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Showing papers by "University of Tokyo published in 2021"


Journal ArticleDOI
TL;DR: The K EGG pathway maps are now integrated with network variation maps in the NETWORK database, as well as with conserved functional units of KEGG modules and reaction modules in the MODULE database, and the KO database for functional orthologs continues to be improved.
Abstract: KEGG (https://www.kegg.jp/) is a manually curated resource integrating eighteen databases categorized into systems, genomic, chemical and health information. It also provides KEGG mapping tools, which enable understanding of cellular and organism-level functions from genome sequences and other molecular datasets. KEGG mapping is a predictive method of reconstructing molecular network systems from molecular building blocks based on the concept of functional orthologs. Since the introduction of the KEGG NETWORK database, various diseases have been associated with network variants, which are perturbed molecular networks caused by human gene variants, viruses, other pathogens and environmental factors. The network variation maps are created as aligned sets of related networks showing, for example, how different viruses inhibit or activate specific cellular signaling pathways. The KEGG pathway maps are now integrated with network variation maps in the NETWORK database, as well as with conserved functional units of KEGG modules and reaction modules in the MODULE database. The KO database for functional orthologs continues to be improved and virus KOs are being expanded for better understanding of virus-cell interactions and for enabling prediction of viral perturbations.

2,087 citations


Journal ArticleDOI
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


Journal ArticleDOI
TL;DR: The Surviving Sepsis Campaign (SSC) guidelines provide evidence-based recommendations on the recognition and management of sepsis and its complications as discussed by the authors, which are either strong or weak, or in the form of best practice statements.
Abstract: Background Sepsis poses a global threat to millions of lives. The Surviving Sepsis Campaign (SSC) guidelines provide evidence-based recommendations on the recognition and management of sepsis and its complications. Methods We formed a panel of 60 experts from 22 countries and 11 members of the public. The panel prioritized questions that are relevant to the recognition and management of sepsis and septic shock in adults. New questions and sections were addressed, relative to the previous guidelines. These questions were grouped under 6 subgroups (screening and early treatment, infection, hemodynamics, ventilation, additional therapies, and long-term outcomes and goals of care). With input from the panel and methodologists, professional medical librarians performed the search strategy tailored to either specific questions or a group of relevant questions. A dedicated systematic review team performed screening and data abstraction when indicated. For each question, the methodologists, with input from panel members, summarized the evidence assessed and graded the quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. The panel generated recommendations using the evidence-to-decision framework. Recommendations were either strong or weak, or in the form of best practice statements. When evidence was insufficient to support a recommendation, the panel was surveyed to generate “in our practice” statements. Results The SSC panel issued 93 statements: 15 best practice statements, 15 strong recommendations, and 54 weak recommendations and no recommendation was provided for 9 questions. The recommendations address several important clinical areas related to screening tools, acute resuscitation strategies, management of fluids and vasoactive agents, antimicrobials and diagnostic tests and the use of additional therapies, ventilation management, goals of care, and post sepsis care. Conclusion The SSC panel issued evidence-based recommendations to help support key stakeholders caring for adults with sepsis or septic shock and their families.

893 citations


Journal ArticleDOI
06 Sep 2021-Nature
TL;DR: The B.617.1.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralizing antibody, compared with that of wild-type spike as discussed by the authors.
Abstract: The B.1.617.2 (Delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha)1. In vitro, B.1.617.2 is sixfold less sensitive to serum neutralizing antibodies from recovered individuals, and eightfold less sensitive to vaccine-elicited antibodies, compared with wild-type Wuhan-1 bearing D614G. Serum neutralizing titres against B.1.617.2 were lower in ChAdOx1 vaccinees than in BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies to the receptor-binding domain and the amino-terminal domain. B.1.617.2 demonstrated higher replication efficiency than B.1.1.7 in both airway organoid and human airway epithelial systems, associated with B.1.617.2 spike being in a predominantly cleaved state compared with B.1.1.7 spike. The B.1.617.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralizing antibody, compared with that of wild-type spike. We also observed that B.1.617.2 had higher replication and spike-mediated entry than B.1.617.1, potentially explaining the B.1.617.2 dominance. In an analysis of more than 130 SARS-CoV-2-infected health care workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx1 vaccine effectiveness against B.1.617.2 relative to non-B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine efficacy against the highly fit and immune-evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era.

839 citations


Journal ArticleDOI
TL;DR: The Surviving Sepsis Campaign (SSC) guidelines provide evidence-based recommendations on the recognition and management of sepsis and its complications as mentioned in this paper, which are either strong or weak, or in the form of best practice statements.
Abstract: Background Sepsis poses a global threat to millions of lives. The Surviving Sepsis Campaign (SSC) guidelines provide evidence-based recommendations on the recognition and management of sepsis and its complications. Methods We formed a panel of 60 experts from 22 countries and 11 members of the public. The panel prioritized questions that are relevant to the recognition and management of sepsis and septic shock in adults. New questions and sections were addressed, relative to the previous guidelines. These questions were grouped under 6 subgroups (screening and early treatment, infection, hemodynamics, ventilation, additional therapies, and long-term outcomes and goals of care). With input from the panel and methodologists, professional medical librarians performed the search strategy tailored to either specific questions or a group of relevant questions. A dedicated systematic review team performed screening and data abstraction when indicated. For each question, the methodologists, with input from panel members, summarized the evidence assessed and graded the quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. The panel generated recommendations using the evidence-to-decision framework. Recommendations were either strong or weak, or in the form of best practice statements. When evidence was insufficient to support a recommendation, the panel was surveyed to generate “in our practice” statements. Results The SSC panel issued 93 statements: 15 best practice statements, 15 strong recommendations, and 54 weak recommendations and no recommendation was provided for 9 questions. The recommendations address several important clinical areas related to screening tools, acute resuscitation strategies, management of fluids and vasoactive agents, antimicrobials and diagnostic tests and the use of additional therapies, ventilation management, goals of care, and post sepsis care. Conclusion The SSC panel issued evidence-based recommendations to help support key stakeholders caring for adults with sepsis or septic shock and their families.

664 citations


Journal ArticleDOI
03 Feb 2021-Nature
TL;DR: This work explores the use of fibrillated cellulose in the fabrication of materials ranging from composites and macrofibres, to thin films, porous membranes and gels, and discusses research directions for the practical exploitation of these structures.
Abstract: Cellulose is the most abundant biopolymer on Earth, found in trees, waste from agricultural crops and other biomass The fibres that comprise cellulose can be broken down into building blocks, known as fibrillated cellulose, of varying, controllable dimensions that extend to the nanoscale Fibrillated cellulose is harvested from renewable resources, so its sustainability potential combined with its other functional properties (mechanical, optical, thermal and fluidic, for example) gives this nanomaterial unique technological appeal Here we explore the use of fibrillated cellulose in the fabrication of materials ranging from composites and macrofibres, to thin films, porous membranes and gels We discuss research directions for the practical exploitation of these structures and the remaining challenges to overcome before fibrillated cellulose materials can reach their full potential Finally, we highlight some key issues towards successful manufacturing scale-up of this family of materials

517 citations


Journal ArticleDOI
25 Aug 2021-Nature
TL;DR: In this paper, a 1m2 panel reactor system with a modified, aluminium-doped strontium titanate particulate photocatalyst was demonstrated to achieve a maximum energy conversion efficiency of 0.76%.
Abstract: The unprecedented impact of human activity on Earth’s climate and the ongoing increase in global energy demand have made the development of carbon-neutral energy sources ever more important. Hydrogen is an attractive and versatile energy carrier (and important and widely used chemical) obtainable from water through photocatalysis using sunlight, and through electrolysis driven by solar or wind energy1,2. The most efficient solar hydrogen production schemes, which couple solar cells to electrolysis systems, reach solar-to-hydrogen (STH) energy conversion efficiencies of 30% at a laboratory scale3. Photocatalytic water splitting reaches notably lower conversion efficiencies of only around 1%, but the system design is much simpler and cheaper and more amenable to scale-up1,2—provided the moist, stoichiometric hydrogen and oxygen product mixture can be handled safely in a field environment and the hydrogen recovered. Extending our earlier demonstration of a 1-m2 panel reactor system based on a modified, aluminium-doped strontium titanate particulate photocatalyst4, we here report safe operation of a 100-m2 array of panel reactors over several months with autonomous recovery of hydrogen from the moist gas product mixture using a commercial polyimide membrane5. The system, optimized for safety and durability, and remaining undamaged on intentional ignition of recovered hydrogen, reaches a maximum STH of 0.76%. While the hydrogen production is inefficient and energy negative overall, our findings demonstrate that safe, large-scale photocatalytic water splitting, and gas collection and separation are possible. To make the technology economically viable and practically useful, essential next steps are reactor and process optimization to substantially reduce costs and improve STH efficiency, photocatalyst stability and gas separation efficiency. Carbon-neutral hydrogen can be produced through photocatalytic water splitting, as demonstrated here with a 100-m2 array of panel reactors that reaches a maximum conversion efficiency of 0.76%.

472 citations


Journal ArticleDOI
Richard J. Abbott1, T. D. Abbott2, Sheelu Abraham3, Fausto Acernese4  +1428 moreInstitutions (155)
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


Journal ArticleDOI
TL;DR: The authors performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci, including genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics.
Abstract: Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies.

378 citations


Journal ArticleDOI
Richard J. Abbott1, T. D. Abbott2, Sheelu Abraham3, Fausto Acernese4  +1692 moreInstitutions (195)
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


Journal ArticleDOI
University of Michigan1, Cornell University2, University of Pennsylvania3, University of Massachusetts Medical School4, Baylor College of Medicine5, University of Naples Federico II6, 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 South Australia32, University of Adelaide33, University of Oviedo34, University of Chicago35, University of Graz36, National Institutes of Health37, City University of New York38, Queens College39, 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, University of Bern51, Kazan Federal University52, University of Oxford53, Oslo University Hospital54, University of Oslo55, University of Crete56, Foundation for Research & Technology – Hellas57, 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.

Journal ArticleDOI
06 Aug 2021-Science
TL;DR: In quantum-confined semiconductor nanostructures, electrons exhibit distinctive behavior compared with that in bulk solids as mentioned in this paper, which enables the design of materials with tunable chemical, physical, electrical, and optical properties.
Abstract: In quantum-confined semiconductor nanostructures, electrons exhibit distinctive behavior compared with that in bulk solids. This enables the design of materials with tunable chemical, physical, electrical, and optical properties. Zero-dimensional semiconductor quantum dots (QDs) offer strong light absorption and bright narrowband emission across the visible and infrared wavelengths and have been engineered to exhibit optical gain and lasing. These properties are of interest for imaging, solar energy harvesting, displays, and communications. Here, we offer an overview of advances in the synthesis and understanding of QD nanomaterials, with a focus on colloidal QDs, and discuss their prospects in technologies such as displays and lighting, lasers, sensing, electronics, solar energy conversion, photocatalysis, and quantum information.

Journal ArticleDOI
TL;DR: In this article, the authors used difference-in-difference estimation to assess whether suicide mortality changed during the COVID-19 pandemic and found that monthly suicide rates decreased by 14% during the first 5 months of the pandemic (February to June 2020).
Abstract: There is increasing concern that the coronavirus disease 2019 (COVID-19) pandemic could harm psychological health and exacerbate suicide risk. Here, based on month-level records of suicides covering the entire Japanese population in 1,848 administrative units, we assessed whether suicide mortality changed during the pandemic. Using difference-in-difference estimation, we found that monthly suicide rates declined by 14% during the first 5 months of the pandemic (February to June 2020). This could be due to a number of complex reasons, including the government's generous subsidies, reduced working hours and school closure. By contrast, monthly suicide rates increased by 16% during the second wave (July to October 2020), with a larger increase among females (37%) and children and adolescents (49%). Although adverse impacts of the COVID-19 pandemic may remain in the long term, its modifiers (such as government subsidies) may not be sustained. Thus, effective suicide prevention-particularly among vulnerable populations-should be an important public health consideration.

Journal ArticleDOI
Richard J. Abbott1, T. D. Abbott2, Sheelu Abraham3, Fausto Acernese4  +1335 moreInstitutions (144)
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.

Journal ArticleDOI
TL;DR: The review discusses the new classes of RiPPs that have been discovered, the advances in the understanding of the installation of both primary and secondary post-translational modifications, and the mechanisms by which the enzymes recognize the leader peptides in their substrates.


Journal ArticleDOI
TL;DR: In this article, the authors present a list of authors who have contributed to the work of the authors of this paper: Akiyama, Kazunori; Algaba, Juan Carlos; Alberdi, Antxon; Alef, Walter; Anantua, Richard; Asada, Keiichi; Azulay, Rebecca; Baczko, Anne-Kathrin; Ball, David; Balokovic, Mislav; Barrett, John; Benson, Bradford A.; Bintley, Dan; Blackburn, Lindy; Blundell
Abstract: Full list of authors: Akiyama, Kazunori; Algaba, Juan Carlos; Alberdi, Antxon; Alef, Walter; Anantua, Richard; Asada, Keiichi; Azulay, Rebecca; Baczko, Anne-Kathrin; Ball, David; Balokovic, Mislav; Barrett, John; Benson, Bradford A.; Bintley, Dan; Blackburn, Lindy; Blundell, Raymond; Boland, Wilfred; Bouman, Katherine L.; Bower, Geoffrey C.; Boyce, Hope Bremer, Michael; Brinkerink, Christiaan D.; Brissenden, Roger; Britzen, Silke; Broderick, Avery E.; Broguiere, Dominique; Bronzwaer, Thomas; Byun, Do-Young; Carlstrom, John E.; Chael, Andrew; Chan, Chi-kwan; Chatterjee, Shami; Chatterjee, Koushik; Chen, Ming-Tang; Chen, Yongjun; Chesler, Paul M.; Cho, Ilje; Christian, Pierre; Conway, John E.; Cordes, James M.; Crawford, Thomas M.; Crew, Geoffrey B.; Cruz-Osorio, Alejandro; Cui, Yuzhu; Davelaar, Jordy; De Laurentis, Mariafelicia; Deane, Roger; Dempsey, Jessica; Desvignes, Gregory; Dexter, Jason; Doeleman, Sheperd S.; Eatough, Ralph P.; Falcke, Heino; Farah, Joseph; Fish, Vincent L.; Fomalont, Ed; Ford, H. Alyson; Fraga-Encinas, Raquel; Friberg, Per; Fromm, Christian M.; Fuentes, Antonio; Galison, Peter; Gammie, Charles F.; Garcia, Roberto; Gelles, Zachary; Gentaz, Olivier; Georgiev, Boris; Goddi, Ciriaco; Gold, Roman; Gomez, Jose L.; Gomez-Ruiz, Arturo I.; Gu, Minfeng; Gurwell, Mark; Hada, Kazuhiro; Haggard, Daryl; Hecht, Michael H.; Hesper, Ronald; Himwich, Elizabeth; Ho, Luis C.; Ho, Paul; Honma, Mareki; Huang, Chih-Wei L.; Huang, Lei; Hughes, David H.; Ikeda, Shiro; Inoue, Makoto; Issaoun, Sara; James, David J.; Jannuzi, Buell T.; Janssen, Michael; Jeter, Britton; Jiang, Wu; Jimenez-Rosales, Alejandra; Johnson, Michael D.; Jorstad, Svetlana; Jung, Taehyun; Karami, Mansour; Karuppusamy, Ramesh; Kawashima, Tomohisa; Keating, Garrett K.; Kettenis, Mark; Kim, Dong-Jin; Kim, Jae-Young; Kim, Jongsoo; Kim, Junhan; Kino, Motoki; Koay, Jun Yi; Kofuji, Yutaro; Koch, Patrick M.; Koyama, Shoko; Kramer, Michael; Kramer, Carsten; Krichbaum, Thomas P.; Kuo, Cheng-Yu; Lauer, Tod R.; Lee, Sang-Sung; Levis, Aviad; Li, Yan-Rong; Li, Zhiyuan; Lindqvist, Michael; Lico, Rocco; Lindahl, Greg; Liu, Jun; Liu, Kuo; Liuzzo, Elisabetta; Lo, Wen-Ping; Lobanov, Andrei P.; Loinard, Laurent; Lonsdale, Colin; Lu, Ru-Sen; MacDonald, Nicholas R.; Mao, Jirong; Marchili, Nicola; Markoff, Sera; Marrone, Daniel P.; Marscher, Alan P.; Marti-Vidal, Ivan; Matsushita, Satoki; Matthews, Lynn D.; Medeiros, Lia; Menten, Karl M.; Mizuno, Izumi; Mizuno, Yosuke; Moran, James M.; Moriyama, Kotaro; Moscibrodzka, Monika; Muller, Cornelia; Musoke, Gibwa; Mus Mejias, Alejandro; Michalik, Daniel; Nadolski, Andrew; Nagai, Hiroshi; Nagar, Neil M.; Nakamura, Masanori; Narayan, Ramesh; Narayanan, Gopal; Natarajan, Iniyan; Nathanail, Antonios; Neilsen, Joey; Neri, Roberto; Ni, Chunchong; Noutsos, Aristeidis; Nowak, Michael A.; Okino, Hiroki; Olivares, Hector; Ortiz-Leon, Gisela N.; Oyama, Tomoaki; Ozel, Feryal; Palumbo, Daniel C. M.; Park, Jongho; Patel, Nimesh; Pen, Ue-Li; Pesce, Dominic W.; Pietu, Vincent; Plambeck, Richard; PopStefanija, Aleksandar; Porth, Oliver; Potzl, Felix M.; Prather, Ben; Preciado-Lopez, Jorge A.; Psaltis, Dimitrios; Pu, Hung-Yi; Ramakrishnan, Venkatessh; Rao, Ramprasad; Rawlings, Mark G.; Raymond, Alexander W.; Rezzolla, Luciano; Ricarte, Angelo; Ripperda, Bart; Roelofs, Freek; Rogers, Alan; Ros, Eduardo; Rose, Mel; Roshanineshat, Arash; Rottmann, Helge; Roy, Alan L.; Ruszczyk, Chet; Rygl, Kazi L. J.; Sanchez, Salvador; Sanchez-Arguelles, David; Sasada, Mahito; Savolainen, Tuomas; Schloerb, F. Peter; Schuster, Karl-Friedrich; Shao, Lijing; Shen, Zhiqiang; Small, Des; Sohn, Bong Won; SooHoo, Jason; Sun, He; Tazaki, Fumie; Tetarenko, Alexandra J.; Tiede, Paul; Tilanus, Remo P. J.; Titus, Michael; Toma, Kenji; Torne, Pablo; Trent, Tyler; Traianou, Efthalia; Trippe, Sascha; van Bemmel, Ilse; van Langevelde, Huib Jan; van Rossum, Daniel R.; Wagner, Jan; Ward-Thompson, Derek; Wardle, John; Weintroub, Jonathan; Wex, Norbert; Wharton, Robert; Wielgus, Maciek; Wong, George N.; Wu, Qingwen; Yoon, Doosoo; Young, Andre; Young, Ken; Younsi, Ziri; Yuan, Feng; Yuan, Ye-Fei; Zensus, J. Anton; Zhao, Guang-Yao; Zhao, Shan-Shan; Event Horizon Telescope Collaboration.-- This is an open access article, original content from this work may be used under the terms of the Creative Commons Attribution 4.0 licence. Any further distribution of this work must maintain attribution to the author(s) and the title of the work, journal citation and DOI.

Journal ArticleDOI
TL;DR: In this paper, the authors conducted 220 deep-phenotype genome-wide association studies (diseases, biomarkers and medication usage) in BioBank Japan (n = 179,000), by incorporating past medical history and text-mining of electronic medical records.
Abstract: Current genome-wide association studies do not yet capture sufficient diversity in populations and scope of phenotypes. To expand an atlas of genetic associations in non-European populations, we conducted 220 deep-phenotype genome-wide association studies (diseases, biomarkers and medication usage) in BioBank Japan (n = 179,000), by incorporating past medical history and text-mining of electronic medical records. Meta-analyses with the UK Biobank and FinnGen (ntotal = 628,000) identified ~5,000 new loci, which improved the resolution of the genomic map of human traits. This atlas elucidated the landscape of pleiotropy as represented by the major histocompatibility complex locus, where we conducted HLA fine-mapping. Finally, we performed statistical decomposition of matrices of phenome-wide summary statistics, and identified latent genetic components, which pinpointed responsible variants and biological mechanisms underlying current disease classifications across populations. The decomposed components enabled genetically informed subtyping of similar diseases (for example, allergic diseases). Our study suggests a potential avenue for hypothesis-free re-investigation of human diseases through genetics.

Journal ArticleDOI
TL;DR: The materials science and materials chemistry of magnetic skyrmions are described using the classification scheme of theskyrmion forming microscopic mechanisms, including the generation of emergent magnetic and electric field by statics and dynamics of skrymions and the inherent magnetoelectric effect.
Abstract: Skyrmion, a concept originally proposed in particle physics half a century ago, can now find the most fertile field for its applicability, that is, the magnetic skyrmion realized in helimagnetic materials. The spin swirling vortex-like texture of the magnetic skyrmion can define the particle nature by topology; that is, all the constituent spin moments within the two-dimensional sheet wrap the sphere just one time. Such a topological nature of the magnetic skyrmion can lead to extraordinary metastability via topological protection and the driven motion with low electric-current excitation, which may promise future application to spintronics. The skyrmions in the magnetic materials frequently show up as the crystal lattice form, e.g., hexagonal lattice, but sometimes as isolated or independent particles. These skyrmions in magnets were initially found in acentric magnets, such as chiral, polar, and bilayered magnets endowed with antisymmetric spin exchange interaction, while the skyrmion host materials have been explored in a broader family of compounds including centrosymmetric magnets. This review describes the materials science and materials chemistry of magnetic skyrmions using the classification scheme of the skyrmion forming microscopic mechanisms. The emergent phenomena and functions mediated by skyrmions are described, including the generation of emergent magnetic and electric field by statics and dynamics of skrymions and the inherent magnetoelectric effect. The other important magnetic topological defects in two or three dimensions, such as biskyrmions, antiskyrmions, merons, and hedgehogs, are also reviewed in light of their interplay with the skyrmions.

Journal ArticleDOI
TL;DR: In this article, a patch-generating land use simulation (PLUS) model is proposed that integrates a land expansion analysis strategy and a cellular automata model based on multi-type random patch seeds to understand the drivers of land expansion and investigate the landscape dynamics in Wuhan, China.

Journal ArticleDOI
TL;DR: In this paper, the authors systematically review and update the vast state-of-the-art literature of amyloid-β (Aβ) science with evidence from basic research studies to human genetic and multi-modal biomarker investigations, which supports a crucial role of Aβ pathway dyshomeostasis in AD pathophysiological dynamics.
Abstract: Breakthroughs in molecular medicine have positioned the amyloid-β (Aβ) pathway at the center of Alzheimer's disease (AD) pathophysiology. While the detailed molecular mechanisms of the pathway and the spatial-temporal dynamics leading to synaptic failure, neurodegeneration, and clinical onset are still under intense investigation, the established biochemical alterations of the Aβ cycle remain the core biological hallmark of AD and are promising targets for the development of disease-modifying therapies. Here, we systematically review and update the vast state-of-the-art literature of Aβ science with evidence from basic research studies to human genetic and multi-modal biomarker investigations, which supports a crucial role of Aβ pathway dyshomeostasis in AD pathophysiological dynamics. We discuss the evidence highlighting a differentiated interaction of distinct Aβ species with other AD-related biological mechanisms, such as tau-mediated, neuroimmune and inflammatory changes, as well as a neurochemical imbalance. Through the lens of the latest development of multimodal in vivo biomarkers of AD, this cross-disciplinary review examines the compelling hypothesis- and data-driven rationale for Aβ-targeting therapeutic strategies in development for the early treatment of AD.

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Ana M. Vicedo-Cabrera1, Ana M. Vicedo-Cabrera2, Noah Scovronick3, Francesco Sera4, Francesco Sera2, Dominic Royé5, Rochelle Schneider, Aurelio Tobias6, Christopher Astrom7, Yuming Guo8, Yasushi Honda9, David M. Hondula10, Rosana Abrutzky11, Shilu Tong, M. de Sousa Zanotti Stagliorio Coelho12, P. H. Nascimento Saldiva12, Eric Lavigne13, Eric Lavigne14, P. Matus Correa15, N. Valdes Ortega15, Haidong Kan16, Samuel Osorio12, Jan Kyselý17, Jan Kyselý18, Aleš Urban18, Aleš Urban17, Hans Orru19, Ene Indermitte19, Jouni J. K. Jaakkola20, Jouni J. K. Jaakkola21, Niilo R.I. Ryti21, M. Pascal, Alexandra Schneider, Klea Katsouyanni22, Klea Katsouyanni23, E Samoli22, Fatemeh Mayvaneh24, Alireza Entezari24, Patrick Goodman, Ariana Zeka25, Paola Michelozzi, Francesca de’Donato, Masahiro Hashizume26, Barrak Alahmad27, M. Hurtado Diaz, C. De La Cruz Valencia, Ala Overcenco, D Houthuijs, Caroline Ameling, Shilpa Rao28, F. Di Ruscio28, Gabriel Carrasco-Escobar29, Xerxes Seposo30, Susana Silva31, Joana Madureira32, Joana Madureira31, Iulian-Horia Holobaca, Simona Fratianni33, Fiorella Acquaotta33, Ho Kim34, Whanhee Lee34, Carmen Iñiguez35, Bertil Forsberg7, Martina S. Ragettli36, Martina S. Ragettli37, Yue Leon Guo38, Yue Leon Guo39, Bing-Yu Chen38, Shanshan Li8, Ben Armstrong2, A. Aleman40, Antonella Zanobetti27, Joel Schwartz27, Tran Ngoc Dang41, Do Van Dung41, N. Gillett, Andy Haines42, Andy Haines2, Matthias Mengel43, Veronika Huber43, Veronika Huber44, Antonio Gasparrini2 
TL;DR: In this article, the authors use empirical data from 732 locations in 43 countries to estimate the mortality burdens associated with the additional heat exposure that has resulted from recent human-induced warming, during the period 1991-2018.
Abstract: Climate change affects human health; however, there have been no large-scale, systematic efforts to quantify the heat-related human health impacts that have already occurred due to climate change. Here, we use empirical data from 732 locations in 43 countries to estimate the mortality burdens associated with the additional heat exposure that has resulted from recent human-induced warming, during the period 1991-2018. Across all study countries, we find that 37.0% (range 20.5-76.3%) of warm-season heat-related deaths can be attributed to anthropogenic climate change and that increased mortality is evident on every continent. Burdens varied geographically but were of the order of dozens to hundreds of deaths per year in many locations. Our findings support the urgent need for more ambitious mitigation and adaptation strategies to minimize the public health impacts of climate change.

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TL;DR: In this article, using ensemble hydrological simulations, the authors show that climate change could reduce water storage in many regions, especially those in the Southern Hemisphere, and highlight the importance of climate change mitigation to avoid adverse water storage impacts and increased droughts.
Abstract: Terrestrial water storage (TWS) modulates the hydrological cycle and is a key determinant of water availability and an indicator of drought. While historical TWS variations have been increasingly studied, future changes in TWS and the linkages to droughts remain unexamined. Here, using ensemble hydrological simulations, we show that climate change could reduce TWS in many regions, especially those in the Southern Hemisphere. Strong inter-ensemble agreement indicates high confidence in the projected changes that are driven primarily by climate forcing rather than land and water management activities. Declines in TWS translate to increases in future droughts. By the late twenty-first century, the global land area and population in extreme-to-exceptional TWS drought could more than double, each increasing from 3% during 1976–2005 to 7% and 8%, respectively. Our findings highlight the importance of climate change mitigation to avoid adverse TWS impacts and increased droughts, and the need for improved water resource management and adaptation.

Journal ArticleDOI
04 Jun 2021-Science
TL;DR: In this article, a damageless reinforcement strategy for hydrogels using strain-induced crystallization was proposed for slide-ring gels in which polyethylene glycol chains are highly oriented and mutually exposed under large deformation.
Abstract: Most tough hydrogels are reinforced by introducing sacrificial structures that can dissipate input energy. However, because the sacrificial damage cannot rapidly recover, the toughness of these gels drops substantially during consecutive cyclic loadings. We propose a damageless reinforcement strategy for hydrogels using strain-induced crystallization. For slide-ring gels in which polyethylene glycol chains are highly oriented and mutually exposed under large deformation, crystallinity forms and melts with elongation and retraction, resulting both in almost 100% rapid recovery of extension energy and excellent toughness of 6.6 to 22 megajoules per cubic meter, which is one order of magnitude larger than the toughness of covalently cross-linked homogeneous gels of polyethylene glycol.

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TL;DR: The authors review the current epidemiological, clinical, pathological and molecular understanding of early-onset colorectal cancer that occurs in patients ≥50 years of age, drawing contrasts with later-ONSet CRC.
Abstract: The incidence of early-onset colorectal cancer (CRC), which occurs in individuals <50 years of age, has been increasing worldwide and particularly in high-income countries. The reasons for this increase remain unknown but plausible hypotheses include greater exposure to potential risk factors, such as a Western-style diet, obesity, physical inactivity and antibiotic use, especially during the early prenatal to adolescent periods of life. These exposures can not only cause genetic and epigenetic alterations in colorectal epithelial cells but also affect the gut microbiota and host immunity. Early-onset CRCs have differential clinical, pathological and molecular features compared with later-onset CRCs. Certain existing resources can be utilized to elucidate the aetiology of early-onset CRC and inform the development of effective prevention, early detection and therapeutic strategies; however, additional life-course cohort studies spanning childhood and young adulthood, integrated with prospective biospecimen collections, omics biomarker analyses and a molecular pathological epidemiology approach, are needed to better understand and manage this disease entity. In this Perspective, we summarize our current understanding of early-onset CRC and discuss how we should strategize future research to improve its prevention and clinical management.

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TL;DR: In this article, the authors present a list of the authors who contributed to the development of this work, including: Akiyama, Kazunori; Algaba, Juan Carlos; Alberdi, Antxon; Anantua, Richard; Asada, Keiichi; Azulay, Rebecca; Baczko, Anne-Kathrin; Ball, David; Balokovic, Mislav; Barrett, John; Benson, Bradford A; Bintley, Dan; Bunderwood, Nissim; Bower, Geoffrey C;
Abstract: Full list of authors: Akiyama, Kazunori; Algaba, Juan Carlos; Alberdi, Antxon; Alef, Walter; Anantua, Richard; Asada, Keiichi; Azulay, Rebecca; Baczko, Anne-Kathrin; Ball, David; Balokovic, Mislav; Barrett, John; Benson, Bradford A.; Bintley, Dan; Blackburn, Lindy; Blundell, Raymond; Boland, Wilfred; Bouman, Katherine L.; Bower, Geoffrey C.; Boyce, Hope Bremer, Michael; Brinkerink, Christiaan D.; Brissenden, Roger; Britzen, Silke; Broderick, Avery E.; Broguiere, Dominique; Bronzwaer, Thomas; Byun, Do-Young; Carlstrom, John E.; Chael, Andrew; Chan, Chi-kwan; Chatterjee, Shami; Chatterjee, Koushik; Chen, Ming-Tang; Chen, Yongjun; Chesler, Paul M.; Cho, Ilje; Christian, Pierre; Conway, John E.; Cordes, James M.; Crawford, Thomas M.; Crew, Geoffrey B.; Cruz-Osorio, Alejandro; Cui, Yuzhu; Davelaar, Jordy; De Laurentis, Mariafelicia; Deane, Roger; Dempsey, Jessica; Desvignes, Gregory; Dexter, Jason; Doeleman, Sheperd S.; Eatough, Ralph P.; Falcke, Heino; Farah, Joseph; Fish, Vincent L.; Fomalont, Ed; Ford, H. Alyson; Fraga-Encinas, Raquel; Freeman, William T.; Friberg, Per; Fromm, Christian M.; Fuentes, Antonio; Galison, Peter; Gammie, Charles F.; Garcia, Roberto; Gentaz, Olivier; Georgiev, Boris; Goddi, Ciriaco; Gold, Roman; Gomez, Jose L.; Gomez-Ruiz, Arturo I.; Gu, Minfeng; Gurwell, Mark; Hada, Kazuhiro; Haggard, Daryl; Hecht, Michael H.; Hesper, Ronald; Ho, Luis C.; Ho, Paul; Honma, Mareki; Huang, Chih-Wei L.; Huang, Lei; Hughes, David H.; Ikeda, Shiro; Inoue, Makoto; Issaoun, Sara; James, David J.; Jannuzi, Buell T.; Janssen, Michael; Jeter, Britton; Jiang, Wu; Jimenez-Rosales, Alejandra; Johnson, Michael D.; Jorstad, Svetlana; Jung, Taehyun; Karami, Mansour; Karuppusamy, Ramesh; Kawashima, Tomohisa; Keating, Garrett K.; Kettenis, Mark; Kim, Dong-Jin; Kim, Jae-Young; Kim, Jongsoo; Kim, Junhan; Kino, Motoki; Koay, Jun Yi; Kofuji, Yutaro; Koch, Patrick M.; Koyama, Shoko; Kramer, Michael; Kramer, Carsten; Krichbaum, Thomas P.; Kuo, Cheng-Yu; Lauer, Tod R.; Lee, Sang-Sung; Levis, Aviad; Li, Yan-Rong; Li, Zhiyuan; Lindqvist, Michael; Lico, Rocco; Lindahl, Greg; Liu, Jun; Liu, Kuo; Liuzzo, Elisabetta; Lo, Wen-Ping; Lobanov, Andrei P.; Loinard, Laurent; Lonsdale, Colin; Lu, Ru-Sen; MacDonald, Nicholas R.; Mao, Jirong; Marchili, Nicola; Markoff, Sera; Marrone, Daniel P.; Marscher, Alan P.; Marti-Vidal, Ivan; Matsushita, Satoki; Matthews, Lynn D.; Medeiros, Lia; Menten, Karl M.; Mizuno, Izumi; Mizuno, Yosuke; Moran, James M.; Moriyama, Kotaro; Moscibrodzka, Monika; Muller, Cornelia; Musoke, Gibwa; Mejias, Alejandro Mus; Michalik, Daniel; Nadolski, Andrew; Nagai, Hiroshi; Nagar, Neil M.; Nakamura, Masanori; Narayan, Ramesh; Narayanan, Gopal; Natarajan, Iniyan; Nathanail, Antonios; Neilsen, Joey; Neri, Roberto; Ni, Chunchong; Noutsos, Aristeidis; Nowak, Michael A.; Okino, Hiroki; Olivares, Hector; Ortiz-Leon, Gisela N.; Oyama, Tomoaki; Ozel, Feryal; Palumbo, Daniel C. M.; Park, Jongho; Patel, Nimesh; Pen, Ue-Li; Pesce, Dominic W.; Pietu, Vincent; Plambeck, Richard; PopStefanija, Aleksandar; Porth, Oliver; Potzl, Felix M.; Prather, Ben; Preciado-Lopez, Jorge A.; Psaltis, Dimitrios; Pu, Hung-Yi; Ramakrishnan, Venkatessh; Rao, Ramprasad; Rawlings, Mark G.; Raymond, Alexander W.; Rezzolla, Luciano; Ricarte, Angelo; Ripperda, Bart; Roelofs, Freek; Rogers, Alan; Ros, Eduardo; Rose, Mel; Roshanineshat, Arash; Rottmann, Helge; Roy, Alan L.; Ruszczyk, Chet; Rygl, Kazi L. J.; Sanchez, Salvador; Sanchez-Arguelles, David; Sasada, Mahito; Savolainen, Tuomas; Schloerb, F. Peter; Schuster, Karl-Friedrich; Shao, Lijing; Shen, Zhiqiang; Small, Des; Sohn, Bong Won; SooHoo, Jason; Sun, He; Tazaki, Fumie; Tetarenko, Alexandra J.; Tiede, Paul; Tilanus, Remo P. J.; Titus, Michael; Toma, Kenji; Torne, Pablo; Trent, Tyler; Traianou, Efthalia; Trippe, Sascha; van Bemmel, Ilse; van Langevelde, Huib Jan; van Rossum, Daniel R.; Wagner, Jan; Ward-Thompson, Derek; Wardle, John; Weintroub, Jonathan; Wex, Norbert; Wharton, Robert; Wielgus, Maciek; Wong, George N.; Wu, Qingwen; Yoon, Doosoo; Young, Andre; Young, Ken; Younsi, Ziri; Yuan, Feng; Yuan, Ye-Fei; Zensus, J. Anton; Zhao, Guang-Yao; Zhao, Shan-Shan; Event Horizon Telescope Collaboration.-- This is an open access article, original content from this work may be used under the terms of the Creative Commons Attribution 4.0 licence. Any further distribution of this work must maintain attribution to the author(s) and the title of the work, journal citation and DOI.

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TL;DR: In this paper, the interplay between CDW and superconductivity in a topological kagome metal has been studied using measurements of resistivity, dc and ac magnetic susceptibility under various pressures up to 6 GPa.
Abstract: ${\mathrm{CsV}}_{3}{\mathrm{Sb}}_{5}$ is a newly discovered ${Z}_{2}$ topological kagome metal showing the coexistence of a charge-density-wave (CDW)-like order at ${T}^{*}=94\text{ }\text{ }\mathrm{K}$ and superconductivity (SC) at ${T}_{c}=2.5\text{ }\text{ }\mathrm{K}$ at ambient pressure. Here, we study the interplay between CDW and SC in ${\mathrm{CsV}}_{3}{\mathrm{Sb}}_{5}$ via measurements of resistivity, dc and ac magnetic susceptibility under various pressures up to 6.6 GPa. We find that the CDW transition decreases with pressure and experience a subtle modification at ${P}_{c1}\ensuremath{\approx}0.6--0.9\text{ }\text{ }\mathrm{GPa}$ before it vanishes completely at ${P}_{c2}\ensuremath{\approx}2\text{ }\text{ }\mathrm{GPa}$. Correspondingly, ${T}_{c}(P)$ displays an unusual $M$-shaped double dome with two maxima around ${P}_{c1}$ and ${P}_{c2}$, respectively, leading to a tripled enhancement of ${T}_{c}$ to about 8 K at 2 GPa. The obtained temperature-pressure phase diagram resembles those of unconventional superconductors, illustrating an intimated competition between CDW-like order and SC. The competition is found to be particularly strong for the intermediate pressure range ${P}_{c1}\ensuremath{\le}P\ensuremath{\le}{P}_{c2}$ as evidenced by the broad superconducting transition and reduced superconducting volume fraction. The modification of CDW order around ${P}_{c1}$ has been discussed based on the band structure calculations. This work not only demonstrates the potential to raise ${T}_{c}$ of the V-based kagome superconductors, but also offers more insights into the rich physics related to the electron correlations in this novel family of topological kagome metals.

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TL;DR: The Clinical Practice Manual for Hepatocellular Carcinoma (HCC) as mentioned in this paper was published by the Japan Society of Hepatology (JSH) expert panel in 2007, with emphasis on the consensus statements and recommendations for the management of HCC.
Abstract: The Clinical Practice Manual for Hepatocellular Carcinoma was published based on evidence confirmed by the Evidence-based Clinical Practice Guidelines for Hepatocellular Carcinoma along with consensus opinion among a Japan Society of Hepatology (JSH) expert panel on hepatocellular carcinoma (HCC). Since the JSH Clinical Practice Guidelines are based on original articles with extremely high levels of evidence, expert opinions on HCC management in clinical practice or consensus on newly developed treatments are not included. However, the practice manual incorporates the literature based on clinical data, expert opinion, and real-world clinical practice currently conducted in Japan to facilitate its use by clinicians. Alongside each revision of the JSH Guidelines, we issued an update to the manual, with the first edition of the manual published in 2007, the second edition in 2010, the third edition in 2015, and the fourth edition in 2020, which includes the 2017 edition of the JSH Guideline. This article is an excerpt from the fourth edition of the HCC Clinical Practice Manual focusing on pathology, diagnosis, and treatment of HCC. It is designed as a practical manual different from the latest version of the JSH Clinical Practice Guidelines. This practice manual was written by an expert panel from the JSH, with emphasis on the consensus statements and recommendations for the management of HCC proposed by the JSH expert panel. In this article, we included newly developed clinical practices that are relatively common among Japanese experts in this field, although all of their statements are not associated with a high level of evidence, but these practices are likely to be incorporated into guidelines in the future. To write this article, coauthors from different institutions drafted the content and then critically reviewed each other's work. The revised content was then critically reviewed by the Board of Directors and the Planning and Public Relations Committee of JSH before publication to confirm the consensus statements and recommendations. The consensus statements and recommendations presented in this report represent measures actually being conducted at the highest-level HCC treatment centers in Japan. We hope this article provides insight into the actual situation of HCC practice in Japan, thereby affecting the global practice pattern in the management of HCC.

Journal ArticleDOI
David V. Conti1, Burcu F. Darst1, Lilit C. Moss1, Edward J. Saunders2  +251 moreInstitutions (100)
TL;DR: This paper conducted a meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants.
Abstract: Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84–5.29) for men of European ancestry to 3.74 (95% CI, 3.36–4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14–2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71–0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction.

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Qi Zhao1, Qi Zhao2, Yuming Guo2, Tingting Ye2, Antonio Gasparrini3, Shilu Tong, Ala Overcenco, Aleš Urban4, Aleš Urban5, Alexandra Schneider, Alireza Entezari6, Ana M. Vicedo-Cabrera7, Antonella Zanobetti8, Antonis Analitis9, Ariana Zeka10, Aurelio Tobias11, Baltazar Nunes12, Baltazar Nunes13, Barrak Alahmad8, Ben Armstrong3, Bertil Forsberg14, Shih-Chun Pan15, Carmen Iñiguez16, Caroline Ameling, César De la Cruz Valencia, Christofer Åström14, Danny Houthuijs, Do Van Dung17, Dominic Royé18, Ene Indermitte19, Eric Lavigne20, Eric Lavigne21, Fatemeh Mayvaneh6, Fiorella Acquaotta22, Francesca de’Donato, Francesco Di Ruscio23, Francesco Sera3, Francesco Sera24, Gabriel Carrasco-Escobar25, Gabriel Carrasco-Escobar26, Haidong Kan27, Hans Orru19, Ho Kim28, Iulian-Horia Holobaca29, Jan Kyselý5, Jan Kyselý4, Joana Madureira30, Joana Madureira12, Joel Schwartz8, Jouni J. K. Jaakkola31, Jouni J. K. Jaakkola32, Klea Katsouyanni9, Klea Katsouyanni33, Magali Hurtado Diaz, Martina S. Ragettli34, Martina S. Ragettli35, Masahiro Hashizume36, Mathilde Pascal, Micheline de Sousa Zanotti Stagliorio Coelho37, Nicolas Valdes Ortega38, Niilo R.I. Ryti31, Noah Scovronick39, Paola Michelozzi, Patricia Matus Correa38, Patrick Goodman, Paulo Hilário Nascimento Saldiva37, Rosana Abrutzky40, Samuel Osorio37, Shilpa Rao23, Simona Fratianni22, Tran Ngoc Dang17, Valentina Colistro41, Veronika Huber42, Veronika Huber43, Whanhee Lee44, Xerxes Seposo11, Yasushi Honda45, Yue Leon Guo15, Yue Leon Guo46, Michelle L. Bell44, Shanshan Li2 
TL;DR: In this paper, the global, regional, and national mortality burden associated with non-optimal ambient temperatures was evaluated using time-series data collected from 750 locations in 43 countries and five meta-predictors.