Nature Medicine最新文献

{"title":"Health effects associated with consumption of processed meat, sugar-sweetened beverages and trans fatty acids: a Burden of Proof study","authors":"Demewoz Haile, Kassandra L. Harding, Susan A. McLaughlin, Charlie Ashbaugh, Vanessa Garcia, Nora M. Gilbertson, Hewan Kifle, Marie C. Parent, Reed J. D. Sorensen, Simon I. Hay, Aleksandr Y. Aravkin, Peng Zheng, Jeffrey D. Stanaway, Christopher J. L. Murray, Michael Brauer","doi":"10.1038/s41591-025-03775-8","DOIUrl":"https://doi.org/10.1038/s41591-025-03775-8","url":null,"abstract":"<p>Previous research suggests detrimental health effects associated with consuming processed foods, including processed meats, sugar-sweetened beverages (SSBs) and trans fatty acids (TFAs). However, systematic characterization of the dose–response relationships between these foods and health outcomes is limited. Here, using Burden of Proof meta-regression methods, we evaluated the associations between processed meat, SSBs and TFAs and three chronic diseases: type 2 diabetes, ischemic heart disease (IHD) and colorectal cancer. We conservatively estimated that—relative to zero consumption—consuming processed meat (at 0.6–57 g d⁻¹) was associated with at least an 11% average increase in type 2 diabetes risk and a 7% (at 0.78–55 g d⁻¹) increase in colorectal cancer risk. SSB intake (at 1.5–390 g d⁻¹) was associated with at least an 8% average increase in type 2 diabetes risk and a 2% (at 0–365 g d⁻¹) increase in IHD risk. TFA consumption (at 0.25–2.56% of daily energy intake) was associated with at least a 3% average increase in IHD risk. These associations each received two-star ratings reflecting weak relationships or inconsistent input evidence, highlighting both the need for further research and—given the high burden of these chronic diseases—the merit of continuing to recommend limiting consumption of these foods.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"25 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144515596","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":"International partnership for governing generative artificial intelligence models in medicine","authors":"Jasmine Chiat Ling Ong, Yilin Ning, Gary S. Collins, Danielle S. Bitterman, Ashley N. Beecy, Robert T. Chang, Alastair K. Denniston, Oscar Freyer, Stephen Gilbert, Anne de Hond, Artuur M. Leeuwenberg, Liang Zhao, John C. W. Lim, Mingxuan Liu, Xiaoxuan Liu, Christopher A. Longhurst, Yian Ma, Yue Qiu, Rupa Sarkar, Bin Sheng, Kuldev Singh, Iris Siu Kwan Tan, Yih Chung Tham, Arun J. Thirunavukarasu, Daniel Shu Wei Ting, Silke Vogel, Rui Zhang, Jianfei Zhao, Wendy W. Chapman, Nigam H. Shah, Karel G. M. Moons, Tien Yin Wong, Nan Liu","doi":"10.1038/s41591-025-03787-4","DOIUrl":"https://doi.org/10.1038/s41591-025-03787-4","url":null,"abstract":"<p>Generative artificial intelligence (GenAI) models, such as generative adversarial networks (GANs) and transformer-based large language models (LLMs), are developing at an accelerated pace and positioned to be integrated into clinical workflows and healthcare systems across the world. However, this rapid rise of GenAI in medicine and healthcare presents not just unprecedented opportunities, but also systemic risks in the integration of this new technology and critical vulnerabilities in terms of safety, governance and regulatory oversight. GenAI and LLMs are non-deterministic in nature, possess broad generalist functionalities, and display evolving capabilities¹. These characteristics challenge conventional regulatory frameworks designed for deterministic, task-specific artificial intelligence (AI) models, such as those for Software as a Medical Device (SaMD).</p><p>Some of the fundamental risks associated with GenAI and LLMs applications in healthcare are clear but yet to be fully addressed by current regulatory framework (‘known unknowns’), whereas other risks and challenges have not yet even surfaced (‘unknown unknowns’). Known unknowns include a lack of transparency in training data (including the possible use of synthetic data for training²), susceptibility to bias, hallucination of incorrect medical content, and potential misuse in high-stakes clinical settings¹ (Box 1).</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"27 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144515850","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":"Exercise therapy and self-management support for individuals with multimorbidity: a randomized and controlled trial","authors":"Søren T. Skou, Mette Nyberg, Mette Dideriksen, Hanne Rasmussen, Jan Arnholtz Overgaard, Christine Bodilsen, Anne Merete B. Soja, Amir Pasha Attarzadeh, Manuel J. Bieder, Nadia P. Dridi, Andreas Heltberg, Peter H. Gæde, Johan L. Reventlow, Sidse Arnfred, Uffe Bodtger, Jan C. Brønd, Lau C. Thygesen, Sanne P. Møller, Madalina Jäger, Alessio Bricca","doi":"10.1038/s41591-025-03779-4","DOIUrl":"https://doi.org/10.1038/s41591-025-03779-4","url":null,"abstract":"<p>Despite increasing individual and societal burden, evidence for effective management strategies of multimorbidity is missing. Exercise therapy and self-management support are promising interventions, but their effect has not been evaluated. We hypothesized that exercise therapy and self-management support were superior to usual care alone in improving health-related quality of life (HRQoL) in individuals with multimorbidity. In this pragmatic multicenter, assessor-blinded randomized controlled trial (MOBILIZE), we enrolled 228 adult patients with two or more selected long-term conditions that limited their daily activities, but who were able to walk at least 3 meters without assistance, and who did not have unstable health conditions, life expectancy less than 12 months, or selected psychiatric conditions. Patients were randomized (1:1) to a 12 week personalized exercise therapy and self-management support program in addition to usual care or usual care alone. The primary outcome was HRQoL (using the EQ-5D-5L (European Quality of Life 5-dimensions 5-level version), ranging from −0.758 to 1, with higher scores being better) at 12 months, while secondary outcomes included functional performance (6 minute walk test and the 30 second chair-stand test), serious adverse events (SAEs), physical activity level (steps per day and minutes per day of at least light intensity measured with accelerometers), disease burden (Bayliss burden of illness measure), depression (Personal Health Questionnaire Depression Scale-8), anxiety (General Anxiety Disorder-7), self-efficacy (Self-Efficacy for Managing Chronic Disease scale), disability (12 item WHO Disability Assessment Schedule) and self-rated health (EQ-VAS (EuroQoL Visual Analog Scale)). In total, 197 of 228 participants (86%) completed the 12 month follow-up. On intention-to-treat analysis the exercise therapy and self-management support program had a statistically significantly greater effect on HRQoL than usual care alone (0.050 versus −0.014; adjusted mean difference, 0.064 points; 95% CI: 0.014–0.115). There were 36 and 48 SAEs in the exercise therapy and self-management group and usual care group, respectively (<i>P</i> = 0.388). Among the other secondary outcomes, only self-rated health was statistically significantly different between the groups (adjusted mean difference, 6.9 points; 95% CI: 1.8–12.1), in favor of the intervention group. In conclusion, this trial suggests that personalized exercise therapy and self-management support are more effective than usual care alone in improving health-related quality of life at 12 months in adults with multimorbidity, without compromising safety. The clinical relevance of the results remains unclear. ClinicalTrials.gov registration: NCT04645732.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"47 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144515851","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":"Updating the evidence on ultra-processed foods and health","authors":"Wanglong Gou, Ju-Sheng Zheng","doi":"10.1038/s41591-025-03782-9","DOIUrl":"https://doi.org/10.1038/s41591-025-03782-9","url":null,"abstract":"A new analysis supports dietary guidelines to reduce the consumption of processed meat, sugar-sweetened beverages and trans-fatty acids — highlighting the need for a collaborative, meticulous health assessment framework for ultra-processed foods.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"40 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144515826","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":"AAV mini-dystrophin gene therapy for Duchenne muscular dystrophy: a phase 1b trial","authors":"Russell J. Butterfield, Perry B. Shieh, Huihua Li, Michael Binks, Tara G. McDonnell, Kelly A. Ryan, Marielle Delnomdedieu, Beth A. Belluscio, Srividya Neelakantan, Daniel I. Levy, Pamela F. Schwartz, Edward C. Smith","doi":"10.1038/s41591-025-03750-3","DOIUrl":"https://doi.org/10.1038/s41591-025-03750-3","url":null,"abstract":"<p>Gene therapy represents a promising approach for Duchenne muscular dystrophy (DMD), a rare X-linked genetic muscle disease. Fordadistrogene movaparvovec (PF-06939926) is an adeno-associated virus serotype 9 gene therapy containing a miniaturized dystrophin being developed for DMD, which aims to restore functional protein to muscle. We present 1-year data from ambulatory and nonambulatory participants in a phase 1b, multicenter, single-arm, open-label trial. Pediatric ambulatory male participants with a genetic DMD diagnosis and receiving stable glucocorticoids received a single intravenous low-dose (<i>n</i> = 3) or high-dose (<i>n</i> = 16) fordadistrogene movaparvovec. The primary endpoint was safety and tolerability at 1 year after dosing. In the ambulatory group, mean ± s.d. age at dosing was 8.6 ± 1.6 years. The most common treatment-emergent adverse events in the ambulatory group were vomiting (<i>n</i> = 15), nausea (<i>n</i> = 10), thrombocytopenia (<i>n</i> = 9), pyrexia (<i>n</i> = 9), decreased appetite (<i>n</i> = 8), fatigue (<i>n</i> = 7) and headache (<i>n</i> = 7). Three treatment-related serious adverse events occurred after dosing (dehydration, acute kidney injury, thrombocytopenia; all resolved within 15 days). In a small nonambulatory group (<i>n</i> = 3), mean ± s.d. age at dosing was 15.1 ± 1.0 years. The most common treatment-emergent adverse events were nausea (<i>n</i> = 3), vomiting (<i>n</i> = 3) and headache (<i>n</i> = 3); two severe treatment-related adverse events (hemolytic uremic syndrome and fatal cardiogenic shock) were observed. In the high-dose ambulatory group, the secondary endpoint of mini-dystrophin quantification showed robust expression. Mean (95% confidence interval) percent of mini-dystrophin-positive fibers for baseline, 2 months and 1 year were 0.1% (0.1–0.2), 20.3% (12.2–29.3) and 34.8% (21.1–49.8), respectively. At the 1-year time point of primary completion, fordadistrogene movaparvovec demonstrated an acceptable safety profile in the ambulatory population. Larger trials are needed to assess the efficacy of the gene therapy in DMD. ClinicalTrials.gov registration no. NCT03362502.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"246 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144500424","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":"Stem cell therapies for diabetes","authors":"Juin Ting Chen, Nidheesh Dadheech, Eddie Han Pin Tan, Natasha Hui Jin Ng, Mickey Boon Chai Koh, James Shapiro, Adrian Kee Keong Teo","doi":"10.1038/s41591-025-03767-8","DOIUrl":"https://doi.org/10.1038/s41591-025-03767-8","url":null,"abstract":"<p>Diabetes has long-term, potentially severe implications for healthspan and lifespan and imposes an immense burden on global healthcare, the economy and society. Although a repertoire of medications is available to treat diabetes, these do not properly address the eventual lack of functional pancreatic beta cells that are needed to secrete insulin and maintain glucose homeostasis. Human islet cell transplantation from deceased donors is an established treatment for insulin-requiring type 1 diabetes, but demand outstrips supply. Substantial scientific and clinical progress has occurred in the last decade toward deriving pancreatic islet-like cells from human pluripotent stem cells, suggesting a potentially limitless solution to the supply issue and a new era in cell therapy for diabetes. Here, we critically review the scientific advances, the clinical trials and the various regulatory considerations that will need to be overcome for human stem cell-derived pancreatic islet-like cells to become the next cell therapy breakthrough for diabetes treatment.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"22 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144500425","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":"Chikungunya virus burden and implications for vaccination programs","authors":"","doi":"10.1038/s41591-025-03812-6","DOIUrl":"https://doi.org/10.1038/s41591-025-03812-6","url":null,"abstract":"Widely spread around the globe, chikungunya virus (CHIKV) is a mosquito-borne virus that can cause severe acute disease, sometimes followed by debilitating chronic joint pain. This study provides estimates of the burden of CHIKV infection on public health for 180 countries and evaluates the potential benefits of vaccination campaigns.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"26 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144500423","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 reference model of circulating hematopoietic stem cells across the lifespan with applications to diagnostics","authors":"N. Furer, N. Rappoport, O. Milman, S. Tavor, A. Lifshitz, A. Bercovich, O. Ben-Kiki, A. Danin, M. Kedmi, Z. Shipony, D. Lipson, E. Meiri, G. Yanai, S. Shapira, N. Arber, S. Berdichevsky, J. Tyner, S. Joshi, D. Landau, S. Ganesan, N. Dusaj, P. Chamely, N. Kaushansky, N. Chapal-Ilani, R. Shamir, A. Tanay, L. Shlush","doi":"10.1038/s41591-025-03716-5","DOIUrl":"https://doi.org/10.1038/s41591-025-03716-5","url":null,"abstract":"<p>With aging, deviation of human blood counts from their normal range accompanies the transition from health to disease. Hematopoietic stem and progenitor cells (HSPCs) deliver life-long multi-lineage output, but their variation across healthy humans with aging, and their diagnostic utility, haven’t been characterized in depth thus far. To address this, we introduced an HSPC reference model using single-cell RNA profiling of circulating CD34⁺ HSPCs from 148 healthy age- and sex-diverse individuals. We characterized physiological circulating HSPC composition, showed that age-related myeloid bias is predominant in older men and defined age-related transcriptional signatures in lymphoid progenitors. We further demonstrated the potential of this resource to facilitate the diagnosis of myelodysplastic syndrome (MDS) from peripheral blood without bone marrow sampling, defining classes of patients with MDS and abnormal lymphocyte, basophil or granulocyte progenitor frequencies. Our resource provides insights into HSPC reference ranges across the lifespan and has the potential to facilitate the clinical applications of single-cell genomics in hematology.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"57 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144500427","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":"Ending the taboo on periods and period problems","authors":"Hilary O. D. Critchley, Ian Roberts, Ally Murji, Michelle Lavin, Lesley Regan, Michael K. Georgieff, Malcolm G. Munro","doi":"10.1038/s41591-025-03778-5","DOIUrl":"https://doi.org/10.1038/s41591-025-03778-5","url":null,"abstract":"<p>Heavy menstrual bleeding (HMB), reflecting excessive menstrual volume, affects quality of life in up to half of all menstruating girls and women^2,3. The blood loss associated with HMB may induce iron deficiency that, when severe, results in iron deficiency anemia (IDA). Iron deficiency, with or without IDA, can adversely affect physical, cognitive and even cardiac function. In pregnancy, anemia can have an adverse effect on both the mother and her fetus, with increased risks of antepartum hemorrhage, prematurity, stillbirth, neonatal death, post-partum hemorrhage (PPH), and maternal mortality. Furthermore, peri-conceptional and prenatal iron deficiency is linked to impaired fetal neurodevelopment and adverse neuro-behavioral effects for the child that persist into adulthood⁴.</p><p>Some 30% of the world’s non-pregnant women are anemic, increasing to over 40% in South Asia, the Eastern Mediterranean and sub-Saharan Africa (WHO Anaemia Action Alliance), with iron deficiency the most common contributory factor. During ‘normal’ periods, approximately 1 mg of iron is lost monthly, but in women with HMB, iron loss may be 5–6 times higher. As a result, independent of culture or geographic location, HMB is the most common cause of iron deficiency and IDA (<u>&gt;</u>50%) in nonpregnant reproductive-aged girls and women. The extent of iron loss associated with HMB can make it impossible for dietary replacement (even with supplementation) before the next period starts, thus establishing a progressive deterioration of iron status.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"18 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144500422","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 hidden human cost of defunded LGBTQIA+ health research","authors":"David J. Kinitz, Micah E. Lubensky, Nguyen K. Tran, Annesa Flentje, Mitchell R. Lunn","doi":"10.1038/s41591-025-03794-5","DOIUrl":"https://doi.org/10.1038/s41591-025-03794-5","url":null,"abstract":"<p>In January 2025, the new US federal administration introduced policies targeting sexual and gender minority (LGBTQIA+) people, human immunodeficiency virus, climate change and vaccinations. Half of the US National Institutes of Health grants terminated since then — over 300 grants totaling more than US $800 million — related to LGBTQIA+ health research¹. Defunding LGBTQIA+ health research in the USA does not just stop essential research and undermine public health but also destabilizes the lives and livelihoods of people who are already navigating systemic adversity^2,3.</p><p>As LGBTQIA+-identified researchers ourselves, we experienced grant terminations and their consequences firsthand. We can only describe our experiences and those of our colleagues as devastating, destabilizing and livelihood destroying. These grant terminations are extremely distressing for LGBTQIA+ researchers and will lead to a loss of talent in both LGBTQIA+ health and broader scientific communities.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"7 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144500426","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}