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Comprehensive, multinational validation of the PREVENT and SCORE2 cardiovascular risk scores, used in the United States and Europe, respectively, in 44 observational studies and 18 randomized trials, shows similar performance for the two risk scores and generally good performance across geographical regions.

Global Burden of Disease analysis found that in 2023, suboptimal diet was estimated to be responsible for 4 million deaths and 97 million morbidity burdens from ischemic heart disease.

Lynch Syndrome (LS) carriers develop tumors with high neoantigen loads. Here, authors perform T-cell receptor (TCR) sequencing to identify circulating TCRβs associated with colorectal cancer and pre-cancers in LS carriers.

GLP-1–GIP–lanifibranor, a single-molecule agonist of GLP-1R, GIPR, PPARα, PPARγ and PPARδ, shows promising therapeutic efficacy against obesity-linked metabolic dysfunction in vitro and in mouse models via synergistic incretin and PPAR activity.

A large-scale study on the replicability of claims from social and behavioural science journals reports that about half of the results replicate in the same patterns as the original study.

Coronary artery disease has several genetic risk factors. Here, the authors develop a model that combines germline and somatic genetic drivers to predict coronary artery disease risk, identifying high-risk individuals not detected by polygenic risk scores alone.

The Scalesia plant radiation displays striking leaf-shape variation within Galápagos microclimates. Genome-wide analyses shows that lobed leaves evolved repeatedly through diversifying selection on diverse developmental regulators.

Here the authors report real-world evidence through a retrospective analysis of a multinational cohort of 1.8 M older adults showing that GLP1RAs and SGLT2 inhibitors carry lower risk for hyperkalemia than sulfonylureas. However, SGLT2 inhibitors increased risk of ketoacidosis. Findings support safety-conscious prescribing for older adults, who are often underrepresented in clinical trials.

Native top-down proteomics reveals epidermal growth factor receptor–estrogen receptor-alpha (EGFR–ER) signaling crosstalk in breast cancer cells and dissociation of nuclear transport factor 2 (NUTF2) dimers to modulate ER signaling and cell growth.

Tumours with alterations in SWI/SNF complex have elevated EZH2 activity, which is associated with poor prognosis and tumour progression. Here, the authors report a phase 2 basket study investigating the safety and efficacy of oral tazemetostat (EZH2 inhibitor) in patients with solid tumours harbouring SWI/SNF driver mutations.

Genome-wide association and fine-mapping analyses of type 1 diabetes (T1D) identify multiple genetic risk signals. Furthermore, a machine learning model, T1GRS, improves the prediction of T1D in individuals with complex risk profiles and identifies genetic subgroups.

When 100 social and behavioural science claims were examined, 34% of reanalyses closely matched the original results, with 74% reaching the same conclusion, revealing limited robustness of single-path analyses and the need to address analytical uncertainty.

Twenty-eight healthy adults were given their first psychedelic experience, 25mg psilocybin, inducing changes detected one hour and one month later. Acute changes in brain function (EEG) and enduring changes in anatomy (DTI) were seen that mapped to psychological changes.

Using data from the Democratic Republic of the Congo, a mathematical transmission model accounting for age, sex and sexual activity is able to identify the role of different transmission routes in the spread of the novel clade Ib of mpox.

DNA-sequencing data from primary tumours and paired metastases from participants in the TRACERx lung study and PEACE autopsy programme are used to analyse the metastatic diversity of advanced non-small cell lung cancer and the seeding patterns that underpin it.

Long-term effects of in utero Chikungunya exposure are not well characterized, although intrapartum exposure is known to be associated with neonatal mortality. Here, the authors assess risk of all-cause hospitalization and mortality up to three years following in-utero exposure in a cohort from Brazil.

Using two-photon imaging in mice, Garborg et al. show that brain movement within the skull is driven by abdominal muscle contractions through mechanical coupling with the abdomen. Simulations suggest that this brain motion could contribute to cerebrospinal fluid circulation.

In this phase 1/2 trial, patients with Ewing sarcoma received trabectedin and low-dose irinotecan at concentrations known to inhibit the activity of the transcription factor EWS::FLI1, leading to encouraging clinical response rates.

The authors resolve 63 structurally diverse haplotype structures for the 22q11.2 deletion syndrome region. Deletion risk differs depending on structure; individuals of African ancestry are enriched for inverted repeats that predispose to inversion.

Repurposing existing drugs for vascular dementia (VaD) could have clinical impact. Here, using Mendelian randomization, researchers tested whether cholesterol, anti-inflammatory or blood pressure drug targets affect risk of VaD, finding little evidence to support repurposing opportunities. A potential benefit was seen for beta-blocker target ADRB1 while ACE inhibition was observed to potentially increase risk of VaD.

Evo 2 is an artificial intelligence-based biological foundation model trained on 9 trillion DNA base pairs spanning all domains of life that predicts functional properties from genomic sequences and provides a rich generative model for researchers in biology.

Th17 cells play critical immunological roles and are exposed to oxidative stress but how the mechanisms behind how they deal with this are not well established. Here the authors suggest a role for Xeroderma Pigmentosum Complementation Group C in the protection of Th17 cells from oxidative stress in a murine model.

Analysis of neuroimaging datasets across five major psychedelics revealed a shared brain signature and provides a comprehensive insight into how these drugs reorganize brain architecture.

Longitudinal metatranscriptomics in a prospective cohort of 1,164 adults hospitalized for COVID-19 reveals that azithromycin offered no apparent anti-inflammatory benefit but enriched the respiratory microbiome with potential pathogens and antimicrobial resistance genes.

cellSTAAR advances noncoding rare variant association analysis by integrating single-cell genomics data.

Hodgson, Huang, Lang et al. show that TDP-43 limits ribonucleoprotein particle condensation into paraspeckles in a concentration- and polymerization-dependent manner. They also link paraspeckle condensation to stress response and neuroprotection.

Single-variant and ultrarare variant burden analyses leveraging exome sequencing data from 22 cohorts identify new risk genes for amyotrophic lateral sclerosis and show cumulative effects of several rare variants on disease risk.

Genome-wide analysis coupled with long-read sequencing identifies a repeat expansion in GOLGA8A associated with high risk for atypical frontotemporal lobar degeneration with ubiquitin-positive inclusions.

The spread of non-native species is likely to be compounded by further climate change and land-use intensification. Here the authors assess the potential distribution of 9,701 naturalized non-native plant species at a 10 × 10-km grid resolution and project shifts under two Shared Socioeconomic Pathways.

A deep-learning approach applied to routine CT scans is used to quantify the health of the thymus in a cohort of patients with cancer, and shows that thymic function is associated with immunotherapy outcomes.

Cayman enables computational analysis of carbohydrate-active enzymes (CAZymes) in microbial community data. It revealed novel mucus-foraging gut microorganisms and differences in gut microbial CAZyme repertoires associated with lifestyle and disease.

Global research prioritization for peatland science engaged 467 participants from 54 countries, identifying 50 priority research questions across carbon dynamics, climate impacts, restoration and management, technological innovation, and community and policy engagement.

Most patients with B-cell leukemia respond to chimeric antigen receptor T cell (CAR T) therapy, yet many relapse due to loss of CAR T function. Here, the authors show that the metabolism of CAR T from short- and long-term responders is different, which may explain why CAR T lose functionality.

Imprinting by influenza viruses can cause a deleterious shift of nearly the entire memory recall response against key, conserved epitopes.

The authors mapped the continental-scale fraction of age-dependent leaf area index and revealed a widespread increase in the fraction of photosynthetically efficient young leaves across the majority of Amazon rainforests over the past decades.

The Amazon faces worsening droughts, yet little is known about large-scale variation in the physiological limits of Amazon trees. Here, the authors reveal family-level conservatism in embolism resistance and estimate that Brazilian and Guiana shield forests are more resistant than Western Amazonia forests.

Here they show that KROX20 marks a stem cell pool in the eyelid’s Meibomian glands whose development and homeostasis is regulated via Notch pathway signaling, thus offering a potential therapeutic target for dry eye disease.

Global Burden of Disease estimates show that between 1990 and 2023, the prevalence and burden of drug use disorders, inclusive of amphetamine, cannabis, cocaine and opioid use, have been increasing in high-income countries, particularly in the USA.

Deconvolution methods infer levels of immune infiltration from bulk expression of tumour samples. Here, authors assess 6 published and 22 community-contributed methods via a DREAM Challenge using in vitro and in silico transcriptional profiles of admixed cancer and healthy immune cells.

Estimates from the Global Burden of Disease study reveal declines in chronic respiratory disease mortality between 1990 and 2023—especially during the COVID-19 pandemic—but the burdens on people affected remain substantial.

This paper conducted a priority-setting exercise to identify ten questions that define the future direction of blue carbon science. It highlights key gaps, emerging challenges and opportunities for advancing climate mitigation, ecosystem management and evidence-based policy.