Nature Medicine最新文献

{"title":"For science to thrive we must protect scientists from harassment","authors":"Peter Singer","doi":"10.1038/s41591-025-03870-w","DOIUrl":"10.1038/s41591-025-03870-w","url":null,"abstract":"Throughout my academic career, I have been a supporter of freedom of thought and expression.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"31 9","pages":"2844-2844"},"PeriodicalIF":50.0,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144874233","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":"Gene editing enables islet transplantation without immunosuppression.","authors":"Karen O'Leary","doi":"10.1038/d41591-025-00053-5","DOIUrl":"10.1038/d41591-025-00053-5","url":null,"abstract":"","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":" ","pages":""},"PeriodicalIF":50.0,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144874234","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":"Health consequences of forced displacements from Gaza","authors":"","doi":"10.1038/d41591-025-00052-6","DOIUrl":"https://doi.org/10.1038/d41591-025-00052-6","url":null,"abstract":"Discover the world’s best science and medicine | Nature.com","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"18 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144857984","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":"Lifestyle changes improve cognition during aging","authors":"","doi":"10.1038/d41591-025-00050-8","DOIUrl":"https://doi.org/10.1038/d41591-025-00050-8","url":null,"abstract":"A 2-year randomized study shows that a holistic lifestyle intervention — integrating diet and cardiovascular monitoring with physical, social and cognitive activities — can improve cognition in older adults at risk of dementia.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"5 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144851592","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":"Dual-vector rAAVrh8 gene therapy for GM2 gangliosidosis: a phase 1/2 trial","authors":"Florian Eichler, Oguz I. Cataltepe, Rrita Daci, Ajit S. Puri, Toloo Taghian, Xuntian Jiang, Mohammed Salman Shazeeb, Anna Kuhn, Asma Hader, Hakki Celik, Zeynep Vardar, Connor J. Lewis, Rebecca Artinian, Amanda Nagy, Behroze Vachha, Robert Thompson, Thomas Gallagher, Scot Bateman, Julia Parzych, Spiro G. Spanakis, Toby A. Vaughn, Kirsten Pier, Erika De Boever, Mary-Alice Abbott, Eleonora D′Ambrosio, Danielle Kokoski, Meghan Blackwood, Elise Drummond, Eva-Maria Ratai, Elise L. Townsend, Haley McLaughlin, Cynthia J. Tifft, Allison M. Keeler, Miguel Sena-Esteves, Heather L. Gray-Edwards, Terence R. Flotte","doi":"10.1038/s41591-025-03822-4","DOIUrl":"10.1038/s41591-025-03822-4","url":null,"abstract":"The dual rAAVrh8-HEXA and rAAVrh8-HEXB vector can restore central nervous system hexosaminidase (Hex) enzyme activity, decrease GM2 levels in cerebrospinal fluid and rescue phenotypic consequences of GM2 gangliosidosis, Tay–Sachs and Sandhoff diseases in animal models following simultaneous bi-thalamic (BiT) injections. Following up on an n = 2 expanded access trial, we initiated a phase 1/2, single-dose, dose-escalation of combined BiT, intra-cisterna magna and intrathecal infusion in children with Tay–Sachs and Sandhoff diseases (six infantile, three juvenile). The BiT injection volume and vector dose were doubled between four cohorts, with the lowest dose matching the earlier expanded access trial. Cerebrospinal fluid HexA enzyme activity, serum total Hex activity and GM2 levels showed a dose-dependent biochemical correction of the disease. Serum Hex activity surpassed 40 nmol h−1 ml−1, two times the lower limit of normal, and neuroimaging demonstrated increased fiber tracts. Correction was greatest at 12 weeks, but in decline by 24 weeks postdosing. Infantile patients experienced global clinical stabilization and prolonged oral feeding without aspiration until 3–3.5 years. Seizures had a later onset, were less frequent, less severe and more responsive to anti-convulsant medication. Adverse events were rare in infantile patients, but worsening dystonia was observed in juvenile patients, who were excluded from ongoing enrollment. ClinicalTrials.gov registration: NCT04669535 and NCT06614569 . A phase 1/2 trial of dual-vector rAAVrh8 gene therapy for GM2 gangliosidosis, administered by bilateral intrathalamic, cisterna magna and intrathecal delivery found a dose-dependent biochemical correction of the disease.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"31 9","pages":"2927-2935"},"PeriodicalIF":50.0,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41591-025-03822-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144851594","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":"A personal health large language model for sleep and fitness coaching","authors":"Justin Khasentino, Anastasiya Belyaeva, Xin Liu, Zhun Yang, Nicholas A. Furlotte, Chace Lee, Erik Schenck, Yojan Patel, Jian Cui, Logan Douglas Schneider, Robby Bryant, Ryan G. Gomes, Allen Jiang, Roy Lee, Yun Liu, Javier Perez, Jameson K. Rogers, Cathy Speed, Shyam Tailor, Megan Walker, Jeffrey Yu, Tim Althoff, Conor Heneghan, John Hernandez, Mark Malhotra, Leor Stern, Yossi Matias, Greg S. Corrado, Shwetak Patel, Shravya Shetty, Jiening Zhan, Shruthi Prabhakara, Daniel McDuff, Cory Y. McLean","doi":"10.1038/s41591-025-03888-0","DOIUrl":"https://doi.org/10.1038/s41591-025-03888-0","url":null,"abstract":"<p>Although large language models (LLMs) show promise for clinical healthcare applications, their utility for personalized health monitoring using wearable device data remains underexplored. Here we introduce the Personal Health Large Language Model (PH-LLM), designed for applications in sleep and fitness. PH-LLM is a version of the Gemini LLM that was finetuned for text understanding and reasoning when applied to aggregated daily-resolution numerical sensor data. We created three benchmark datasets to assess multiple complementary aspects of sleep and fitness: expert domain knowledge, generation of personalized insights and recommendations and prediction of self-reported sleep quality from longitudinal data. PH-LLM achieved scores that exceeded a sample of human experts on multiple-choice examinations in sleep medicine (79% versus 76%) and fitness (88% versus 71%). In a comprehensive evaluation involving 857 real-world case studies, PH-LLM performed similarly to human experts for fitness-related tasks and improved over the base Gemini model in providing personalized sleep insights. Finally, PH-LLM effectively predicted self-reported sleep quality using a multimodal encoding of wearable sensor data, further demonstrating its ability to effectively contextualize wearable modalities. This work highlights the potential of LLMs to revolutionize personal health monitoring via tailored insights and predictions from wearable data and provides datasets, rubrics and benchmark performance to further accelerate personal health-related LLM research.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"472 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144840329","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":"Anti-PD-1 therapy in unresectable desmoplastic melanoma: the phase 2 SWOG S1512 trial","authors":"Kari L. Kendra, Shay L. Bellasea, Zeynep Eroglu, Siwen Hu-Lieskovan, Katie M. Campbell, William E. Carson, David A. Wada, Jose A. Plaza, Jeffrey A. Sosman, Gino K. In, Alexandra Ikeguchi, John Hyngstrom, Andrew S. Brohl, I. Khushalani Nikhil, Joseph Markowitz, George Negrea, Samer Kasbari, Gary C. Doolittle, Umang Swami, Toni Roberts, Boban N. Mathew, Egmidio Medina, Ignacio Baselga-Carretero, Cynthia R. Gonzalez, Ivan Perez Garcilazo, Agustin Vega-Crespo, Jia Ming Chen, Nataly Naser Al-Deen, Sapna P. Patel, Elad Sharon, James Moon, Michael C. Wu, Antoni Ribas","doi":"10.1038/s41591-025-03875-5","DOIUrl":"https://doi.org/10.1038/s41591-025-03875-5","url":null,"abstract":"<p>Desmoplastic melanoma is a distinct subtype of melanoma known to have preexisting immune infiltrates and high ultraviolet light damage, resulting in a high tumor mutational burden. We hypothesized that this may result in high response rates with single-agent anti-programmed death protein 1 (PD-1) therapy. SWOG S1512 was a two-cohort clinical trial testing the activity of pembrolizumab in patients with surgically resectable (cohort A) and unresectable (cohort B) desmoplastic melanoma. Here we report on the cohort B single-arm clinical trial, which enrolled 27 patients with unresectable desmoplastic melanoma receiving pembrolizumab 200 mg intravenously every 3 weeks for up to 2 years, with the primary endpoint of complete response rate. The complete response rate was 37% (95% confidence interval: 19–58%), and the post hoc endpoint of objective response rate was 89% (95% confidence interval: 71–98%). The estimated secondary endpoints of 3-year melanoma-specific progression-free survival and overall survival were 84% and 96%, respectively, with only one patient having died from melanoma progression. Ten patients (37%) experienced grade 3 or 4 adverse events, and nine patients (33%) discontinued treatment because of adverse events. Patients with advanced desmoplastic melanoma have a high response rate to single-agent PD-1 blockade therapy, supporting single-agent anti-PD-1 as the treatment of choice, but are limited by a frequency of toxicities that is numerically higher than in other patient populations. ClinicalTrials.gov identifier: NCT02775851</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"27 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144840340","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":"Virtual reality-based versus standard cognitive behavioral therapy for paranoia in schizophrenia spectrum disorders: a randomized controlled trial","authors":"Ulrik N. Jeppesen, Ditte L. Vernal, Anne Sofie Due, Lise S. Mariegaard, Amy E. Pinkham, Stephen F. Austin, Maarten Vos, Mads J. Christensen, Nina K. Hansen, Lisa C. Smith, Carsten Hjorthøj, Wim Veling, Merete Nordentoft, Louise B. Glenthøj","doi":"10.1038/s41591-025-03880-8","DOIUrl":"https://doi.org/10.1038/s41591-025-03880-8","url":null,"abstract":"<p>Paranoia is a distressing and prevalent symptom in schizophrenia spectrum disorders. Virtual reality-based cognitive behavioral therapy for paranoia (VR-CBTp) has been proposed to augment behavioral interventions by providing controlled and safe virtual environments in which social situations inducing paranoid anxiety can be manipulated, allowing for new therapeutical possibilities such as gradual exposure and repetition. This assessor-masked, randomized parallel group superiority trial investigated the efficacy of VR-CBTp compared to standard CBTp. Participants were randomized to receive ten sessions of VR-CBTp or CBTp, both on top of treatment as usual. Intention-to-treat analyses included 254 participants (VR-CBTp: <i>n</i> = 126, CBTp: <i>n</i> = 128). Outcomes were assessed at baseline, treatment cessation and follow-up (6 months after treatment cessation). The primary outcome was Ideas of Persecution subscale from the Green Paranoid Thoughts Scale, measured at treatment cessation. There was not a statistically significant between-group difference on the primary outcome at endpoint (effect estimate: 2% in favor of VR-CBTp; 95% confidence interval: −11% to +17%; Cohen’s <i>d</i> = 0.04; <i>P</i> = 0.77, based on exponentiated log-transformed data). No deaths or violent incidents involving law enforcement occurred during the study. In conclusion, VR-CBTp was not superior to CBTp in reducing schizophrenia-spectrum-disorders-related paranoia. ClinicalTrials.gov registration: NCT04902066.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"95 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144825395","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":"Why menstrual cycle irregularities belong in brain research","authors":"Carina Heller, Erynn Christensen, Elle M. Murata, Nicole Petersen, Kathleen Casto, Shae Datta, Bart Larsen, Hector Arciniega","doi":"10.1038/s41591-025-03879-1","DOIUrl":"https://doi.org/10.1038/s41591-025-03879-1","url":null,"abstract":"The menstrual cycle requires tight orchestration between the brain and body, and irregularities can be both the cause and the consequence of wide-ranging health issues. Embracing this complexity, instead of excluding individuals with irregular menstrual patterns from research, could reveal novel brain–body interactions, advance neuroscience and improve health outcomes for those affected.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"37 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144825370","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":"Biological and health effects of fire smoke exposure","authors":"Mijung Oh,&nbsp;Katherine E. Zychowski","doi":"10.1038/s41591-025-03866-6","DOIUrl":"10.1038/s41591-025-03866-6","url":null,"abstract":"A new study leverages powerful multi-omics techniques to analyze immune dysregulation in smoke-exposed individuals, offering crucial insights for the development of novel diagnostics and interventions.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"31 9","pages":"2863-2864"},"PeriodicalIF":50.0,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144819229","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}