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Covalent Adaptable Networks: Toward Stimuli‐Responsive Dynamic Thermosets through Continuous Development and Improvements in Covalent Adaptable Networks (CANs) (Adv. Mater. 20/2020)

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Advanced Materials 2020年第20期32卷

作者： Maciej Podgórski Benjamin D. Fairbanks Bruce E. Kirkpatrick Matthew McBride Alina Martinez Adam Dobson Nicholas J. Bongiardina Christopher N. Bowman Department of Chemical and Biological Engineering University of Colorado UCB 596 Boulder CO 80309 USA Department of Polymer Chemistry Faculty of Chemistry Maria Curia‐Sklodowska University pl. Marii Curie‐Sklodowskiej 5 Lublin 20‐031 Poland Medical Scientist Training Program School of Medicine University of Colorado Aurora CO 80045 USA Materials Science and Engineering Program University of Colorado Boulder CO 80309 USA

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Comparative Performance of Machine Learning Models in Reducing Unnecessary Targeted Prostate Biopsies

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European urology oncology 2025年

作者： Fuyao Chen Roxana Esmaili Ghazal Khajir Tal Zeevi Moritz Gross Michael Leapman Preston Sprenkle Amy C Justice Sandeep Arora Jeffrey C Weinreb Michael Spektor Steffan Huber Peter A Humphrey Angelique Levi Lawrence H Staib Rajesh Venkataraman Darryl T Martin John A Onofrey Department of Biomedical Engineering Yale University New Haven CT USA Medical Scientist Training Program Yale School of Medicine New Haven CT USA. Department of Radiology and Biomedical Imaging Yale University New Haven CT USA Charité Center for Diagnostic and Interventional Radiology Charité-Universitätsmedizin Berlin Berlin Germany. Department of Urology Yale University New Haven CT USA. Department of Biomedical Engineering Yale University New Haven CT USA. VA Connecticut Healthcare West Haven CT USA Department of Internal Medicine Yale University New Haven CT USA. Department of Radiology and Biomedical Imaging Yale University New Haven CT USA. Department of Pathology Yale University New Haven CT USA. Department of Electrical Engineering Yale University New Haven CT USA. Eigen Health Grass Valley CA USA. Department of Urology Yale University New Haven CT USA. Electronic address: john.onofrey@yale.edu.

BACKGROUND AND OBJECTIVE:Conventional core needle biopsy for prostate cancer diagnosis can lead to diagnostic uncertainty and complications, prompting exploration of alternative risk assessment approaches that use clinical and imaging features. Our aim was to evaluate the effectiveness of machine learning (ML) models in reducing unnecessary biopsies. METHODS:We conducted a retrospective analysis of data for 1884 patients across two academic centers who underwent prostate magnetic resonance imaging and biopsy between 2016 and 2020 or 2004 and 2011. Twelve ML models were assessed for prediction of clinically significant prostate cancer (csPCa; Gleason grade group ≥2) using combinations of clinical features, including patient age, prostate-specific antigen level and density, Prostate Imaging-Reporting and Data System/Likert score, lesion volume, and gland volume. The models were trained and validated using a tenfold split for intrasite, intersite, and combined-site data sets. Model effectiveness was evaluated using the area under the receiver operating characteristic curve and decision curve analysis. KEY FINDINGS AND LIMITATIONS:The best-performing ML model would reduce the number of biopsies by 13.07% at a false-negative rate of 1.91%. Performance was consistent across sites, although the study is limited by the small number of centers and the absence of specific clinical data. CONCLUSIONS AND CLINICAL IMPLICATIONS:ML-enhanced clinical models provide an effective and generalizable approach for prediction of csPCa using standard clinical data. These models allow personalized risk assessment and follow-up, support clinical decision-making, and improve workflow efficiency. PATIENT SUMMARY:Models that are enhanced by machine learning can predict the severity of prostate cancer and help doctors in tailoring treatments for individual patients. This approach can simplify health care decisions and improve clinical efficiency.

关键词： Machine learning Multiparametric magnetic resonance imaging Prostate Imaging-Reporting and Data System Prostate cancer Prostate-specific antigen density Unnecessary biopsies

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Publisher Correction: Female aging: when translational models don't translate

Nature aging

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Nature aging 2024年第1期4卷 164页

作者： Gabrielle Gilmer Zachary R Hettinger Yetsa Tuakli-Wosornu Elizabeth Skidmore Julie K Silver Rebecca C Thurston Dawn A Lowe Fabrisia Ambrosio Discovery Center for Musculoskeletal Recovery Schoen Adams Research Institute at Spaulding Rehabilitation Boston MA USA. Department of Physical Medicine and Rehabilitation Spaulding Rehabilitation Hospital Charlestown MA USA. Medical Scientist Training Program School of Medicine University of Pittsburgh Pittsburgh PA USA. Cellular and Molecular Pathology Graduate Program University of Pittsburgh Pittsburgh PA USA. Department of Physical Medicine & Rehabilitation Harvard Medical School Boston MA USA. Department of Geriatric Medicine University of Pittsburgh Pittsburgh PA USA. Department of Social and Behavioral Sciences Yale School of Public Health Yale University New Haven CT USA. Department of Physical Medicine and Rehabilitation University of Pittsburgh School of Medicine Pittsburgh PA USA. Department of Occupational Therapy School of Health and Rehabilitation Sciences University of Pittsburgh Pittsburgh PA USA. Department of Physical Medicine and Rehabilitation Massachusetts General Hospital Boston MA USA. Department of Physical Medicine and Rehabilitation Brigham and Women's Hospital Boston MA USA. Department of Psychiatry University of Pittsburgh School of Medicine Pittsburgh PA USA. Divisions of Rehabilitation Science and Physical Therapy Department of Rehabilitation Medicine University of Minnesota Minneapolis MN USA. Discovery Center for Musculoskeletal Recovery Schoen Adams Research Institute at Spaulding Rehabilitation Boston MA USA. fambrosio@mgh.harvard.edu. Department of Physical Medicine and Rehabilitation Spaulding Rehabilitation Hospital Charlestown MA USA. fambrosio@mgh.harvard.edu. Department of Physical Medicine & Rehabilitation Harvard Medical School Boston MA USA. fambrosio@mgh.harvard.edu.

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The radial organization of neuronal primary cilia is acutely disrupted by seizure and ischemic brain injury

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Frontiers in Biology 2017年第2期12卷 124-138页

作者： Gregory W. Kirschen Hanxiao Liu Tracy Lang Xuelin Liang Shaoyu Ge Qiaojie Xiong Medical Scientist Training Program (MSTP) Stony Brook University Stony Brook NY 11794 USA Molecular & Cellular Pharmacology Program Stony Brook University Stony Brook NY 11794 USA Department of Neurobiology & Behavior Stony Brook University Stony Brook NY 11794 USA Simons Summer Research Program (SSRP)

BACKGROUND： Neuronal primary cilia are sensory organelles that are critically involved in the proper growth, development, and function of the central nervous system （CNS）. Recent work also suggests that they signal in the context of CNS injury, and that abnormal ciliary signaling may be implicated in neurological diseases. METHODS： We quantified the distribution of neuronal primary cilia alignment throughout the normal adult mouse brain by immunohistochemical staining for the primary cilia marker adenylyl cyclase Ⅲ （ACⅢ） and measuring the angles of primary cilia with respect to global and local coordinate planes. We then introduced two different models of acute brain insult--temporal lobe seizure and cerebral ischemia, and re-examined neuronal primary cilia distribution, as well as ciliary lengths and the proportion of neurons harboring cilia. RESULTS： Under basal conditions, cortical cilia align themselves radially with respect to the cortical surface, while cilia in the dentate gyms align themselves radially with respect to the granule cell layer. Cilia of neurons in the striatum and thalamus, by contrast, exhibit a wide distribution of ciliary arrangements. In both cases of acute brain insult, primary cilia alignment was significantly disrupted in a region-specific manner, with areas affected by the insult preferentially disrupted. Further, the two models promoted differential effects on ciliary lengths, while only the ischemia model decreased the proportion of ciliated cells. CONCLUSIONS： These findings provide evidence for the regional anatomical organization of neuronal primary cilia in the adult brain and suggest that various brain insults may disrupt this organization.

关键词： cerebral cortex dentate gyrus temporal lobe seizure cerebral ischemia

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LEAD-m6A-seq for Locus-Specific Detection ofN6-Methyladenosine and Quantification of Differential Methylation

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Angewandte Chemie 2020年第2期133卷

作者： Dr. Yuru Wang Dr. Zijie Zhang Caraline Sepich-Poore Dr. Lisheng Zhang Dr. Yu Xiao Prof. Chuan He Department of Biochemistry and Molecular Biology University of Chicago Chicago IL 60637 USA Department of Chemistry University of Chicago Chicago IL 60637 USA Institute for Biophysical Dynamics University of Chicago Chicago IL 60637 USA Howard Hughes Medical Institute University of Chicago Chicago IL 60637 USA University of Chicago Medical Scientist Training Program Chicago IL 60637 USA

N 6 -methyladenosine (m 6 A) is a crucial RNA chemical mark which plays important roles in various biological processes. The development of highly multiplexed, cost-effective, and easy-to-operate methodologies for locus-specific analysis of m 6 A is critical for advancing our understanding of the roles of this modification. Herein, we report a method which builds upon the principle of the previously reported SELECT approach by significantly improving its efficiency and coupling it to next generation sequencing technology for high-throughput validation and detection of m 6 A modification at selected sites (LEAD-m 6 A-seq). Through probing cDNA extension mediated by Bst DNA polymerase at and near target cellular sites by sequencing, we evaluated m 6 A modification at these sites, and estimated differential methylation levels (0–84 %) upon in vitro demethylation by the m 6 A demethylase FTO with high reproducibility. We envision that this strategy can be readily used for testing a greater number of sites with a broad dynamic range and modified to study other RNA modifications.

关键词： epitranscriptomics N6-methyladenosine primer extension RNA modification RNA methylation

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Author Correction: Secreted nucleases reclaim extracellular DNA during biofilm development

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NPJ biofilms and microbiomes 2024年第1期10卷 116页

作者： Stephen M Lander Garth Fisher Blake A Everett Peter Tran Arthur Prindle Department of Biochemistry and Molecular Genetics Feinberg School of Medicine Chicago 60611 IL USA. Medical Scientist Training Program Feinberg School of Medicine Northwestern University Chicago 60611 IL USA. Center for Synthetic Biology Northwestern University Evanston 60208 IL USA. Department of Chemical and Biological Engineering Northwestern University Evanston 60208 IL USA. Department of Biochemistry and Molecular Genetics Feinberg School of Medicine Chicago 60611 IL USA. arthur.prindle@northwestern.edu. Center for Synthetic Biology Northwestern University Evanston 60208 IL USA. arthur.prindle@northwestern.edu. Department of Chemical and Biological Engineering Northwestern University Evanston 60208 IL USA. arthur.prindle@northwestern.edu. Department of Microbiology-Immunology Feinberg School of Medicine Chicago 60611 IL USA. arthur.prindle@northwestern.edu. Chan Zuckerberg Biohub Chicago Chicago IL 60642 USA. arthur.prindle@northwestern.edu.

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Publisher Correction: Global estimates on the number of people blind or visually impaired by cataract: a meta-analysis from 2000 to 2020

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Eye (London, England) 2024年第11期38卷 2229-2231页

作者： Konrad Pesudovs Hugh R. Taylor Tabassom Sedighi Rupert R. A. Bourne Shahina Pardhan Van Charles Lansingh John H. Kempen Ian Tapply Arthur G. Fernandes Maria Vittoria Cicinelli Alessandro Arrigo Nicolas Leveziel Serge Resnikoff Seth Flaxman Mukkharram M. Bikbov Tasanee Braithwaite Alain Bron Ching-Yu Cheng Monte A. Del Monte Joshua R. Ehrlich Leon B. Ellwein David Friedman João M. Furtado Gus Gazzard Ronnie George M. Elizabeth Hartnett Jost B. Jonas Rim Kahloun Moncef Khairallah Rohit C. Khanna Janet Leasher Julie-Anne Little Vinay Nangia Michal Nowak Tunde Peto Pradeep Ramulu Fotis Topouzis Mitiadis Tsilimbaris Ya Xing Wang Ningli Wang Paul Svitil Briant Theo Vos Katrin Burkart Kaleb Coberly Xiaochen Dai Stephen S. Lim Tomislav Mestrovic Ali H. Mokdad Christopher J. L. Murray Jaimie D. Steinmetz Awoke Misganaw Yohannes Habtegiorgis Abate Mohammad Abdollahi Mozhan Abdollahi Ayele Mamo Abebe Olumide Abiodun Richard Gyan Aboagye Woldu Aberhe Abrha Hasan Abualruz Hiwa Abubaker Ali Eman Abu-Gharbieh Salahdein Aburuz Tadele Girum Girum Adal Mesafint Molla Adane Isaac Yeboah Addo Qorinah Estiningtyas Sakilah Adnani Muhammad Sohail Afzal Muhammad Umair Shahin Aghamiri Bright Opoku Ahinkorah Aqeel Ahmad Sajjad Ahmad Ali Ahmadi Siamak Sabour Ayman Ahmed Haroon Ahmed Ahmad Samir Alfaar Abid Ali Syed Shujait Shujait Ali Awais Altaf Hubert Amu Emmanuel Manu Sofia Androudi Rodrigo Anguita Abhishek Anil Rimple Jeet Kaur Muhammad Aaqib Shamim Saeid Anvari Anayochukwu Edward Anyasodor Francis Appiah Jalal Arabloo Haleh Ayatollahi Mosab Arafat Damelash Areda Reza Arefnezhad Brhane Berhe Aregawi Akeza Awealom Asgedom Tahira Ashraf Seyyed Shamsadin Athari Bantalem Tilaye Tilaye Atinafu Birhan Tsegaw Taye Maha Moh’d Wahbi Atout Alok Atreya Ahmed Y. Azzam Hassan Babamohamadi Sara Bagherieh Yogesh Bahurupi Atif Amin Baig Shumaila Nargus Biswajit Banik Mainak Bardhan Saurav Basu Kavita Batra Nebiyou Simegnew Bayileyegn Fatemeh Bazvand Addisu Shunu Beyene Awoke Masrie Asrat Derese Devidas S. Bhagat Akshaya Srikanth Bhagavathula Pankaj Bh Medicine & Health University of New South Wales Sydney NSW Australia School of Optometry and Vision Science University of New South Wales Sydney NSW Australia School of Population and Global Health University of Melbourne Carlton VIC Australia Vision and Eye Research Institute Anglia Ruskin University Cambridge UK HelpMeSee Instituto Mexicano de Oftalmologia Santiago de Querétaro Mexico University of Miami Gables FL USA University of Utah Salt Lake City UT USA Chief Medical Office HelpMeSee New York NY USA Mexican Institute of Ophthalmology Queretaro Mexico Department of Ophthalmology Massachusetts Eye and Ear/Shepens Eye Research Institute/Harvard Medical School Boston MA USA Eye Unit MyungSung Christian Medical Center (MCM) Comprehensive Specialized Hospital and MyungSun Medical College Addis Ababa Ethiopia Department of Ophthalmology Addis Ababa University Addis Ababa Ethiopia Sight for Souls Bellevue WA USA Department of Ophthalmology Harvard University Boston MA USA Eye Unit MyungSung Medical College Addis Ababa Ethiopia Addenbrooke’s Hospital Cambridge UK Department of Ophthalmology Cambridge University Hospitals Cambridge UK Federal University of Sao Paolo Sao Paolo SP Brazil University of Calgary Calgary AB Canada Department of Ophthalmology and Visual Sciences Federal University of São Paulo Sao Paulo Brazil School of Medicine Vita-Salute San Raffaele University Milan Italy Department of Ophthalmology IRCCS San Raffaele Scientific Institute Milan Italy Department of Ophthalmology San Raffaele Scientific Institute Milano Italy IRCCS San Raffaele Scientific Institute Vita-Salute University Milan Italy Scientific Institute San Raffaele Hospital Vita-Salute University Milan Italy University of Poitiers Poitiers France CHU de Poitiers Poitiers France Ophthalmology Department CHU de Poitiers (Poitiers University Hospital) Poitiers France Unité 1084 National Institute of Health and Medical Research (INSERM) Poitiers France

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Precision targeting of β-catenin induces tumor reprogramming and immunity in hepatocellular cancers

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Nature communications 2025年第1期16卷 5009页

作者： Brandon M Lehrich Evan R Delgado Tyler M Yasaka Silvia Liu Catherine Cao Yuqing Liu Mohammad N Taheri Xiangnan Guan Hartmut Koeppen Sucha Singh Vik Meadows Jia-Jun Liu Anya Singh-Varma Yekaterina Krutsenko Minakshi Poddar T Kevin Hitchens Lesley M Foley Binyong Liang Alex Rialdi Ravi P Rai Panari Patel Madeline Riley Aaron Bell Reben Raeman Tulin Dadali Jason J Luke Ernesto Guccione Mo R Ebrahimkhani Amaia Lujambio Xin Chen Martin Maier Yulei Wang Wendy Broom Junyan Tao Satdarshan P Monga Organ Pathobiology and Therapeutics Institute University of Pittsburgh School of Medicine Pittsburgh PA USA. Department of Pharmacology and Chemical Biology University of Pittsburgh School of Medicine Pittsburgh PA USA. Pittsburgh Liver Research Center University of Pittsburgh and University of Pittsburgh Medical Center Pittsburgh PA USA. Medical Scientist Training Program University of Pittsburgh Pittsburgh PA USA. Department of Pathology Division of Experimental Pathology University of Pittsburgh School of Medicine Pittsburgh PA USA. Department of Bioengineering Swanson School of Engineering University of Pittsburgh Pittsburgh PA USA. Translational Medicine Genentech Inc. San Francisco CA USA. University of Pittsburgh School of Medicine Pittsburgh PA USA. Hepatic Surgery Center Department of Surgery Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China. Department of Oncological Sciences Icahn School of Medicine at Mount Sinai New York NY USA. Alnylam Pharmaceuticals Boston MA USA. UPMC Hillman Cancer Center and University of Pittsburgh Pittsburgh PA USA. Cancer Biology Program University of Hawaii Cancer Center Honolulu HI USA. Organ Pathobiology and Therapeutics Institute University of Pittsburgh School of Medicine Pittsburgh PA USA. junyantao2010@***. Department of Pharmacology and Chemical Biology University of Pittsburgh School of Medicine Pittsburgh PA USA. junyantao2010@***. Pittsburgh Liver Research Center University of Pittsburgh and University of Pittsburgh Medical Center Pittsburgh PA USA. junyantao2010@***. Organ Pathobiology and Therapeutics Institute University of Pittsburgh School of Medicine Pittsburgh PA USA. smonga@pitt.edu. Department of Pharmacology and Chemical Biology University of Pittsburgh School of Medicine Pittsburgh PA USA. smonga@pitt.edu. Pittsburgh Liver Research Center University of Pittsburgh and University of Pittsburgh Medical Center Pittsburgh PA USA. smonga

First-line immune checkpoint inhibitor (ICI) combinations show responses in subsets of hepatocellular carcinoma (HCC) patients. Nearly half of HCCs are Wnt-active with mutations in CTNNB1 (encoding for β-catenin), AXIN1/2, or APC, and demonstrate heterogeneous and limited benefit to ICI due to an immune excluded tumor microenvironment. We show significant tumor responses in multiple β-catenin-mutated immunocompetent HCC models to a novel siRNA encapsulated in lipid nanoparticle targeting CTNNB1 (LNP-CTNNB1). Both single-cell and spatial transcriptomics reveal cellular and zonal reprogramming, along with activation of immune regulatory transcription factors IRF2 and POU2F1, re-engaged type I/II interferon signaling, and alterations in both innate and adaptive immunity upon β-catenin suppression with LNP-CTNNB1 at early- and advanced-stage disease. Moreover, ICI enhances response to LNP-CTNNB1 in advanced-stage disease by preventing T cell exhaustion and through formation of lymphoid aggregates (LA). In fact, expression of an LA-like gene signature prognosticates survival for patients receiving atezolizumab plus bevacizumab in the IMbrave150 phase III trial and inversely correlates with CTNNB1-mutatational status in this patient cohort. In conclusion, LNP-CTNNB1 is efficacious as monotherapy and in combination with ICI in CTNNB1-mutated HCCs through impacting tumor cell-intrinsic signaling and remodeling global immune surveillance, providing rationale for clinical investigations.

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Correction to: The potential use of tideglusib as an adjuvant radio-therapeutic treatment for glioblastoma multiforme cancer stem-like cells

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Pharmacological reports : PR 2021年第1期73卷 316页

作者： Jolie Bou-Gharios Sahar Assi Hisham F Bahmad Hussein Kharroubi Tarek Araji Reda M Chalhoub Farah Ballout Hayat Harati Youssef Fares Wassim Abou-Kheir Department of Anatomy Cell Biology and Physiological Sciences Faculty of Medicine American University of Beirut Bliss Street DTS Bldg Room 116-B Riad el Solh PO Box 110236/41 Beirut 1107-2020 Lebanon. Neuroscience Research Center Lebanese University Faculty of Medicine Beirut Lebanon. Arkadi M. Rywlin M.D. Department of Pathology and Laboratory Medicine Mount Sinai Medical Center Miami Beach FL USA. Medical Scientist Training Program College of Medicine Medical University of South Carolina Charleston SC USA. Neuroscience Research Center Lebanese University Faculty of Medicine Beirut Lebanon. yfares@ul.edu.lb. Department of Anatomy Cell Biology and Physiological Sciences Faculty of Medicine American University of Beirut Bliss Street DTS Bldg Room 116-B Riad el Solh PO Box 110236/41 Beirut 1107-2020 Lebanon. wa12@aub.edu.lb.

The original article can be found online.

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Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the Global Burden of Disease Study 2021

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The Lancet 2023年第10397期402卷 203-234页

作者： Ong, Kanyin Liane Stafford, Lauryn K. McLaughlin, Susan A. Boyko, Edward J. Vollset, Stein Emil Smith, Amanda E. Dalton, Bronte E. Duprey, Joe Cruz, Jessica A. Hagins, Hailey Lindstedt, Paulina A. Aali, Amirali Abate, Yohannes Habtegiorgis Abate, Melsew Dagne Abbasian, Mohammadreza Abbasi-Kangevari, Zeinab Abbasi-Kangevari, Mohsen ElHafeez, Samar Abd Abd-Rabu, Rami Abdulah, Deldar Morad Abdullah, Abu Yousuf Md Abedi, Vida Abidi, Hassan Aboagye, Richard Gyan Abolhassani, Hassan Abu-Gharbieh, Eman Abu-Zaid, Ahmed Adane, Tigist Demssew Adane, Denberu Eshetie Addo, Isaac Yeboah Adegboye, Oyelola A. Adekanmbi, Victor Adepoju, Abiola Victor Adnani, Qorinah Estiningtyas Sakilah Afolabi, Rotimi Felix Agarwal, Gina Aghdam, Zahra Babaei Agudelo-Botero, Marcela Arriagada, Constanza Elizabeth Aguilera Agyemang-Duah, Williams Ahinkorah, Bright Opoku Ahmad, Danish Ahmad, Rizwan Ahmad, Sajjad Ahmad, Aqeel Ahmadi, Ali Ahmadi, Keivan Ahmed, Ali Ahmed, Luai A. Ahmed, Syed Anees Ajami, Marjan Akinyemi, Rufus Olusola Al Hamad, Hanadi Al Hasan, Syed Mahfuz AL-Ahdal, Tareq Mohammed Ali Alalwan, Tariq A. Al-Aly, Ziyad AlBataineh, Mohammad T. Alcalde-Rabanal, Jacqueline Elizabeth Alemi, Sharifullah Ali, Hassam Alinia, Tahereh Aljunid, Syed Mohamed Almustanyir, Sami Al-Raddadi, Rajaa M. Alvis-Guzman, Nelson Amare, Firehiwot Ameyaw, Edward Kwabena Amiri, Sohrab Amusa, Ganiyu Adeniyi Andrei, Catalina Liliana Anjana, Ranjit Mohan Ansar, Adnan Ansari, Golnoosh Ansari-Moghaddam, Alireza Anyasodor, Anayochukwu Edward Arabloo, Jalal Aravkin, Aleksandr Y. Areda, Demelash Arifin, Hidayat Arkew, Mesay Armocida, Benedetta Arnlov, Johan Artamonov, Anton A. Arulappan, Judie Aruleba, Raphael Taiwo Arumugam, Ashokan Aryan, Zahra Asemu, Mulu Tiruneh Asghari-Jafarabadi, Mohammad Askari, Elaheh Asmelash, Daniel Astell-Burt, Thomas Athar, Mohammad Athari, Seyyed Shamsadin Atout, Maha Moh'd Wahbi Avila-Burgos, Leticia Awaisu, Ahmed Azadnajafabad, Sina Darshan, B.B. Babamohamadi, Hassan Badar, Muhammad Badawi, Alaa Badiye, Ashish D. Baghcheghi, Nayereh Baghe Institute for Health Metrics and Evaluation School of Medicine General Medicine Service Department of Veterans Affairs Seattle WA United States Department of Health Metrics Sciences School of Medicine Faculty of Medicine France Department of Clinical Governance and Quality Improvement Aleta Wondo Hospital Aleta Wondo Ethiopia Department of Nursing Woldia University Woldia Ethiopia Department of Nursing Department of Orthopedic Surgery Orthopaedic Surgery Social Determinants of Health Research Center Non-communicable Diseases Research Center Epidemiology Department Evidence-Based Practice Center Community and Maternity Nursing Unit University of Duhok Duhok Iraq School of Planning Faculty of Environment Department of Public Health Sciences Penn State College of Medicine Pennsylvania State University Hershey PA United States Biocomplexity Institute Virginia Tech Blacksburg VA United States College of Medicine Department of Public Health Laboratory Technology Sciences Department Department of Family and Community Health University of Health and Allied Sciences Ho Ghana Research Center for Immunodeficiencies Department of Biosciences and Nutrition Karolinska University Hospital Huddinge Sweden Clinical Sciences Department Department of Surgery Department of Surgery Department of Obstetrics & Gynecology College of Graduate Health Sciences University of Tennessee Memphis TN United States Department of Obstetrics & Gynecology Department of Clinical and Psychosocial Epidemiology Department of Anesthesia and Critical Care Centre for Social Research in Health Quality and Systems Performance Unit Cancer Institute NSW Sydney NSW Australia Department of Public Health and Tropical Medicine HIV and Infectious Diseases Department Jhpiego Abuja Nigeria Adolescent Research and Care Department Adolescent Friendly Research Initiative and Care Ado Ekiti Nigeria Department of Epidemiology Department of Epidemiology and Medical Statistics Department of Family Medicine McMaster University

Background: Diabetes is one of the leading causes of death and disability worldwide, and affects people regardless of country, age group, or sex. Using the most recent evidentiary and analytical framework from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD), we produced location-specific, age-specific, and sex-specific estimates of diabetes prevalence and burden from 1990 to 2021, the proportion of type 1 and type 2 diabetes in 2021, the proportion of the type 2 diabetes burden attributable to selected risk factors, and projections of diabetes prevalence through 2050. Methods: Estimates of diabetes prevalence and burden were computed in 204 countries and territories, across 25 age groups, for males and females separately and combined;these estimates comprised lost years of healthy life, measured in disability-adjusted life-years (DALYs;defined as the sum of years of life lost [YLLs] and years lived with disability [YLDs]). We used the Cause of Death Ensemble model (CODEm) approach to estimate deaths due to diabetes, incorporating 25 666 location-years of data from vital registration and verbal autopsy reports in separate total (including both type 1 and type 2 diabetes) and type-specific models. Other forms of diabetes, including gestational and monogenic diabetes, were not explicitly modelled. Total and type 1 diabetes prevalence was estimated by use of a Bayesian meta-regression modelling tool, DisMod-MR 2.1, to analyse 1527 location-years of data from the scientific literature, survey microdata, and insurance claims;type 2 diabetes estimates were computed by subtracting type 1 diabetes from total estimates. Mortality and prevalence estimates, along with standard life expectancy and disability weights, were used to calculate YLLs, YLDs, and DALYs. When appropriate, we extrapolated estimates to a hypothetical population with a standardised age structure to allow comparison in populations with different age structures. We used the comparative r

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