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Probabilistic genotype-phenotype maps reveal mutational robustness of RNA folding, spin glasses, and quantum circuits

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Physical Review Research 2025年第1期7卷 013118-013118页

作者： Anna Sappington Vaibhav Mohanty Department of Electrical Engineering and Computer Science Massachusetts Institute of Technology Cambridge Massachusetts 02139 USA Harvard-MIT Program in Health Sciences and Technology Harvard Medical School Boston Massachusetts 02115 USA and Massachusetts Institute of Technology Cambridge Massachusetts 02139 USA Harvard/MIT MD-PhD Program Harvard Medical School Boston Massachusetts 02115 USA and Massachusetts Institute of Technology Cambridge Massachusetts 02139 USA Department of Chemistry and Chemical Biology Harvard University Cambridge Massachusetts 02138 USA

Recent studies of genotype-phenotype maps have reported universally enhanced phenotypic robustness to genotype mutations, a feature essential to evolution. Virtually all of these studies make a simplifying assumption that each genotype—represented as a sequence—maps deterministically to a single phenotype, such as a discrete structure. Here we introduce probabilistic genotype-phenotype (PrGP) maps, where each genotype maps to a vector of phenotype probabilities, as a more realistic and universal language for investigating robustness in a variety of physical, biological, and computational systems. We study three model systems to show that PrGP maps offer a generalized framework which can handle uncertainty emerging from various physical sources: (1) thermal fluctuation in RNA folding, (2) external field disorder in the spin-glass ground state search problem, and (3) superposition and entanglement in quantum circuits, which are realized experimentally on IBM quantum computers. In all three cases, we observe a biphasic robustness scaling which is enhanced relative to random expectation for more frequent phenotypes and approaches random expectation for less frequent phenotypes. We derive an analytical theory for the behavior of PrGP robustness, and we demonstrate that the theory is highly predictive of empirical robustness.

关键词： Quantum computers

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Incorporating Gender-Neutral Language in IRB Materials: Perceptions of IRB Professionals

Ethics and Human Research

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Ethics and Human Research 2025年第3期47卷 30-39页

作者： Nellis, Kevin L. Lichtman, Ronnie Birnbaum, Jeffrey Friedman, Stanley Zwicklbauer, Elise Executive director of Human Research Protections and Quality Assurance at the Research Foundation for the State University of New York (SUNY) Downstate Health Sciences University (DHSU) United States Midwife and Emeritus at the SUNY DHSU an adjunct at Lehman College of the City University of New York and a member of the SUNY DHSU IRB United States of pediatrics at SUNY DHSU and a principal investigator and executive director of Health & Education Alternatives for Teens (“HEAT”) and a former IRB member United States Retired distinguished teaching of physiology and pharmacology a former SUNY DHSU faculty member a former director of the MD/PhD program and former IRB vice chair United States Medical student at the SUNY DHSU College of Medicine United States

This study investigated the perceptions of institutional review board (IRB) professionals regarding the use of gender-neutral language in IRB guidance and informed consent documents, and whether respondents’ IRBs incorporated gender-neutral language in those documents. A survey was disseminated to a diverse group of IRB professionals whose emails were generated from a list received from the Office for Human Research Protections. Responses indicated substantial endorsement of gender-neutral language, although actual usage remains limited. The findings suggest that while the willingness to adopt inclusive language is high, barriers such as resource limitations and a lack of regulatory guidelines often impede its broader application. This study underscores the importance of developing explicit guidelines and resources to facilitate the adoption of gender-neutral language, enhancing inclusivity in research settings. © 2025 by The Hastings Center. All rights reserved.

关键词： gender-neutral language human research protection program (HRPP) inclusivity in research institutional review boards (IRBs) IRB consent form templates IRB forms IRB guidance language implementation survey study

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Influence of the metabolic and inflammatory profile in patients with frozen shoulder – systematic review and meta-analysis

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BMC Musculoskeletal Disorders 2025年第1期26卷 1-25页

作者： Hamed-Hamed, Dina Rodríguez-Pérez, Celia Pruimboom, Leo Navarro-Ledesma, Santiago Clinical Medicine and Public Health PhD Program Faculty of Health Sciences University of Granada Granada Spain Hospital Universitario de Melilla C. Luis de Ostáriz 12 Melilla 52005 Spain Department of Nutrition and Food Science University of Granada Granada Spain Institute of Nutrition and Food Technology ‘José Mataix’ (INYTA) Biomedical Research Centre (CIBM) University of Granada Avda. del Conocimiento S/N Granada 18016 Spain Instituto de Investigación Biosanitaria Ibs.GRANADA Granada 18012 Spain University Chair in Clinical Psychoneuroimmunology (University of Granada and PNI Europe) Melilla Spain Faculty of Health Sciences Campus of Melilla. Querol Street 5 Melilla 52004 Spain

Background: Frozen Shoulder (FS), also known as adhesive shoulder capsulitis, is characterized by a fibrotic inflammatory process of unknown origin, with the most prominent symptoms being pain, stiffness, and reduced joint mobility. Methods: The systematic review and meta-analysis presented herein provide insights into the pathogenesis of this condition, as well as common metabolic biomarkers potentially implicated in FS, such as glycated hemoglobin (HbA1c), and inflammatory biomarkers, including interleukins (IL-1, IL-6) and tumor necrosis factor alpha (TNF-α). Dyslipidemia and hormonal factors, such as thyroid dysfunctions, are also examined. Results: A total of 7,499 individuals were included in the meta-analysis, and one additional study collected 28,416 blood samples from individuals with FS from biobanks. The meta-analysis of metabolic variables showed that HbA1c was the most significantly elevated marker in FS, with a standardized mean difference (Smd) of μ^ = 0.3970 (95% CI: 0.0998 to 0.6943), indicating a moderate effect. Glucose showed a mean difference of -0.28 (95% CI: -0.60 to 0.05), which was not statistically significant, suggesting that short-term fluctuations in glucose levels may not be as relevant as long-term metabolic control. Cholesterol had a standardized difference of 0.278 (95% CI: 0.171 to 0.385), being significantly higher in FS. For triglycerides, the Smd was μ^ = 1.0318 (95% CI: -1.0027 to 3.0664), indicating high heterogeneity and preventing a clear conclusion. Hypothyroidism was also evaluated, with a total Smd of 0.067, a total variance of 0.0021, and a 95% confidence interval of -0.024 to 0.158, confirming no association between FS and thyroid function. Regarding inflammatory biomarkers, IL-1β was the most predominant, showing significantly higher levels in FS, with an Smd of μ^ = 2.2671 (95% CI: 0.5750 to 3.9591). TNF-α had a mean difference of μ^ = 0.7814 (95% CI: 0.1013 to 1.4615), reflecting a significant difference from zero (z

关键词： Biomarkers Cytokines Frozen shoulder Inflammation Interleukins Metabolism

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Human papilloma virus (HPV) mediated cancers: an insightful update

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Journal of Translational Medicine 2025年第1期23卷 1-25页

作者： Baba, Sadaf Khursheed Alblooshi, Shahad Shahdad Eissa Yaqoob, Reem Behl, Shalini Al Saleem, Mansour Rakha, Emad A. Malik, Fayaz Singh, Mayank Macha, Muzafar A. Akhtar, Mohammed Kalim Houry, Walid A. Bhat, Ajaz A. Al Menhali, Asma Zheng, Zhi-Ming Mirza, Sameer Department of Chemistry College of Science (COS) United Arab Emirates University (UAEU) P.O. Box 15551 Al Ain United Arab Emirates Department of Biology College of Science (COS) United Arab Emirates University (UAEU) Al Ain United Arab Emirates Omics Centre of Excellence M42 Health Abu Dhabi United Arab Emirates Department of Applied Medical Sciences Applied College Qassim University Qassim Saudi Arabia Histopathology Department School of Medicine University of Nottingham Nottingham United Kingdom Department of Pathology Hamad Medical Corporation Doha Qatar Division of Cancer Pharmacology CSIR-Indian Institute of Integrative Medicine Jammu and Kashmir Srinagar 190005 India Department of Medical Oncology (Lab) Dr. BRAIRCH All India Institute of Medical Sciences (AIIMS) New Delhi 110029 India Watson-Crick Centre for Molecular Medicine Islamic University of Science and Technology Kashmir Awantipora 192122 India Department of Biochemistry University of Toronto Toronto M5G 1M1 ON Canada Department of Chemistry University of Toronto Toronto M5S 3H6 ON Canada Metabolic and Mendelian Disorders Clinical Research Program Precision OMICs Research & Translational Science Sidra Medicine Doha Qatar Tumor Virus RNA Biology Section HIV Dynamics and Replication Program Center for Cancer Research National Cancer Institute National Institutes of Health Frederick MD United States Zayed Bin Sultan Centre for Health Sciences United Arab Emirates University (UAEU) Al Ain United Arab Emirates

Human papillomavirus (HPV), a DNA virus, is a well-documented causative agent of several cancers, including cervical, vulvar, vaginal, penile, anal, and head & neck cancers. Major factors contributing to HPV-related cancers include persistent infection and the oncogenic potential of particular HPV genotypes. High-risk HPV strains, particularly HPV-16 and HPV-18, are responsible for over 70% of cervical cancer cases worldwide, as well as a significant proportion of other genital and head and neck cancers. At the molecular level, the oncogenic activity of these viruses is driven by the overexpression of E6 and E7 oncoproteins. These oncoproteins dysregulate the cell cycle, inhibit apoptosis, and promote the accumulation of DNA damage, ultimately transforming normal cells into cancerous ones. This review aims to provide a comprehensive overview of the recent advances in HPV-related cancer biology and epidemiology. The review highlights the molecular pathways of HPV-driven carcinogenesis, focusing on the role of viral oncoproteins in altering host cell targets and disrupting cellular signalling pathways. The review explores the therapeutic potential of these viral proteins, and discusses current diagnostic and treatment strategies for HPV-associated cancers. Furthermore, the review highlights the critical role of HPV in the development of various malignancies, emphasizing the persistent challenges in combating these cancers despite advancements in vaccination and therapeutic strategies. We also emphasize recent breakthroughs in utilizing biomarkers to monitor cancer therapy responses, such as mRNAs, miRNAs, lncRNAs, proteins, and genetic markers. We hope this review will serve as a valuable resource for researchers working on HPV, providing insights that can guide future investigations into this complex virus, which continues to be a major contributor to global morbidity and mortality. © The Author(s) 2025.

关键词： Apoptosis Cancer Cell cycle E6 E7 HPV Oncoproteins Therapeutics

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Self-assembling protein nanoparticles for cytosolic delivery of nucleic acids and proteins

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Nature Biotechnology 2025年 1-14页

作者： Eweje, Feyisayo Ibrahim, Vanessa Shajii, Aram Walsh, Michelle L. Ahmad, Kiran Alrefai, Assma Miyasato, Dominie Davis, Jessie R. Ham, Hyunok Li, Kaicheng Roehrl, Michael Haller, Carolyn A. Liu, David R. Chen, Jiaxuan Chaikof, Elliot L. Department of Surgery Beth Israel Deaconess Medical Center Harvard Medical School BostonMA United States Harvard and MIT Division of Health Science and Technology Massachusetts Institute of Technology CambridgeMA United States Harvard/MIT MD–PhD Program BostonMA United States Wyss Institute of Biologically Inspired Engineering Harvard University BostonMA United States Department of Chemistry and Chemical Biology Harvard University CambridgeMA United States Howard Hughes Medical Institute Harvard University CambridgeMA United States Merkin Institute of Transformative Technologies in Healthcare Broad Institute of MIT and Harvard CambridgeMA United States Department of Pathology Beth Israel Deaconess Medical Center Harvard Medical School BostonMA United States

Intracellular delivery of biomacromolecules is hampered by low efficiency and cytotoxicity. Here we report the development of elastin-based nanoparticles for therapeutic delivery (ENTER), a recombinant elastin-like polypeptide (ELP)-based delivery system for effective cytosolic delivery of biomacromolecules in vitro and in vivo. Through iterative design, we developed fourth-generation ELPs fused to cationic endosomal escape peptides (EEPs) that self-assemble into pH-responsive micellar nanoparticles and enable cytosolic entry of cargo following endocytic uptake. In silico screening of α-helical peptide libraries led to the discovery of an EEP (EEP13) with 48% improved protein delivery efficiency versus a benchmark peptide. Our lead ELP–EEP13 showed similar or superior performance compared to lipid-based transfection reagents in the delivery of mRNA-encoded, DNA-encoded and protein-form Cre recombinase and CRISPR gene editors as well as short interfering RNAs to multiple cell lines and primary cell types. Intranasal administration of ELP–EEP13 combined with Cre protein achieved efficient editing of lung epithelial cells in reporter mice. © The Author(s), under exclusive licence to Springer Nature America, Inc. 2025.

关键词： Glycoproteins

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Correction to: Environmental consequences of interacting effects of changes in stratospheric ozone, ultraviolet radiation, and climate: UNEP Environmental Effects Assessment Panel, Update 2024 (Photochemical & Photobiological sciences, (2025), 24, 3, (357-392), 10.1007/s43630-025-00687-x)

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Photochemical and Photobiological sciences 2025年第5期24卷 863-865页

作者： Neale, Patrick J. Hylander, Samuel Banaszak, Anastazia T. Häder, Donat-P. Rose, Kevin C. Vione, Davide Wängberg, Sten-Åke Jansen, Marcel A. K. Busquets, Rosa Andersen, Mads P. Sulbæk Madronich, Sasha Hanson, Mark L. Schikowski, Tamara Solomon, Keith R. Sulzberger, Barbara Wallington, Timothy J. Heikkilä, Anu M. Pandey, Krishna K. Andrady, Anthony L. Bruckman, Laura S. White, Christopher C. Zhu, Liping Bernhard, Germar H. Bais, Alkiviadis Aucamp, Pieter J. Chiodo, Gabriel Cordero, Raúl R. Petropavlovskikh, Irina Neale, Rachel E. Olsen, Catherine M. Hales, Simon Lal, Aparna Lingham, Gareth Rhodes, Lesley E. Young, Antony R. Robson, T. Matthew Robinson, Sharon A. Barnes, Paul W. Bornman, Janet F. Harper, Anna B. Lee, Hanna Calderón, Roy Mackenzie Ossola, Rachele Paul, Nigel D. Revell, Laura E. Wang, Qing-Wei Zepp, Richard G. Environmental Research Center Smithsonian Institution EdgewaterMD United States Centre for Ecology and Evolution in Microbial Model Systems Linnaeus University Kalmar Sweden Unidad Académica de Sistemas Arrecifales Universidad Nacional Autónoma de México Puerto Morelos Mexico Erlangen Germany Department of Biological Sciences and Department of Civil and Environmental Engineering Rensselaer Polytechnic Institute TroyNY United States Department of Chemistry University of Turin Turin Italy Department of Marine Sciences University of Gothenburg Gotheburg Sweden School of Biological Earth and Environmental Sciences Environmental Research Institute University College Cork Cork Ireland Chemical and Pharmaceutical Sciences Kingston University London Kingston Upon Thames United Kingdom Civil Environmental & Geomatic Engineering University College London London United Kingdom Department of Chemistry and Biochemistry California State University NorthridgeCA United States Atmospheric Chemistry Observations and Modeling National Center for Atmospheric Research BoulderCO United States USDA UV-B Monitoring and Research Program Colorado State University Fort. CollinsCO United States Department of Environment and Geography University of Manitoba WinnipegMB Canada Working Group Environmental Epidemiology IUF-Leibniz Research Institute for Environmental Medicine Düsseldorf Germany Department of Environment and Health School of Public Health University of Bielefeld Bielefeld Germany School of Environmental Sciences University of Guelph GuelphON Canada Retired From Eawag Swiss Federal Institute of Aquatic Science and Technology Dübendorf Switzerland Center for Sustainable Systems School for Environment and Sustainability University of Michigan Ann ArborMI United States Climate Research Finnish Meteorological Institute Helsinki Finland Indian Academy of Wood Science Bengaluru India Chemical and Biomolecular Engineering North Carolina State University RaleighN

This work is not a product of the U.S. Government or the U.S. Environmental Protection Agency, and the author is not doing this work in any governmental capacity. This research was not performed or funded by EPA and was not subject to EPA’s quality system requirements. The views expressed in this journal article are those of the author(s) and do not necessarily represent the views or the policies of the U.S. Environmental Protection Agency. The original article has been corrected. © The Author(s), under exclusive licence to the European Photochemistry Association, European Society for Photobiology 2025.

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Multimodal identification of the mouse brain using simultaneous Ca²⁺ imaging and fMRI

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Communications Biology 2025年第1期8卷 1-14页

作者： Mandino, Francesca Horien, Corey Shen, Xilin Desrosiers-Grégoire, Gabriel Luo, Wendy Markicevic, Marija Constable, R. Todd Papademetris, Xenophon Chakravarty, Mallar M. Betzel, Richard F. Lake, Evelyn M. R. Department of Radiology and Biomedical Imaging Yale University School of Medicine New Haven CT United States Interdepartmental Neuroscience Program Yale University School of Medicine New Haven CT United States MD/PhD program Yale University School of Medicine New Haven CT United States Computational Brain Anatomy Laboratory Douglas Mental Health University Institute Montreal QC Canada Integrated Program in Neuroscience McGill University Montreal QC Canada Department of Biomedical Engineering Yale University School of Medicine New Haven CT United States Department of Neurosurgery Yale University School of Medicine New Haven CT United States Deparment of Biomedical Informatics and Data Science Yale University New Haven CT United States Department of Psychological and Brain Sciences Indiana University Bloomington IN United States Wu Tsai Institute Yale University New Haven CT United States

Individual differences in neuroimaging are of interest to clinical and cognitive neuroscientists based on their potential for guiding the personalized treatment of various heterogeneous neurological conditions and diseases. Despite many advantages, the prevailing modality in this field—blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI)—suffers from low spatiotemporal resolution and specificity as well as a propensity for noise and spurious signal corruption. To better understand individual differences in BOLD-fMRI data, we can use animal models where fMRI, alongside complementary but more invasive contrasts, can be accessed. Here, we apply simultaneous wide-field fluorescence calcium imaging and BOLD-fMRI in mice to interrogate individual differences using a connectome-based identification framework adopted from the human fMRI literature. This approach yields high spatiotemporal resolution cell-type specific signals (here, from glia, excitatory, as well as inhibitory interneurons) from the whole cortex. We found mouse multimodal connectome-based identification to be successful and explored various features of these data. © The Author(s) 2025.

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Dural arteriovenous fistula (DAVF) after venous sinus stent (VSS) for presumed idiopathic intracranial hypertension (IIH): A case report and literature review

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Radiology case reports 2025年第1期20卷 817-822页

作者： Fatma Shakarchi Avery Zhou Tuan Anh Nguyen Saif Aldeen Alryalat Osama Al Deyabat Fernando Ahumada Peter Mortensen Orlando Diaz Andrew G Lee Climate Centre International Red Cross Red Crescent Movement Geneva Switzerland. Health and Natural Sciences Space Generation Advisory Council Vienna Austria. University of Nevada Las Vegas School of Medicine Las Vegas NV USA. Tri-Institutional MD-PhD Program Weill Cornell/Rockefeller/Sloan-Kettering New York NY USA. Department of Ophthalmology Houston Methodist Hospital Houston TX USA. Department of Neuroradiology Houston Methodist Hospital Houston TX USA. Departments of Ophthalmology Neurology and Neurosurgery Weill Cornell Medicine New York NY USA. Department of Ophthalmology University of Texas Medical Branch Galveston TX USA. University of Texas MD Anderson Cancer Center Houston TX USA. Texas A&M College of Medicine TX USA. Department of Ophthalmology The University of Iowa Hospitals and Clinics Iowa City IA USA.

Dural arteriovenous fistulas (DAVFs) are rare but significant intracranial vascular malformations that are usually idiopathic and can lead to severe complications like venous hypertension and intracranial hemorrhage. We present 2 cases of DAVF occurring after venous sinus stenting (VSS) for presumed idiopathic intracranial hypertension (IIH) in a 51-year-old and a 52-year-old female. In both patients, Cognard type 1 DAVF was detected by Catheter angiography and successfully obliterated with Onyx™ embolization. These cases suggest that VSS may either unmask pre-existing DAVFs by altering intracranial pressure dynamics or induce new fistula formation by angiogenic factors or stent-induced hemodynamic changes. Clinicians should maintain an index of suspicion for DAVF in patients with persistent symptoms post-VSS and catheter angiography might be needed to detect the DAVFs.

关键词： Case report Dural arteriovenous fistula Idiopathic intracranial hypertension Venous sinus stent

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Interferon-γ orchestrates leptomeningeal anti-tumour response

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Nature 2025年 1-10页

作者： Remsik, Jan Tong, Xinran Kunes, Russell Z. Li, Min Jun Estrera, Rachel Snyder, Jenna Thomson, Clark Osman, Ahmed M. Chabot, Kiana Sener, Ugur T. Wilcox, Jessica A. Isakov, Danielle Wang, Helen Bale, Tejus A. Chaligné, Ronan Sun, Joseph C. Brown, Chrysothemis Pe’er, Dana Boire, Adrienne Human Oncology & Pathogenesis Program Memorial Sloan Kettering Cancer Center New York NY United States Laboratory for Immunology of Metastatic Ecosystems Center for Cancer Biology VIB Leuven Belgium Department of Oncology KU Leuven Leuven Belgium BCMB Allied Program Graduate School of Medical Sciences Weill Cornell Medicine New York NY United States Program for Computational and Systems Biology Sloan Kettering Institute Memorial Sloan Kettering Cancer Center New York NY United States Department of Statistics Columbia University New York NY United States Gerstner Sloan Kettering Graduate School of Biomedical Sciences Memorial Sloan Kettering Cancer Center New York NY United States Department of Neurology Memorial Sloan Kettering Cancer Center New York NY United States Department of Pathology and Laboratory Medicine Memorial Sloan Kettering Cancer Center New York NY United States Immunology Program Sloan Kettering Institute Memorial Sloan Kettering Cancer Center New York NY United States Department of Pediatrics Memorial Sloan Kettering Cancer Center New York NY United States Immunology and Microbial Pathogenesis Program Weill Cornell Medical College New York NY United States Howard Hughes Medical Institute Memorial Sloan Kettering Cancer Center New York NY United States Medical Scientist Training Program University of California San Diego La Jolla CA United States Department of Women’s and Children’s Health Karolinska Institutet Solna Sweden College of Osteopathic Medicine New York Institute of Technology Glen Head NY United States Department of Neurology & Department of Medical Oncology Mayo Clinic Rochester MN United States Tri-Institutional MD-PhD Program Weill Cornell Medicine New York NY United States

Metastasis to the cerebrospinal-fluid-filled leptomeninges, or leptomeningeal metastasis, represents a fatal complication of solid tumours1. Multimodal analyses of clinical specimens reveal substantial inflammatory in...

Metastasis to the cerebrospinal-fluid-filled leptomeninges, or leptomeningeal metastasis, represents a fatal complication of solid tumours¹. Multimodal analyses of clinical specimens reveal substantial inflammatory infiltrate in leptomeningeal metastases with enrichment of IFNγ and resulting downstream signalling. Here, to investigate and overcome this futile anti-tumour response within the leptomeninges, we developed syngeneic lung cancer, breast cancer and melanoma leptomeningeal-metastasis mouse models. We show that transgenic host mice lacking IFNγ or its receptor fail to control the growth of leptomeningeal metastases growth. Leptomeningeal overexpression of Ifng through a targeted adeno-associated-virus-based system controls cancer cell growth independent of adaptive immunity. Using a suite of transgenic hosts, we demonstrate that leptomeningeal T cells generate IFNγ to actively recruit and activate peripheral myeloid cells, generating a diverse spectrum of dendritic cell subsets. Independent of antigen presentation, migratory CCR7⁺ dendritic cells orchestrate the influx, proliferation and cytotoxic action of natural killer cells to control cancer cell growth in the leptomeninges. This study identifies unique, leptomeninges-specific IFNγ signalling and suggests an immune-therapeutic approach against tumours within this space. © The Author(s) 2025.

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Changing life expectancy in European countries 1990–2021: a subanalysis of causes and risk factors from the Global Burden of Disease Study 2021

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The Lancet Public health 2025年第3期10卷 e172-e188页

作者： Steel, Nicholas Bauer-Staeb, Clarissa Maria Mercedes Ford, John A. Abbafati, Cristiana Abdalla, Mohammed Altigani Abdelkader, Atef Abdi, Parsa Zuñiga, Roberto Ariel Abeldaño Abiodun, Olugbenga Olusola Abolhassani, Hassan Abu-Gharbieh, Eman Abukhadijah, Hana J. Abu-Zaid, Ahmed Addo, Isaac Yeboah Addolorato, Giovanni Adekanmbi, Victor Adetunji, Juliana Bunmi Adeyeoluwa, Temitayo Esther Agardh, Emilie E. Agyemang-Duah, Williams Ahmad, Danish Ahmed, Ayman Ahmed, Syed Anees Akinosoglou, Karolina Akkaif, Mohammed Ahmed Al Awaidy, Salah Al Hasan, Syed Mahfuz Al Zaabi, Omar Ali Mohammed Aldridge, Robert W. Algammal, Abdelazeem M. Al-Gheethi, Adel Ali Saeed Ali, Abid Ali, Mohammed Usman Ali, Syed Shujait Ali, Waad Alicandro, Gianfranco Alif, Sheikh Mohammad Al-Jumaily, Adel Allebeck, Peter Alrawashdeh, Ahmad Al-Rifai, Rami H. Alsabri, Mohammed A. Alshahrani, Najim Z. Aluh, Deborah Oyine Al-Wardat, Mohammad Al-Zyoud, Walid A. Amiri, Sohrab Anderlini, Deanna Andrei, Catalina Liliana Anil, Abhishek Anvari, Saeid Anyasodor, Anayochukwu Edward Appiah, Seth Christopher Yaw Aquilano, Michele Arabloo, Jalal Arafat, Mosab Areda, Demelash Aremu, Abdulfatai Armani, Keivan Armocida, Benedetta Ärnlöv, Johan Asaduzzaman, Muhammad Astell-Burt, Thomas Aujayeb, Avinash Ausloos, Marcel Azadnajafabad, Sina Aziz, Shahkaar Azzam, Ahmed Y. Babu, Giridhara Rathnaiah Badache, Andreea Corina Badiye, Ashish D. Bahramian, Saeed Baig, Atif Amin Baker, Jennifer L. Bansal, Hansi Bärnighausen, Till Winfried Barone, Mark Thomaz Ugliara Barrow, Amadou Barteit, Sandra Bashir, Shahid Bashiru, Hameed Akande Basso, João Diogo Bastan, Mohammad-Mahdi Basu, Sanjay Batra, Kavita Bauckneht, Matteo Baune, Bernhard T. Beghi, Massimiliano Beiranvand, Maryam Béjot, Yannick Bell, Michelle L. Bello, Olorunjuwon Omolaja Belo, Luis Beloukas, Apostolos Beneke, Alice A. Bettencourt, Paulo J.G. Bhagavathula, Akshaya Srikanth Bhala, Neeraj Bhaskar, Sonu Bisulli, Francesca Bjørge, Tone Bodunrin, Aadam Olalekan Carvajal, Alejandro Botero Bouaoud, Souad Brayne, Carol Brenner, H Department of Primary Care and Public Health University of East Anglia Norwich United Kingdom Office for Health Improvement and Disparities Department of Health and Social Care London United Kingdom Department of Legal and Economic Studies La Sapienza University Rome Italy Rome Italy Hull York Medical School University of Hull Hull United Kingdom Department of Mathematics and Sciences Ajman University Ajman United Arab Emirates Department of Medicine Memorial University St. John's NL Canada Postgraduate Department University of Sierra Sur Miahuatlan de Porfirio Diaz Mexico Yhteiskuntadatatieteen keskus (Centre for Social Data Science) Helsinki Finland Department of Internal Medicine Federal Medical Centre Abuja Nigeria Research Center for Immunodeficiencies Tehran University of Medical Sciences Tehran Iran Department of Medical Biochemistry and Biophysics Karolinska Institutet (Karolinska Institute) Stockholm Sweden Department of Clinical Sciences University of Sharjah Sharjah United Arab Emirates Department of Biopharmaceutics and Clinical Pharmacy University of Jordan Amman Jordan Medical Research Center Hamad Medical Corporation Doha Qatar Department of Biochemistry and Molecular Medicine Alfaisal University Riyadh Saudi Arabia College of Graduate Health Sciences University of Tennessee Memphis TN United States School of Medicine Sydney NSW Australia Centre for Social Research in Health University of New South Wales Sydney NSW Australia Internal Medicine and Alcohol Related Disease Unit Fondazione Policlinico Universitario A. Gemelli IRCCS Rome Italy Department of Medical and Surgical Sciences Università Cattolica di Roma (Catholic University of Rome) Rome Italy Department of Obstetrics and Gynecology University of Texas Medical Branch Galveston TX United States Department of Biochemistry Osun State University Osogbo Nigeria Department of Pharmacology and Therapeutics University of Medical Sciences Ondo Ondo Nigeria Department of Veteri

Background: Decades of steady improvements in life expectancy in Europe slowed down from around 2011, well before the COVID-19 pandemic, for reasons which remain disputed. We aimed to assess how changes in risk factors and cause-specific death rates in different European countries related to changes in life expectancy in those countries before and during the COVID-19 pandemic. Methods: We used data and methods from the Global Burden of Diseases, Injuries, and Risk Factors Study 2021 to compare changes in life expectancy at birth, causes of death, and population exposure to risk factors in 16 European Economic Area countries (Austria, Belgium, Denmark, Finland, France, Germany, Greece, Iceland, Ireland, Italy, Luxembourg, the Netherlands, Norway, Portugal, Spain, and Sweden) and the four UK nations (England, Northern Ireland, Scotland, and Wales) for three time periods: 1990–2011, 2011–19, and 2019–21. Changes in life expectancy and causes of death were estimated with an established life expectancy cause-specific decomposition method, and compared with summary exposure values of risk factors for the major causes of death influencing life expectancy. Findings: All countries showed mean annual improvements in life expectancy in both 1990–2011 (overall mean 0·23 years [95% uncertainty interval [UI] 0·23 to 0·24]) and 2011–19 (overall mean 0·15 years [0·13 to 0·16]). The rate of improvement was lower in 2011–19 than in 1990–2011 in all countries except for Norway, where the mean annual increase in life expectancy rose from 0·21 years (95% UI 0·20 to 0·22) in 1990–2011 to 0·23 years (0·21 to 0·26) in 2011–19 (difference of 0·03 years). In other countries, the difference in mean annual improvement between these periods ranged from –0·01 years in Iceland (0·19 years [95% UI 0·16 to 0·21] vs 0·18 years [0·09 to 0·26]), to –0·18 years in England (0·25 years [0·24 to 0·25] vs 0·07 years [0·06 to 0·08]). In 2019–21, there was an overall decrease in mean annual life expectancy a

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