Nature Medicine最新文献

{"title":"Effects of volenrelaxin in worsening heart failure with preserved ejection fraction: a phase 2 randomized trial","authors":"Barry A. Borlaug, Jeffrey M. Testani, Mark C. Petrie, Zhenzhong Wang, Jonathan Cunningham, Kirkwood F. Adams, Offer Amir, Jan Bělohlávek, Edimar Bocchi, Aguinaldo Freitas, Miguel Hominal, Toshiaki Kadokami, Bela Merkely, Christopher A. Miller, Julio Nuñez, Subodh Verma, Mehmet Birhan Yilmaz, Ena Oru, Flora Sam","doi":"10.1038/s41591-025-03939-6","DOIUrl":"https://doi.org/10.1038/s41591-025-03939-6","url":null,"abstract":"<p>Relaxin is a peptide hormone that may decrease circulatory congestion and improve kidney function. In this study, we conducted a double-blind, international, multicenter trial to test whether volenrelaxin, a long-acting form of human relaxin, can improve left atrial (LA) function, reduce congestion and improve kidney function in patients with heart failure and preserved ejection fraction (HFpEF). We randomly assigned patients with New York Heart Association (NYHA) class II–IV HFpEF and recent heart failure (HF) decompensation to 25-mg, 50-mg or 100-mg volenrelaxin or placebo administered subcutaneously once weekly. The primary outcome was the change in LA reservoir strain at 26 weeks, with key secondary endpoints including changes in N-terminal pro-B-type natriuretic peptide (NT-proBNP), estimated glomerular filtration rate (eGFR) and safety. The trial was stopped early by the sponsor because of evidence for worsening congestion after 332 participants had been enrolled (mean age 74 years, 49% women, mean body mass index 30.6 kg m⁻², 31.9% NYHA class III–IV). Compared to placebo, 25-mg volenrelaxin improved LA reservoir strain (+3.9%, 95% confidence interval (CI): 1.1–6.6, <i>P</i> = 0.006) but did not have effects on this outcome at 50-mg (+1.3%, 95% CI: −1.3 to 3.9, <i>P</i> = 0.332) or 100-mg (+0.9%, 95% CI: −1.8 to 3.6, <i>P</i> = 0.521) doses. At 26 weeks, volenrelaxin (pooling all dosages) increased NT-proBNP levels (+24.5%, 95% CI: 2.0–51.8) and had no significant effect on eGFR (+2.2 ml min⁻¹ 1.73 m⁻², 95% CI: −1.8 to 6.3). Volenrelaxin was also associated with a non-significant increase in risk for HF hospitalization compared to placebo (hazard ratio = 2.64, 95% CI: 0.93–7.56, <i>P</i> = 0.070), along with signals for an increased number of cardiovascular and renal serious adverse events (odds ratio = 2.52, 95% CI: 0.95–6.68, <i>P</i> = 0.056). In conclusion, despite some evidence for improvement in LA function at a low dose, treatment with this long-acting form of human relaxin was associated with worsening congestion in patients with recently decompensated HFpEF. ClinicalTrials.gov identifier: NCT05592275.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"27 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144920715","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":"Aluminum in childhood vaccines not linked to chronic diseases","authors":"","doi":"10.1038/d41591-025-00055-3","DOIUrl":"https://doi.org/10.1038/d41591-025-00055-3","url":null,"abstract":"A study of over 1.2 million children found no links between aluminum-adjuvanted childhood vaccines and over 50 chronic diseases, including neurological, autoimmune and allergic conditions.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"25 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144915843","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 eyecare foundation model for clinical assistance: a randomized controlled trial","authors":"Yilan Wu, Bo Qian, Tingyao Li, Yiming Qin, Zhouyu Guan, Tingli Chen, Yali Jia, Ping Zhang, Dian Zeng, Sayoko Moroi, Rajiv Raman, Benjamin Sommer Thinggaard, Frederik Pedersen, José Alogo Obiang Ñehe, Tengku Ain Kamalden, Yukun Zhou, Yixiao Jin, Huating Li, An Ran Ran, Dawei Yang, Ziyao Meng, Qingsheng Peng, Ying Feng Zheng, Dingqiao Wang, Hongwei Ji, Pengxiao Zang, Changchang Yin, Jie Shen, Youxin Chen, Weihong Yu, Rongping Dai, Chenxi Zhang, Xinyu Zhao, Xiangning Wang, Yan Chen, Qiang Wu, Hongbin Xie, Simon K. H. Szeto, Julia Y. Y. Chan, Victor T. T. Chan, Hua-Tao Xie, Ruili Wei, Jin Li, Weizhi Ma, Lei Zhu, Hongqiu Wang, Huazhu Fu, Wenxiao Wang, Shan Lin, Zejun Xu, Nian Guan, Xiao Zhang, Andrzej Grzybowski, Monika Gołębiowska-Bogaj, Maciej Gawęcki, Adrian Smedowski, Wojciech Szaraniec, You Wu, Yang Wen, Xiang Chen, Yuanqi Yao, Lee-Ling Lim, Carol Y. Cheung, Gavin Siew Wei Tan, Jakob Grauslund, Paisan Ruamviboonsuk, Sobha Sivaprasad, Pearse A. Keane, Ya Xing Wang, Yih-Chung Tham, Ching-Yu Cheng, Tien Yin Wong, Bin Sheng","doi":"10.1038/s41591-025-03900-7","DOIUrl":"https://doi.org/10.1038/s41591-025-03900-7","url":null,"abstract":"<p>In the context of an increasing need for clinical assessments of foundation models, we developed EyeFM, a multimodal vision–language eyecare copilot, and conducted a multifaceted evaluation, including retrospective validations, multicountry efficacy validation as a clinical copilot and a double-masked randomized controlled trial (RCT). EyeFM was pretrained on 14.5 million ocular images from five imaging modalities paired with clinical texts from global, multiethnic datasets. Efficacy validation invited 44 ophthalmologists across North America, Europe, Asia and Africa in primary and specialty care settings, highlighting its utility as a clinical copilot. The RCT—a parallel, single-center, double-masked study—assessed EyeFM as a clinical copilot in retinal disease screening among a high-risk population in China. A total of 668 participants (mean age 57.5 years, 79.5% male) were randomized to 16 ophthalmologists, equally allocated into intervention (with EyeFM copilot) and control (standard care) groups. The primary endpoint indicated that ophthalmologists with EyeFM copilot achieved higher correct diagnostic rate (92.2% versus 75.4%, <i>P</i> &lt; 0.001) and referral rate (92.2% versus 80.5%, <i>P</i> &lt; 0.001). Secondary outcome indicated improved standardization score of clinical reports (median 33 versus 37, <i>P</i> &lt; 0.001). Participant satisfaction with the screening was similar between groups, whereas the intervention group demonstrated higher compliance with self-management (70.1% versus 49.1%, <i>P</i> &lt; 0.001) and referral suggestions (33.7% versus 20.2%, <i>P</i> &lt; 0.001) at follow-up. Post-deployment evaluations indicated strong user acceptance. Our study provided evidence that implementing EyeFM copilot can improve the performance of ophthalmologists and the outcome of patients. Chinese Clinical Trial Registry registration: ChiCTR2500095518.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"23 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144910784","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":"Influenza vaccine strain selection with an AI-based evolutionary and antigenicity model","authors":"Wenxian Shi, Jeremy Wohlwend, Menghua Wu, Regina Barzilay","doi":"10.1038/s41591-025-03917-y","DOIUrl":"https://doi.org/10.1038/s41591-025-03917-y","url":null,"abstract":"<p>Current vaccines provide limited protection against rapidly evolving viruses. For example, Centers for Disease Control and Prevention estimates show that the overall influenza vaccine effectiveness against outpatient illness in the United States averaged below 40% between 2012 and 2021. Moreover, the clinical outcomes of a vaccine can be assessed only retrospectively. Here we propose an in silico method named VaxSeer that predicts the antigenic match of vaccine candidates with circulating viruses, in the context of the viruses’ relative dominance in the future influenza season. Based on 10 years of retrospective evaluation using sequencing and antigenicity data, our approach consistently selects strains with better empirical antigenic matches to circulating viruses than annual recommendations. Finally, our predicted estimate of antigenic match exhibits a strong correlation with influenza vaccine effectiveness and reduction in disease burden, highlighting the promise of this framework to drive the vaccine selection process.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"10 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144910781","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":"Global distribution of research efforts, disease burden, and impact of US public funding withdrawal","authors":"Leo Schmallenbach,&nbsp;Maximilian Bley,&nbsp;Till W. Bärnighausen,&nbsp;Cassidy R. Sugimoto,&nbsp;Carolin Lerchenmüller,&nbsp;Marc J. Lerchenmueller","doi":"10.1038/s41591-025-03923-0","DOIUrl":"10.1038/s41591-025-03923-0","url":null,"abstract":"Evaluating whether research aligns with the global burden of disease is essential for equitable and effective scientific progress and improvement of human health. Without systematic evaluation of this alignment, science cannot respond to shifting health needs. Here we analyzed the distribution between research and disease, linking 8.6 million disease-specific publications to two decades of global disease burden data using a triangulated large language model approach. We find that since 1999, research and disease burden have seemingly become much more aligned; however, this is mainly because of regional declines in communicable disease burden, whereas the noncommunicable disease burden has increased and globalized. Meanwhile, research effort has not changed to match changes in disease burden. Our simulations suggest that without intentional alignment, the research–disease divergence will probably widen by a third over the next two decades, and be substantially accelerated by the reduction of US public funding for international research. Aligning research with health needs will require strategic investments, improved global coordination, open science policies and stronger, more equitable international partnerships to build resilience in a fragile research ecosystem. Longitudinal analyses reveal misalignment between global research efforts and disease burden; the gap is expected to widen substantially over the next two decades by the withdrawal of US public funding for international research.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"31 9","pages":"3101-3109"},"PeriodicalIF":50.0,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41591-025-03923-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144906382","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":"Allogeneic CD19-targeting T cells for treatment-refractory systemic lupus erythematosus: a phase 1 trial","authors":"Xiaobing Wang, Yi Zhang, Huimin Wang, Xin Wu, Chao He, Suxian Lin, Kun Pang, Yang Li, Yue Chen, Xiaojing Tang, Xin Liu, Jiazheng Wang, Songying Ye, Ran Yan, Tongxiang Guan, Bing Dai, Jing Lu, Haiyan He, Li Lin, Hongjuan Lu, Ting Li, Ling Zhou, Lingying Ye, Juan Zhao, Yanfang Liu, Na Ta, Jun Wu, Wanshi Cai, Zhe Wan, Shasha Zhang, Ruya Sun, Xueqiang Zhao, Jiasheng Wang, Yong Lin, Beifang Ning, Zhengqing Zhao, Xiaofeng Tang, Juan Du, Zhiguo Mao, Yanran He, Hongli Zheng, Lingyun Sun, Xin Lin, Huji Xu","doi":"10.1038/s41591-025-03899-x","DOIUrl":"https://doi.org/10.1038/s41591-025-03899-x","url":null,"abstract":"<p>Commercial autologous anti-CD19 chimeric antigen receptor-T cell therapies are effective in B cell malignancies and autoimmune diseases but are limited by personalized manufacturing, high costs and the risk from random chimeric antigen receptor insertion into the genome. To overcome these challenges, we developed YTS109, a hypoimmune allogeneic T cell product engineered using CRISPR–Cas9 to knock out <i>TRAC</i>, <i>PD1</i>, <i>HLA-A</i>, <i>HLA-B</i> and <i>CIITA</i>, with a CD19-targeting synthetic TCR and antigen receptor (STAR) precisely integrated into the <i>TRAC</i> locus to enable physiological, TCR-like signaling. As part of a multi-disease cohort trial, this article includes all enrolled five patients with severe, refractory systemic lupus erythematosus (SLE) complicated by lupus nephritis, who received lymphodepletion followed by YTS109 at 3 × 10⁶ STAR⁺ T cells per kg body weight. Primary endpoints were safety and SLE responder index 4 at month (M) 3. Secondary endpoints included clinical remission and quality-of-life outcomes through to M6. YTS109 was well tolerated, with only mild cytokine release syndrome and no graft-versus-host disease. All five patients in the SLE cohort achieved SLE responder index 4 response at M3, which was sustained through to M6. Four of five patients showed a rapid and sustained reduction in SLE disease activity score (mean 31.30–5.35 by M6), while one patient showed a mild refractory flare-up at M6. Quality-of-life improvements were observed across all four instruments in five patients by 6 months after infusion. Renal biopsies further confirmed resolution of inflammation and tissue restoration. These results demonstrate that YTS109 induced immune resetting and clinical remission, including renal structural restoration, potentially offering a promising therapy for refractory SLE with severe lupus nephritis, pending further validation. ClinicalTrials.gov registration: NCT06379646.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"28 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144906298","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 HbA1c: multimodal risk profiles improve diabetes prevention and diagnosis","authors":"","doi":"10.1038/s41591-025-03924-z","DOIUrl":"10.1038/s41591-025-03924-z","url":null,"abstract":"An AI model that integrates data from continuous glucose monitoring, microbiome analysis, physical activity levels and wearable sensors reveals hidden glycemic heterogeneity among individuals with identical HbA1c values. These nuances could improve the stratification of metabolic risk in decentralized clinical studies.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"31 9","pages":"2871-2872"},"PeriodicalIF":50.0,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144906300","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":"Tirzepatide leads to weight reduction in people with obesity due to MC4R deficiency","authors":"Pallav Bhatnagar, Nadia N. Ahmad, Xuan Li, Matthew Coghlan, Lee M. Kaplan, I. Sadaf Farooqi","doi":"10.1038/s41591-025-03913-2","DOIUrl":"https://doi.org/10.1038/s41591-025-03913-2","url":null,"abstract":"<p>The magnitude of weight reduction in the SURMOUNT-1 trial of the dual GLP-1 and GIP receptor agonist tirzepatide suggests that this treatment may be particularly effective in addressing the treatment needs of people with severe obesity (body mass index &gt;40 kg m⁻²), some of whom may carry rare penetrant genetic variants. Here we investigated the clinical response of men and women in the SURMOUNT-1 trial who carried pathogenic mutations in the melanocortin 4 receptor (<i>MC4R</i>) gene, the most common genetic cause of obesity. We found that 32 of 2,291 people (1.4%) for whom data were available carried pathogenic <i>MC4R</i> mutations. At baseline, <i>MC4R</i> mutation carriers exhibited a higher body mass index compared with noncarriers (40 kg m⁻² versus 38 kg m⁻²; <i>P</i> = 0.036). In the treatment arm, the weight loss trajectory over 72 weeks was comparable in both groups: 18.3% weight reduction in <i>MC4R</i> mutation carriers versus 19.9% in noncarriers. We conclude that tirzepatide is an effective treatment for the most common genetic subtype of obesity, MC4R deficiency.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"31 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144901719","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":"Publisher Correction: 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, Nikhil I. Khushalani, 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/s41591-025-03975-2","DOIUrl":"https://doi.org/10.1038/s41591-025-03975-2","url":null,"abstract":"<p>Correction to: <i>Nature Medicine</i> https://doi.org/10.1038/s41591-025-03875-5, published online 14 August 2025.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"3 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144906051","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":"What USAID cuts mean for future mortality rates","authors":"","doi":"10.1038/d41591-025-00054-4","DOIUrl":"https://doi.org/10.1038/d41591-025-00054-4","url":null,"abstract":"The recent defunding of USAID could lead to more than 14 million deaths, mostly in low- and middle-income countries, including 4.5 million child deaths — according to a study combining retrospective and forecasting analyses.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"16 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144901720","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}