Gut metagenomes of Asian octogenarians reveal metabolic potential expansion and distinct microbial species associated with aging phenotypes.

Autor: Ravikrishnan A; Genome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR), 60 Biopolis Street, Genome, Singapore, 138672, Republic of Singapore., Wijaya I; Genome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR), 60 Biopolis Street, Genome, Singapore, 138672, Republic of Singapore., Png E; Genome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR), 60 Biopolis Street, Genome, Singapore, 138672, Republic of Singapore., Chng KR; Genome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR), 60 Biopolis Street, Genome, Singapore, 138672, Republic of Singapore., Ho EXP; Genome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR), 60 Biopolis Street, Genome, Singapore, 138672, Republic of Singapore., Ng AHQ; Genome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR), 60 Biopolis Street, Genome, Singapore, 138672, Republic of Singapore., Mohamed Naim AN; Genome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR), 60 Biopolis Street, Genome, Singapore, 138672, Republic of Singapore., Gounot JS; Genome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR), 60 Biopolis Street, Genome, Singapore, 138672, Republic of Singapore., Guan SP; Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Republic of Singapore., Hanqing JL; Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Republic of Singapore., Guan L; Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Republic of Singapore., Li C; Genome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR), 60 Biopolis Street, Genome, Singapore, 138672, Republic of Singapore., Koh JY; Genome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR), 60 Biopolis Street, Genome, Singapore, 138672, Republic of Singapore., de Sessions PF; Genome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR), 60 Biopolis Street, Genome, Singapore, 138672, Republic of Singapore., Koh WP; Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Republic of Singapore.; Singapore Institute for Clinical Sciences (SICS), Agency for Science Technology and Research (A*STAR), 30 Medical Drive, Brenner Centre for Molecular Medicine, Singapore, 117609, Republic of Singapore., Feng L; Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Republic of Singapore., Ng TP; Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Republic of Singapore., Larbi A; Singapore Immunology Network (SigN), Agency for Science Technology and Research (A*STAR), 8A Biomedical Grove, Immunos, Singapore, 138648, Republic of Singapore., Maier AB; Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Republic of Singapore.; Department of Human Movement Sciences, @AgeAmsterdam, Faculty of Behavioural and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, Amsterdam, The Netherlands., Kennedy BK; Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Republic of Singapore., Nagarajan N; Genome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR), 60 Biopolis Street, Genome, Singapore, 138672, Republic of Singapore. nagarajann@gis.a-star.edu.sg.; Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Republic of Singapore. nagarajann@gis.a-star.edu.sg.

Publikováno v: Nature communications [Nat Commun] 2024 Sep 05; Vol. 15 (1), pp. 7751. Date of Electronic Publication: 2024 Sep 05.

Artificial intelligence and real-world data for drug and food safety - A regulatory science perspective.

Autor: Thakkar S; Center for Drug Evaluations and Research (CDER), Food and Drug Administration (FDA), USA., Slikker W Jr; National Center for Toxicological Research (NCTR), Food and Drug Administration (FDA), USA., Yiannas F; Food and Drug Administration (FDA), USA., Silva P; Canadian Food Inspection Agency (CFIA), Canada., Blais B; Canadian Food Inspection Agency (CFIA), Canada., Chng KR; National Centre for Food Science, Singapore Food Agency (SFA), Singapore., Liu Z; National Center for Toxicological Research (NCTR), Food and Drug Administration (FDA), USA., Adholeya A; The Energy and Resources Institute (TERI), New Delhi, India., Pappalardo F; University of Catania, Italy., Soares MDLC; Brazilian Health Regulatory Agency (ANVISA), Brazil., Beeler PE; Swissmedic, Bern, Switzerland; University of Zurich, Zurich, Switzerland., Whelan M; Joint Research Center (JRC), Spain., Roberts R; Apconix, UK., Borlak J; Hannover Medical School, Germany., Hugas M; European Food Safety Authority (EFSA), Italy., Torrecilla-Salinas C; Joint Research Center (JRC), Spain., Girard P; Swissmedic, Bern, Switzerland., Diamond MC; Center for Devices and Radiological Health (CDRH), Food and Drug Administration (FDA), USA., Verloo D; European Food Safety Authority (EFSA), Italy., Panda B; Jawaharlal Nehru University (JNU), New Delhi, India., Rose MC; Burroughs Wellcome Fund (BWF), USA., Jornet JB; European Medical Agency (EMA), the Netherlands., Furuhama A; National Institute of Health Sciences (NIHS), Japan., Fang H; National Center for Toxicological Research (NCTR), Food and Drug Administration (FDA), USA., Kwegyir-Afful E; Center for Food Safety and Applied Nutrition (CFSAN), Food and Drug Administration (FDA), USA., Heintz K; Center for Food Safety and Applied Nutrition (CFSAN), Food and Drug Administration (FDA), USA., Arvidson K; Center for Food Safety and Applied Nutrition (CFSAN), Food and Drug Administration (FDA), USA., Burgos JG; European Medical Agency (EMA), the Netherlands., Horst A; Swissmedic, Bern, Switzerland., Tong W; National Center for Toxicological Research (NCTR), Food and Drug Administration (FDA), USA. Electronic address: Weida.tong@fda.hhs.gov.

Publikováno v: Regulatory toxicology and pharmacology : RTP [Regul Toxicol Pharmacol] 2023 May; Vol. 140, pp. 105388. Date of Electronic Publication: 2023 Apr 13.

Long-term ecological and evolutionary dynamics in the gut microbiomes of carbapenemase-producing Enterobacteriaceae colonized subjects.

Autor: Kang JTL; Genome Institute of Singapore, Singapore, Singapore., Teo JJY; Genome Institute of Singapore, Singapore, Singapore., Bertrand D; Genome Institute of Singapore, Singapore, Singapore., Ng A; Genome Institute of Singapore, Singapore, Singapore., Ravikrishnan A; Genome Institute of Singapore, Singapore, Singapore., Yong M; Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Ng OT; Institute of Infectious Diseases and Epidemiology, Tan Tock Seng Hospital, Singapore, Singapore., Marimuthu K; Institute of Infectious Diseases and Epidemiology, Tan Tock Seng Hospital, Singapore, Singapore., Chen SL; Genome Institute of Singapore, Singapore, Singapore.; Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Chng KR; Genome Institute of Singapore, Singapore, Singapore., Gan YH; Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Nagarajan N; Genome Institute of Singapore, Singapore, Singapore. nagarajann@gis.a-star.edu.sg.; Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. nagarajann@gis.a-star.edu.sg.

Publikováno v: Nature microbiology [Nat Microbiol] 2022 Oct; Vol. 7 (10), pp. 1516-1524. Date of Electronic Publication: 2022 Sep 15.

Metagenomics-enabled microbial surveillance.

Autor: Ko KKK; Laboratory of Metagenomic Technologies and Microbial Systems, Genome Institute of Singapore, Singapore, Singapore.; Department of Microbiology, Singapore General Hospital, Singapore, Singapore.; Department of Molecular Pathology, Singapore General Hospital, Singapore, Singapore.; Duke-NUS Medical School, Singapore, Singapore.; Yong Loo Lin School of Medicine, National Univerisity of Singapore, Singapore, Singapore., Chng KR; Laboratory of Metagenomic Technologies and Microbial Systems, Genome Institute of Singapore, Singapore, Singapore.; National Centre for Food Science, Singapore Food Agency, Singapore, Singapore., Nagarajan N; Laboratory of Metagenomic Technologies and Microbial Systems, Genome Institute of Singapore, Singapore, Singapore. nagarajann@gis.a-star.edu.sg.; Yong Loo Lin School of Medicine, National Univerisity of Singapore, Singapore, Singapore. nagarajann@gis.a-star.edu.sg.

Publikováno v: Nature microbiology [Nat Microbiol] 2022 Apr; Vol. 7 (4), pp. 486-496. Date of Electronic Publication: 2022 Apr 01.

A global metagenomic map of urban microbiomes and antimicrobial resistance.

Autor: Danko D; Weill Cornell Medicine, New York, NY, USA; The Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, New York, NY, USA., Bezdan D; Weill Cornell Medicine, New York, NY, USA; The Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, New York, NY, USA; Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany; NGS Competence Center Tübingen (NCCT), University of Tübingen, Tübingen, Germany., Afshin EE; Weill Cornell Medicine, New York, NY, USA; The Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, New York, NY, USA., Ahsanuddin S; Icahn School of Medicine at Mount Sinai, New York, NY, USA., Bhattacharya C; Weill Cornell Medicine, New York, NY, USA; The Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, New York, NY, USA., Butler DJ; Weill Cornell Medicine, New York, NY, USA; The Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, New York, NY, USA., Chng KR; Genome Institute of Singapore, A(∗)STAR, Singapore, Singapore., Donnellan D; Weill Cornell Medicine, New York, NY, USA; The Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, New York, NY, USA., Hecht J; Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain., Jackson K; Weill Cornell Medicine, New York, NY, USA; The Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, New York, NY, USA., Kuchin K; Weill Cornell Medicine, New York, NY, USA; The Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, New York, NY, USA., Karasikov M; ETH Zurich, Department of Computer Science, Biomedical Informatics Group, Zurich, Switzerland; University Hospital Zurich, Biomedical Informatics Research, Zurich, Switzerland; Swiss Institute of Bioinformatics, Lausanne, Switzerland., Lyons A; Weill Cornell Medicine, New York, NY, USA; The Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, New York, NY, USA., Mak L; Weill Cornell Medicine, New York, NY, USA; The Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, New York, NY, USA., Meleshko D; Weill Cornell Medicine, New York, NY, USA; The Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, New York, NY, USA., Mustafa H; ETH Zurich, Department of Computer Science, Biomedical Informatics Group, Zurich, Switzerland; University Hospital Zurich, Biomedical Informatics Research, Zurich, Switzerland; Swiss Institute of Bioinformatics, Lausanne, Switzerland., Mutai B; Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain; Kenya Medical Research Institute - Kisumu, Kisumu, Kenya., Neches RY; Department of Energy, Joint Genome Institute, Lawrence Berkeley National Laboratory, Berkeley, CA, USA., Ng A; Genome Institute of Singapore, A(∗)STAR, Singapore, Singapore., Nikolayeva O; Independent Researcher, Zurich, Switzerland., Nikolayeva T; Independent Researcher, Zurich, Switzerland., Png E; Genome Institute of Singapore, A(∗)STAR, Singapore, Singapore., Ryon KA; Weill Cornell Medicine, New York, NY, USA; The Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, New York, NY, USA., Sanchez JL; Weill Cornell Medicine, New York, NY, USA; The Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, New York, NY, USA., Shaaban H; Weill Cornell Medicine, New York, NY, USA; The Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, New York, NY, USA., Sierra MA; Weill Cornell Medicine, New York, NY, USA; The Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, New York, NY, USA., Thomas D; Weill Cornell Medicine, New York, NY, USA; The Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, New York, NY, USA., Young B; Weill Cornell Medicine, New York, NY, USA; The Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, New York, NY, USA., Abudayyeh OO; Massachusetts Institute of Technology, McGovern Institute for Brain Research, Cambridge, MA, USA., Alicea J; Weill Cornell Medicine, New York, NY, USA; The Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, New York, NY, USA., Bhattacharyya M; Machine Intelligence Unit, Indian Statistical Institute, Kolkata, India; Centre for Artificial Intelligence and Machine Learning, Indian Statistical Institute, Kolkata, India., Blekhman R; University of Minnesota, Minneapolis, MN, USA., Castro-Nallar E; Universidad Andres Bello, Center for Bioinformatics and Integrative Biology, Facultad de Ciencias de la Vida, Santiago, Chile., Cañas AM; Weill Cornell Medicine, New York, NY, USA; The Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, New York, NY, USA., Chatziefthimiou AD; Weill Cornell Medicine, New York, NY, USA; The Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, New York, NY, USA., Crawford RW; California State University, Sacramento, Sacramento, CA, USA., De Filippis F; Department of Agricultural Sciences, Division of Microbiology, University of Naples Federico II, Naples, Italy; Task Force on Microbiome Studies, University of Naples Federico II, Naples, Italy., Deng Y; University of Hawaii John A. Burns School of Medicine, Honolulu, HI, USA., Desnues C; Aix-Marseille Université, Mediterranean Institute of Oceanology, Université de Toulon, CNRS, IRD, UM 110, Marseille, France., Dias-Neto E; Medical Genomics group, A.C.Camargo Cancer Center, São Paulo - SP, Brazil., Dybwad M; Norwegian Defence Research Establishment FFI, Kjeller, Norway., Elhaik E; Department of Biology, Lund University, Lund, Sweden., Ercolini D; Department of Agricultural Sciences, Division of Microbiology, University of Naples Federico II, Naples, Italy; Task Force on Microbiome Studies, University of Naples Federico II, Naples, Italy., Frolova A; Institute of Molecular Biology and Genetics of National Academy of Sciences of Ukraine, Kyiv, Ukraine; Kyiv Academic University, Kyiv, Ukraine., Gankin D; Massachusetts Institute of Technology, McGovern Institute for Brain Research, Cambridge, MA, USA., Gootenberg JS; Massachusetts Institute of Technology, McGovern Institute for Brain Research, Cambridge, MA, USA., Graf AB; University of Applied Sciences Vienna, Vienna, Austria., Green DC; Department of Analytical, Environmental and Forensic Sciences, King's College London, London, UK., Hajirasouliha I; Weill Cornell Medicine, New York, NY, USA; The Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, New York, NY, USA., Hastings JJA; Weill Cornell Medicine, New York, NY, USA; The Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, New York, NY, USA., Hernandez M; University of Colorado at Boulder, Boulder, CO, USA., Iraola G; Microbial Genomics Laboratory, Institut Pasteur de Montevideo, Montevideo, Uruguay; Center for Integrative Biology, Universidad Mayor, Santiago de Chile, Santiago, Chile; Wellcome Sanger Institute, Hinxton, UK., Jang S; Institut Pasteur Korea, Seoul, South Korea., Kahles A; ETH Zurich, Department of Computer Science, Biomedical Informatics Group, Zurich, Switzerland; Kyiv Academic University, Kyiv, Ukraine; C+, Research Center in Technologies for Society, School of Engineering, Universidad del Desarrollo, Santiago, Chile., Kelly FJ; Department of Analytical, Environmental and Forensic Sciences, King's College London, London, UK., Knights K; Weill Cornell Medicine, New York, NY, USA; The Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, New York, NY, USA., Kyrpides NC; Department of Energy, Joint Genome Institute, Lawrence Berkeley National Laboratory, Berkeley, CA, USA., Łabaj PP; State Key Laboratory of Genetic Engineering (SKLGE) and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai, China; Małopolska Centre of Biotechnology, Jagiellonian University, Kraków, Poland; Boku University Viennna, Vienna, Austria., Lee PKH; School of Energy and Environment, City University of Hong Kong, Hong Kong SAR, China., Leung MHY; School of Energy and Environment, City University of Hong Kong, Hong Kong SAR, China., Ljungdahl PO; Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden., Mason-Buck G; Department of Analytical, Environmental and Forensic Sciences, King's College London, London, UK., McGrath K; Microba, 388 Queen St, Brisbane City, QLD 4000, Australia., Meydan C; Weill Cornell Medicine, New York, NY, USA; The Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, New York, NY, USA., Mongodin EF; University of Maryland School of Medicine, Institute for Genome Sciences, Baltimore, MD, USA., Moraes MO; Fundação Oswaldo Cruz, Rio de Janeiro - RJ, Brazil., Nagarajan N; Genome Institute of Singapore, A(∗)STAR, Singapore, Singapore., Nieto-Caballero M; University of Colorado at Boulder, Boulder, CO, USA., Noushmehr H; University of São Paulo, Ribeirão Preto Medical School, Ribeirão Preto - SP, Brazil., Oliveira M; Instituto de Patologia e Imunologia Molecular da Universidade do Porto, Porto, Portugal., Ossowski S; Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain; Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany; NGS Competence Center Tübingen (NCCT), University of Tübingen, Tübingen, Germany., Osuolale OO; Applied Environmental Metagenomics and Infectious Diseases Research (AEMIDR), Department of Biological Sciences, Elizade University, Ilara-Mokin, Nigeria., Özcan O; Acibadem Mehmet Ali Aydınlar University, Istanbul, Turkey., Paez-Espino D; Department of Energy, Joint Genome Institute, Lawrence Berkeley National Laboratory, Berkeley, CA, USA., Rascovan N; Microbial Paleogenomics Unit, Institut Pasteur, CNRS UMR2000, Paris 75015, France., Richard H; Sorbonne University, Faculty of Science, Institute of Biology Paris-Seine, Laboratory of Computational and Quantitative Biology, Paris, France; Robert Koch Institute, Berlin, Germany., Rätsch G; ETH Zurich, Department of Computer Science, Biomedical Informatics Group, Zurich, Switzerland; University Hospital Zurich, Biomedical Informatics Research, Zurich, Switzerland; Swiss Institute of Bioinformatics, Lausanne, Switzerland., Schriml LM; University of Maryland School of Medicine, Institute for Genome Sciences, Baltimore, MD, USA., Semmler T; Robert Koch Institute, Berlin, Germany., Sezerman OU; Acibadem Mehmet Ali Aydınlar University, Istanbul, Turkey., Shi L; Center for Pharmacogenomics, School of Life Sciences and Shanghai Cancer Center, Fudan University, Shanghai, China; State Key Laboratory of Genetic Engineering (SKLGE) and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai, China., Shi T; The Center for Bioinformatics and Computational Biology, Shanghai Key Laboratory of Regulatory Biology, the Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China., Siam R; University of Medicine and Health Sciences, St. Kitts, West Indies and American University in Cairo, Cairo, Egypt., Song LH; 108 Military Central Hospital, Hanoi, Vietnam; Vietnamese-German Center for Medical Research (VG-CARE), Hanoi, Vietnam., Suzuki H; Keio University, Tokyo, Japan., Court DS; Department of Analytical, Environmental and Forensic Sciences, King's College London, London, UK., Tighe SW; University of Vermont, Burlington, VT, USA., Tong X; School of Energy and Environment, City University of Hong Kong, Hong Kong SAR, China., Udekwu KI; Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden; SciLife EVP, Department of Aquatic Sciences Assessment, Swedish University of Agricultural Sciences, Uppsala, Sweden., Ugalde JA; Millennium Initiative for Collaborative Research on Bacterial Resistance, Santiago, Chile; C+, Research Center in Technologies for Society, School of Engineering, Universidad del Desarrollo, Santiago, Chile., Valentine B; Weill Cornell Medicine, New York, NY, USA; The Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, New York, NY, USA., Vassilev DI; Faculty of Mathematics and Informatics, Sofia University 'St. Kliment Ohridski,' Sofia, Bulgaria., Vayndorf EM; Institute of Arctic Biology, University of Alaska, Fairbanks, Fairbanks, AK, USA., Velavan TP; Institute of Tropical Medicine, Univeristätsklinikum Tübingen, Tübingen, Germany; Faculty of Medicine, Duy Tan University, Da Nang, Vietnam., Wu J; The Center for Bioinformatics and Computational Biology, Shanghai Key Laboratory of Regulatory Biology, the Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China., Zambrano MM; Corporación Corpogen-Research Center, Bogotá, Colombia., Zhu J; Weill Cornell Medicine, New York, NY, USA; The Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, New York, NY, USA., Zhu S; State Key Laboratory of Genetic Engineering (SKLGE) and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai, China; Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China., Mason CE; Weill Cornell Medicine, New York, NY, USA; The Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, New York, NY, USA; The WorldQuant Initiative for Quantitative Prediction, Weill Cornell Medicine, New York, NY, USA. Electronic address: chm2042@med.cornell.edu.

Publikováno v: Cell [Cell] 2021 Jun 24; Vol. 184 (13), pp. 3376-3393.e17. Date of Electronic Publication: 2021 May 26.