitudinal serological studies are urgently needed to determine the extent and duration of immunity to SARS-CoV-2. Even in the event of apparent elimination, SARS-CoV-2 surveillance should be maintained because a resurgence in contagion could be possible as late as 2024.

Journal ArticleDOI
TL;DR: The extrapulmonary organ-specific pathophysiology, presentations and management considerations for patients with COVID-19 are reviewed to aid clinicians and scientists in recognizing and monitoring the spectrum of manifestations, and in developing research priorities and therapeutic strategies for all organ systems involved.
Abstract: Although COVID-19 is most well known for causing substantial respiratory pathology, it can also result in several extrapulmonary manifestations. These conditions include thrombotic complications, myocardial dysfunction and arrhythmia, acute coronary syndromes, acute kidney injury, gastrointestinal symptoms, hepatocellular injury, hyperglycemia and ketosis, neurologic illnesses, ocular symptoms, and dermatologic complications. Given that ACE2, the entry receptor for the causative coronavirus SARS-CoV-2, is expressed in multiple extrapulmonary tissues, direct viral tissue damage is a plausible mechanism of injury. In addition, endothelial damage and thromboinflammation, dysregulation of immune responses, and maladaptation of ACE2-related pathways might all contribute to these extrapulmonary manifestations of COVID-19. Here we review the extrapulmonary organ-specific pathophysiology, presentations and management considerations for patients with COVID-19 to aid clinicians and scientists in recognizing and monitoring the spectrum of manifestations, and in developing research priorities and therapeutic strategies for all organ systems involved.

Journal ArticleDOI
TL;DR: In this paper, the expression of viral entry-associated genes in single-cell RNA-sequencing data from multiple tissues from healthy human donors was investigated, and co-detected these transcripts in specific respiratory, corneal and intestinal epithelial cells, potentially explaining the high efficiency of SARS-CoV-2 transmission.
Abstract: We investigated SARS-CoV-2 potential tropism by surveying expression of viral entry-associated genes in single-cell RNA-sequencing data from multiple tissues from healthy human donors. We co-detected these transcripts in specific respiratory, corneal and intestinal epithelial cells, potentially explaining the high efficiency of SARS-CoV-2 transmission. These genes are co-expressed in nasal epithelial cells with genes involved in innate immunity, highlighting the cells' potential role in initial viral infection, spread and clearance. The study offers a useful resource for further lines of inquiry with valuable clinical samples from COVID-19 patients and we provide our data in a comprehensive, open and user-friendly fashion at www.covid19cellatlas.org.

Journal ArticleDOI
TL;DR: TIMER2.0 (http://timer.cistrome.org/) provides more robust estimation of immune infiltration levels for The Cancer Genome Atlas (TCGA) or user-provided tumor profiles using six state-of-the-art algorithms.
Abstract: Tumor progression and the efficacy of immunotherapy are strongly influenced by the composition and abundance of immune cells in the tumor microenvironment. Due to the limitations of direct measurement methods, computational algorithms are often used to infer immune cell composition from bulk tumor transcriptome profiles. These estimated tumor immune infiltrate populations have been associated with genomic and transcriptomic changes in the tumors, providing insight into tumor-immune interactions. However, such investigations on large-scale public data remain challenging. To lower the barriers for the analysis of complex tumor-immune interactions, we significantly improved our previous web platform TIMER. Instead of just using one algorithm, TIMER2.0 (http://timer.cistrome.org/) provides more robust estimation of immune infiltration levels for The Cancer Genome Atlas (TCGA) or user-provided tumor profiles using six state-of-the-art algorithms. TIMER2.0 provides four modules for investigating the associations between immune infiltrates and genetic or clinical features, and four modules for exploring cancer-related associations in the TCGA cohorts. Each module can generate a functional heatmap table, enabling the user to easily identify significant associations in multiple cancer types simultaneously. Overall, the TIMER2.0 web server provides comprehensive analysis and visualization functions of tumor infiltrating immune cells.

Journal ArticleDOI
TL;DR: The PICRUSt2 algorithm includes steps that optimize genome prediction, including placing sequences into a reference phylogeny rather than relying on predictions limited to reference OTUs, and basing predictions on a larger database of reference genomes and gene families, and enabling predictions of complex phenotypes and integration of custom databases.
Abstract: To the Editor — One limitation of microbial community marker-gene sequencing is that it does not provide information about the functional composition of sampled communities. PICRUSt1 was developed in 2013 to predict the functional potential of a bacterial community on the basis of marker gene sequencing profiles, and now we present PICRUSt2 (https://github. com/picrust/picrust2), which improves on the original method. Specifically, PICRUSt2 contains an updated and larger database of gene families and reference genomes, provides interoperability with any operational taxonomic unit (OTU)-picking or denoising algorithm, and enables phenotype predictions. Benchmarking shows that PICRUSt2 is more accurate than PICRUSt and other competing methods overall. PICRUSt2 also allows the addition of custom reference databases. We highlight these improvements and also important caveats regarding the use of predicted metagenomes. The most common method for profiling bacterial communities is to sequence the conserved 16S rRNA gene. Functional profiles cannot be directly identified using 16S rRNA gene sequence data owing to strain variation, so several methods have been developed to predict microbial community functions from taxonomic profiles (amplicon sequences) alone1–5. Shotgun metagenomics sequencing (MGS), which sequences entire genomes rather than marker genes, can also be used to characterize the functions of a community, but does not work well if there is host contamination — for example, in a biopsy — or if there is very little community biomass. PICRUSt (hereafter “PICRUSt1”) was developed for prediction of functions from 16S marker sequences, and it is widely used but has some limitations. Standard PICRUSt1 workflows require input sequences to be OTUs generated from closed-reference OTU-picking against a compatible version of the Greengenes database6. Due to this restriction to reference OTUs, the default PICRUSt1 workflow is incompatible with sequence denoising methods, which produce amplicon sequence variants (ASVs) rather than OTUs. ASVs have finer resolution, allowing closely related organisms to be more readily distinguished. Furthermore, the bacterial reference databases used by PICRUSt1 have not been updated since 2013 and lack thousands of recently added gene families. We expected that optimizing genome prediction would improve accuracy of functional predictions. Therefore, the PICRUSt2 algorithm (Fig. 1a) includes steps that optimize genome prediction, including placing sequences into a reference phylogeny rather than relying on predictions limited to reference OTUs (Fig. 1b); basing predictions on a larger database of reference genomes and gene families (Fig. 1c); more stringently predicting pathway abundance (Supplementary Fig. 1); and enabling predictions of complex phenotypes and integration of custom databases. PICRUSt2 integrates existing open-source tools to predict genomes of environmentally sampled 16S rRNA gene sequences. ASVs are placed into a reference tree, which is used as the basis of functional predictions. 0 5,000 10,000 15,000 20,000

Journal ArticleDOI
Carly G. K. Ziegler, Samuel J. Allon, Sarah K. Nyquist, Ian M. Mbano1, Vincent N. Miao, Constantine N. Tzouanas, Yuming Cao2, Ashraf S. Yousif3, Julia Bals3, Blake M. Hauser4, Blake M. Hauser3, Jared Feldman4, Jared Feldman3, Christoph Muus4, Christoph Muus5, Marc H. Wadsworth, Samuel W. Kazer, Travis K. Hughes, Benjamin Doran, G. James Gatter5, G. James Gatter6, G. James Gatter3, Marko Vukovic, Faith Taliaferro7, Faith Taliaferro5, Benjamin E. Mead, Zhiru Guo2, Jennifer P. Wang2, Delphine Gras8, Magali Plaisant9, Meshal Ansari, Ilias Angelidis, Heiko Adler, Jennifer M.S. Sucre10, Chase J. Taylor10, Brian M. Lin4, Avinash Waghray4, Vanessa Mitsialis7, Vanessa Mitsialis11, Daniel F. Dwyer11, Kathleen M. Buchheit11, Joshua A. Boyce11, Nora A. Barrett11, Tanya M. Laidlaw11, Shaina L. Carroll12, Lucrezia Colonna13, Victor Tkachev4, Victor Tkachev7, Christopher W. Peterson13, Christopher W. Peterson14, Alison Yu7, Alison Yu15, Hengqi Betty Zheng15, Hengqi Betty Zheng13, Hannah P. Gideon16, Caylin G. Winchell16, Philana Ling Lin7, Philana Ling Lin16, Colin D. Bingle17, Scott B. Snapper7, Scott B. Snapper11, Jonathan A. Kropski18, Jonathan A. Kropski10, Fabian J. Theis, Herbert B. Schiller, Laure-Emmanuelle Zaragosi9, Pascal Barbry9, Alasdair Leslie1, Alasdair Leslie19, Hans-Peter Kiem13, Hans-Peter Kiem14, JoAnne L. Flynn16, Sarah M. Fortune4, Sarah M. Fortune3, Sarah M. Fortune5, Bonnie Berger6, Robert W. Finberg2, Leslie S. Kean7, Leslie S. Kean4, Manuel Garber2, Aaron G. Schmidt3, Aaron G. Schmidt4, Daniel Lingwood3, Alex K. Shalek, Jose Ordovas-Montanes, Nicholas E. Banovich, Alvis Brazma, Tushar J. Desai, Thu Elizabeth Duong, Oliver Eickelberg, Christine S. Falk, Michael Farzan20, Ian A. Glass, Muzlifah Haniffa, Peter Horvath, Deborah T. Hung, Naftali Kaminski, Mark A. Krasnow, Malte Kühnemund, Robert Lafyatis, Haeock Lee, Sylvie Leroy, Sten Linnarson, Joakim Lundeberg, Kerstin B. Meyer, Alexander V. Misharin, Martijn C. Nawijn, Marko Nikolic, Dana Pe'er, Joseph E. Powell, Stephen R. Quake, Jay Rajagopal, Purushothama Rao Tata, Emma L. Rawlins, Aviv Regev, Paul A. Reyfman, Mauricio Rojas, Orit Rosen, Kourosh Saeb-Parsy, Christos Samakovlis, Herbert B. Schiller, Joachim L. Schultze, Max A. Seibold, Douglas P. Shepherd, Jason R. Spence, Avrum Spira, Xin Sun, Sarah A. Teichmann, Fabian J. Theis, Alexander M. Tsankov, Maarten van den Berge, Michael von Papen, Jeffrey A. Whitsett, Ramnik J. Xavier, Yan Xu, Kun Zhang 
28 May 2020-Cell
TL;DR: The data suggest that SARS-CoV-2 could exploit species-specific interferon-driven upregulation of ACE2, a tissue-protective mediator during lung injury, to enhance infection.

Journal ArticleDOI
TL;DR: Multisystem inflammatory syndrome in children associated with SARS-CoV-2 led to serious and life-threatening illness in previously healthy children and adolescents.
Abstract: Background Understanding the epidemiology and clinical course of multisystem inflammatory syndrome in children (MIS-C) and its temporal association with coronavirus disease 2019 (Covid-19)...

Journal ArticleDOI
TL;DR: A study of 246 individuals with seasonal respiratory virus infections randomized to wear or not wear a surgical face mask showed that masks can significantly reduce detection of coronavirus and influenza virus in exhaled breath and may help interrupt virus transmission.
Abstract: We identified seasonal human coronaviruses, influenza viruses and rhinoviruses in exhaled breath and coughs of children and adults with acute respiratory illness. Surgical face masks significantly reduced detection of influenza virus RNA in respiratory droplets and coronavirus RNA in aerosols, with a trend toward reduced detection of coronavirus RNA in respiratory droplets. Our results indicate that surgical face masks could prevent transmission of human coronaviruses and influenza viruses from symptomatic individuals.

Journal ArticleDOI
TL;DR: Community-level intervention and prevention efforts, including health communication strategies, designed to reach these groups could help address various mental health conditions associated with the COVID-19 pandemic.
Abstract: The coronavirus disease 2019 (COVID-19) pandemic has been associated with mental health challenges related to the morbidity and mortality caused by the disease and to mitigation activities, including the impact of physical distancing and stay-at-home orders.* Symptoms of anxiety disorder and depressive disorder increased considerably in the United States during April-June of 2020, compared with the same period in 2019 (1,2). To assess mental health, substance use, and suicidal ideation during the pandemic, representative panel surveys were conducted among adults aged ≥18 years across the United States during June 24-30, 2020. Overall, 40.9% of respondents reported at least one adverse mental or behavioral health condition, including symptoms of anxiety disorder or depressive disorder (30.9%), symptoms of a trauma- and stressor-related disorder (TSRD) related to the pandemic† (26.3%), and having started or increased substance use to cope with stress or emotions related to COVID-19 (13.3%). The percentage of respondents who reported having seriously considered suicide in the 30 days before completing the survey (10.7%) was significantly higher among respondents aged 18-24 years (25.5%), minority racial/ethnic groups (Hispanic respondents [18.6%], non-Hispanic black [black] respondents [15.1%]), self-reported unpaid caregivers for adults§ (30.7%), and essential workers¶ (21.7%). Community-level intervention and prevention efforts, including health communication strategies, designed to reach these groups could help address various mental health conditions associated with the COVID-19 pandemic.

Journal ArticleDOI
TL;DR: RAAS Inhibitors in Patients with Covid-19 show low levels of renin–angiotensin-converting enzyme 2 levels and activity in humans, but the effects are still uncertain.
Abstract: RAAS Inhibitors in Patients with Covid-19 The effects of renin–angiotensin–aldosterone system blockers on angiotensin-converting enzyme 2 levels and activity in humans are uncertain. The authors hy...

Journal ArticleDOI
TL;DR: This Consensus Statement issues a call to action for all cancer researchers to standardize assays and report metadata in studies of cancer-associated fibroblasts to advance the understanding of this important cell type in the tumour microenvironment.
Abstract: Cancer-associated fibroblasts (CAFs) are a key component of the tumour microenvironment with diverse functions, including matrix deposition and remodelling, extensive reciprocal signalling interactions with cancer cells and crosstalk with infiltrating leukocytes. As such, they are a potential target for optimizing therapeutic strategies against cancer. However, many challenges are present in ongoing attempts to modulate CAFs for therapeutic benefit. These include limitations in our understanding of the origin of CAFs and heterogeneity in CAF function, with it being desirable to retain some antitumorigenic functions. On the basis of a meeting of experts in the field of CAF biology, we summarize in this Consensus Statement our current knowledge and present a framework for advancing our understanding of this critical cell type within the tumour microenvironment.

Journal ArticleDOI
Peter J. Campbell1, Gad Getz2, Jan O. Korbel3, Joshua M. Stuart4  +1329 moreInstitutions (238)
06 Feb 2020-Nature
TL;DR: The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.
Abstract: Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1,2,3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10,11,12,13,14,15,16,17,18.

Journal ArticleDOI
31 Mar 2020-Science
TL;DR: The national emergency response appears to have delayed the growth and limited the size of the COVID-19 epidemic in China, averting hundreds of thousands of cases by 19 February (day 50), and suspending intracity public transport, closing entertainment venues, and banning public gatherings were associated with reductions in case incidence.
Abstract: Responding to an outbreak of a novel coronavirus [agent of coronavirus disease 2019 (COVID-19)] in December 2019, China banned travel to and from Wuhan city on 23 January 2020 and implemented a national emergency response. We investigated the spread and control of COVID-19 using a data set that included case reports, human movement, and public health interventions. The Wuhan shutdown was associated with the delayed arrival of COVID-19 in other cities by 2.91 days. Cities that implemented control measures preemptively reported fewer cases on average (13.0) in the first week of their outbreaks compared with cities that started control later (20.6). Suspending intracity public transport, closing entertainment venues, and banning public gatherings were associated with reductions in case incidence. The national emergency response appears to have delayed the growth and limited the size of the COVID-19 epidemic in China, averting hundreds of thousands of cases by 19 February (day 50).

Journal ArticleDOI
TL;DR: A set of 169 radiomics features was standardized, which enabled verification and calibration of different radiomics software and could be excellently reproduced.
Abstract: Background Radiomic features may quantify characteristics present in medical imaging. However, the lack of standardized definitions and validated reference values have hampered clinical use. Purpose To standardize a set of 174 radiomic features. Materials and Methods Radiomic features were assessed in three phases. In phase I, 487 features were derived from the basic set of 174 features. Twenty-five research teams with unique radiomics software implementations computed feature values directly from a digital phantom, without any additional image processing. In phase II, 15 teams computed values for 1347 derived features using a CT image of a patient with lung cancer and predefined image processing configurations. In both phases, consensus among the teams on the validity of tentative reference values was measured through the frequency of the modal value and classified as follows: less than three matches, weak; three to five matches, moderate; six to nine matches, strong; 10 or more matches, very strong. In the final phase (phase III), a public data set of multimodality images (CT, fluorine 18 fluorodeoxyglucose PET, and T1-weighted MRI) from 51 patients with soft-tissue sarcoma was used to prospectively assess reproducibility of standardized features. Results Consensus on reference values was initially weak for 232 of 302 features (76.8%) at phase I and 703 of 1075 features (65.4%) at phase II. At the final iteration, weak consensus remained for only two of 487 features (0.4%) at phase I and 19 of 1347 features (1.4%) at phase II. Strong or better consensus was achieved for 463 of 487 features (95.1%) at phase I and 1220 of 1347 features (90.6%) at phase II. Overall, 169 of 174 features were standardized in the first two phases. In the final validation phase (phase III), most of the 169 standardized features could be excellently reproduced (166 with CT; 164 with PET; and 164 with MRI). Conclusion A set of 169 radiomics features was standardized, which enabled verification and calibration of different radiomics software. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Kuhl and Truhn in this issue.

Journal ArticleDOI
TL;DR: In the UK and the USA, risk of reporting a positive test for COVID-19 was increased among front-line health-care workers, and adequacy of PPE, clinical setting, and ethnic background were also important factors.
Abstract: Summary Background Data for front-line health-care workers and risk of COVID-19 are limited. We sought to assess risk of COVID-19 among front-line health-care workers compared with the general community and the effect of personal protective equipment (PPE) on risk. Methods We did a prospective, observational cohort study in the UK and the USA of the general community, including front-line health-care workers, using self-reported data from the COVID Symptom Study smartphone application (app) from March 24 (UK) and March 29 (USA) to April 23, 2020. Participants were voluntary users of the app and at first use provided information on demographic factors (including age, sex, race or ethnic background, height and weight, and occupation) and medical history, and subsequently reported any COVID-19 symptoms. We used Cox proportional hazards modelling to estimate multivariate-adjusted hazard ratios (HRs) of our primary outcome, which was a positive COVID-19 test. The COVID Symptom Study app is registered with ClinicalTrials.gov, NCT04331509. Findings Among 2 035 395 community individuals and 99 795 front-line health-care workers, we recorded 5545 incident reports of a positive COVID-19 test over 34 435 272 person-days. Compared with the general community, front-line health-care workers were at increased risk for reporting a positive COVID-19 test (adjusted HR 11·61, 95% CI 10·93–12·33). To account for differences in testing frequency between front-line health-care workers and the general community and possible selection bias, an inverse probability-weighted model was used to adjust for the likelihood of receiving a COVID-19 test (adjusted HR 3·40, 95% CI 3·37–3·43). Secondary and post-hoc analyses suggested adequacy of PPE, clinical setting, and ethnic background were also important factors. Interpretation In the UK and the USA, risk of reporting a positive test for COVID-19 was increased among front-line health-care workers. Health-care systems should ensure adequate availability of PPE and develop additional strategies to protect health-care workers from COVID-19, particularly those from Black, Asian, and minority ethnic backgrounds. Additional follow-up of these observational findings is needed. Funding Zoe Global, Wellcome Trust, Engineering and Physical Sciences Research Council, National Institutes of Health Research, UK Research and Innovation, Alzheimer's Society, National Institutes of Health, National Institute for Occupational Safety and Health, and Massachusetts Consortium on Pathogen Readiness.

Journal ArticleDOI
05 Feb 2020-Nature
TL;DR: The characterization of 4,645 whole-genome and 19,184 exome sequences, covering most types of cancer, identifies 81 single-base substitution, doublet- base substitution and small-insertion-and-deletion mutational signatures, providing a systematic overview of the mutational processes that contribute to cancer development.
Abstract: Somatic mutations in cancer genomes are caused by multiple mutational processes, each of which generates a characteristic mutational signature1. Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium2 of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), we characterized mutational signatures using 84,729,690 somatic mutations from 4,645 whole-genome and 19,184 exome sequences that encompass most types of cancer. We identified 49 single-base-substitution, 11 doublet-base-substitution, 4 clustered-base-substitution and 17 small insertion-and-deletion signatures. The substantial size of our dataset, compared with previous analyses3–15, enabled the discovery of new signatures, the separation of overlapping signatures and the decomposition of signatures into components that may represent associated—but distinct—DNA damage, repair and/or replication mechanisms. By estimating the contribution of each signature to the mutational catalogues of individual cancer genomes, we revealed associations of signatures to exogenous or endogenous exposures, as well as to defective DNA-maintenance processes. However, many signatures are of unknown cause. This analysis provides a systematic perspective on the repertoire of mutational processes that contribute to the development of human cancer. The characterization of 4,645 whole-genome and 19,184 exome sequences, covering most types of cancer, identifies 81 single-base substitution, doublet-base substitution and small-insertion-and-deletion mutational signatures, providing a systematic overview of the mutational processes that contribute to cancer development.

Journal ArticleDOI
TL;DR: The peer-reviewed and preprint literature pertaining to cardiovascular considerations related to COVID-19 are reviewed to highlight gaps in knowledge that require further study pertinent to patients, health care workers, and health systems.

Journal ArticleDOI
Marina Pollán1, Beatriz Pérez-Gómez1, Roberto Pastor-Barriuso1, Jesús Oteo1, Miguel A. Hernán2, Miguel A. Hernán3, Mayte Pérez-Olmeda1, Jose L Sanmartín, Aurora Fernández-García1, Aurora Fernández-García4, Israel Cruz1, Nerea Fernández de Larrea1, Marta Molina, Francisco Rodríguez-Cabrera1, Mariano Martín, Paloma Merino-Amador4, Jose León Paniagua1, Juan F Muñoz-Montalvo, Faustino Blanco, Raquel Yotti1, Rodrigo Gutiérrez Fernández, Saturnino Mezcua Navarro, Matías Salinero Hernández, Manuel Cuenca-Estrella, Pablo Fernández-Navarro, Ana Avellón, Giovanni Fedele, Jesús Oteo Iglesias, María Teresa Pérez Olmeda, Maria Elena Martinez, Francisco D. Rodríguez-Cabrera1, Susana Padrones Fernández, José Manuel Rumbao Aguirre, José M. Navarro Marí, Begoña Palop Borrás, Ana Belén Pérez Jiménez, Manuel Rodríguez-Iglesias, Ana María Calvo Gascón, María Luz Lou Alcaine, Ignacio Donate Suárez, Oscar Suárez Álvarez, Mercedes Rodríguez Pérez, Margarita Cases Sanchís, Carlos Javier Villafáfila Gomila, Lluis Carbo Saladrigas, Adoración Hurtado Fernández, Antonio Oliver, Elías Castro Feliciano, María Noemí González Quintana, José María Barrasa Fernández, María Araceli Hernández Betancor, Melisa Hernández Febles, Leopoldo Martín Martín, Luis-Mariano López López, Teresa Ugarte Miota, Inés De Benito Población, María Sagrario Celada Pérez, María Natalia Vallés Fernández, Tomás Maté Enríquez, Miguel Villa Arranz, Marta Domínguez-Gil González, Isabel Fernández-Natal, Gregoria Megías Lobón, Juan Luis Muñoz Bellido, Pilar Ciruela, Ariadna Mas i Casals, Maria Doladé Botías, M. Angeles Marcos Maeso, Dúnia Pérez del Campo, Antonio Félix de Castro, Ramón Limón Ramírez, Maria Francisca Elías Retamosa, Manuela Rubio González, María Sinda Blanco Lobeiras, Alberto Fuentes Losada, Antonio Aguilera, Germán Bou, Yolanda Caro, Noemí Marauri, Luis Miguel Soria Blanco, Isabel González, Montserrat Hernández Pascual, Roberto Alonso Fernández, Natalia Cabrera Castro, Aurora Tomás Lizcano, Cristóbal Ramírez Almagro, M. Hernández, Nieves Ascunce Elizaga, María Ederra Sanz, Carmen Ezpeleta Baquedano, Ana Bustinduy Bascaran, Susana Iglesias Tamayo, Luis Elorduy Otazua, Rebeca Benarroch Benarroch, Jesús Lopera Flores, Antonia Vázquez de la Villa 
TL;DR: In this paper, a nationwide population-based study aims to estimate the seroprevalence of SARS-CoV-2 infection in Spain at national and regional level.

Journal ArticleDOI
Nicole M. Kuderer, Toni K. Choueiri1, Dimpy P. Shah2, Yu Shyr3  +236 moreInstitutions (26)
TL;DR: The outcomes of a cohort of patients with cancer and COVID-19 are characterised and potential prognostic factors for mortality and severe illness are identified and race and ethnicity, obesity status, cancer type, type of anticancer therapy, and recent surgery were not associated with mortality.