Nature MedicinePub Date : 2025-01-28DOI: 10.1038/s41591-024-03473-x
Phaedra Henley, Anselme Shyaka
{"title":"The Marburg virus outbreak is a critical moment for Rwanda’s one health policy","authors":"Phaedra Henley, Anselme Shyaka","doi":"10.1038/s41591-024-03473-x","DOIUrl":"https://doi.org/10.1038/s41591-024-03473-x","url":null,"abstract":"<p>The Marburg virus disease (MVD) outbreak in Rwanda underscores the serious threat posed by zoonotic diseases. These pathogens, which are transmitted between animals and humans through direct contact or environmental factors, result in an estimated 2.4 billion infections and 2.2 million deaths annually<sup>1</sup>. MVD, which originates from bats, can spread rapidly to humans, with a fatality rate as high as 88%<sup>2</sup>. As of 10 October 2024, Rwanda has 58 confirmed cases of MVD, including 15 deaths<sup>3</sup>. This crisis highlights the urgent need for Rwanda to fully operationalize its One Health policy to address the interconnected risks of human, animal and environmental health.</p><p>Outbreaks of MVD occur when humans are in contact with infected animals, including green monkeys, pigs and Egyptian fruit bats, which are known carriers of the virus<sup>2,4</sup>. After zoonotic spillover (when the virus transmits from animals to humans), it can spread between humans through bodily fluids or contaminated surfaces such as bedding<sup>2</sup>. While isolating cases and implementing public health measures are crucial, preventing future outbreaks requires an integrated One Health approach to mitigate the risks of MVD and other zoonotic diseases.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"35 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143050424","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}
Nature MedicinePub Date : 2025-01-28DOI: 10.1038/s41591-024-03468-8
Olivia M. Altonji, Courtney M. Peterson
{"title":"Intermittent fasting is good for losing (some) weight","authors":"Olivia M. Altonji, Courtney M. Peterson","doi":"10.1038/s41591-024-03468-8","DOIUrl":"https://doi.org/10.1038/s41591-024-03468-8","url":null,"abstract":"A large, randomized controlled trial comparing three time-restricted eating (TRE) windows found that time-restricted eating at any time of day is a promising strategy for losing weight — but does not reduce visceral adipose tissue.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"2 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143050131","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}
Nature MedicinePub Date : 2025-01-27DOI: 10.1038/s41591-024-03452-2
Pierre Masselot, Malcolm N. Mistry, Shilpa Rao, Veronika Huber, Ana Monteiro, Evangelia Samoli, Massimo Stafoggia, Francesca de’Donato, David Garcia-Leon, Juan-Carlos Ciscar, Luc Feyen, Alexandra Schneider, Klea Katsouyanni, Ana Maria Vicedo-Cabrera, Kristin Aunan, Antonio Gasparrini
{"title":"Estimating future heat-related and cold-related mortality under climate change, demographic and adaptation scenarios in 854 European cities","authors":"Pierre Masselot, Malcolm N. Mistry, Shilpa Rao, Veronika Huber, Ana Monteiro, Evangelia Samoli, Massimo Stafoggia, Francesca de’Donato, David Garcia-Leon, Juan-Carlos Ciscar, Luc Feyen, Alexandra Schneider, Klea Katsouyanni, Ana Maria Vicedo-Cabrera, Kristin Aunan, Antonio Gasparrini","doi":"10.1038/s41591-024-03452-2","DOIUrl":"https://doi.org/10.1038/s41591-024-03452-2","url":null,"abstract":"<p>Previous health impact assessments of temperature-related mortality in Europe indicated that the mortality burden attributable to cold is much larger than for heat. Questions remain as to whether climate change can result in a net decrease in temperature-related mortality. In this study, we estimated how climate change could affect future heat-related and cold-related mortality in 854 European urban areas, under several climate, demographic and adaptation scenarios. We showed that, with no adaptation to heat, the increase in heat-related deaths consistently exceeds any decrease in cold-related deaths across all considered scenarios in Europe. Under the lowest mitigation and adaptation scenario (SSP3-7.0), we estimate a net death burden due to climate change increasing by 49.9% and cumulating 2,345,410 (95% confidence interval = 327,603 to 4,775,853) climate change-related deaths between 2015 and 2099. This net effect would remain positive even under high adaptation scenarios, whereby a risk attenuation of 50% is still insufficient to reverse the trend under SSP3-7.0. Regional differences suggest a slight net decrease of death rates in Northern European countries but high vulnerability of the Mediterranean region and Eastern Europe areas. Unless strong mitigation and adaptation measures are implemented, most European cities should experience an increase of their temperature-related mortality burden.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"49 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143050425","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}
Nature MedicinePub Date : 2025-01-27DOI: 10.1038/s41591-024-03481-x
Sarah Kohn, Alon Diament, Anastasia Godneva, Raja Dhir, Adina Weinberger, Yotam Reisner, Hagai Rossman, Eran Segal
{"title":"Phenome-wide associations of sleep characteristics in the Human Phenotype Project","authors":"Sarah Kohn, Alon Diament, Anastasia Godneva, Raja Dhir, Adina Weinberger, Yotam Reisner, Hagai Rossman, Eran Segal","doi":"10.1038/s41591-024-03481-x","DOIUrl":"https://doi.org/10.1038/s41591-024-03481-x","url":null,"abstract":"<p>Sleep tests commonly diagnose sleep disorders, but the diverse sleep-related biomarkers recorded by such tests can also provide broader health insights. In this study, we leveraged the uniquely comprehensive data from the Human Phenotype Project cohort, which includes 448 sleep characteristics collected from 16,812 nights of home sleep apnea test monitoring in 6,366 adults (3,043 male and 3,323 female participants), to study associations between sleep traits and body characteristics across 16 body systems. In this analysis, which identified thousands of significant associations, visceral adipose tissue (VAT) was the body characteristic that was most strongly correlated with the peripheral apnea–hypopnea index, as adjusted by sex, age and body mass index (BMI). Moreover, using sleep characteristics, we could predict over 15% of body characteristics, spanning 15 of the 16 body systems, in a held-out set of individuals. Notably, sleep characteristics contributed more to the prediction of certain insulin resistance, blood lipids (such as triglycerides) and cardiovascular measurements than to the characteristics of other body systems. This contribution was independent of VAT, as sleep characteristics outperformed age, BMI and VAT as predictors for these measurements in both male and female participants. Gut microbiome-related pathways and diet (especially for female participants) were notably predictive of clinical obstructive sleep apnea symptoms, particularly sleepiness, surpassing the prediction power of age, BMI and VAT on these symptoms. Together, lifestyle factors contributed to the prediction of over 50% of the sleep characteristics. This work lays the groundwork for exploring the associations of sleep traits with body characteristics and developing predictive models based on sleep monitoring.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"4 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143044091","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}
Nature MedicinePub Date : 2025-01-27DOI: 10.1038/s41591-024-03480-y
Ali Aminian, Abdullah Aljabri, Sarah Wang, James Bena, Daniela S. Allende, Hana Rosen, Eileen Arnold, Rickesha Wilson, Alex Milinovich, Rohit Loomba, Arun J. Sanyal, Naim Alkhouri, Jamile Wakim-Fleming, Sobia N. Laique, Srinivasan Dasarathy, Arthur J. McCullough, Steven E. Nissen
{"title":"Long-term liver outcomes after metabolic surgery in compensated cirrhosis due to metabolic dysfunction-associated steatohepatitis","authors":"Ali Aminian, Abdullah Aljabri, Sarah Wang, James Bena, Daniela S. Allende, Hana Rosen, Eileen Arnold, Rickesha Wilson, Alex Milinovich, Rohit Loomba, Arun J. Sanyal, Naim Alkhouri, Jamile Wakim-Fleming, Sobia N. Laique, Srinivasan Dasarathy, Arthur J. McCullough, Steven E. Nissen","doi":"10.1038/s41591-024-03480-y","DOIUrl":"https://doi.org/10.1038/s41591-024-03480-y","url":null,"abstract":"<p>No therapy has been shown to reduce the risk of major adverse liver outcomes (MALO) in patients with cirrhosis due to metabolic dysfunction-associated steatohepatitis (MASH). The Surgical Procedures Eliminate Compensated Cirrhosis In Advancing Long-term (SPECCIAL) observational study compared the effects of metabolic surgery and nonsurgical treatment in patients with obesity and compensated histologically proven MASH-related cirrhosis. Using a doubly robust estimation methodology to balance key baseline characteristics between groups, the time-to-incident MALO was compared between 62 patients (68% female) who underwent metabolic surgery and 106 nonsurgical controls (71% female), with a mean follow-up of 10.0 ± 4.5 years. The 15 year cumulative incidence of MALO was 20.9% (95% confidence interval (CI), 2.5–35.9%) in the surgical group compared with 46.4% (95% CI, 25.6–61.3%) in the nonsurgical group, with an adjusted hazard ratio of 0.28 (95% CI, 0.12–0.64), <i>P</i> = 0.003. The 15 year cumulative incidence of decompensated cirrhosis was 15.6% (95% CI, 0–31.3%) in the surgical group compared with 30.7% (95% CI, 12.9–44.8%) in the nonsurgical group, with an adjusted hazard ratio of 0.20 (95% CI, 0.06–0.68), <i>P</i> = 0.01. Among patients with compensated MASH-related cirrhosis and obesity, metabolic surgery, compared with nonsurgical management, was associated with a significantly lower risk of incident MALO. In the absence of approved medical therapies for compensated MASH-related cirrhosis, metabolic surgery may represent a safe and effective therapeutic option to influence the trajectory of cirrhosis.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"174 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143044090","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}
Nature MedicinePub Date : 2025-01-25DOI: 10.1038/s41591-024-03443-3
Scott Kopetz, Takayuki Yoshino, Eric Van Cutsem, Cathy Eng, Tae Won Kim, Harpreet Singh Wasan, Jayesh Desai, Fortunato Ciardiello, Rona Yaeger, Timothy S. Maughan, Elena Beyzarov, Xiaoxi Zhang, Graham Ferrier, Xiaosong Zhang, Josep Tabernero
{"title":"Encorafenib, cetuximab and chemotherapy in BRAF-mutant colorectal cancer: a randomized phase 3 trial","authors":"Scott Kopetz, Takayuki Yoshino, Eric Van Cutsem, Cathy Eng, Tae Won Kim, Harpreet Singh Wasan, Jayesh Desai, Fortunato Ciardiello, Rona Yaeger, Timothy S. Maughan, Elena Beyzarov, Xiaoxi Zhang, Graham Ferrier, Xiaosong Zhang, Josep Tabernero","doi":"10.1038/s41591-024-03443-3","DOIUrl":"https://doi.org/10.1038/s41591-024-03443-3","url":null,"abstract":"<p>Encorafenib + cetuximab (EC) is approved for previously treated BRAF V600E-mutant metastatic colorectal cancer (mCRC) based on the BEACON phase 3 study. Historically, first-line treatment of BRAF V600E-mutant mCRC with chemotherapy regimens has had limited efficacy. The phase 3 BREAKWATER study investigated EC+mFOLFOX6 versus standard of care (SOC) in patients with previously untreated BRAF V600E mCRC. The dual primary endpoint of progression-free survival is event driven; data were not mature at data cutoff. BREAKWATER met the other dual primary endpoint of objective response rate, demonstrating significant and clinically relevant improvement in objective response rate (EC+mFOLFOX6: 60.9%; SOC: 40.0%; odds ratio, 2.443; 95% confidence interval (CI): 1.403–4.253; 99.8% CI: 1.019–5.855; one-sided <i>P</i> = 0.0008). Median duration of response was 13.9 versus 11.1 months. At this first interim analysis of overall survival, the hazard ratio was 0.47 (95% CI: 0.318–0.691; repeated CI: 0.166–1.322). Serious adverse event rates were 37.7% versus 34.6%. The safety profiles were consistent with those known for each agent. BREAKWATER demonstrated a significantly improved response rate that was durable for first-line EC+mFOLFOX6 versus SOC in patients with BRAF V600E mCRC. ClinicalTrials.gov identifier: NCT04607421.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"10 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143035159","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}
Nature MedicinePub Date : 2025-01-24DOI: 10.1038/s41591-024-03486-6
Christian Kurzeder, Bich Doan Nguyen-Sträuli, Ilona Krol, Alexander Ring, Francesc Castro-Giner, Manuel Nüesch, Simran Asawa, Yu Wei Zhang, Selina Budinjas, Ana Gvozdenovic, Maren Vogel, Angela Kohler, Cvetka Grašič Kuhar, Fabienne D. Schwab, Viola Heinzelmann-Schwarz, Walter Paul Weber, Christoph Rochlitz, Denise Vorburger, Heike Frauchiger-Heuer, Isabell Witzel, Andreas Wicki, Gabriela M. Kuster, Marcus Vetter, Nicola Aceto
{"title":"Digoxin for reduction of circulating tumor cell cluster size in metastatic breast cancer: a proof-of-concept trial","authors":"Christian Kurzeder, Bich Doan Nguyen-Sträuli, Ilona Krol, Alexander Ring, Francesc Castro-Giner, Manuel Nüesch, Simran Asawa, Yu Wei Zhang, Selina Budinjas, Ana Gvozdenovic, Maren Vogel, Angela Kohler, Cvetka Grašič Kuhar, Fabienne D. Schwab, Viola Heinzelmann-Schwarz, Walter Paul Weber, Christoph Rochlitz, Denise Vorburger, Heike Frauchiger-Heuer, Isabell Witzel, Andreas Wicki, Gabriela M. Kuster, Marcus Vetter, Nicola Aceto","doi":"10.1038/s41591-024-03486-6","DOIUrl":"https://doi.org/10.1038/s41591-024-03486-6","url":null,"abstract":"<p>The presence of circulating tumor cell (CTC) clusters is associated with disease progression and reduced survival in a variety of cancer types. In breast cancer, preclinical studies showed that inhibitors of the Na<sup>+</sup>/K<sup>+</sup> ATPase suppress CTC clusters and block metastasis. Here we conducted a prospective, open-label, proof-of-concept study in women with metastatic breast cancer, where the primary objective was to determine whether treatment with the Na<sup>+</sup>/K<sup>+</sup> ATPase inhibitor digoxin could reduce mean CTC cluster size. An analysis of nine patients treated daily with a maintenance digoxin dose (0.7–1.4 ng ml<sup>−1</sup> serum level) revealed a mean cluster size reduction of −2.2 cells per cluster upon treatment (<i>P</i> = 0.003), meeting the primary endpoint of the study. Mechanistically, transcriptome profiling of CTCs highlighted downregulation of cell–cell adhesion and cell-cycle-related genes upon treatment with digoxin, in line with its cluster-dissolution activity. No treatment-related adverse events occurred. Thus, our data provide a first-in-human proof of principle that digoxin treatment leads to a partial CTC cluster dissolution, encouraging larger follow-up studies with refined Na<sup>+</sup>/K<sup>+</sup> ATPase inhibitors and that include clinical outcome endpoints. ClinicalTrials.gov identifier: NCT03928210.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"2 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143026968","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}
Nature MedicinePub Date : 2025-01-24DOI: 10.1038/s41591-024-03430-8
Caitlin Bond, Olivia J. Bednarski, Dibyadyuti Datta, Ruth Namazzi, Robert O. Opoka, Giselle Lima-Cooper, Anthony Batte, Keerthi Udumula, Deepali Balasubramani, Marilyn Vasquez, Ana Rodriguez, Claire Liepmann, Paul Bangirana, Marco Abreu, Tae-Hwi Schwantes-An, Yi Zhao, Tarek M. El-Achkar, Nathan W. Schmidt, Chandy C. John, Andrea L. Conroy
{"title":"Elevated uric acid levels, mortality and cognitive impairment in children with severe malaria","authors":"Caitlin Bond, Olivia J. Bednarski, Dibyadyuti Datta, Ruth Namazzi, Robert O. Opoka, Giselle Lima-Cooper, Anthony Batte, Keerthi Udumula, Deepali Balasubramani, Marilyn Vasquez, Ana Rodriguez, Claire Liepmann, Paul Bangirana, Marco Abreu, Tae-Hwi Schwantes-An, Yi Zhao, Tarek M. El-Achkar, Nathan W. Schmidt, Chandy C. John, Andrea L. Conroy","doi":"10.1038/s41591-024-03430-8","DOIUrl":"https://doi.org/10.1038/s41591-024-03430-8","url":null,"abstract":"<p>We investigated the role of uric acid in the pathogenesis of severe malaria (SM) in two independent cohorts of children with SM. Hyperuricemia (blood uric acid ≥ 7 mg dl<sup>−1</sup>) was present in 25% of children with SM and was associated with increased in-hospital mortality and postdischarge mortality in both cohorts. Increased blood uric acid levels were also associated with worse scores in overall cognition in children with SM < 5 years old in both cohorts. Hemolysis of infected red blood cells and impaired renal excretion of uric acid were the primary drivers of hyperuricemia in SM. Hyperuricemia was associated with multiple complications of SM, including acute kidney injury, acidosis, impaired perfusion, coma and intestinal injury with increases in the abundance of Gram-negative uricase-producing pathobionts (<i>Escherichia</i> and <i>Shigella</i>) in the stool. Clinical trials evaluating uric acid-lowering medications as adjunctive therapy for children with SM should be considered to improve survival and protect neurodevelopment.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"13 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143026989","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}
Nature MedicinePub Date : 2025-01-23DOI: 10.1038/s41591-024-03436-2
{"title":"Imatinib and the dawn of precision cancer therapy","authors":"","doi":"10.1038/s41591-024-03436-2","DOIUrl":"https://doi.org/10.1038/s41591-024-03436-2","url":null,"abstract":"Brian J. Druker describes how his research on imatinib validated protein kinases as therapeutic targets for cancer and led to a life-saving treatment for leukemia.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"57 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143020381","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}
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