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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.

Cofactors such as NAD⁺/NADH are essential in modern metabolism, and their prebiotic analogues may have played a key role in the non-enzymatic coupling of protometabolic reactions. Here, the authors show that prebiotically plausible pyridinium/1,4-dihydropyridine pair simultaneously mediates oxidative decarboxylation and reductive amination of pyruvate without enzymes.

Exposome analyses across 34 countries showed that social exposures were associated with faster functional brain aging and physical exposures with faster structural brain aging.

Alpha-oscillation EEG brain clocks reveal accelerated brain aging in dementia, while country-level inequality strongly shapes brain age gaps, supporting scalable screening in underserved, resource-limited settings.

This study found COVID-19 vaccination offers added protection against reinfection in children and adolescents with prior infection but variable effectiveness across variants. Findings support vaccination benefits beyond infection-acquired immunity.

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.

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.

The CMS experiment at CERN reports one of the highest-precision measurements of the W boson mass, finding it in line with standard model predictions and at odds with recent anomalous measurements.

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.

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.

Extracellular vesicles carrying diverse molecules circulate the body. Here, the authors show that blood-borne vesicles containing specific miRNAs boost synaptic function and sociability in mice, revealing a non-canonical pathway for social behavior.

Androgen activity in the male embryonic hindbrain prolongs hindbrain differentiation in male individuals and drives sex differences in the incidence and prognosis of posterior fossa type A (PFA) ependymoma, an aggressive childhood brain tumour.

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).

Salladay-Perez and colleagues explore senescence induction in human and mouse macrophages using multiomic profiling. They characterize a p21⁺TREM2⁺ senescent macrophage population, which they functionally implicate in inflammaging and liver disease.

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.

SARS-CoV-2 seroprevalence surveys provide estimates of the extent of prior infection in a population. In this nationally representative survey from Mexico, the authors estimate seroprevalence after the first epidemic wave at ~25%, with variation by region, age, socioeconomic status, and education level.

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.

Kozlova et al. report a functional role for NDRG1 in regulating R-loops and DNA repair, thereby linking cancer-associated fibroblast-derived extracellular matrix to chemotherapy responses in pancreatic cancer.

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.

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.

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 authors present SVclone, a computational method for inferring the cancer cell fraction of structural variants from whole-genome sequencing data.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

It remains unclear why some BRCA-deficient high-grade serous carcinomas (HGSC) do not respond to platinum-based therapy. Here, multi-omic analysis of BRCA1- and BRCA2-deficient HGSC attributes co-occurring mutations, DNA repair deficiency and tumor microenvironment features to short survival in these patients.

DNA damage burden and inadequate repair in CUX2⁺ cortical layer 2/3 excitatory neurons contributes to selective vulnerability in neuroinflammatory injury.

With the generation of large pan-cancer whole-exome and whole-genome sequencing projects, a question remains about how comparable these datasets are. Here, using The Cancer Genome Atlas samples analysed as part of the Pan-Cancer Analysis of Whole Genomes project, the authors explore the concordance of mutations called by whole exome sequencing and whole genome sequencing techniques.

Multi-omics datasets pose major challenges to data interpretation and hypothesis generation owing to their high-dimensional molecular profiles. Here, the authors develop ActivePathways method, which uses data fusion techniques for integrative pathway analysis of multi-omics data and candidate gene discovery.

Cancers evolve as they progress under differing selective pressures. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, the authors present the method TrackSig the estimates evolutionary trajectories of somatic mutational processes from single bulk tumour data.

From 2014–2017, marine heatwaves caused global mass coral bleaching, where the corals lose their symbiotic algae. The authors find, this event exceeded the severity of all prior global bleaching events in recorded history, with approximately half the world’s reefs bleaching and 15% experiencing substantial mortality.

Curiosity detected over 20 organic molecules in 3.5-billion-year-old Martian rocks using a wet chemistry experiment, showing complex carbon compounds can survive for billions of years and may preserve clues about Mars’ past habitability

The transcription factor ATF4 is shown to regulate double-stranded DNA repair within vulnerable CUX2⁺ upper-layer 2/3 cortical neurons, enabling their survival during development.

Escherichia coli is widespread in healthy breastfed infants, yet its ecological role is unclear. Here, the authors provide insights into the mechanisms supporting its persistence and co-existence with dominant Bifidobacterium, including potential cross-feeding of human milk oligosaccharides.

Meta-analysis of genome-wide association studies on Alzheimer’s disease and related dementias identifies new loci and enables generation of a new genetic risk score associated with the risk of future Alzheimer’s disease and dementia.

Guan, Ocampo and colleagues report the discovery and mechanistic dissection of Al3Cas12f, a metagenome-derived miniature nuclease that retains notable genome-editing capacity. They engineer an RKK variant, which boosts editing and helps overcome the potency threshold that has limited compact editors.

Analysis of cancer genome sequencing data has enabled the discovery of driver mutations. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium the authors present DriverPower, a software package that identifies coding and non-coding driver mutations within cancer whole genomes via consideration of mutational burden and functional impact evidence.

In this study the authors consider the structural variants (SVs) present within cancer cases of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. They report hundreds of genes, including known cancer-associated genes for which the nearby presence of a SV breakpoint is associated with altered expression.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

In somatic cells the mechanisms maintaining the chromosome ends are normally inactivated; however, cancer cells can re-activate these pathways to support continuous growth. Here, the authors characterize the telomeric landscapes across tumour types and identify genomic alterations associated with different telomere maintenance mechanisms.

An analysis of 2,954 genomes from 38 cancer subtypes identified 19,166 retrotransposition events in 35% of samples. Aberrant LINE-1 retrotranspositions can lead to the deletion of tumor-suppressor genes as well as the amplification of oncogenes.

Robustness checks and reproduction of analyses with existing and updated data based on 110 articles in economics and political science journals with data and code-sharing requirements found high levels of robustness and reproducibility and determined that robustness was not dependent on author characteristics or data availability.

Momin et al. develop an antibody–siRNA conjugate to inhibit the secretion of osteopontin by the TREM2⁺ macrophages that expand during human atrial fibrillation. In mice, this approach reduced fibrosis and atrial fibrillation vulnerability.

A pan-cancer genomic analysis reports the effects of structural variations on chromatin domains (TADs). Most TAD disruptions do not result in appreciable changes in expression of nearby genes.

Whole-genome sequencing data from more than 2,500 cancers of 38 tumour types reveal 16 signatures that can be used to classify somatic structural variants, highlighting the diversity of genomic rearrangements in cancer.

Spinster homolog 2 (SPNS2) exports sphingosine-1- 26 phosphate (S1P) out of cells. Here, the authors show that SPNS2 has antiporter-like activity, exporting S1P while importing glucose, revealing a mechanism linking SPNS2 to glucose homeostasis with clinical implications.

A single-cell multiomic atlas of the human maternal–fetal interface across pregnancy reveals cell types, states and spatial niches, developmental tissue architectures and transcriptional programmes, and identifies cell types with roles in pre-eclampsia, spontaneous preterm birth and miscarriage.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

The characterization of 4,645 whole-genome and 19,184 exome sequences, covering most types of cancer, identifies 81 single-base substitution, doublet-base substitution and small-insertion-and-deletion mutational signatures, providing a systematic overview of the mutational processes that contribute to cancer development.

Appel et al. found that deceptive networks reached over 37 million Facebook and 3 million Instagram users during the 2020 US elections, with the majority of this exposure driven by 3 networks and amplified by ordinary users resharing the content.