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Global analysis of obesity trends from 1980 to 2024 in 200 countries and territories using data from 4,050 population-based studies reveals that framing obesity as a single global epidemic masks the highly varied dynamics across countries and age groups.

Using inbred medaka strains, the authors mapped 59 genetic loci linked to heart rate. Gene editing validated conserved genes affecting heart rate and morphology, highlighting the power of isogenic strains in uncovering mechanisms of cardiac traits and disease.

Understanding collective behaviour is an important aspect of managing the pandemic response. Here the authors show in a large global study that participants that reported identifying more strongly with their nation reported greater engagement in public health behaviours and support for public health policies in the context of the pandemic.

Analysis combining multiple global tree databases reveals that whether a location is invaded by non-native tree species depends on anthropogenic factors, but the severity of the invasion depends on the native species diversity.

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.

CheckMate 650 was a multicohort phase 2 trial designed to study the safety and clinical activity of nivolumab plus ipilimumab combination therapy in patients with metastatic castration-resistant prostate cancer. Here the authors report the results of the randomized portion of the trial, including three different immunotherapy treatment cohorts and a current standard-of-care chemotherapy cohort (cabazitaxel).

By comparing newly produced RNA in the nucleus with mature RNA in the cytosol, genetic variants that control gene expression showed striking differences in localization and biological mechanisms, helping explain how they contribute to disease.

In this work, authors show that alpibectir boosts ethionamide efficacy against Mycobacterium tuberculosis by enhancing its bioactivation and also shows intrinsic activity. The ethionamide-alpibectir combination (AlpE) is bactericidal in mice and active against drug-resistant strains.

The functional impact of most missense variants remains unknown. Here the authors perform deep mutational scanning of the tumor suppressor SMARCB1 and find missense mutations that retain detectable protein expression but disrupt function similar to protein-null mutations

SbmA is a proton-driven transporter that imports antimicrobial peptides andstructurally resembles the transmembrane domain of ABC-transporters. Here, authors show through cryo-EM structures, EPR spectroscopy, and MD simulations that SbmA undergoes ABC-transporter-like conformational changes consistent with an alternating-access transport mechanism.

AlphaFold’s success in protein structure predictions has led to similar attempts to predict interactomes. Here, the authors demonstrate that AI-based screens are very limited in discovering truly novel interactions compared to experimental screens, exposing open challenges in interaction prediction.

Mycobacterium tuberculosis owes its success partly to its ability to enter a ‘dormant’, non-replicative state, reactivating years or even decades after initial infection. In this work, authors find that a key alteration in a gene involved in this dormancy response has evolved, or is evolving, in parallel in human-adapted lineages across the globe.

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.

A large-scale proteomics analysis of the dark proteome by the TransCODE Consortium reveals many translated non-canonical open reading frames to encode microproteins and peptideins.

Endocrine therapies are the main adjuvant therapy for estrogen receptor positive breast cancer, but 30% of patients recur. Here, the authors discover that endocrine therapy upregulates Rac1 signalling component P-Rex1, and inhibition of Rac1 reduces tumour growth in refractory breast cancer models.

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.

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.

The effects of global biodiversity loss on local plant communities have been equivocal. Across 57,398 European time series, covering > 100 years, local plant diversity gains are often associated with rises in generalist and non-native plants.

A randomized trial in Ecuadorian high schools showed youth videos of both STEM and entrepreneurship role models. This caused both girls and boys to be less likely to enrol in STEM college majors, with girls choosing business and boys other fields.

In a biomarker-driven trial evaluating radiotherapy with erlotinib, everolimus or dasatinib in patients with newly diagnosed diffuse intrinsic pontine glioma, the primary endpoint of overall survival was not met, but features associated with long-term survival were defined, and everolimus emerged as a potential candidate for further testing.

Community-based fact-checking is increasingly adopted by social media platforms, but its real-world impact remains unclear. Here, the authors show that community notes can reduce the spread of misleading posts on X/Twitter, yet often arrive too late to curb early virality.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Analysis of 258 ancient genomes from southern Germany reveals a major demographic shift during the late fifth century, yet family structures persisted from Late Roman times, demonstrating cultural continuity despite profound demographic reorganization.

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.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

The APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer’s disease, but it is not deterministic. Here, the authors show that common genetic variation changes how APOE-ε4 influences cognition.

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.

The genomewide meta-analysis of lumbar spinal stenosis LSS identifies 73 previously unreported loci in addition to 15 known loci and highlights spinal degeneration as a key pathogenic mechanism. Overall, the findings expand knowledge of the genetic background of LSS.

By tuning graphene’s electronic density of states, the study shows electrode electronic structure—not just the electrolyte—dominates reorganization energy and thus controls outer-sphere electron-transfer rates at solid–liquid interfaces.

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

RNA velocity is a widely used method to predict the fate of single cells. Here the authors show that the concept can be adapted to predict the fate of individual human subjects, using RNA velocity of whole blood at a single point in time to predict future clinical outcomes and treatment responses.

The study identifies novel genetic variants linked to core cerebrospinal fluid Alzheimer’s Disease biomarkers using a genome-wide analysis, showing how endophenotypes can identify genes and disease mechanisms not captured by case-control studies.

The identification of cellular targets for natural products that potently inhibit the growth of cancer cell lines implicates oxysterol-binding proteins in the growth of cancer cells. These natural products, termed ORPphilins, also affect sphingomyelin biosynthesis.

Emmett and colleagues evaluate the frequency, magnitude and clinical significance of early prostate-specific membrane antigen (PSMA) upregulation in patients with metastatic castrate-resistant prostate cancer treated with enzalutamide with or without ¹⁷⁷Lu-PSMA-617.

Authors investigate ancient DNA from animal remains and identify multiple signatures of ancient zoonotic pathogens. They find ancient pathogen genomics from archaeological animal remains may inform zoonotic disease emergence.

Polymer thin films that emit and absorb circularly polarised light are promising in achieving important technological advances, but the origin of the large chiroptical effects in such films has remained elusive. Here the authors demonstrate that in non-aligned polymer thin films, large chiroptical effects are caused by magneto-electric coupling, not structural chirality as previously assumed.

SpaMosaic is a mosaic integration method for spatial omics data that enables cross-modality and cross-batch integration using contrastive learning and graph neural networks.

Analyses of snRNA genes in a French cohort of people with rare disorders, with validation through international collaboration, identify monoallelic and biallelic variants in RNU2-2 as frequent causes of neurodevelopmental disorders with epilepsy.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

Whole-genome sequencing data for 2,778 cancer samples from 2,658 unique donors across 38 cancer types is used to reconstruct the evolutionary history of cancer, revealing that driver mutations can precede diagnosis by several years to decades.

While autoinhibited architectures of talin are known from cryo-electron microscopy, its behaviour in solution has remained underexplored. Here, the authors use size-exclusion chromatography coupled with in-line small-angle X-ray scattering, Monte Carlo modeling and AlphaFold predictions to determine the conformational landscape of full-length talin in solution, showing that this cytoplasmic adapter protein does not adopt a single compact structure but instead populates a broad, flexible conformational ensemble characterized by R3 subdomain repositioning and partial F3-R9 subdomain disengagement.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

Molecular precursors containing V, Bi and Zn are thermally transformed into oxide materials. Detailed studies reveal and characterise the formation of amorphous intermediates, a new kinetic polymorph of BiVO₄, and incorporation of Zn dopants.