Oropouche virus (OROV) was reported in Cuba in May 2024 and rapidly spread throughout the country. Here, among 147 reverse-transcription polymerase chain reaction-positive cases identified from May to July 2024, we sequenced 39 whole genomes of OROV. Phylogenetic analysis revealed that all sequences formed a monophyletic cluster nested within the reassortant lineage, named OROVBR-2015–2025, which has been circulating extensively in Brazil since 2023. Additional phylogeographic analyses demonstrated that the Cuban subclade probably originated from a single viral introduction from the Brazilian state of Acre in early February 2024, followed by cryptic circulation until its identification in May. The introduction probably occurred in the central region of the country, from which the virus spread and established secondary transmission hubs in the western and eastern regions. These findings underscore the capacity of OROV to spread well beyond South America, which was considered its endemic

Extracorporeal liver cross-circulation (ELC) using gene-edited porcine liver xenografts offers a potential bridge therapy for liver failure. We previously performed five ELC procedures in four brain-dead human decedents, during which the recipients developed severe thrombocytopenia. The porcine liver xenografts maintained their parenchymal structure, with immune cell infiltration and detectable IgM deposition on endothelial cells. Here, to investigate the underlying host–xenograft interactions, we performed longitudinal proteomic, lipidomic and metabolomic profiling of 64 blood samples, alongside spatial transcriptomics and histology of 25 porcine liver xenograft and 3 native human liver biopsies. Spatial transcriptomic analysis revealed progressive infiltration of human immune cells (predominantly inflammatory macrophages and neutrophils) in the xenografts, concurrent with the loss of porcine Kupffer-like macrophages and T cells. Distinct human and porcine complement dynamics were obs

Broadly neutralizing antibodies (bnAbs) are a promising tool for HIV prevention and treatment. Here we conducted a first-in-human, phase 1 trial of the bispecific 10E8.4/iMab antibody, which consists of a 10E8.4 arm binding the HIV-1 envelope glycoprotein membrane-proximal external region and an ibalizumab (iMab) arm binding the human CD4 molecule. 10E8.4/iMab was administered intravenously (IV) or subcutaneously (SC). Safety/tolerability within 2 weeks of 10E8.4/iMab administration (primary outcome) and the pharmacokinetics (PK), antiviral activity, induction of anti-10E8.4/iMab antibodies, longitudinal CD4+ and CD8+ T cell counts and long-term safety (secondary outcomes) were evaluated. 54 participants living with HIV (PLWH) or without HIV (PLWoH) received 10E8.4/iMab or placebo. In arm 1, PLWoH received 10E8.4/iMab 0.3 mg kg−1 IV, 1 mg kg−1 SC, or 1 mg kg−1 IV (n = 3 each). In arm 2, PLWoH received 10E8.4/iMab 3 mg kg−1 IV, 10 mg kg−1 IV or 30 mg kg−1 IV (n = 6 each). In arms 3/3a,

Chronotherapy promises to improve medicine by aligning treatment with the body’s internal clock. As this idea moves into clinical trials, a high-profile retraction reveals the ups and downs of circadian medicine.

Immune checkpoint inhibitors (ICIs) are a standard treatment across cancers, yet most patients do not respond, and existing biomarkers generalize poorly across tumor types and therapies. Here we present COMPASS, a pan-cancer foundation model that predicts immunotherapy response from bulk tumor transcriptomes using a concept bottleneck transformer. COMPASS encodes gene expression through 44 biologically grounded immune concepts representing immune cell states, tumor−microenvironment interaction and signaling pathways. Trained on 10,184 tumors across 33 cancer types, COMPASS achieves better average performance than 22 methods across 16 clinical cohorts spanning seven cancers and six ICIs, improving accuracy by 8.5% and area under the precision-recall curve by 15.7% on average across cohorts. COMPASS generalizes to cancer types and treatments not represented during fine-tuning and may inform indication selection and patient stratification. In survival analyses, patients classified by COMP

Aging profoundly remodels the immune system, impairing defense, repair and homeostatic function across tissues. Because the immune system operates in every organ, its deterioration has been proposed to drive or exacerbate systemic dysfunction and accelerate overall biological aging, making it an attractive biomarker and target for geroscience-guided trials. Despite this central role, there is no consensus on how to quantify immune aging, especially in clinical trials. Here, we establish a translational framework to identify immune aging biomarkers for this purpose. We define five evaluation criteria for immune aging biomarkers and apply these to candidate biomarkers, discussing their utility in the context of a major international healthspan competition, XPRIZE Healthspan. Metrics encapsulating multidimensional aspects of immune function, inflammaging scores and functional assays performed best against our selection criteria. Finally, we identify promising emerging measures, together w

An analysis of code availability in the open-access published literature shows that code sharing in clinical prediction models remains limited and reveals significant variability in practices and docu...

A small epilepsy monitoring study shows that a moderated, large language model-based chat interface lets patients converse with their electroencephalography monitoring in real time, using a smartphone...

Heart failure with reduced ejection fraction carries a poor prognosis. Although guideline-directed medical therapy reduces morbidity and mortality, its real-world utilization is low. Accordingly, we conducted an open-label randomized trial (POLY-HF) at two centers enrolling a predominantly underserved population to test whether a polypill strategy improves cardiac function in heart failure. Adults with heart failure and left ventricular ejection fraction ≤40% were randomized to a once-daily polypill containing metoprolol succinate (25/50/100/150 mg), spironolactone 12.5 mg and empagliflozin 10 mg, or rapid uptitration of individual guideline-directed medical therapy medications (‘enhanced usual care’). Participants also continued treatment with a renin-angiotensin system inhibitor or sacubitril/valsartan as a separate pill. The primary endpoint was ejection fraction as assessed by cardiac magnetic resonance imaging at 6 months. Secondary endpoints included clinical outcomes and adheren

From caring for a loved one with cancer to developing tools that predict cachexia risk, CANCAN researcher Ed Reznik is showing how something as routine as body weight data could help clinicians stay o...

Detection of Alzheimer’s disease (AD) before the development of clinical symptoms is critical for enabling the use of new treatments. Circular RNAs (circRNAs) are highly stable non-coding RNAs enriched in the brain that can cross the blood–brain barrier. Here, analyzing blood data from 1,221 individuals with AD and healthy individuals, we identified 34 circRNAs associated with AD status. A predictive model including these 34 circRNAs was comparable to plasma phosphorylated Tau-217 (pTau217) in classifying AD based on biomarker-confirmed (amyloid-β and Tau) status and replicated in independent samples from the Knight-Alzheimer Disease Research Center (n = 551: 76 AD, 475 cognitively unimpaired) and preclinical A4 (n = 1,767) cohorts. Classification of biomarker-confirmed status by blood circRNAs (area under the curve (AUC) = 0.945) had a higher predictive ability than plasma pTau217 (AUC = 0.877) and was further improved in the integrated model (circRNA+pTau217 AUC = 0.977). This model

Nature Medicine - MAGIC: an international network for evaluating generative artificial intelligence in global health

📊 New Nature Medicine study: daily multivitamin supplementation delayed cognitive aging by ~2 years versus placebo in 5,203 COSMOS par… #Cognitivedecline #COSMOStrial #Epigeneticaging #Multivitamin #NatureMedicine

Blood pressure (BP)-lowering therapy reduces cardiovascular risk, but whether its proportional benefits increase with longer treatment duration remains unclear. We conducted an individual participant-level data meta-analysis of 51 randomized trials from the Blood Pressure Lowering Treatment Trialistsʼ Collaboration (358,642 participants; median follow-up: 4.2 years). Using Cox proportional hazards models, we estimated time-stratified hazard ratios (HRs) for major cardiovascular events (MACE; fatal or non-fatal stroke, ischemic heart disease or heart failure) across annual follow-up intervals up to more than 5 years, standardized to a 5-mmHg systolic BP reduction. Network meta-analysis examined whether temporal patterns differed across antihypertensive drug classes. Annual MACE incidence was highest during year 1 (3.0% treatment versus 3.6% control), declined during years 1−5 and then rose at more than 5 years (3.1% versus 3.4%). BP lowering reduced MACE risk, with benefits established

New phase 2b trial of aleniglipron, an oral GLP-1 receptor agonist for weight management, published in Nature Medicine. Oral formulations could overcome injecti… #Aleniglipron #Clinicaltrial #GLP1agonist #NatureMedicine #Obesitytreatment

Controlled human influenza infection studies can uniquely interrogate the early immune factors associated with clinical outcome. In this study, 27 healthy volunteers with low strain-specific serum neutralizing antibody levels were challenged with influenza A/H3N2 virus. Twenty-two became infected, with 18 developing mild-to-moderate symptoms and four remaining asymptomatic. Local and systemic immune profiling revealed innate pathways that engaged more rapidly and to a higher level in symptomatic participants. Earlier monocyte and dendritic cell activation correlated with higher symptom scores but also enhanced natural killer and CD8+ T cell activation thereafter. At baseline, peripheral blood mononuclear cells from symptomatic participants were more responsive to in vitro challenge, indicating a predisposition to divergent immunological outcomes at the time of virus exposure that was subsequently modulated by infection. These results show that human innate cell responsiveness is a pred

🐷 Pig liver xenografts successfully functioned in human extracorporeal trials, producing the first comprehensive multiomics safety data. Nat… #Geneediting #Liverfailure #NatureMedicine #Organtransplant #Xenotransplantation

In a large-scale study, a new tool called Esophageal AI-Guided malignant Lesion Evaluation uses artificial intelligence to enhance esophageal cancer detection through noncontrast computed tomography, ...

A multi-ancestry genome-wide association study meta-analysis across 2,563,755 individuals identifies 26 risk loci for fibromyalgia, including HTT, and finds genetic correlations with chronic pain and ...

Re-administration of adeno-associated virus (AAV)-mediated gene therapy remains challenging due to neutralizing antibodies (NAbs) induced by the initial dose. We previously conducted a single-arm trial showing that single-dose administration of AAV-hOTOF gene therapy in individuals with OTOF-related deafness is safe and leads to hearing improvements. Here we initially demonstrate that AAV1-hOTOF re-administration to the contralateral ear in Otof−/− mice with peak serum NAb titers successfully rescued hearing with limited immune activation. After a protocol amendment of our trial, four patients (aged 2.2–3.4 years) with pre-existing NAbs (titers 1:135–1:3,645), who had previously received a single dose of the gene therapy, were enrolled to receive a second dose in the contralateral ear, as part of the ongoing trial, with a follow-up ranging from 26 weeks to 52 weeks. The primary endpoint was the occurrence of dose-limiting toxicities at 6 weeks and secondary endpoints included safety an

Large frontier models such as GPT-5 and Gemini have demonstrated remarkable performance in a wide range of health application benchmarks. However, underneath the seemingly promising results lie salient growth areas, especially in cutting-edge frontiers such as multimodal reasoning. Here we systematically apply and integrate a series of adversarial stress tests to assess the robustness of flagship models and health benchmarks. Our study reveals prevalent brittleness in the presence of simple adversarial transformations: leading systems can guess the correct answer even with key inputs removed yet may get confused by the slightest prompt alterations while fabricating convincing but flawed reasoning traces. Using clinician-guided rubrics, we demonstrate that popular health benchmarks vary widely in what they truly measure. Our study reveals considerable gaps between benchmark performance and the robustness evidence needed to support claims about multimodal medical reasoning in health appl