Nature Medicine最新文献

{"title":"A consensus-based guideline for personalized bacteriophage therapy","authors":"Silvia Würstle, Simone C. Lieberknecht-Jouy, Anja Düchting, Holger Lößner, Pieter-Jan Ceyssens, Jean-Paul Pirnay, Mathieu de Jode, Shawna McCallin, Lorenz Leitner, Christian Willy, Sebastian Leptihn, Imke Korf, Evgeny A. Idelevich, Martin Witzenrath, Timo Faltus, Peter Ruth, Henning Blume, Manuel Cornely, Helmut Fickenscher, Mathias W. Pletz, Sylvia Hafkemeyer, Christine Rohde, Oleg Krut, Wolfgang Beyer, Oliver Hartwich, Ulrich Matt, Rebecca L. Knoll, Münevver Demir, Jens Hammerl, Stefanie Barbirz, Mirjam Stahl, Renate Krüger, Joachim Bugert, Melanie Kempe, Paul E. Turner, Benjamin Chan, Tristan Ferry, Maria J. G. T. Vehreschild, Annika Y. Classen, on behalf of the guideline group ‘Personalized Bacteriophage Therapy’ of the Association of the Scientific Medical Societies in Germany","doi":"10.1038/s41591-026-04654-6","DOIUrl":"10.1038/s41591-026-04654-6","url":null,"abstract":"Bacteriophages (phages) — viruses that selectively infect bacteria — are a promising option for personalized therapy of difficult-to-treat bacterial infections. Clinical implementation in many countries worldwide, however, faces multiple hurdles, including a lack of consensus on general principles for phage therapy, infrastructural requirements, procedures for quality-assured phage selection and preparation, clinical administration, monitoring and documentation. Existing guidance provides limited practical direction across the entire translational pathway and lacks inspection-ready specifications to support both pharmacies and clinical sites. These gaps impede safe and transparent clinical use and effective regulatory oversight. Likewise, there are no established processes to identify research questions that will be key to advancing clinical phage research in the future. To address these needs, this consensus-based guideline was developed within the methodological framework of the Association of the Scientific Medical Societies in Germany under the leadership of the German Society for Infectious Diseases. It was created through a collaborative effort involving 20 professional societies, patient advocacy groups and regulatory authorities and 18 international experts. The guideline provides over 60 recommendations on core principles, infrastructure, preparation and quality control, administration and future research. Recommendations are supported by international societies, organizations and stakeholders. By providing clear and practice-oriented recommendations, this consensus statement paves the way for the safe and standardized use of personalized phage therapy. This consensus-based guideline provides clear and practice-oriented recommendations for the safe and standardized use of personalized phage therapy in the clinic.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"32 10","pages":"3578-3594"},"PeriodicalIF":52.5,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41591-026-04654-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How genes shape personality and experience.","authors":"Karen O'Leary","doi":"10.1038/d41591-026-00046-y","DOIUrl":"https://doi.org/10.1038/d41591-026-00046-y","url":null,"abstract":"","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":" ","pages":""},"PeriodicalIF":52.5,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149002309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial Expression of Concern: SWI/SNF-mutant cancers depend on catalytic and non-catalytic activity of EZH2.","authors":"Kimberly H Kim, Woojin Kim, Thomas P Howard, Francisca Vazquez, Aviad Tsherniak, Jennifer N Wu, Weishan Wang, Jeffrey R Haswell, Loren D Walensky, William C Hahn, Stuart H Orkin, Charles W M Roberts","doi":"10.1038/s41591-026-04708-9","DOIUrl":"https://doi.org/10.1038/s41591-026-04708-9","url":null,"abstract":"","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":" ","pages":""},"PeriodicalIF":52.5,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149002317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Levetiracetam therapeutically targets GABAergic synapses in diffuse midline glioma","authors":"Tara Barron, Richard Drexler, Aaron Mochizuki, Evan Cantor, Kiarash Shamardani, Pamelyn J. Woo, Neeraj Soni, Dana Tlais, Andrea Franson, Samantha Lyons, Truman Knowles, Shannon Raber, Vilina Mehta, Michael A. Quezada, Michael B. Keough, Samin Malaki Jahan, Linh Thuy Vo, Enrique Herrera Castañeda, Kathryn R. Taylor, Lijun Ni, Kim Kilian, Samuel H. Wu, Franz L. Ricklefs, Ulrich Schüller, Sabine Mueller, Paul G. Fisher, Cynthia J. Campen, Hannes Vogel, Sonia Partap, Kai Kaila, Carl Koschmann, Michelle Monje","doi":"10.1038/s41591-026-04646-6","DOIUrl":"10.1038/s41591-026-04646-6","url":null,"abstract":"Antiseizure medications, such as levetiracetam, are commonly used in glioma patients. Retrospective analyses evaluating effects of antiseizure medications on glioma patient survival have yielded inconsistent results, probably due to confounding factors of glioma subtype and drug class. Here we present retrospective real-world clinical data that demonstrate longer overall survival for children with diffuse midline glioma (DMG) who were taking levetiracetam, which was not evident in pediatric patients with hemispheric high-grade glioma. In preclinical models, levetiracetam reduces glioma proliferation and tumor burden, extending survival of mice bearing DMG orthotopic xenografts. These beneficial effects were not found in hemispheric high-grade glioma patient-derived orthotopic xenograft models. The subtype-specificity of this antiproliferative effect of levetiracetam is congruent with recent findings that GABAergic neuron-to-glioma synapses promote glioma growth in DMG but not hemispheric high-grade glioma. We demonstrate here that levetiracetam attenuates low-frequency GABAergic synaptic transmission in a glioma-specific manner, reducing GABAergic synaptic currents in DMG but not in healthy neurons. This effect is independent of action on SV2A, the chief mechanism by which levetiracetam functions to prevent and treat seizures. Taken together, these findings indicate a promising approach to target GABAergic synapses in DMG and suggest that use of levetiracetam in DMG should be further studied in future prospective clinical studies. Results of this study show in experimental models and data from patient cohorts that the antiseizure medication levetiracetam is associated with longer survival and reduced tumor growth in diffuse midline glioma, but not hemispheric high-grade glioma, by selectively dampening GABAergic synaptic signaling, independently of its canonical SV2A-mediated primary antiseizure mechanism.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"32 10","pages":"3792-3800"},"PeriodicalIF":52.5,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41591-026-04646-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148990684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-specific biological aging clocks across organs and omics.","authors":"Zhiyuan Song, Derek Fong, Naowal Azraf Rahman, Michael R Duggan, Qu Tian, Jian Zeng, Xia Zhou, Chunrui Zou, Michael S Rafii, Li Shen, Paul Thompson, Eleanor M Simonsick, Keenan A Walker, Andrew Zalesky, Christos Davatzikos, Paul Aisen, Luigi Ferrucci, Susan M Resnick, Junhao Wen","doi":"10.1038/s41591-026-04662-6","DOIUrl":"10.1038/s41591-026-04662-6","url":null,"abstract":"<p><p>Sex differentially shapes aging, neurodevelopment and neurodegenerative diseases such as Alzheimer's disease (AD). However, most biological aging clocks (artificial intelligence-predicted age minus chronological age) were trained on sex-pooled samples and implicitly assume sex invariance.Here we developed 38 sex-specific biological aging clocks across 15 organ systems. We first demonstrate the importance of sex-stratified training for constructing sex-specific healthy normative references and then reveal marked divergence between female and male clocks. Key genetic parameters and Mendelian randomization results indicate that organ-specific aging liability and its relationships to cardiometabolic, endocrine and mental traits are configured differently in females and males. Proteomic analyses identify distinct, organ-resolved synaptic, immune, vascular and metabolic networks that differentially track female and male biological aging. In longitudinal survival analyses, sex-specific clocks predict whole-body systemic diseases and all-cause mortality in a sex-dependent and organ-dependent manner. Further analyses reveal sex-dependent associations between the brain aging clock and cognitive decline trajectory during a preclinical AD clinical trial. Sex-stratified clocks may offer distinct value by defining biological age against sex-appropriate normative references and revealing sex-dependent genetic, molecular and clinical signatures that pooled models may obscure. Meanwhile, sex-pooled and sex-interaction approaches remain valuable, as human aging and disease also share fundamental biological similarities between females and males. Together, these findings reveal sex-specific biological aging signatures in aging, AD and systemic health, highlighting the need for explicitly sex-stratified modeling approaches.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":" ","pages":""},"PeriodicalIF":52.5,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13681238/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148983321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Liquid biopsy for early detection of pancreatic ductal adenocarcinoma","authors":"Caiming Xu,&nbsp;Alessandro Mannucci,&nbsp;Haiyong Han,&nbsp;Ruben M. Munoz,&nbsp;Derek Cridebring,&nbsp;Sourat Darabi,&nbsp;Yuji Toiyama,&nbsp;Yoshinaga Okugawa,&nbsp;Gagandeep Singh,&nbsp;Mustafa Raoof,&nbsp;Joon Oh Park,&nbsp;James Lin,&nbsp;Gregory Idos,&nbsp;Michael J. Demeure,&nbsp;Erkut Borazanci,&nbsp;Douglas B. Evans,&nbsp;Susan Tsai,&nbsp;Eunsung Jun,&nbsp;Carlos Becerra,&nbsp;Scott A. Celinski,&nbsp;Laleh Melstrom,&nbsp;Vincent Chung,&nbsp;Guixin Zhang,&nbsp;Dong Shang,&nbsp;David L. Bartlett,&nbsp;Mitsuro Kanda,&nbsp;Song Cheol Kim,&nbsp;Valsamo Anagnastou,&nbsp;Giulia Martina Cavestro,&nbsp;John S. Bolton,&nbsp;Ali H. Zaidi,&nbsp;Daniel Von Hoff,&nbsp;Ajay Goel","doi":"10.1038/s41591-026-04625-x","DOIUrl":"10.1038/s41591-026-04625-x","url":null,"abstract":"There is no clinically relevant blood-based assay for the detection of early-stage pancreatic ductal adenocarcinoma (PDAC), a solid malignancy characterized by poor outcomes. Here we developed, validated and tested a blood-based microRNA (miRNA) assay (which included hsa-miR-142-3p, hsa-miR-30c-5p, hsa-miR-335-5p, hsa-miR-340-5p, hsa-miR-200b-3p, hsa-miR-1260b, hsa-miR-145-3p, hsa-miR-145-5p, hsa-miR-429 and hsa-miR-200a-3p) and a composite score, PANXEON (PANcreatic cancer eXosome Early detectiON), that integrates the miRNA signature with carbohydrate antigen 19-9 for the detection of early-stage PDAC. We conducted an international, multicenter, observational, prospective biomarker study that involved 1,785 individuals with and without PDAC from four countries. The miRNA signature achieved an area under the receiver operating characteristic curve of 88.6% in the testing cohort, with a sensitivity of 83.8% for early-stage PDAC, while showing minimal cross-reactivity with other gastrointestinal cancers. In a cohort of 19 individuals, the miRNA signature levels decreased during neoadjuvant chemotherapy and after surgery and increased before disease recurrence. When combined with carbohydrate antigen 19-9 levels, this blood assay demonstrated a sensitivity of 86.8% for stage I–II PDAC, false-positive rates of 3.2% in low-risk controls and 15.6% in high-risk controls in the testing cohort. PANXEON demonstrates potential for detecting high-grade dysplasia in individuals with high-risk pancreatic cysts (64.3%). Collectively, we present a composite biomarker that may complement existing strategies for the detection of early-stage PDAC and warrants further large-scale prospective studies. ClinicalTrials.gov registration: NCT06388967 . In a prospective study involving 1,785 individuals from four countries, the PANXEON exosome-based biomarker, combined with carbohydrate antigen 19-9 levels, achieves high sensitivity for the detection of early-stage pancreatic cancer.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"32 10","pages":"3781-3791"},"PeriodicalIF":52.5,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148983371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EBV reactivation priming of the peripheral immune system in multiple sclerosis relapse.","authors":"Devin A King, Shrishti Saxena, Danielle Caefer, Kyle C Downer, Laura E Saucier, Ethan Goodman, Jonmichael Aracena, Alena Zhirova, Anthilia Alchanat, Saoirse Nolan, Hrishikesh Lokhande, Howard L Weiner, Benjamin E Gewurz, Tanuja Chitnis","doi":"10.1038/s41591-026-04665-3","DOIUrl":"10.1038/s41591-026-04665-3","url":null,"abstract":"<p><p>Despite decades of research, the cellular and molecular events preceding multiple sclerosis (MS) relapse remain incompletely understood. Here, in this observational study of longitudinal blood samples from patients with relapsing-remitting MS, we used single-cell RNA sequencing, bulk transcriptomics, multiparameter flow cytometry and targeted viral reverse transcription quantitative polymerase chain reaction (RT-qPCR) to construct a time-resolved atlas of immune perturbations surrounding relapse. A reproducible pre-relapse signature in monocytes and B cells, emerging up to 3 months before clinical onset, was enriched for host genes responsive to Epstein-Barr virus (EBV) lytic reactivation factors. RT-qPCR confirmed elevated EBV LMP-1 transcripts in pre-relapse B cells, and flow cytometry demonstrated expansion of CD11c⁺ atypical B cell populations displaying EBV surface protein gp350. Pre-relapse transcriptional modules overlapped with MS genome-wide association study (GWAS) risk loci and EBNA-2-bound enhancers, suggesting that inherited MS susceptibility and EBV-responsive programs operate through shared regulatory elements. How this peripheral activation relates to central nervous system lesion formation remains to be established. These findings nonetheless suggest that EBV reactivation, when occurring within a genetically predisposed peripheral immune environment, is a proximal precursor of MS relapse.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":" ","pages":""},"PeriodicalIF":52.5,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148983408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Factor IX Padua AAV gene therapy in adolescents with hemophilia B: a phase 1 trial","authors":"Feng Xue,&nbsp;Ai Zhang,&nbsp;Mankai Ju,&nbsp;Xia Wu,&nbsp;Bingqi Xu,&nbsp;Xiaolei Pei,&nbsp;Yuhua Wang,&nbsp;Wei Liu,&nbsp;Aiguo Liu,&nbsp;Wei Jiang,&nbsp;Xinyue Dai,&nbsp;Yunfei Chen,&nbsp;Xiaofan Liu,&nbsp;Rongfeng Fu,&nbsp;Ting Sun,&nbsp;Wenjing Gu,&nbsp;Jing Zheng,&nbsp;Zengmin Du,&nbsp;Caifeng Yang,&nbsp;Xiao Xiao,&nbsp;Renchi Yang,&nbsp;Qun Hu,&nbsp;Lei Zhang","doi":"10.1038/s41591-026-04636-8","DOIUrl":"10.1038/s41591-026-04636-8","url":null,"abstract":"Adeno-associated virus (AAV)-mediated factor IX Padua gene therapy has demonstrated good safety and efficacy in adult patients with hemophilia B, but its safety and efficacy in adolescent patients with hemophilia B remain unknown. Here we report a multicenter, single-arm, phase 1 study involving 11 adolescent participants (aged 12–18 years) with severe or moderately severe hemophilia B (factor IX coagulant activity (FIX:C) ≤2 IU dl−1) in China. All of them received the AAV gene therapy BBM-H901 at a dose of 5 × 1012 vector genomes per kilogram of body weight and were then enrolled in a 52-week follow-up. The primary endpoint was safety. No dose-limiting toxicity was observed throughout the study. The most common adverse events included elevation of white blood cell count, elevation of neutrophil count and rash associated with corticosteroid use. One serious adverse event and two grade 3 adverse events occurred. Abnormal liver function was observed in one participant, with elevated alanine aminotransferase (197.0 U l−1) and aspartate aminotransferase (75.0 U l−1) levels, which returned to normal 4 weeks after immunosuppression therapy. The key secondary endpoints included the mean (s.d.) FIX:C at week 52 following infusion, which was 41.8 (30.1) IU dl−1 (one-stage SynthASil method), and the mean annualized bleeding rate, which decreased from 13.9 to 0.5. In this study, we show that the gene therapy drug BBM-H901 for hemophilia B is safe in adolescent patients, providing initial insights into its efficacy. ClinicalTrials.gov identifier: NCT05709288 . In this single-arm phase 1 trial, an AAV gene therapy carrying the Padua variant of factor IX was well tolerated in 11 adolescents with hemophilia B and led to reductions in annualized bleeding rate.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"32 10","pages":"3853-3861"},"PeriodicalIF":52.5,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148983313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond the breakthrough for RAS-driven cancers","authors":"Rich C. King,&nbsp;Erica S. Tsang,&nbsp;Jennifer J. Knox","doi":"10.1038/s41591-026-04610-4","DOIUrl":"10.1038/s41591-026-04610-4","url":null,"abstract":"Two early clinical studies of selective KRASG12D inhibitors show encouraging activity in advanced cancers with G12D mutations, signaling a transformative change in the treatment landscape for RAS-driven cancers with potential applications across tumor types and stages of disease.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"32 9","pages":"3138-3139"},"PeriodicalIF":52.5,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148965712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"On-premise medical AI agents for reliable clinical decision-making","authors":"Li Zhang,&nbsp;Georg Wölflein,&nbsp;Dyke Ferber,&nbsp;Junhao Liang,&nbsp;Zunamys I. Carrero,&nbsp;Xuewei Wu,&nbsp;Julien Vibert,&nbsp;Jan Clusmann,&nbsp;Lino Möhrmann,&nbsp;Elena E. Möhrmann,&nbsp;Catharina Wichmann,&nbsp;Fabian Wolf,&nbsp;Tim Lenz,&nbsp;Jakob Nikolas Kather","doi":"10.1038/s41591-026-04609-x","DOIUrl":"10.1038/s41591-026-04609-x","url":null,"abstract":"Autonomous clinical artificial intelligence (AI) agents powered by large language models (LLMs), meaning systems that can complete a diagnostic workflow without continuous human input, are increasingly capable of supporting complex reasoning and decision-making. Clinical translation, however, remains limited by two unmet requirements: institutionally governed deployment and reliable decision-time uncertainty estimation. Here we developed and evaluated a fully on-premise clinical agent that couples local operational control with a multi-perspective reliability framework to support selective autonomy. Across two Medical Information Mart for Intensive Care IV (MIMIC-IV)-derived benchmarks, the agent achieved 90.04% accuracy on a seven-disease task and 83.8% accuracy on a four-disease task, approaching a cloud baseline on the primary benchmark. To assess decision-time reliability, we quantified internal-likelihood, language-based and behavioral-stability measures for diagnosis and reasoning. Diagnostic behavioral consistency provided the strongest discrimination of correctness (area under the curve (AUC) = 0.860) and remained informative under stress testing (AUC = 0.875). At a consistency threshold of 0.90, 49.4% of cases were retained at 98.9% diagnostic accuracy. These findings support a practical framework for institutionally governed clinical agents in which decision-time reliability signals identify a lower-risk subset for autonomous handling and defer the remainder for review. An autonomous clinical AI agent enhances decision-making through on-premise deployment and reliability metrics, achieving high diagnostic accuracy and selective autonomy.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"32 10","pages":"3705-3716"},"PeriodicalIF":52.5,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41591-026-04609-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148977277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}