Nature Medicine最新文献

{"title":"Addendum: Aberrant epithelial GREM1 expression initiates colonic tumorigenesis from cells outside the stem cell niche.","authors":"Hayley Davis, Shazia Irshad, Mukesh Bansal, Hannah Rafferty, Tatjana Boitsova, Chiara Bardella, Emma Jaeger, Annabelle Lewis, Luke Freeman-Mills, Francesc C Giner, Pedro Rodenas-Cuadrado, Sreelakshmi Mallappa, Susan Clark, Huw Thomas, Rosemary Jeffery, Richard Poulsom, Manuel Rodriguez-Justo, Marco Novelli, Runjan Chetty, Andrew Silver, Owen J Sansom, Florian R Greten, Lai Mun Wang, James E East, Ian Tomlinson, Simon J Leedham","doi":"10.1038/s41591-026-04736-5","DOIUrl":"https://doi.org/10.1038/s41591-026-04736-5","url":null,"abstract":"","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":" ","pages":""},"PeriodicalIF":52.5,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149149107","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":"Author Correction: Natural killer T cells and CD8⁺ T cells are dispensable for T cell-dependent allergic airway inflammation.","authors":"Jyoti Das, Paul Eynott, Ray Jupp, Alfred Bothwell, Luc Van Kaer, Yufang Shi, Gobardhan Das","doi":"10.1038/s41591-026-04709-8","DOIUrl":"https://doi.org/10.1038/s41591-026-04709-8","url":null,"abstract":"","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":" ","pages":""},"PeriodicalIF":52.5,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137648","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":"MAGIC: an international network for evaluating generative artificial intelligence in global health","authors":"Rui Yang,Weihao Xuan,Tianyu Liu,Danielle S. Bitterman,Gary S. Collins,Karthik Adapa,Kwesi Nyan Amissah-Arthur,Tianxi Cai,Simão Campos,Hanqun Cao,Josip Car,Carol Y. Cheung,Mona Diab,Chido Dzinotyiwei,Siqi Ge,Marzyeh Ghassemi,Ethan Goh,Benjamin Alan Goldstein,Mary-Anne Hartley,Yulan He,Pheng Ann Heng,Chuan Hong,Michelle María Jiménez de Tavárez,Yuhe Ke,Pearse A. Keane,Eva C. Keller,Rubayat Khan,Phuoc V. Le,Marc Lecoultre,Jisan Lee,Huitao Li,Yuan Luo,Vukosi Marivate,Bilal A. Mateen,Melissa D. McCradden,Maryam Mustafa,Joyce Nakatumba-Nabende,Yilin Ning,Jasmine Chiat Ling Ong,Yifan Peng,Sameer Pujari,Ihsan Ayyub Qazi,Dino Rech,Iain Beehuat Tan,Patrick Tan,Douglas Teodoro,Yih Chung Tham,Arun James Thirunavukarasu,Daniel Shu Wei Ting,Lorainne Tudor Car,Joao Ricardo Nickenig Vissoci,Chunhua Weng,Matthew Yu Heng Wong,Yunze Xiao,Xuhai Xu,Carl Yang,Naoto Yokoya,Kunyu Yu,Chaofan Zhang,Rui Zhang,James Zou,Karel G. M. Moons,Nigam H. Shah,Tien Yin Wong,Eric J. Topol,Nan Liu","doi":"10.1038/s41591-026-04706-x","DOIUrl":"https://doi.org/10.1038/s41591-026-04706-x","url":null,"abstract":"","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"8 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149091920","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":"Extended follow-up of in vivo BCMA CAR-T therapy in relapsed/refractory multiple myeloma","authors":"Jia Xu, Lin Liu, Wei Xie, Liman Su, Weijiayi Wang, Chenggong Li, Qiaolin Liu, Yun Kang, Yinqiang Zhang, Wenjing Luo, Zhongpei Huang, Chun Zhang, Chunyan Sun, Yu Hu, Heng Mei","doi":"10.1038/s41591-026-04704-z","DOIUrl":"https://doi.org/10.1038/s41591-026-04704-z","url":null,"abstract":"Data on long-term outcomes of in vivo chimeric antigen receptor T cell (CAR‑T) therapy remain scarce. We previously reported preliminary safety and efficacy data of in vivo B-cell maturation antigen (BCMA) CAR‑T (ESO-T01), in four patients with relapsed/refractory multiple myeloma, without leukapheresis and lymphodepletion, with up to 3 months of follow-up. The primary endpoints included safety and tolerability, while the secondary endpoints comprised efficacy, pharmacokinetics and pharmacodynamics. All patients developed dual-phase cytokine release syndrome (grades 1–3) and hematotoxicities (grade ≥3). One patient developed grade 1 immune effector cell-associated neurotoxicity syndrome. The objective response rate reached 100% (two stringent complete response and two partial response). Here we update the data on long‑term safety and response durability with a maximal follow‑up of 15 months. No immunogenicity‑ or integration‑related toxicities occurred, and no important adverse events related to ESO-T01 emerged beyond the initial report. Of the four patients, one maintained stringent complete response for 15 months. The median progression-free survival was 4.0 (range 3.0–15.0) months. After progression, diverse salvage therapies extended overall survival to 5.5–10.9 months after infusion. Three patients experienced relapse or progression, all with extramedullary involvement, and eventually died during follow-up. One patient achieved durable response with robust expansion from ex vivo CAR-T. Collectively, these updated results provide additional insights on the safety and efficacy of in vivo CAR-T therapies. The limited persistence observed necessitates the further optimization of the in vivo CAR-T platform. ClinicalTrials.gov identifier: NCT06691685.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"25 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149087649","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":"An open vision-language model for diverse medical applications","authors":"Andrew Sellergren, Sahar Kazemzadeh, Fereshteh Mahvar, Atilla Kiraly, Madeleine Traverse, Timo Kohlberger, Chufan Gao, Ronnachai Jaroensri, Shawn Xu, Fayaz Jamil, Cían Hughes, Charles Lau, Justin Chen, Liron Yatziv, Tiffany Chen, Bram Sterling, Stefanie Anna Baby, Susanna Maria Baby, Jeremy Lai, Samuel Schmidgall, Lu Yang, Kejia Chen, Per Bjornsson, Shashir Reddy, Ryan Brush, Kenneth Philbrick, Bashir Sadjad, Mercy Asiedu, Ines Mezerreg, Howard Hu, Howard Yang, Richa Tiwari, Sunny Jansen, Preeti Singh, Yubin Kim, Daniel McDuff, Catherine Kozlowski, Rachelle Sico, Aishwarya Kamath, Johan Ferret, Shreya Pathak, Nino Vieillard, Ramona Merhej, Sarah Perrin, Tatiana Matejovicova, Alexandre Ramé, Morgane Riviere, Louis Rouillard, Thomas Mesnard, Geoffrey Cideron, Jean-bastien Grill, Sabela Ramos, Edouard Yvinec, Michelle Casbon, Elena Buchatskaya, Jean-Baptiste Alayrac, Dmitry Lepikhin, Vlad Feinberg, Sebastian Borgeaud, Alek Andreev, Cassidy Hardin, Robert Dadashi, Léonard Hussenot, Armand Joulin, Olivier Bachem, Clement Farabet, Joelle Barral, Tris Warkentin, Jonathon Shlens, David Fleet, Shekoofeh Azizi, Victor Cotruta, Omar Sanseviero, Gus Martins, Phoebe Kirk, Anand Rao, Yossi Matias, Katherine Chou, Avinatan Hassidim, Dale Webster, Shravya Shetty, Kavi Goel, Yun Liu, Can Kirmizibayrak, David F. Steiner, Rory Pilgrim, Daniel Golden, Lin Yang","doi":"10.1038/s41591-026-04626-w","DOIUrl":"10.1038/s41591-026-04626-w","url":null,"abstract":"Artificial intelligence has high potential for impact in healthcare applications, but its training and deployment are challenging due to diverse data, a complex spectrum of possible tasks and important privacy needs. High-performing foundation models that enable data-efficient fine-tuning for diverse downstream tasks can meaningfully accelerate development in this domain. We introduce MedGemma, a collection of medical vision-language foundation models based on Gemma 3. MedGemma demonstrates advanced medical understanding and reasoning across images and text and multiple medical imaging domains, exceeding the performance of similarly sized generative models while maintaining the general capabilities of the Gemma base models. For out-of-distribution tasks, MedGemma achieves improvements of 2.6–10% in medical image question answering, 15.5–18.1% in chest X-ray finding classification and 10.8% in agentic evaluations compared with the base models. Our results show that fine-tuning MedGemma can be more effective than fine-tuning the base Gemma 3 model for medical tasks, particularly in the setting of limited training data. We additionally introduce MedSigLIP, a medically tuned vision encoder derived from SigLIP. MedSigLIP powers the visual understanding capabilities of MedGemma and, as an encoder, achieves performance comparable to or better than that of many specialized medical image encoders. Taken together, the MedGemma collection provides a strong foundation of medical image and text capabilities, with the potential to accelerate medical research and the development of downstream applications. MedGemma, a collection of medical vision-language foundation models based on Gemma 3, demonstrates advanced medical understanding and reasoning across images and text and multiple medical imaging domains, exceeding the performance of similarly sized generative models while maintaining the general capabilities of the Gemma base models.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"32 10","pages":"3695-3704"},"PeriodicalIF":52.5,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41591-026-04626-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149087648","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":"Global and regional reference curves for pain across the lifespan in 6.1 million individuals in 118 countries","authors":"Matt Fillingim, Christophe Tanguay-Sabourin, Lindsay Neuert, Azin Zare, Jax Norman, Gianluca V. Guglietti, Lise Hobeika, Abimbola Ayorinde, Ahmad Salimzadeh, Ahmad-reza Jamshidi, Aqeel M. Alenazi, Arash Tehrani-Banihashemi, Bader A. Alqahtani, Beatriz Olaya, Benjamin Longo Mbenza, Bibilola Oladeji, Brenda Penninx, Buddhi Paudyal, Caique de Melo, Chantal Berna, Clarissa Humberg, Pascal Claudepierre, Elisa Smith, Elizabeth VanDenKerkhof, Erik J. Giltay, Esther Garcia-Esquinas, Faisal Parlindungan, Fatima Qayyum Abbasi, Fernando Rodríguez Artalejo, Gareth T. Jones, Gary Slade, Hanifa Bouziri, Herta Flor, Hiroyasu Iso, Ian Gilron, Imad Uthman, Ingris Peláez-Ballestas, Jean-Paul Divengi Nzambi, Jose Luis Ayuso-Mateos, Josep Maria Haro, Julia Wager, Juliana Barcellos de Souza, Kazutoshi Nakamura, Keiko Yamada, Lisa-Marie Rau, Makram Talih, Marcus J. Beasley, María Dueñas, Marie Zins, Marta Miret, Melissa Wake, Mirza Zaka Pratama","doi":"10.1038/s41591-026-04696-w","DOIUrl":"https://doi.org/10.1038/s41591-026-04696-w","url":null,"abstract":"Pain is the leading cause of disability worldwide, yet no harmonized self-reported reference framework exists to characterize how its burden is distributed across the lifespan and world regions. In this study, we harmonized individual-level self-reported pain data from 6,125,459 participants across 902 population-based data sources in 118 countries to establish global reference trajectories of pain. We implemented these trajectories in an open-access benchmarking platform for positioning external datasets against global pain norms. Pain prevalence ranged from roughly 2% for facial pain to 40% for back pain, was consistently higher in women across all 11 anatomical sites (risk ratio range: 1.08−1.83) and increased most steeply before age 55 years. Contrary to existing estimates that generally project higher prevalence of pain conditions in higher Human Development Index (HDI) regions, we found that individuals in the lowest HDI countries experienced a substantially higher late-life prevalence of any bodily pain than those in the highest (risk difference: 30.6 percentage points (95% confidence interval: 26.9−34.3)), with low back pain approaching twice the prevalence at the oldest ages. Globally, 18.3% of pain burden across anatomical sites was attributable to three modifiable risk factors (smoking, obesity and low income), but this varied from 12.6% in sub-Saharan Africa to 27.1% in eastern Europe, indicating that the factors underlying pain in lower-HDI settings remain poorly characterized. Together, these reference trajectories provide a common framework for defining and comparing pain burden and informing more equitable global surveillance and prevention.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"36 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149087651","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":"Oral small-molecule GLP-1RA safiglipron versus dapagliflozin in type 2 diabetes: a randomized, double-blind, active-comparator-controlled phase 3 trial","authors":"Lixin Guo \u0000 (郭立新), Dongni Yu \u0000 (于冬妮), Yimei Xu \u0000 (徐奕玫), Guo Tang \u0000 (唐果), Liang Peng \u0000 (彭亮), Chao Meng \u0000 (孟超), Meng Zhao \u0000 (赵猛), Wen Hu \u0000 (胡文), Debin Huang \u0000 (黄德斌), Chaoyang Zeng \u0000 (曾朝阳), Lei Yu \u0000 (于磊), Guangxiu Wu \u0000 (吴光秀), Lihui Zhang \u0000 (张力辉), Yuan Gao \u0000 (高远), Tingyan Zhong \u0000 (钟庭艳), Zi Ye \u0000 (叶子), on behalf of the OUTSTAND-2 Investigator Group","doi":"10.1038/s41591-026-04713-y","DOIUrl":"https://doi.org/10.1038/s41591-026-04713-y","url":null,"abstract":"Safiglipron is an oral small-molecule glucagon-like peptide-1 (GLP-1) receptor agonist administered without fasting or dietary restrictions. We evaluated its efficacy and safety versus dapagliflozin in OUTSTAND-2, a phase 3, multicenter, randomized, double-blind, double-dummy, active-comparator-controlled trial conducted at 98 sites in China. We randomized 810 adults (mean hemoglobin A1C (HbA1c) 8.60%, median diabetes duration 5.0 years, 35.7% women) to safiglipron 30 mg (n = 202), safiglipron 60 mg (n = 203), safiglipron 90 mg (n = 203) or dapagliflozin 10 mg (n = 202) for 32 weeks, followed by a 20-week active-treatment extension. For the primary endpoint, treatment differences versus dapagliflozin in change from baseline in HbA1c at week 32 under the primary non-inferiority estimand were −0.30% (95% confidence interval (CI): −0.51 to −0.09), −0.22% (−0.44 to −0.01) and −0.40% (−0.62 to −0.19) for safiglipron 30 mg, 60 mg and 90 mg, respectively, establishing non-inferiority for all three doses (all P < 0.0001; non-inferiority margin 0.4%). Under the treatment policy estimand, 90 mg met the prespecified statistical criterion for superiority (difference −0.25%; 95% CI: −0.45 to −0.05; one-sided P = 0.0067), whereas 60 mg did not (P = 0.0789), after which fixed-sequence testing stopped. HbA1c target attainment rates with safiglipron versus dapagliflozin were 54.9−63.5% versus 36.5% for HbA1c <7.0% and 38.9−48.6% versus 16.1% for HbA1c ≤6.5%. Mean body weight changes were −2.35%, −3.55%, −4.17% and −3.60% for safiglipron 30 mg, safiglipron 60 mg, safiglipron 90 mg and dapagliflozin, respectively. Fasting plasma glucose, seven-point self-monitored blood glucose profiles, waist circumference, HOMA-β, HOMA-IR and changes in treatment satisfaction showed varying degrees of improvement from baseline with both safiglipron and dapagliflozin. Rescue therapy was used by 0.5−1.5% versus 0% of participants, respectively. Gastrointestinal adverse events were more frequent with safiglipron and mostly mild or moderate; adverse events led to treatment discontinuation in 4.0%, 4.0%, 3.9% and 1.5% of participants, respectively. Safiglipron provides an effective oral treatment option for adults with type 2 diabetes inadequately controlled with metformin. ClinicalTrials.gov identifier: NCT06589765.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"75 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149087652","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":"The missing links in agentic AI autonomy","authors":"Mahmud Omar,&nbsp;Raja-Elie E. Abdulnour,&nbsp;Girish N. Nadkarni","doi":"10.1038/s41591-026-04658-2","DOIUrl":"10.1038/s41591-026-04658-2","url":null,"abstract":"A new study tackles issues around operational and decisional trust of agentic artificial intelligence (AI), using locally deployed, on-premise agents and consistency-based gating to refer uncertain cases — but what happens after referral remains untested.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"32 10","pages":"3539-3540"},"PeriodicalIF":52.5,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149091923","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":"Small quantity lipid-based nutritional supplementation and measles vaccination coverage in children aged 6−23 months: a pragmatic cluster-randomized trial","authors":"Cécile Cazes,&nbsp;Baba Waru Goni,&nbsp;Delphine Gabillard,&nbsp;Olumuyiwa Owolabi,&nbsp;Brice Yapi,&nbsp;Juliet Nabunje,&nbsp;Irine Atanga,&nbsp;Ariong’o M. Akinyi,&nbsp;Serge Danho,&nbsp;Eric Balestre,&nbsp;Anani Badje,&nbsp;Fatima Idriss,&nbsp;Mohammed Kasim,&nbsp;Muhammad M. Audu Bukarti,&nbsp;Chikezie Ugonna Emeka,&nbsp;Michelle Chouinard,&nbsp;Jean-Paul Mushenvula,&nbsp;Soma Bahonan,&nbsp;Mélanie Plazy,&nbsp;Ousmane Abdoulaye,&nbsp;Umar Chiroma,&nbsp;Hadiza Maina Adam,&nbsp;Camille Montfort,&nbsp;Nuru Suleiman Muhammad,&nbsp;Renaud Becquet,&nbsp;Kevin P. Q. Phelan","doi":"10.1038/s41591-026-04675-1","DOIUrl":"10.1038/s41591-026-04675-1","url":null,"abstract":"Undernutrition and infectious diseases pose a double threat to child survival, especially in areas with a high malnutrition burden and low vaccination coverage. In this study, we evaluated whether distributing preventive small-quantity lipid-based nutrient supplements (SQ-LNS) alongside routine immunization services may increase vaccine uptake in a pediatric, pragmatic, cluster-randomized controlled trial in northern Nigeria. Twenty geographically defined clusters across two Local Government Areas were randomized 1:1 to the NutriVax strategy (intervention) or standard National Program of Immunization (NPI) services (control). NutriVax provided a monthly ration of SQ-LNS to children aged 6−23 months after routine NPI delivery at primary healthcare centers. The primary outcome was coverage of the first dose of measles-containing vaccine (MCV1) verified by vaccination card among children aged 12−23 months, assessed in an endline population-based household cross-sectional survey 12 months after conducting a similar baseline survey. The endline survey included 1,604 children (801 control, 803 NutriVax); 48% of children surveyed in intervention clusters had ever received SQ-LNS. The odds of receiving card-verified MCV1 were two times higher in the NutriVax arm than in the control arm (odds ratio = 2.08, 95% confidence interval (CI): 1.30−3.35, P = 0.004). The difference-in-differences, cluster conditional analysis indicated a 20.1 percentage-point (pp) increase in MCV1 coverage from baseline (95% CI: 13.7−26.5 pp, P &lt; 0.0001) relative to the control arm. Co-delivering SQ-LNS with routine immunization substantially improved card-verified MCV1 uptake, supporting a scalable strategy to make progress toward targets set by the World Health Organizationʼs Immunization Agenda 2030 in similar settings. ClinicalTrials.gov identifier: NCT06387511 . A pragmatic, superiority, cluster-randomized trial done in Yobe State, northern Nigeria, found that distributing small-quantity lipid-based nutrient supplements alongside routine immunization services substantially increased measles vaccination uptake in children aged 12−23 months.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"32 10","pages":"3622-3632"},"PeriodicalIF":52.5,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41591-026-04675-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149087654","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":"Urine cell-free RNA for bladder cancer detection and treatment response prediction","authors":"Kevin J. Liu, William Y. Shi, Monica C. Nesselbush, Nick A. Phillips, Kathleen E. Mach, Bogdan Luca, Ravi K. Bajpai, Isabel Jabara, Jordan C. Cheng, Takeshi Sugio, Navika Shukla, Emily C. Shen, Ivy Lee Koh, Douglas J. Wu, Chih-Long Liu, Diego Almanza, Soyeong Jun, Feng Tian, Emily G. Hamilton, Christian R. Hoerner, Rui Wang, Mohammad S. Esfahani, Angela Hui, Vinh La, Grace Holton, Gabriela Rodriguez, Timothy J. Lee, Xi Ling, Nikitha Kalahasti, Spoorthi Vallamkonda, Patrick Mullane, Simon B. Chen, Eugene Shkolyar, Kris Prado, Ali Raza Khaki, Emily Chan, Mark K. Buyyounouski, Alice C. Fan, Eila C. Skinner, Ash A. Alizadeh, Joseph C. Liao, Maximilian Diehn","doi":"10.1038/s41591-026-04673-3","DOIUrl":"https://doi.org/10.1038/s41591-026-04673-3","url":null,"abstract":"Urine biomarkers promise to improve noninvasive detection and molecular characterization of genitourinary malignancies. Here we describe urine random priming and affinity capture of cell-free RNA (cfRNA) fragments for enrichment analysis by sequencing (uRARE-seq), a liquid biopsy method for urine cfRNA profiling, and apply it to 683 urine samples from patients with cancer and controls. Urine cfRNA contained transcripts from genitourinary tissues and, in patients with prostate, kidney or bladder cancer, tumor-derived transcripts. uRARE-seq demonstrated 95% sensitivity at 90% specificity for detecting localized bladder cancer. The method outperformed urine tumor DNA analysis and was unaffected by the presence of field-effect mutations. Urine cfRNA analysis also sensitively detected minimal residual disease and distinguished complete molecular responses after surgery from those after intravesical Bacillus Calmette–Guérin (BCG). Pretreatment urine from complete responders to BCG was enriched for T cell and other immune signatures, suggesting a preexisting antitumor immune response, whereas nonresponders showed higher expression of proliferation-related genes. In pretreatment urine from 114 patients, this biological difference enabled development of a biomarker predicting likelihood of response to BCG versus chemotherapy (area under the curve 0.93) that was strongly associated with risk of recurrence. Urine cfRNA analysis is therefore a promising biomarker approach for bladder cancer and potentially other urologic malignancies, although prospective studies are needed to assess its clinical utility.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"166 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149087655","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}