Nature Medicine最新文献

{"title":"Antibiotics reduce vaccine responses in infants","authors":"","doi":"10.1038/d41591-025-00028-6","DOIUrl":"https://doi.org/10.1038/d41591-025-00028-6","url":null,"abstract":"Neonatal antibiotic exposure was found to negatively impact vaccine responses, probably mediated by decreased Bifidobacterium levels — which highlights potential strategies for enhancing vaccine efficacy in infants.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"44 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143890187","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":"Promoting transparency in AI for biomedical and behavioral research","authors":"Tina Hernandez-Boussard, Aaron Y. Lee, Julia Stoyanovich, Laura Biven","doi":"10.1038/s41591-025-03680-0","DOIUrl":"https://doi.org/10.1038/s41591-025-03680-0","url":null,"abstract":"<p>Recent advancements in artificial intelligence (AI) in healthcare have highlighted the need for transparency, including explainability, interpretability, and accountability across the AI lifecycle^1,2. Transparency ensures stakeholders can make informed decisions about data and model reuse, fostering trust and fairness while aligning with regulatory frameworks. However, the concept of transparency lacks a clear definition for both biomedical research and clinical care, resulting in inconsistent practices.</p><p>This Correspondence focuses on transparency within the realm of AI-driven biomedical and behavioral research. Although the effect of AI on clinical care is crucial, this discussion centers on its implications for research, addressing gaps in data reuse, model generalization and fairness. The National Institutes of Health (NIH) Office of Data Science Strategy (ODSS) convened a workshop that brought together leading experts in AI, healthcare and ethics to examine transparency in this context³. The workshop findings highlight practical solutions tailored to research contexts, addressing documentation standards, patient and community co-design, and oversight mechanisms to achieve equitable outcomes.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"46 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143890189","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":"D3S-001 in advanced solid tumors with KRASG12C mutations: a phase 1 trial","authors":"Byoung Chul Cho, Shun Lu, Myung Ah Lee, Zhengbo Song, John J. Park, Sun Min Lim, Ziming Li, Jun Zhao, Gary Richardson, Yanqiao Zhang, Jun Zhang, Anwen Liu, Herbert H. Loong, Cheng Chen, Jia Wang, Yandong Shen, Zifei Fan, Qian Chen, Hui Wang, Jing Zhang, Zhi Jian Chen, Melissa L. Johnson, Tony Mok","doi":"10.1038/s41591-025-03688-6","DOIUrl":"https://doi.org/10.1038/s41591-025-03688-6","url":null,"abstract":"<p>D3S-001 is a next-generation KRAS-G12C inhibitor (G12Ci) designed to enhance target engagement efficiency and overcome growth factor-induced nucleotide exchange. D3S-001 was evaluated in a phase 1a dose-escalation study in patients with advanced solid tumors harboring <i>KRAS</i>^G12C mutation (<i>N</i> = 42) and a phase 1b expansion cohort of patients with non-small-cell lung cancer (NSCLC) whose disease progressed after prior G12Ci therapy (<i>N</i> = 20). The primary endpoints were safety and determination of the maximum tolerated dose. Secondary endpoints included pharmacokinetics, confirmed objective response rate (ORR) and disease control rate. D3S-001 demonstrated dose-dependent pharmacokinetics and no dose-limiting toxicities, and the maximum tolerated dose was not reached. Grade 3 treatment-related adverse events were reported in seven patients (16.7%) in the G12Ci-naive dose-escalation cohort and two patients (10.0%) in the G12Ci-pretreated NSCLC expansion cohort. There were no grade 4 or 5 treatment-related adverse events. D3S-001 600 mg was selected as the dose for further investigation based on pharmacokinetics. Confirmed ORR in the G12Ci-naive population was 73.5% overall (25 of 34), and 66.7% (14 of 21), 88.9% (8 of 9) and 75.0% (3 of 4) in patients with NSCLC, colorectal cancer and pancreatic ductal adenocarcinoma, respectively. Among patients with G12Ci-pretreated NSCLC, ORR was 30.0% (6 of 20) and disease control rate was 80.0% (16 of 20). This study demonstrates the safety and tolerability of D3S-001 monotherapy with promising antitumor activity. The phase 1b expansion phase is ongoing. ClinicalTrials.gov identifier: NCT05410145.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"35 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143884918","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":"SPIRIT 2025 statement: updated guideline for protocols of randomized trials","authors":"An-Wen Chan, Isabelle Boutron, Sally Hopewell, David Moher, Kenneth F. Schulz, Gary S. Collins, Ruth Tunn, Rakesh Aggarwal, Michael Berkwits, Jesse A. Berlin, Nita Bhandari, Nancy J. Butcher, Marion K. Campbell, Runcie C. W. Chidebe, Diana R. Elbourne, Andrew J. Farmer, Dean A. Fergusson, Robert M. Golub, Steven N. Goodman, Tammy C. Hoffmann, John P. A. Ioannidis, Brennan C. Kahan, Rachel L. Knowles, Sarah E. Lamb, Steff Lewis, Elizabeth Loder, Martin Offringa, Philippe Ravaud, Dawn P. Richards, Frank W. Rockhold, David L. Schriger, Nandi L. Siegfried, Sophie Staniszewska, Rod S. Taylor, Lehana Thabane, David J. Torgerson, Sunita Vohra, Ian R. White, Asbjørn Hróbjartsson","doi":"10.1038/s41591-025-03668-w","DOIUrl":"https://doi.org/10.1038/s41591-025-03668-w","url":null,"abstract":"<p>The protocol of a randomized trial is the foundation for study planning, conduct, reporting and external review. However, trial protocols vary in their completeness and often do not address key elements of design and conduct. The SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) statement was first published in 2013 as guidance to improve the completeness of trial protocols. Periodic updates incorporating the latest evidence and best practices are needed to ensure that the guidance remains relevant to users. Here, we aimed to systematically update the SPIRIT recommendations for minimum items to address in the protocol of a randomized trial. We completed a scoping review and developed a project-specific database of empirical and theoretical evidence to generate a list of potential changes to the SPIRIT 2013 checklist. The list was enriched with recommendations provided by lead authors of existing SPIRIT/CONSORT (Consolidated Standards of Reporting Trials) extensions (Harms, Outcomes, Non-pharmacological Treatment) and other reporting guidelines (TIDieR). The potential modifications were rated in a three-round Delphi survey followed by a consensus meeting. Overall, 317 individuals participated in the Delphi consensus process and 30 experts attended the consensus meeting. The process led to the addition of two new protocol items, revision to five items, deletion/merger of five items, and integration of key items from other relevant reporting guidelines. Notable changes include a new open science section, additional emphasis on the assessment of harms and description of interventions and comparators, and a new item on how patients and the public will be involved in trial design, conduct and reporting. The updated SPIRIT 2025 statement consists of an evidence-based checklist of 34 minimum items to address in a trial protocol, along with a diagram illustrating the schedule of enrollment, interventions and assessments for trial participants. To facilitate implementation, we also developed an expanded version of the SPIRIT 2025 checklist and an accompanying explanation and elaboration document. Widespread endorsement and adherence to the updated SPIRIT 2025 statement have the potential to enhance the transparency and completeness of trial protocols for the benefit of investigators, trial participants, patients, funders, research ethics committees, journals, trial registries, policymakers, regulators and other reviewers.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"138 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143884917","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 stochasticity of biological aging","authors":"David H. Meyer, Björn Schumacher","doi":"10.1038/s41591-025-03687-7","DOIUrl":"https://doi.org/10.1038/s41591-025-03687-7","url":null,"abstract":"<p>The recent <i>Nature Medicine</i> World View by M. Arfan Ikram¹ cites our article on the role of stochasticity in aging clocks as evidence for limited biological information from age predictors². Following a further Correspondence by Ferrucci et al.³, we find it important to clarify the roles of stochasticity in aging and in age prediction and to have an open debate on this topic.</p><p>The idea of aging as a genetically controlled process began with Cynthia Kenyon’s observation that a mutation in the <i>daf-2</i> gene doubled the lifespan of worms. This led to the identification of mechanisms of aging that could be targeted genetically but also pharmacologically to slow the aging process. For example, treating mice with the mTOR inhibitor rapamycin extended lifespan⁴, and current clinical studies of the effects of GLP-1 receptor agonists have shown a reduction in age-related diseases, from heart disease to kidney disease⁵. In fact, the oldest lifespan-extending intervention, calorie restriction, was shown to provide beneficial effects on health in humans⁶.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"43 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143884777","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":"Broad rim lesions are a new pathological and imaging biomarker for rapid disease progression in multiple sclerosis","authors":"Luisa Klotz, Joost Smolders, Jussi Lehto, Markus Matilainen, Lukas Lütje, Luzia Buchholz, Stefanie Albrecht, Carolin Walter, Julian Varghese, Heinz Wiendl, Marjo Nylund, Christian Thomas, Maria Gardberg, Aletta M. R. van den Bosch, Laura Airas, Inge Huitinga, Tanja Kuhlmann","doi":"10.1038/s41591-025-03625-7","DOIUrl":"https://doi.org/10.1038/s41591-025-03625-7","url":null,"abstract":"<p>Current multiple sclerosis (MS) treatments reduce relapse activity but have limited impact on disease progression. Clinical trials targeting progression often fail because of insufficient understanding of its underlying mechanisms. This study analyzed a clinically well-characterized MS autopsy cohort from the Netherland Brain Bank (186 individuals) from which we selected donors exhibiting opposite disease trajectories of slow versus rapid progression. We performed extensive unbiased histology and spatial transcriptomics, which unveiled a distinct MS lesion type marked by an extensive myeloid cell rim with cellular and transcriptional signatures of innate immune activation, inflammatory cytokine production, unfolded protein response and apoptosis. Presence of this particular lesion type was linked to rapid disease progression. An independent translocator protein 18-kDa positron emission tomography study (114 individuals) validates the association between lesions with a broad myeloid cell rim and disease progression in individuals with MS. Our findings offer crucial insights into the mechanisms behind MS progression, identifying broad rim lesions as a biomarker for rapid disease progression and potentially guiding patient selection for future therapeutic trials targeting central nervous system intrinsic inflammation.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"45 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143884916","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: Autologous T cell therapy for PRAME+ advanced solid tumors in HLA-A*02+ patients: a phase 1 trial","authors":"Martin Wermke, Dejka M. Araujo, Manik Chatterjee, Apostolia M. Tsimberidou, Tobias A. W. Holderried, Amir A. Jazaeri, Ran Reshef, Carsten Bokemeyer, Winfried Alsdorf, Katrin Wetzko, Peter Brossart, Katrin Aslan, Linus Backert, Sebastian Bunk, Jens Fritsche, Swapna Gulde, Silvana Hengler, Norbert Hilf, Mohammad B. Hossain, Jens Hukelmann, Mamta Kalra, Delfi Krishna, M. Alper Kursunel, Dominik Maurer, Andrea Mayer-Mokler, Regina Mendrzyk, Ali Mohamed, Karine Pozo, Arun Satelli, Marilena Letizia, Heiko Schuster, Oliver Schoor, Claudia Wagner, Hans-Georg Rammensee, Carsten Reinhardt, Harpreet Singh-Jasuja, Steffen Walter, Toni Weinschenk, Jason J. Luke, Cedrik M. Britten","doi":"10.1038/s41591-025-03731-6","DOIUrl":"https://doi.org/10.1038/s41591-025-03731-6","url":null,"abstract":"<p>Correction to: <i>Nature Medicine</i> https://doi.org/10.1038/s41591-025-03650-6, published online 9 April 2025.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"14 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143885407","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":"Effect of felzartamab on the molecular phenotype of antibody-mediated rejection in kidney transplant biopsies","authors":"Matthias Diebold, Patrick T. Gauthier, Katharina A. Mayer, Martina Mackova, Christian Hinze, Jessica Chang, Uptal D. Patel, Ekkehard Schütz, Bernd Jilma, Eva Schrezenmeier, Klemens Budde, Georg A. Böhmig, Philip F. Halloran","doi":"10.1038/s41591-025-03653-3","DOIUrl":"https://doi.org/10.1038/s41591-025-03653-3","url":null,"abstract":"<p>A recent randomized controlled trial demonstrated that treatment with anti-CD38 monoclonal antibody felzartamab suppressed antibody-mediated rejection (ABMR) in kidney transplant patients but with recurrence after treatment in some patients. Here we examined the molecular effects of 6 months of felzartamab treatment on biopsies from the trial using genome-wide microarray analysis, comparing pretreatment, end-of-treatment (week 24) and posttreatment (week 52) biopsies from ten patients treated with felzartamab and ten patients in the placebo group. Felzartamab reduced molecular ABMR activity scores in all nine patients with baseline ABMR activity, selectively suppressing interferon gamma-inducible and natural killer cell transcripts, with minimal effect on ABMR stage-related endothelial transcripts. Suppression was often incomplete when ABMR activity was intense, and molecular recurrence was nearly universal by week 52. However, we also found that felzartamab had parenchymal benefits at week 52, slowing the trajectories of molecular injury scores beyond the treatment period, suggesting that suppression of ABMR activity could potentially slow future progression to kidney failure. These data provide preliminary molecular insights into the effects of CD38-directed treatment for ABMR, which have the potential to inform future therapeutic strategies.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"9 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143884915","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":"Personalized inhaled bacteriophage therapy for treatment of multidrug-resistant Pseudomonas aeruginosa in cystic fibrosis","authors":"Benjamin K. Chan, Gail L. Stanley, Kaitlyn E. Kortright, Albert C. Vill, Mrinalini Modak, Isabel M. Ott, Ying Sun, Silvia Würstle, Casey N. Grun, Barbara I. Kazmierczak, Govindarajan Rajagopalan, Zachary M. Harris, Clemente J. Britto, Jill Stewart, Jaideep S. Talwalkar, Casey R. Appell, Nauman Chaudary, Sugeet K. Jagpal, Raksha Jain, Adaobi Kanu, Bradley S. Quon, John M. Reynolds, Charlotte C. Teneback, Quynh-Anh Mai, Veronika Shabanova, Paul E. Turner, Jonathan L. Koff","doi":"10.1038/s41591-025-03678-8","DOIUrl":"https://doi.org/10.1038/s41591-025-03678-8","url":null,"abstract":"<p>Bacteriophage (phage) therapy, which uses lytic viruses as antimicrobials, is a potential strategy to address the antimicrobial resistance crisis. Cystic fibrosis, a disease complicated by recurrent <i>Pseudomonas aeruginosa</i> pulmonary infections, is an example of the clinical impact of antimicrobial resistance. Here, using a personalized phage therapy strategy that selects phages for a predicted evolutionary trade-off, nine adults with cystic fibrosis (eight women and one man) of median age 32 (range 22–46) years were treated with phages on a compassionate basis because their clinical course was complicated by multidrug-resistant or pan-drug-resistant <i>Pseudomonas</i> that was refractory to prior courses of standard antibiotics. The individuals received a nebulized cocktail or single-phage therapy without adverse events. Five to 18 days after phage therapy, sputum <i>Pseudomonas</i> decreased by a median of 10⁴ CFU ml⁻¹, or a mean difference of 10² CFU ml⁻¹ (<i>P</i> = 0.006, two-way analysis of variance with Dunnett’s multiple-comparisons test), without altering sputum microbiome, and an analysis of sputum <i>Pseudomonas</i> showed evidence of trade-offs that decreased antibiotic resistance or bacterial virulence. In addition, an improvement of 6% (median) and 8% (mean) predicted FEV₁ was observed 21–35 days after phage therapy (<i>P</i> = 0.004, Wilcoxon signed-rank <i>t</i>-test), which may reflect the combined effects of decreased bacterial sputum density and phage-driven trade-offs. These results show that a personalized, nebulized phage therapy trade-off strategy may affect clinical and microbiologic endpoints, which must be evaluated in larger clinical trials.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"13 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143884919","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":"Cerebrospinal fluid biomarker predicts dementia onset and progression in Alzheimer’s disease","authors":"","doi":"10.1038/s41591-025-03700-z","DOIUrl":"https://doi.org/10.1038/s41591-025-03700-z","url":null,"abstract":"Proteomics analyses of thousands of proteins in human cerebrospinal fluid reveal that the ratio of two proteins can be used to predict future dementia or cognitive resilience among people with Alzheimer’s disease brain pathology.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"80 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143880485","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}