Nature Medicine最新文献

{"title":"Air pollution interventions for health","authors":"John S. Ji, Francesca Dominici, Nelson Gouveia, Frank J. Kelly, Maria Neira","doi":"10.1038/s41591-025-03929-8","DOIUrl":"10.1038/s41591-025-03929-8","url":null,"abstract":"Air pollution, a leading environmental health risk, claims millions of lives yearly, impacting health across the lifespan. Despite widespread acknowledgement of air pollution-related disease burdens, eliminating air pollution remains challenging. Many regions are reliant on fossil fuels or biomass for basic survival, and developed economies striving to reduce air pollution face persistent barriers. Climate change complicates intervention efforts, as rising temperatures and extreme weather (for example, wildfires, dust storms) intensify air pollution. Traditional interventions may falter under worsening climate conditions, requiring integrated mitigation, adaptation and resilient infrastructure to yield environmental and health benefits. In this narrative Review, we evaluate multilevel interventions at the national, community and individual levels, discussing what works and does not work, with illustrative case examples. No single intervention suffices; efficacy depends on context, shaped by enforcement and equity. Integrated strategies are needed to address the root causes of air pollution and mitigate the devastating health impacts. The detrimental impact of air pollution on health is well known, but why is it so difficult to control? This Review evaluates multilevel interventions in the context of the evolving climate crisis and discusses what works and does not work.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"31 9","pages":"2888-2900"},"PeriodicalIF":50.0,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144901416","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":"Perioperative IDH inhibition in treatment-naive IDH-mutant glioma: a pilot trial","authors":"Katharine J. Drummond, Montana Spiteri, Sarah A. Cain, Jordan Jones, Sammy Shaya, Monique Topp, Tianyao Lu, Robert Tobler, Adam L. Valkovic, Zachery Moore, Oluwaseun E. Fatunla, Jurgen Kriel, Joel J. D. Moffet, Heidi McAlpine, Marius Rosier, Hefei Guan, James Dimou, Verena Schadewaldt, Samuel Roberts-Thomson, David McArdle, Elaine Lui, Moritz Voelker-Albert, Simone di Sanzo, Brunda Nijagal, Vinod K. Narayana, Camilla B. Mitchell, Joseph H. A. Vissers, Sean Grimmond, Mark A. Rosenthal, Lucy M. Palmer, Sarah A. Best, Saskia Freytag, James R. Whittle","doi":"10.1038/s41591-025-03884-4","DOIUrl":"https://doi.org/10.1038/s41591-025-03884-4","url":null,"abstract":"<p>Mutant isocitrate dehydrogenase (mIDH) inhibition significantly improves progression-free survival in patients with mIDH WHO grade 2 glioma; however, a large proportion of patients will progress, and mechanisms of adaptation to mIDH inhibition remain poorly understood. Perioperative studies with evaluation of paired pre- and post-treatment samples enable detailed understanding of drug response, facilitating biomarker development, but are rare in glioma owing to safety and cost concerns. Here we conducted a single-arm, open-label feasibility perioperative trial in patients with mIDH1 low-grade glioma, treatment naive to radiation and chemotherapy, with safusidenib (AB-218/DS-1001b), an orally available small-molecule inhibitor of mIDH1. As of 8 November 2024, 10 patients were enrolled and have completed the perioperative component, with a median follow-up of 14 months. Patients continue postoperative safusidenib with ongoing follow-up for safety and efficacy. The primary endpoint showed the feasibility and acceptability of conducting a two-stage perioperative trial. One patient experienced a serious surgery-related adverse event, and ten reported safusidenib-related adverse events; most were grade 1, and one experienced grade 3 elevation of transaminases. Tumor 2-hydroxyglutarate quantification revealed on-target activity, associated with alterations in differentiation programs and neural excitability, functionally validated in post hoc analysis by patch-clamp electrophysiology. Taken together, these results provide a detailed investigation of observations associated with mIDH inhibition in glioma. The study shows the safety and feasibility of this perioperative approach, which can be applied broadly in clinical trial design, serving as proof of concept for advancing drug development in glioma. ClinicalTrials.gov registration: NCT05577416.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"9 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144901619","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":"Genetic and molecular landscape of comorbidities in people living with HIV","authors":"Javier Botey-Bataller, Nienke van Unen, Marc Blaauw, Willem A. J. W. Vos, Louise van Eekeren, Nadira Vadaq, Vasiliki Matzaraki, Annelies Verbon, Albert L. Groenendijk, Jéssica C. dos Santos, Maartje C. P. Cleophas, Janneke E. Stalenhoef, Marvin A. H. Berrevoets, Xun Jiang, Manoj K. Gupta, Nhan Nguyen, Cheng-Jian Xu, Leo A. B. Joosten, Mihai G. Netea, André J. A. M. van der Ven, Yang Li","doi":"10.1038/s41591-025-03887-1","DOIUrl":"https://doi.org/10.1038/s41591-025-03887-1","url":null,"abstract":"<p>People living with HIV (PLHIV) have an increased susceptibility to non-AIDS comorbidities. In this study, we systematically profiled 1,342 PLHIV across five omics layers and immune function. We found latent factors, resulting from integrating epigenomics, transcriptomics, proteomics, metabolomics and immune responses, linked to cardiovascular diseases, the presence of carotid plaque and chronic obstructive pulmonary disease in PLHIV. Mapping four omics layers to genetic variation identified 5,962 molecular quantitative trait loci, illustrating a common genetic regulation in PLHIV compared to healthy individuals. By performing Mendelian randomization, we uncovered host genetic-driven changes in baseline molecules causally related to immune responses upon stimulation with inactivated pathogens. Lastly, we uncovered that the inflammasome, genetically regulated by the <i>NLRP12</i> locus, contributes to systemic inflammation across multiple molecular layers. This study offers a unique catalog of genetic and molecular determinants of immune function in PLHIV and elucidates molecular pathways driving inter-individual variation in immune response and comorbidities.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"17 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144901351","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":"AI-driven reclassification of multiple sclerosis progression","authors":"Habib Ganjgahi, Dieter A. Häring, Piet Aarden, Gordon Graham, Yang Sun, Stephen Gardiner, Wendy Su, Claude Berge, Antje Bischof, Elizabeth Fisher, Laura Gaetano, Stefan P. Thoma, Bernd C. Kieseier, Thomas E. Nichols, Alan J. Thompson, Xavier Montalban, Fred D. Lublin, Ludwig Kappos, Douglas L. Arnold, Robert A. Bermel, Heinz Wiendl, Chris C. Holmes","doi":"10.1038/s41591-025-03901-6","DOIUrl":"https://doi.org/10.1038/s41591-025-03901-6","url":null,"abstract":"<p>Multiple sclerosis (MS) affects 2.9 million people. Traditional classification of MS into distinct subtypes poorly reflects its pathobiology and has limited value for prognosticating disease evolution and treatment response, thereby hampering drug discovery. Here we report a data-driven classification of MS disease evolution by analyzing a large clinical trial database (approximately 8,000 patients, 118,000 patient visits and more than 35,000 magnetic resonance imaging scans) using probabilistic machine learning. Four dimensions define MS disease states: physical disability, brain damage, relapse and subclinical disease activity. Early/mild/evolving (EME) MS and advanced MS represent two poles of a disease severity spectrum. Patients with EME MS show limited clinical impairment and minor brain damage. Transitions to advanced MS occur via brain damage accumulation through inflammatory states, with or without accompanying symptoms. Advanced MS is characterized by moderate to high disability levels, radiological disease burden and risk of disease progression independent of relapses, with little probability of returning to earlier MS states. We validated these results in an independent clinical trial database and a real-world cohort, totaling more than 4,000 patients with MS. Our findings support viewing MS as a disease continuum. We propose a streamlined disease classification to offer a unifying understanding of the disease, improve patient management and enhance drug discovery efficiency and precision.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"1 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144901622","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":"AI-based diagnosis of acute aortic syndrome from noncontrast CT","authors":"Yujian Hu, Yilang Xiang, Yan-Jie Zhou, Yangyan He, Dehai Lang, Shifeng Yang, Xiaolong Du, Chunlan Den, Youyao Xu, Gaofeng Wang, Zhengyao Ding, Jingyong Huang, Wenjun Zhao, Xuejun Wu, Donglin Li, Qianqian Zhu, Zhenjiang Li, Chenyang Qiu, Ziheng Wu, Yunjun He, Chen Tian, Yihui Qiu, Zuodong Lin, Xiaolong Zhang, Lin Hu, Yuan He, Zhenpeng Yuan, Xiaoxiang Zhou, Rong Fan, Ruihan Chen, Wenchao Guo, Jing Xu, Jianpeng Zhang, Tony C. W. Mok, Zi Li, Mannudeep K. Kalra, Le Lu, Wenbo Xiao, Xiaoqiang Li, Yun Bian, Chengwei Shao, Guofu Wang, Wei Lu, Zhengxing Huang, Minfeng Xu, Hongkun Zhang","doi":"10.1038/s41591-025-03916-z","DOIUrl":"https://doi.org/10.1038/s41591-025-03916-z","url":null,"abstract":"<p>The accurate and timely diagnosis of acute aortic syndrome (AAS) in patients presenting with acute chest pain remains a clinical challenge. Aortic computed tomography (CT) angiography is the imaging protocol of choice in patients with suspected AAS. However, due to economic and workflow constraints in China, the majority of suspected patients initially undergo noncontrast CT as the initial imaging testing, and CT angiography is reserved for those at higher risk. Although noncontrast CT can reveal specific signs indicative of AAS, its diagnostic efficacy when used alone has not been well characterized. Here we present an artificial intelligence-based warning system, iAorta, using noncontrast CT for AAS identification in China, which demonstrates remarkably high accuracy and provides clinicians with interpretable warnings. iAorta was evaluated through a comprehensive step-wise study. In the multicenter retrospective study (<i>n</i> = 20,750), iAorta achieved a mean area under the receiver operating curve of 0.958 (95% confidence interval 0.950–0.967). In the large-scale real-world study (<i>n</i> = 137,525), iAorta demonstrated consistently high performance across various noncontrast CT protocols, achieving a sensitivity of 0.913–0.942 and a specificity of 0.991–0.993. In the prospective comparative study (<i>n</i> = 13,846), iAorta demonstrated the capability to significantly shorten the time to correct diagnostic pathway for patients with initial false suspicion from an average of 219.7 (115–325) min to 61.6 (43–89) min. Furthermore, for the prospective pilot deployment that we conducted, iAorta correctly identified 21 out of 22 patients with AAS among 15,584 consecutive patients presenting with acute chest pain and under noncontrast CT protocol in the emergency department. For these 21 AAS-positive patients, the average time to diagnosis was 102.1 (75–133) min. Finally, iAorta may help prevent delayed or missed diagnoses of AAS in settings where noncontrast CT remains the only feasible initial imaging modality—such as in resource-limited regions or in patients who cannot receive, or did not receive, intravenous contrast.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"15 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144901623","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: Meta-prediction of coronary artery disease risk","authors":"Shang-Fu Chen,&nbsp;Sang Eun Lee,&nbsp;Hossein Javedani Sadaei,&nbsp;Jun-Bean Park,&nbsp;Ahmed Khattab,&nbsp;Jie-Fu Chen,&nbsp;Corneliu Henegar,&nbsp;Nathan E. Wineinger,&nbsp;Evan D. Muse,&nbsp;Ali Torkamani","doi":"10.1038/s41591-025-03925-y","DOIUrl":"10.1038/s41591-025-03925-y","url":null,"abstract":"","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"31 9","pages":"3204-3204"},"PeriodicalIF":50.0,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41591-025-03925-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144883254","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":"Evolution of claudin18.2 therapies in gastroesophageal cancers","authors":"Samuel J. Klempner,&nbsp;Raghav Sundar","doi":"10.1038/s41591-025-03898-y","DOIUrl":"10.1038/s41591-025-03898-y","url":null,"abstract":"A pair of phase 1 trials evaluating antibody–drug conjugates identify potential strategies to treat advanced gastroesophageal cancers and highlight the rapid expansion of claudin18.2-targeting drug development in solid tumors.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"31 9","pages":"2861-2862"},"PeriodicalIF":50.0,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144883255","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":"Location matters for brain gene therapy in lysosomal disorders","authors":"Guilherme Baldo","doi":"10.1038/s41591-025-03914-1","DOIUrl":"10.1038/s41591-025-03914-1","url":null,"abstract":"A study demonstrates the feasibility of a multi-site infusion approach to ensure broad distribution of an adeno-associated virus-based gene therapy for GM2 gangliosidosis, providing valuable lessons for the treatment of this and other rare lysosomal storage disorders.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"31 9","pages":"2859-2860"},"PeriodicalIF":50.0,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144883257","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":"First-line sacituzumab tirumotecan with tagitanlimab in advanced non-small-cell lung cancer: a phase 2 trial.","authors":"Shaodong Hong, Qiming Wang, Ying Cheng, Yongzhong Luo, Xiujuan Qu, Haibo Zhu, Zhenyu Ding, Xingya Li, Lin Wu, Yan Wang, Sheng Hu, Enwen Wang, Anwen Liu, Yuping Sun, Yun Fan, Feng Ye, Kaihua Lu, Jian Fang, Yuping Shen, Xiaoping Jin, Junyou Ge, Li Zhang, Wenfeng Fang","doi":"10.1038/s41591-025-03883-5","DOIUrl":"10.1038/s41591-025-03883-5","url":null,"abstract":"<p><p>Sacituzumab tirumotecan (sac-TMT, also known as MK-2870 or SKB264) is an antibody-drug conjugate targeting trophoblast cell surface antigen 2. We report the initial findings from the ongoing phase 2 OptiTROP-Lung01 study, evaluating the combination of sac-TMT and tagitanlimab (KL-A167), an anti-PD-L1 antibody, as first-line therapy in patients with advanced or metastatic non-small-cell lung cancer who lack actionable genomic alterations (cohorts 1A and 1B). Cohort 1A received sac-TMT (5 mg kg^-1, every 3 weeks) plus tagitanlimab (1,200 mg, every 3 weeks) in each 3-week cycle, whereas cohort 1B was treated with sac-TMT (5 mg kg^-1, every 2 weeks) plus tagitanlimab (900 mg, every 2 weeks) in each 4-week cycle, in a nonrandomized manner until disease progression or unacceptable toxicity. The primary endpoints included safety and objective response rate. This study was not powered for formal hypothesis testing. A total of 40 and 63 patients were enrolled in cohorts 1A and 1B, respectively. The median age was 63 years in both cohorts. An Eastern Cooperative Oncology Group performance status of 1 was observed in 97.5% and 85.7% of patients in cohorts 1A and 1B, respectively. In cohorts 1A and 1B, the most common grade ≥3 treatment-related adverse events were decreased neutrophil count (30.0% and 34.9%), decreased white blood cell count (5.0% and 19.0%) and anemia (5.0% and 19.0%). No treatment-related deaths were observed. After median follow-ups of 19.3 months for cohort 1A and 13.0 months for cohort 1B, the confirmed objective response rate in the full analysis set was 40.0% (16 of 40) and 66.7% (42 of 63), the disease control rate was 85.0% and 92.1% and median progression-free survival was 15.4 months (95% confidence interval 6.7-17.9) and not reached for cohorts 1A and 1B, respectively. sac-TMT plus tagitanlimab showed promising efficacy as a first-line treatment for advanced or metastatic non-small-cell lung cancer, with a manageable safety profile. ClinicalTrials.gov registration: NCT05351788 .</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":" ","pages":""},"PeriodicalIF":50.0,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144883256","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":"A plasma proteomics-based candidate biomarker panel predictive of amyotrophic lateral sclerosis.","authors":"Ruth Chia, Ruin Moaddel, Justin Y Kwan, Memoona Rasheed, Paola Ruffo, Natalie Landeck, Paolo Reho, Rosario Vasta, Andrea Calvo, Cristina Moglia, Antonio Canosa, Umberto Manera, Allison Snyder, Sara Saez-Atienzar, Maurizio Grassano, Maura Brunetti, Federico Casale, Anindita Ray, Kumar Arvind, Betul Comertpay, Min Zhu, J Raphael Gibbs, Camille Alba, Ted M Dawson, Liana S Rosenthal, Anna J Hall, Alexander Y Pantelyat, Derek P Narendra, Debra J Ehrlich, Keenan A Walker, Peter Kosa, Bibiana Bielekova, Josephine M Egan, Julián Candia, Toshiko Tanaka, Luigi Ferrucci, Clifton L Dalgard, Sonja W Scholz, Adriano Chiò, Bryan J Traynor","doi":"10.1038/s41591-025-03890-6","DOIUrl":"10.1038/s41591-025-03890-6","url":null,"abstract":"<p><p>Identifying a reliable biomarker for amyotrophic lateral sclerosis (ALS) is crucial for clinical practice. Here, in this cross-sectional study, we used the Olink Explore 3072 platform to investigate plasma proteomics as a biomarker tool for this neurodegenerative condition. Thirty-three proteins were differentially abundant in the plasma of patients with ALS (n = 183) versus controls (n = 309). We replicated our findings in an independent cohort (n = 48 patients with ALS and n = 75 controls). We then applied machine learning to create a model that diagnosed ALS with high accuracy (area under the curve, 98.3%). By analyzing plasma samples from individuals before ALS symptoms emerged, we estimated the age of clinical onset and showed that the disease process-impacting skeletal muscle, nerves and energy metabolism-occurs years before symptoms appear. Our research suggests that plasma proteins can be a biomarker for this fatal disease and offers molecular insights into its prodromal phase.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":" ","pages":""},"PeriodicalIF":50.0,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144883253","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}