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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

REDD+ projects reduced deforestation, but less than claimed. Synthesising 44 projects, this study finds about 11 times over-crediting due to selection bias in control areas and modelling approaches and concludes that ex post certification is needed.

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.

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.

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.

Application of large language models (LLMs) for automating complex and data-intensive crop phenotype analysis remains unexplored. Here, the authors integrate LLM with curated toolkit for phenotype extraction, visualization, and model training and show its ability to reduce technical barriers and enhance accessibility.

Maize cultivar evolution boosts maize yield, yet the response pattern of maize to extreme climates is unclear. This study clarifies the synergy and trade-off mechanisms underlying the increase of yield per unit area and adaptation to extreme climates.

This study analyzes 15,572 pathway-specific, georeferenced Natural Climate Solution implementation constraint observations in 137 countries, finding that lack of policy coordination or implementation capacity are most-observed barriers to scaling up.

A study of reproducibility in a stratified random sample of 600 papers published from 2009 to 2018 in 62 journals spanning the social and behavioural sciences finds higher reproducibility among more recent papers and papers from journals that require data sharing.

JWST phase-curve observations reveal that the two innermost TRAPPIST-1 planets emit thermal radiation consistent with bare rocky surfaces, indicating that both lack thick atmospheres.

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).

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.

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.

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.

A high-resolution spectroscopic analysis reveals ultralow amounts of heavy elements in the star SDSS J0715−7334. The star originates from the Large Magellanic Cloud and probably formed directly after the first stars through dust cooling.

Here, the authors show the mechanism by which Streptococcus pneumoniae can, through natural variation of a capsule transcriptional control element, alter capsule size and the course of serotype-specific infection with implications for vaccine escape.

A sample of X-ray-weak active galactic nuclei at high redshift may be accreting above the Eddington limit. This could explain their large masses without the need for heavy supermassive black hole seeds at cosmic dawn.

Precision oncology requires access to high quality data, as well as the application of current technologies. Here, the authors use federated learning to predict clinical outcomes in anal cancer patients across 16 centres as part of the atomCAT consortium.

Effective target engagement of drugs relies on them achieving sufficient intracellular concentrations. Here, using a multimodal imaging pipeline the authors demonstrate that uneven distribution and uptake of PARP inhibitors in ovarian cancer patient-derived explant models correlates with therapeutic response.

A turbulent history of early naturalists and the maritime explorers who hosted them fascinates Andrew Robinson.

Andrew Robinson reviews five of the best science picks.

Most advanced triple-negative breast cancers remain resistant to immunotherapy. Here, the authors discover that RIPK1-driven necroptosis in both tumor and stromal compartments is essential for effective immunogenic cell death-based therapy and immune checkpoint blockade.

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.

The rapid evolution of SARS-CoV-2 challenges antibody therapeutics, but glycan-masked antigens enable isolation of class 3 monoclonal antibodies that potently neutralize diverse Omicron variants and reveal cross-reactive epitopes.

A star in a primordial dwarf galaxy has preserved the elements produced by the first generation of stars. The star lacks heavy elements but exhibits an extreme amount of carbon, suggesting that low-energy explosions can seed the initial chemistry of early galaxies.

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.

Adsorption of trace transition-metal cations endows common Ca/Mg-carbonates and phyllosilicates with catalytic activity for electrochemical CO2 reduction under planetary conditions, potentially promoting prebiotic chemistry and the origin of life.

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.

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.

Decreased brain volumes and increased NfL levels can be observed earlier than disease diagnosis in short-tandem-repeat-associated neurological diseases.

Superconductivity in twisted bilayer WSe₂ evolves smoothly with twist angle and emerges near Fermi surface reconstruction, linking previously distinct phase diagrams and clarifying its correlated origin.

In a large UK-based primary care randomized trial, immediate artificial intelligence (AI)-driven prioritization of chest X-rays did not significantly shorten time to computed tomography or lung cancer diagnosis versus standard workflow, suggesting that AI-based prioritization alone is unlikely to accelerate the lung cancer diagnostic pathway.

Clostridium perfringens lacking perfringolysin O toxin isolated from preterm infants metabolizes human milk oligosaccharide disialyllacto-N-tetraose to produce metabolites that promote the growth of commensal bifidobacteria, inhibit pathogens and suppress inflammation in an organoid model.

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.

Genomic analyses applied to 14 childhood- and adult-onset psychiatric disorders identifies five underlying genomic factors that explain the majority of the genetic variance of the individual disorders.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

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.

Widespread declines in common species raise concerns, but links to extinction risk and climate change remain unclear. Here, the authors show that many small climate change effects can accumulate to drive rapid population extinction in a common iconic bird.

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.

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.

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.

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.

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.

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.

Results of the phase 2 POLAR trial show that biomarker-guided treatment in patients with metastatic pancreatic cancer based on homologous repair deficiency leads to encouraging clinical response rates in immune cell-infiltrated tumors.

A nine-year transit-timing campaign has measured the extremely low masses and densities of four large planets orbiting the young star V1298 Tau, which are now predicted to contract and form a typical compact super-Earth and sub-Neptune system.

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.