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Proteogenomic analysis of enriched HGSOC tumor epithelium identifies prognostic signatures and therapeutic vulnerabilities (vol 8, 68, 2024)

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NPJ PRECISION ONCOLOGY 2024年第1期8卷 1-17页

作者： Bateman, Nicholas W. Abulez, Tamara Soltis, Anthony R. McPherson, Andrew Choi, Seongmin Garsed, Dale W. Pandey, Ahwan Tian, Chunqiao Hood, Brian L. Conrads, Kelly A. Teng, Pang-ning Oliver, Julie Gist, Glenn Mitchell, Dave Litzi, Tracy J. Tarney, Christopher M. Crothers, Barbara A. Mhawech-Fauceglia, Paulette Dalgard, Clifton L. Wilkerson, Matthew D. Pierobon, Mariaelena Petricoin, Emanuel F. Yan, Chunhua Meerzaman, Daoud Bodelon, Clara Wentzensen, Nicolas Lee, Jerry S. H. Huntsman, David G. Shah, Sohrab Shriver, Craig D. Phippen, Neil T. Darcy, Kathleen M. Bowtell, David D. L. Conrads, Thomas P. Maxwell, G. Larry Gynecologic Cancer Center of Excellence Gynecologic Surgery and Obstetrics Uniformed Services University of the Health Sciences Bethesda MD USA The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc Bethesda MD USA The John P. Murtha Cancer Center Research Program Department of Surgery Uniformed Services University and Walter Reed National Military Medical Center Bethesda MD USA Women’s Health Integrated Research Center Women’s Service Line Inova Health System Falls Church VA USA The American Genome Center Collaborative Health Initiative Research Program Department of Anatomy Physiology and Genetics Uniformed Services University of the Health Sciences Bethesda MD USA Department of Computational Oncology Memorial Sloan Kettering Cancer Center Manhattan NY USA Peter MacCallum Cancer Centre Parkville Melbourne Victoria Australia Sir Peter MacCallum Department of Oncology The University of Melbourne Parkville Victoria Australia The Joint Pathology Center Defense Health Agency National Capital Region Medical Directorate Silver Spring MD USA Department of Anatomic Pathology Division of Gynecologic Pathology University of Southern California Los Angeles CA USA Center for Applied Proteomics and Molecular Medicine George Mason University Manassas VA USA Center for Biomedical Informatics and Information Technology National Cancer Institute Rockville MD USA Division of Cancer Epidemiology and Genetics National Cancer Institute Rockville MD USA Ellison Institute for Transformative Medicine University of Southern California Los Angeles CA USA Department of Pathology and Laboratory Medicine The University of British Columbia Vancouver British Columbia Canada The Cancer Imaging Archive National Cancer Institute Bethesda MD USA The Ohio State University Columbus OH USA Duke University Medical Center Durham NC USA University of Virginia Charlottesville VA USA University of Chicago Chicago IL USA MD Anderson Comprehensive Cancer

We performed a deep proteogenomic analysis of bulk tumor and laser microdissection enriched tumor cell populations from high-grade serous ovarian cancer (HGSOC) tissue specimens spanning a broad spectrum of purity. We identified patients with longer progression-free survival had increased immune-related signatures and validated proteins correlating with tumor-infiltrating lymphocytes in 65 tumors from an independent cohort of HGSOC patients, as well as with overall survival in an additional 126 HGSOC patient cohort. We identified that homologous recombination deficient (HRD) tumors are enriched in pathways associated with metabolism and oxidative phosphorylation that we validated in independent patient cohorts. We further identified that polycomb complex protein BMI-1 is elevated in HR proficient (HRP) tumors, that elevated BMI-1 correlates with poor overall survival in HRP but not HRD HGSOC patients, and that HRP HGSOC cells are uniquely sensitive to BMI-1 inhibition.

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Electronic and vibrational properties of Pu3M(M=Al, Ga, In, and Tl): A first-principles study

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Physical Review B 2019年第18期100卷 184101-184101页

作者： Menglei Li Yu Yang Fawei Zheng Cong Wang Ping Zhang Department of Physics Capital Normal University Beijing 100048 China LCP Institute of Applied Physics and Computational Mathematics Beijing 100088 China Center for Fusion Energy Science and Technology CAEP Beijing 100084 China Beijing Computational Science Research Center Beijing 100084 China Center for Applied Physics and Technology Peking University HEDPS Beijing 100871 China Compression Science Research Center CAEP Mianyang 621900 China

We investigated the structural, electronic, magnetic, and phonon properties of Pu3M, where M = Al, Ga, In, and Tl, using first-principles calculations with the spin-orbit coupling taken into consideration. All four compounds are found to contain transverse phonons along [011] and [111] that remarkably soften at the boundaries of the first Brillouin zone, corresponding to the M and R points. Through detailed analyses of the vibrational modes and bond strengths, we reveal that all four types of M atoms have softer bonding with neighboring Pu than Pu-Pu bond, which accounts for the phonon softening and may shed light on the δ-stabilization of Pu by trivalent metal doping. In addition, we find that, due to the missing p−d hybridization, Pu3Al behaves quite differently from the other three Pu3M compounds. For example, Pu3Al has an unexpected equilibrium volume and high-frequency disentangled optical branches of phonons.

关键词： Chemical bonding Phonons Actinides Face-centered cubic Density functional calculations

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Lessons Learned from Assessing Trustworthy AI in Practice

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Digital Society 2023年第3期2卷 1-25页

作者： Vetter, Dennis Amann, Julia Bruneault, Frédérick Coffee, Megan Düdder, Boris Gallucci, Alessio Gilbert, Thomas Krendl Hagendorff, Thilo van Halem, Irmhild Hickman, Eleanore Hildt, Elisabeth Holm, Sune Kararigas, Georgios Kringen, Pedro Madai, Vince I. Wiinblad Mathez, Emilie Tithi, Jesmin Jahan Westerlund, Magnus Wurth, Renee Zicari, Roberto V. Computational Vision and Artificial Intelligence Lab Goethe University Frankfurt Frankfurt Am Main Germany Z-Inspection® Initiative Venice Italy Health Ethics and Policy Lab ETH Zurich Zurich Switzerland Strategy and Innovation Careum Foundation Zurich Switzerland Philosophie Departement Collège André-Laurendeau Montréal Canada École Des Médias Université du Québec À Montréal Montréal Canada Department of Medicine Division of Infectious Diseases and Immunology New York University Grossman School of Medicine New York City USA Department of Computer Science University of Copenhagen Copenhagen Denmark Digital Life Initiative Cornell Tech New York City USA Cluster of Excellence “Machine Learning: New Perspectives for Science” University of Tuebingen Tuebingen Germany School of Law University of Bristol Bristol UK Center for the Study of Ethics in the Professions Illinois Institute of Technology Chicago USA Department of Business Management and Analytics Arcada University of Applied Sciences Helsinki Finland Department of Food & Resource Economics University of Copenhagen Copenhagen Denmark Department of Physiology Faculty of Medicine University of Iceland Reykjavik Iceland QUEST Centre for Responsible Research Berlin Institute of Health Charité Universitätsmedizin Berlin Berlin Germany Faculty of Computing Engineering and the Built Environment School of Computing and Digital Technology Birmingham City University Birmingham UK Parallel Computing Labs Intel Santa Clara USA School of Economics Innovation and Technology Kristiania University College Oslo Norway Data Science Graduate School Seoul National University Seoul South Korea

Building artificial intelligence (AI) systems that adhere to ethical standards is a complex problem. Even though a multitude of guidelines for the design and development of such trustworthy AI systems exist, these guidelines focus on high-level and abstract requirements for AI systems, and it is often very difficult to assess if a specific system fulfills these requirements. The Z-Inspection® process provides a holistic and dynamic framework to evaluate the trustworthiness of specific AI systems at different stages of the AI lifecycle, including intended use, design, and development. It focuses, in particular, on the discussion and identification of ethical issues and tensions through the analysis of socio-technical scenarios and a requirement-based framework for ethical and trustworthy AI. This article is a methodological reflection on the Z-Inspection® process. We illustrate how high-level guidelines for ethical and trustworthy AI can be applied in practice and provide insights for both AI researchers and AI practitioners. We share the lessons learned from conducting a series of independent assessments to evaluate the trustworthiness of real-world AI systems, as well as key recommendations and practical suggestions on how to ensure a rigorous trustworthiness assessment throughout the lifecycle of an AI system. The results presented in this article are based on our assessments of AI systems in the healthcare sector and environmental monitoring, where we used the framework for trustworthy AI proposed in the Ethics Guidelines for Trustworthy AI by the European Commission’s High-Level Expert Group on AI. However, the assessment process and the lessons learned can be adapted to other domains and include additional frameworks.

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PLUMED Tutorials: a collaborative, community-driven learning ecosystem

arXiv

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arXiv 2024年

作者： Tribello, Gareth A. Bonomi, Massimiliano Bussi, Giovanni Camilloni, Carlo Armstrong, Blake I. Arsiccio, Andrea Aureli, Simone Ballabio, Federico Bernetti, Mattia Bonati, Luigi Brookes, Samuel G.H. Faidon Brotzakis, Z. Capelli, Riccardo Ceriotti, Michele Chan, Kam-Tung Cossio, Pilar Dasetty, Siva Donadio, Davide Ensing, Bernd Ferguson, Andrew L. Fraux, Guillaume Gale, Julian D. Gervasio, Francesco Luigi Giorgino, Toni Herringer, Nicholas S.M. Hocky, Glen M. Hoff, Samuel E. Invernizzi, Michele Languin-Cattoën, Olivier Leone, Vanessa Limongelli, Vittorio Lopez-Acevedo, Olga Marinelli, Fabrizio Martinez, Pedro Febrer Masetti, Matteo Mehdi, Shams Michaelides, Angelos Murtada, Mhd Hussein Parrinello, Michele Piaggi, Pablo M. Pietropaolo, Adriana Pietrucci, Fabio Pipolo, Silvio Pritchard, Claire Raiteri, Paolo Raniolo, Stefano Rapetti, Daniele Rizzi, Valerio Rydzewski, Jakub Salvalaglio, Matteo Schran, Christoph Seal, Aniruddha Zadeh, Armin Shayesteh Silva, Tomás F.D. Spiwok, Vojtěch Stirnemann, Guillaume Sucerquia, Daniel Tiwary, Pratyush Valsson, Omar Vendruscolo, Michele Voth, Gregory A. White, Andrew D. Wu, Jiangbo Centre for Quantum Materials and Technology School of Mathematics and Physics Queen’s University Belfast United Kingdom Institut Pasteur Université Paris Cité CNRS UMR 3528 Computational Structural Biology Unit Paris France Via Bonomea 265 Trieste34136 Italy Department of Biosciences University of Milano Milano Italy School of Molecular and Life Sciences Curtin University GPO Box U1987 PerthWA6845 Australia Coriolis Pharma Fraunhoferstrasse 18b Martinsried82152 Germany School of Pharmaceutical Sciences University of Geneva Rue Michel-Servet 1 GenevaCH-1206 Switzerland Institute of Pharmaceutical Sciences of Western Switzerland University of Geneva GenevaCH-1206 Switzerland Swiss Bioinformatics Institute University of Geneva GenevaCH-1206 Switzerland Via Celoria 26 Milan20133 Italy Department of Biomolecular Sciences University of Urbino "Carlo Bo" Piazza Rinascimento 6 Urbino61029 Italy Department of Pharmacy and Biotechnology Alma Mater Studiorum University of Bologna Via Belmeloro 6 Bologna40126 Italy Atomistic Simulations Italian Institute of Technology Genova Italy Yusuf Hamied Department of Chemistry University of Cambridge CambridgeCB2 1EW United Kingdom Institute for Bioinnovation Biomedical Sciences Research Center "Alexander Fleming" Vari16672 Greece Laboratory of Computational Science and Modeling Institut des Matériaux École Polytechnique Fédérale de Lausanne Lausanne1015 Switzerland Department of Chemistry University of California Davis DavisCA95616 United States Center for Computational Mathematics Flatiron Institute New YorkNY10010 United States Center for Computational Biology Flatiron Institute New YorkNY10010 United States Pritzker School of Molecular Engineering University of Chicago ChicagoIL60637 United States AI4Science Lab Informatics Institute University of Amsterdam Science Park 904 Amsterdam1098 XH Netherlands Computational Chemistry Group Van’t Hoff Institute for Molecular Sciences Unive

In computational physics, chemistry, and biology, the implementation of new techniques in a shared and open source software lowers barriers to entry and promotes rapid scientific progress. However, effectively training new software users presents several challenges. Common methods like direct knowledge transfer and in-person workshops are limited in reach and comprehensiveness. Furthermore, while the COVID-19 pandemic highlighted the benefits of online training, traditional online tutorials can quickly become outdated and may not cover all the software’s functionalities. To address these issues, here we introduce "PLUMED Tutorials", a collaborative model for developing, sharing, and updating online tutorials. This initiative utilizes repository management and continuous integration to ensure compatibility with software updates. Moreover, the tutorials are interconnected to form a structured learning path and are enriched with automatic annotations to provide broader context. This paper illustrates the development, features, and advantages of PLUMED Tutorials, aiming to foster an open community for creating and sharing educational resources. © 2024, CC BY.

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Shock oscillation in highly underexpanded jets

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Chinese Physics B 2018年第9期27卷 396-409页

作者： Xiao-Peng Li Rui Zhou Xiao-Ping Chen Xue-Jun Fan Guo-Shan Xie China Special Equipment Inspection and Research Institute Beijing 100029 China Laboratory of Computational Physics Institute of Applied Physics and Computational Mathematics Beijing 100094 China Key Laboratory of Fluid Transmission Technology of Zhejiang Province Zhejiang Sci- Tech University Hangzhou 310018 China State Key Laboratory of High Temperature Gas Dynamics Institute of Mechanics Chinese Academy of Sciences Beijing 1O0190 China

The oscillatory motions of shocks in highly underexpanded jets with nozzle pressure ratios of 5.60, 7.47, 9.34, and11.21 are quantitatively studied by using large eddy simulation. Two types of shock oscillations are observed： one is the Mach disk oscillation in the streamwise direction and the other is the shock oscillation in the radial direction. It is found that the Mach disk moves quickly in the middle of the oscillatory region but slowly at the top or bottom boundaries. The oscillation cycles of Mach disk are the same for different cases, and are all dominated by an axisymmetric mode of 5.298 k Hz. For the oscillation in the radial direction, the shocks oscillate more toward the jet centerline but less in the jet shear layer, and the oscillation magnitude is an increasing function of screech amplitude. The cycles of the radial shock oscillation switch randomly between the two screech frequencies for the first two cases. However, the oscillation periodicity is more complex for the jets with high nozzle pressure ratios of 9.34 and 11.21 than for the jets with the low nozzle pressure ratios of 5.6 and 7.47. In addition, the shock oscillation characteristics are also captured by coarse mesh and Smagorinsky model,but the coarse mesh tends to predict a slower and weaker shock oscillation.

关键词： highly underexpanded jets shock oscillation large eddy simulation

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Phonon-Enhanced Nonlinearities in Hexagonal Boron Nitride

arXiv

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arXiv 2021年

作者： Ginsberg, Jared S. Jadidi, M. Mehdi Zhang, Jin Chen, Cecilia Y. Tancogne-Dejean, Nicolas Chae, Sang Hoon Patwardhan, Gauri N. Xian, Lede Watanabe, Kenji Taniguchi, Takashi Hone, James Rubio, Angel Gaeta, Alexander L. Department of Applied Physics and Applied Mathematics Columbia University New YorkNY10027 United States Max Planck Institute for Structure and Dynamics of Matter Center for Free-Electron Laser Science Hamburg22761 Germany Department of Electrical Engineering Columbia University New YorkNY10027 United States Department of Mechanical Engineering Columbia University New YorkNY10027 United States School of Electrical and Electronic Engineering Nanyang Technological University Singapore639798 Singapore School of Materials Science and Engineering Nanyang Technological University Singapore639798 Singapore School of Applied and Engineering Physics Cornell University IthacaNY14853 United States Research Center for Functional Materials National Institute for Materials Science 1-1 Namiki Tsukuba305-0044 Japan International Center for Materials Nanoarchitectonics National Institute for Materials Science 1-1 Namiki Tsukuba305-0044 Japan Center for Computational Quantum Physics Simons Foundation Flatiron Institute New YorkNY10010 United States

We investigate optical nonlinearities that are induced and enhanced due to the strong phonon resonance in hexagonal boron nitride. We predict and observe large sub-picosecond duration signals due to four-wave mixing (FWM) during resonant excitation. The resulting FWM signal allows for time-resolved observation of the crystal motion. In addition, we observe enhancements of third-harmonic generation with resonant pumping at the hBN transverse optical phonon. Phonon-induced nonlinear enhancements are also predicted to yield large increases in high-harmonic efficiencies. Copyright © 2021, The Authors. All rights reserved.

关键词： Four wave mixing

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Giant isolated attosecond pulses from two-color laser plasma interactions

arXiv

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arXiv 2020年

作者： Zhang, Yuxue X. Rykovanov, S. Shi, Mingyuan Zhong, C.L. He, X.T. Qiao, B. Zepf, M. Center for Applied Physics and Technology HEDPS SKLNPT School of Physics Peking University Beijing100871 China Helmholtz Institute Jena Jena07743 Germany Laser Fusion Research Center China Academy of Engineering Physics Mianyang621900 China Institute of Optics and Quantum Electronics Friedrich Schiller University Jena 07743 Germany Collaborative Innovation Center of IFSA Shanghai Jiao Tong Univ. Shanghai200240 China Institute of Applied Physics and Computational Mathematics Beijing100094 China

A new regime in the interaction of a two-colour (ω,2ω) laser with a nanometre-scale foil is identified, resulting in the emission of extremely intense, isolated attosecond pulses - even in the case of multi-cycle lasers. For foils irradiated by lasers exceeding the blow-out field strength (i.e. capable of fully separating electrons from the ion background), the addition of a second harmonic field results in the stabilization of the foil up to the blow-out intensity. This is then followed by a sharp transition to transparency that essentially occurs in a single optical cycle. During the transition cycle, a dense, nanometre-scale electron bunch is accelerated to relativistic velocities and emits a single, strong attosecond pulse with a peak intensity approaching that of the laser field. Copyright © 2020, The Authors. All rights reserved.

关键词： Blowouts

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Deep neural network for Wannier function centers

arXiv

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arXiv 2019年

作者： Zhang, Linfeng Chen, Mohan Wu, Xifan Wang, Han Weinan, E. Car, Roberto Program in Applied and Computational Mathematics Princeton University PrincetonNJ08544 United States CAPT HEDPS College of Engineering Peking University Beijing100871 China Department of Physics Temple University PhiladelphiaPA19122 United States Laboratory of Computational Physics Institute of Applied Physics and Computational Mathematics Huayuan Road 6 Beijing100088 China Department of Mathematics and Program in Applied and Computational Mathematics Princeton University PrincetonNJ08544 United States Beijing Institute of Big Data Research Beijing100871 China Department of Chemistry Department of Physics Program in Applied and Computational Mathematics Princeton Institute for the Science and Technology of Materials Princeton University PrincetonNJ08544 United States

We introduce a deep neural network (DNN) model that assigns the position of the centers of the electronic charge in the snapshots of a molecular dynamics trajectory. The electronic centers are uniquely specified by the unitary transformation that maps the occupied eigenstates onto maximally localized Wannier functions. In combination with deep potential molecular dynamics, a DNN approach to model the atomic potential energy surface at the ab initio density functional level of theory, the scheme makes possible to predict the dielectric properties of insulators for samples and trajectories inaccessible to direct ab initio simulation, without loss of accuracy. As an example, we report calculations of the infrared absorption spectra of light and heavy water at a dispersion inclusive hybrid functional level of theory, finding good agreement with experiment. Extensions to other spectroscopies, like Raman and sum frequency generation, are discussed. Copyright © 2019, The Authors. All rights reserved.

关键词： Quantum chemistry

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Low-energy interference structure with attosecond temporal resolution

arXiv

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arXiv 2020年

作者： Song, Xiaohong Jia, Wenbin Liu, Xiwang Zhang, Hongdan Xue, Qibing Lin, Cheng Quan, Wei Chen, Jing Liu, XiaoJun Yang, Weifeng Research Center for Advanced Optics and Photoelectronics Department of Physics College of Science Shantou University Guangdong Shantou515063 China Department of Mathematics College of Science Shantou University Guangdong Shantou515063 China Key Laboratory of Intelligent Manufacturing Technology of MOE Shantou University Guangdong Shantou515063 China State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics Wuhan Institute of Physics and Mathematics Chinese Academy of Sciences Wuhan430071 China HEDPS Center for Applied Physics and Technology Collaborative Innovation Center of IFSA Peking University Beijing100084 China Institute of Applied Physics and Computational Mathematics P. O. Box 8009 Beijing100088 China

Accessing precisely to the phase variation of electronic wave-packet (EWP) provides unprecedented spatiotemporal information of microworld. A radial interference pattern at near-zero energy has been widely observed in experiments of strong-field photoionization. However, the underlying physical picture of this interference pattern is still under debate. Here we report an experimental and theoretical investigation of this low-energy interference structure (LEIS) in mid-infrared laser fields. We clarify that the LEIS arises due to the soft-recollision mechanism, which was previously found to play a pivotal role in producing the pronounced low-energy structure. Specifically, the LEIS is induced by the interference between direct and soft-recollision EWPs launched within a 1/18 laser-cycle time scale in our experiments. Moreover, the observation of LEIS is independent of laser wavelength and specific atomic targets. Our result opens a promising new avenue for retrieving the structure and dynamics of EWPs in atoms and molecules with attosecond time resolution. Copyright © 2020, The Authors. All rights reserved.

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Global, regional, and national age-sex-specific burden of diarrhoeal diseases, their risk factors, and aetiologies, 1990–2021, for 204 countries and territories: a systematic analysis for the Global Burden of Disease Study 2021

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The Lancet Infectious Diseases 2025年第5期25卷 519-536页

作者： Kyu, Hmwe Hmwe Vongpradith, Avina Dominguez, Regina-Mae Villanueva Ma, Jianing Albertson, Samuel B. Novotney, Amanda Khalil, Ibrahim A. Troeger, Christopher E. Doxey, Matthew C. Ledesma, Jorge R. Sirota, Sarah Brooke Bender, Rose Grace Swetschinski, Lucien R. Cunningham, Matthew Spearman, Sandra Abate, Yohannes Habtegiorgis Abd Al Magied, Abdallah H.A. El Hafeez, Samar Abd Abdoun, Meriem Abera, Bayeh Abidi, Hassan Aboagye, Richard Gyan Abtew, Yonas Derso Abualruz, Hasan Abu-Gharbieh, Eman Abukhadijah, Hana J. Aburuz, Salahdein Addo, Isaac Yeboah Adekanmbi, Victor Adetunji, Charles Oluwaseun Oluwaseun Adeyeoluwa, Temitayo Esther Adhikary, Ripon Kumar Adnani, Qorinah Estiningtyas Sakilah Adra, Saryia Adzigbli, Leticia Akua Afolabi, Aanuoluwapo Adeyimika Afzal, Muhammad Sohail Afzal, Saira Agampodi, Suneth Buddhika Agide, Feleke Doyore Ahinkorah, Bright Opoku Ahmad, Aqeel Ahmad, Sajjad Ahmed, Ayman Ahmed, Haroon Ahmed, Saeed Akinosoglou, Karolina Akter, Ema Al Awaidy, Salah Alajlani, Muaaz M. Alam, Khurshid Albakri, Almaza Albashtawy, Mohammed Aldhaleei, Wafa A. Algammal, Abdelazeem M. Al-Gheethi, Adel Ali Saeed Ali, Abid Ali, Syed Shujait Ali, Waad Alif, Sheikh Mohammad Aljunid, Syed Mohamed Al-Marwani, Sabah Almazan, Joseph Uy Al-Mekhlafi, Hesham M. Almustanyir, Sami Alqahatni, Saleh A. Alrawashdeh, Ahmad Al-Rifai, Rami H. Alsabri, Mohammed A. Altaf, Awais Altirkawi, Khalid A. Alvis-Guzman, Nelson Alvis-Zakzuk, Nelson J. Alyahya, Mohammad Sharif Ibrahim Al-Zyoud, Walid A. Amugsi, Dickson A. Andrei, Catalina Liliana Antoni, Sebastien Anuoluwa, Boluwatife Stephen Anuoluwa, Iyadunni Adesola Anwar, Saleha Anwari, Palwasha Apostol, Geminn Louis Carace Arabloo, Jalal Arafat, Mosab Aravkin, Aleksandr Y. Areda, Demelash Aregawi, Brhane Berhe Aremu, Abdulfatai Arndt, Michael Benjamin Asgedom, Akeza Awealom Ashraf, Tahira Athari, Seyyed Shamsadin Atreya, Alok Ayele, Firayad Azadi, Davood Azhar, Gulrez Shah Aziz, Shahkaar Azzam, Ahmed Y. Babu, Giridhara Rathnaiah Taghanaki, Pegah Bahrami Bahramian, Saeed Balakrishnan, Senthi Department of Health Metrics Sciences School of Medicine Institute for Health Metrics and Evaluation University of Washington Seattle 98195 WA United States Institute for Health Metrics and Evaluation University of Washington Seattle WA United States Department of Health Metrics Sciences School of Medicine University of Washington Seattle WA United States Center for Biostatistics Ohio State University Columbus OH United States Department of Global Health University of Washington Seattle WA United States Urban Indian Health Institute Seattle Indian Health Board Seattle WA United States School of Medicine Yale University New Haven CT United States Department of Clinical Governance and Quality Improvement Aleta Wondo General Hospital Aleta Wondo Ethiopia College of Pharmacy Ajman University Ajman United Arab Emirates Department of Epidemiology Alexandria University Alexandria Egypt Department of Medicine University of Sétif Algeria Sétif Algeria Department of Health Sétif Algeria Department of Medical Microbiology Bahir Dar University Bahir Dar Ethiopia Department of Biology Ghent University Ghent Belgium Laboratory Technology Sciences Department Yasuj University of Medical Sciences Yasuj Iran Department of Family and Community Health University of Health and Allied Sciences Ho Ghana Department of Biomedical Science Arba Minch University Arba Minch Ethiopia Department of Nursing Al Zaytoonah University of Jordan Amman Jordan Amman Jordan Department of Clinical Sciences Sharjah United Arab Emirates Department of Biopharmaceutics and Clinical Pharmacy University of Jordan Amman Jordan Medical Research Center-Academic Health System Hamad Medical Corporation Doha Qatar College of Pharmacy University of Jordan Amman Jordan Department of Therapeutics United Arab Emirates University Al Ain United Arab Emirates School of Medicine University of Sydney Sydney NSW Australia Centre for Social Research in Health University of New South Wales Syd

Background: Diarrhoeal diseases claim more than 1 million lives annually and are a leading cause of death in children younger than 5 years. Comprehensive global estimates of the diarrhoeal disease burden for specific age groups of children younger than 5 years are scarce, and the burden in children older than 5 years and in adults is also understudied. We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2021 to assess the burden of, and trends in, diarrhoeal diseases overall and attributable to 13 pathogens, as well as the contributions of associated risk factors, in children and adults in 204 countries and territories from 1990 to 2021. Methods: We used the Cause of Death Ensemble modelling strategy to analyse vital registration data, verbal autopsy data, mortality surveillance data, and minimally invasive tissue sampling data. We used DisMod-MR (version 2.1), a Bayesian meta-regression tool, to analyse incidence and prevalence data identified via systematic reviews, population-based surveys, and claims and inpatient data. We calculated diarrhoeal disability-adjusted life-years (DALYs) as the sum of years of life lost (YLLs) and years lived with disability (YLDs) for each location, year, and age–sex group. For aetiology estimation, we used a counterfactual approach to quantify population-attributable fractions (PAFs). Additionally, we estimated the diarrhoeal disease burden attributable to the independent effects of risk factors using the comparative risk assessment framework. Findings: In 2021, diarrhoeal diseases caused an estimated 1·17 million (95% uncertainty interval 0·793–1·62) deaths globally, representing a 60·3% (50·6–69·0) decrease since 1990 (2·93 million [2·31–3·73] deaths). The most pronounced decline was in children younger than 5 years, with a 79·2% (72·4–84·6) decrease in diarrhoeal deaths. Global YLLs also decreased substantially, from 186 million (147–221) in 1990 to 51·4 million (39·9–65·9) in 2021. In 2021, an e

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