Nature Medicine最新文献

{"title":"Author Correction: Single-cell guided prenatal derivation of primary fetal epithelial organoids from human amniotic and tracheal fluids","authors":"Mattia Francesco Maria Gerli, Giuseppe Calà, Max Arran Beesley, Beatrice Sina, Lucinda Tullie, Kylin Yunyan Sun, Francesco Panariello, Federica Michielin, Joseph R. Davidson, Francesca Maria Russo, Brendan C. Jones, Dani Do Hyang Lee, Savvas Savvidis, Theodoros Xenakis, Ian C. Simcock, Anna A. Straatman-Iwanowska, Robert A. Hirst, Anna L. David, Christopher O’Callaghan, Alessandro Olivo, Simon Eaton, Stavros P. Loukogeorgakis, Davide Cacchiarelli, Jan Deprest, Vivian S. W. Li, Giovanni Giuseppe Giobbe, Paolo De Coppi","doi":"10.1038/s41591-025-03504-1","DOIUrl":"10.1038/s41591-025-03504-1","url":null,"abstract":"","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"31 2","pages":"699-699"},"PeriodicalIF":58.7,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41591-025-03504-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142991022","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":"Neoadjuvant nivolumab and chemotherapy in early estrogen receptor-positive breast cancer: a randomized phase 3 trial","authors":"Sherene Loi, Roberto Salgado, Giuseppe Curigliano, Roberto Iván Romero Díaz, Suzette Delaloge, Carlos Ignacio Rojas García, Marleen Kok, Cristina Saura, Nadia Harbeck, Elizabeth A. Mittendorf, Denise A. Yardley, Alberto Suárez Zaizar, Facundo Rufino Caminos, Andrei Ungureanu, Joaquin G. Reinoso-Toledo, Valentina Guarneri, Daniel Egle, Felipe Ades, Misena Pacius, Aparna Chhibber, Rajalakshmi Chandra, Raheel Nathani, Thomas Spires, Jenny Qun Wu, Lajos Pusztai, Heather McArthur","doi":"10.1038/s41591-024-03414-8","DOIUrl":"10.1038/s41591-024-03414-8","url":null,"abstract":"Patients with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2−) primary breast cancer (BC) have low pathological complete response (pCR) rates with neoadjuvant chemotherapy. A subset of ER+/HER2− BC contains dense lymphocytic infiltration. We hypothesized that addition of an anti-programmed death 1 agent may increase pCR rates in this BC subtype. We conducted a randomized, multicenter, double-blind phase 3 trial to investigate the benefit of adding nivolumab to neoadjuvant chemotherapy in patients with newly diagnosed, high-risk, grade 3 or 2 (ER 1 to ≤10%) ER+/HER2− primary BC. In total, 510 patients were randomized to receive anthracycline and taxane-based chemotherapy with either intravenous nivolumab or placebo. The primary endpoint of pCR was significantly higher in the nivolumab arm compared with placebo (24.5% versus 13.8%; P = 0.0021), with greater benefit observed in patients with programmed death ligand 1-positive tumors (VENTANA SP142 ≥1%: 44.3% versus 20.2% respectively). There were no new safety signals identified. Of the five deaths that occurred in the nivolumab arm, two were related to study drug toxicity; no deaths occurred in the placebo arm. Adding nivolumab to neoadjuvant chemotherapy significantly increased pCR rates in high-risk, early-stage ER+/HER2− BC, particularly among patients with higher stromal tumor-infiltrating lymphocyte levels or programmed death ligand 1 expression, suggesting a new treatment paradigm that emphasizes the role of immunotherapy and T cell immunosurveillance in luminal disease. Clinical trials.gov identifier: NCT04109066 In the CheckMate 7FL trial, neoadjuvant nivolumab and chemotherapy in patients with newly diagnosed, high-risk estrogen receptor-positive breast cancer led to an increased pathological complete response rate compared with neoadjuvant chemotherapy alone, and this increase was associated with immune-related biomarkers and estrogen receptor expression.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"31 2","pages":"433-441"},"PeriodicalIF":58.7,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41591-024-03414-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142991065","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":"Our Future Health: a unique global resource for discovery and translational research","authors":"Michael B. Cook, Saskia C. Sanderson, John E. Deanfield, Fiona Reddington, Andrew Roddam, David J. Hunter, Raghib Ali","doi":"10.1038/s41591-024-03438-0","DOIUrl":"https://doi.org/10.1038/s41591-024-03438-0","url":null,"abstract":"Our Future Health has recruited more than 1 million participants in the UK, with biobanked bloods, making it the largest consented cohort of its type in the world.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"57 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142991023","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":"Mapping the effectiveness and risks of GLP-1 receptor agonists","authors":"Yan Xie, Taeyoung Choi, Ziyad Al-Aly","doi":"10.1038/s41591-024-03412-w","DOIUrl":"https://doi.org/10.1038/s41591-024-03412-w","url":null,"abstract":"<p>Glucagon-like peptide 1 receptor agonists (GLP-1RAs) are increasingly being used to treat diabetes and obesity. However, their effectiveness and risks have not yet been systematically evaluated in a comprehensive set of possible health outcomes. Here, we used the US Department of Veterans Affairs databases to build a cohort of people with diabetes who initiated GLP-1RA (<i>n</i> = 215,970) and compared them to those who initiated sulfonylureas (<i>n</i> = 159,465), dipeptidyl peptidase 4 (DPP4) inhibitors (<i>n</i> = 117,989) or sodium−glucose cotransporter-2 (SGLT2) inhibitors (<i>n</i> = 258,614), a control group composed of an equal proportion of individuals initiating sulfonylureas, DPP4 inhibitors and SGLT2 inhibitors (<i>n</i> = 536,068), and a control group of 1,203,097 individuals who continued use of non-GLP-1RA antihyperglycemics (usual care). We used a discovery approach to systematically map an atlas of the associations of GLP-1RA use versus each comparator with 175 health outcomes. Compared to usual care, GLP-1RA use was associated with a reduced risk of substance use and psychotic disorders, seizures, neurocognitive disorders (including Alzheimer’s disease and dementia), coagulation disorders, cardiometabolic disorders, infectious illnesses and several respiratory conditions. There was an increased risk of gastrointestinal disorders, hypotension, syncope, arthritic disorders, nephrolithiasis, interstitial nephritis and drug-induced pancreatitis associated with GLP-1RA use compared to usual care. The results provide insights into the benefits and risks of GLP-1RAs and may be useful for informing clinical care and guiding research agendas.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"46 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142991070","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 high-performance brain–computer interface for finger decoding and quadcopter game control in an individual with paralysis","authors":"Matthew S. Willsey,&nbsp;Nishal P. Shah,&nbsp;Donald T. Avansino,&nbsp;Nick V. Hahn,&nbsp;Ryan M. Jamiolkowski,&nbsp;Foram B. Kamdar,&nbsp;Leigh R. Hochberg,&nbsp;Francis R. Willett,&nbsp;Jaimie M. Henderson","doi":"10.1038/s41591-024-03341-8","DOIUrl":"10.1038/s41591-024-03341-8","url":null,"abstract":"People with paralysis express unmet needs for peer support, leisure activities and sporting activities. Many within the general population rely on social media and massively multiplayer video games to address these needs. We developed a high-performance, finger-based brain–computer-interface system allowing continuous control of three independent finger groups, of which the thumb can be controlled in two dimensions, yielding a total of four degrees of freedom. The system was tested in a human research participant with tetraplegia due to spinal cord injury over sequential trials requiring fingers to reach and hold on targets, with an average acquisition rate of 76 targets per minute and completion time of 1.58 ± 0.06 seconds—comparing favorably to prior animal studies despite a twofold increase in the decoded degrees of freedom. More importantly, finger positions were then used to control a virtual quadcopter—the number-one restorative priority for the participant—using a brain-to-finger-to-computer interface to allow dexterous navigation around fixed- and random-ringed obstacle courses. The participant expressed or demonstrated a sense of enablement, recreation and social connectedness that addresses many of the unmet needs of people with paralysis. A finger-based brain–computer interface was developed for a person with tetraplegia to allow him to fly a virtual quadcopter, an innovation that can lead to improved social connectedness, recreation and a sense of enablement.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"31 1","pages":"96-104"},"PeriodicalIF":58.7,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41591-024-03341-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142991069","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":"Prenatal blood tests can reveal maternal cancer","authors":"","doi":"10.1038/d41591-025-00006-y","DOIUrl":"https://doi.org/10.1038/d41591-025-00006-y","url":null,"abstract":"A study detected hidden cancers in almost half of all pregnant people who were referred for cancer screening following an abnormal or unreportable prenatal blood test result.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"31 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142991068","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":"Long-term safety of lentiviral or gammaretroviral gene-modified T cell therapies","authors":"Julie K. Jadlowsky, Elizabeth O. Hexner, Amy Marshall, Stephan A. Grupp, Noelle V. Frey, James L. Riley, Elizabeth Veloso, Holly McConville, Walter Rogal, Cory Czuczman, Wei-Ting Hwang, Yimei Li, Rachel M. Leskowitz, Olivia Farrelly, Jayashree Karar, Shannon Christensen, Julie Barber-Rotenberg, Avery Gaymon, Naomi Aronson, Wendy Bernstein, Jan Joseph Melenhorst, Aoife M. Roche, John K. Everett, Sonja A. Zolnoski, Alexander G. McFarland, Shantan Reddy, Angelina Petrichenko, Emma J. Cook, Carole Lee, Vanessa E. Gonzalez, Kathleen Alexander, Irina Kulikovskaya, Ángel Ramírez-Fernández, Janna C. Minehart, Marco Ruella, Saar I. Gill, Stephen J. Schuster, Adam D. Cohen, Alfred L. Garfall, Payal D. Shah, David L. Porter, Shannon L. Maude, Bruce L. Levine, Donald L. Siegel, Anne Chew, Stephen McKenna, Lester Lledo, Megan M. Davis, Gabriela Plesa, Friederike Herbst, Edward A. Stadtmauer, Pablo Tebas, Amanda DiNofia, Andrew Haas, Naomi B. Haas, Regina Myers, Donald M. O’Rourke, Jakub Svoboda, Janos L. Tanyi, Richard Aplenc, Jeffrey M. Jacobson, Andrew H. Ko, Roger B. Cohen, Carl H. June, Frederic D. Bushman, Joseph A. Fraietta","doi":"10.1038/s41591-024-03478-6","DOIUrl":"https://doi.org/10.1038/s41591-024-03478-6","url":null,"abstract":"<p>Long-term risks of gene therapy are not fully understood. In this study, we evaluated safety outcomes in 783 patients over more than 2,200 total patient-years of observation from 38 T cell therapy trials. The trials employed integrating gammaretroviral or lentiviral vectors to deliver engineered receptors to target HIV-1 infection or cancer. Eighteen patients (2.3%) developed secondary malignancies after treatment, with a median onset of 1.94 years (range: 51 d to 14 years). Where possible, incident tumor samples were analyzed for vector copy number, revealing no evidence of high-level marking or other indications of insertional mutagenesis. One T cell lymphoma was detected, but malignant T cells were not marked by vector integration. Analysis of vector integration sites in 176 patients revealed no pathological insertions linked to secondary malignancies, although, in some cases, integration in or near specific genes, including tumor suppressor genes, was associated with modest clonal expansion and sustained T cell persistence. These findings highlight the safety of engineered T cell therapies.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"17 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142989694","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 expanding repertoire of brain–computer interfaces","authors":"Nick F. Ramsey,&nbsp;Mariska J. Vansteensel","doi":"10.1038/s41591-024-03440-6","DOIUrl":"10.1038/s41591-024-03440-6","url":null,"abstract":"Brain–computer interfaces are expanding from functional to recreational applications, as evidenced by a study in which a person with tetraplegia controlled a recreational virtual drone, but their clinical utility is still uncertain.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"31 1","pages":"31-32"},"PeriodicalIF":58.7,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142991067","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":"Artificial intelligence in drug development","authors":"Kang Zhang,&nbsp;Xin Yang,&nbsp;Yifei Wang,&nbsp;Yunfang Yu,&nbsp;Niu Huang,&nbsp;Gen Li,&nbsp;Xiaokun Li,&nbsp;Joseph C. Wu,&nbsp;Shengyong Yang","doi":"10.1038/s41591-024-03434-4","DOIUrl":"10.1038/s41591-024-03434-4","url":null,"abstract":"Drug development is a complex and time-consuming endeavor that traditionally relies on the experience of drug developers and trial-and-error experimentation. The advent of artificial intelligence (AI) technologies, particularly emerging large language models and generative AI, is poised to redefine this paradigm. The integration of AI-driven methodologies into the drug development pipeline has already heralded subtle yet meaningful enhancements in both the efficiency and effectiveness of this process. Here we present an overview of recent advancements in AI applications across the entire drug development workflow, encompassing the identification of disease targets, drug discovery, preclinical and clinical studies, and post-market surveillance. Lastly, we critically examine the prevailing challenges to highlight promising future research directions in AI-augmented drug development. This Review explores the state-of-the-art applications of artificial intelligence in small-molecule drug development, from target identification and drug synthesis up to clinical trial design and conduct.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"31 1","pages":"45-59"},"PeriodicalIF":58.7,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142990098","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":"How patient advocates influence health policy","authors":"Elizabeth Kasimu Mutunga","doi":"10.1038/s41591-024-03444-2","DOIUrl":"10.1038/s41591-024-03444-2","url":null,"abstract":"Scientists can learn the power of storytelling and coalition-building from patient advocates.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"31 1","pages":"18-18"},"PeriodicalIF":58.7,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142987485","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}