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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.

Atmospheric river (AR) characteristics, particularly AR shape associated with large-scale circulation, as well as interactions with other weather systems, significantly influence surface warming over Antarctic ice shelves and their future stability.

The cellular origin and developmental trajectory of DICER1 syndrome-associated tumors are currently unknown. Here, the authors employ a lineage-traceable genetically modified mouse model for DICER1 syndrome to identify universal fibroblasts as the likely cellular origin of mouse Dicer1 sarcoma and map their developmental trajectory, findings that are validated in human DICER1 mesenchymal tumors.

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.

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.

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.

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.

Phosphorus locked in carbonate rocks from seven global sites shows simultaneous marine phosphorus spikes during major mass extinctions. Modelling ties high marine phosphorus to eutrophication, CO2 drawdown, and global cooling.

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.

Links between type 1 diabetes and neurocognitive traits remain unclear. Here, the authors integrate genetic and single‑cell epigenomic data to show brain‑cell, especially microglial, involvement and identify shared genetic mechanisms connecting diabetes with cognition and neuropsychiatric risk.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer due to late detection and rapid progression. Here, the authors integrate multi-regional whole genome and RNA sequencing to characterize intratumoural heterogeneity and evolutionary trajectories underlying the malignant transformation of intraductal papillary mucinous neoplasms into invasive PDAC.

Plasma ctDNA testing for FGFR alterations in metastatic urothelial carcinoma shows high concordance with tissue testing and identifies additional patients with actionable alterations. Here, the authors show that clinical uptake of ctDNA FGFR testing can be combined with tissue-based approaches.

How motor cortex (M1) circuits adaptively organize action sequences during learning remains unclear. Here, the authors show that M1 somatostatin interneurons actively encode and regulate the temporal structure of action sequences, enabling efficient, task-specific motor execution.

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.

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.

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.

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.

Given rising diabetes prevalence globally, access to diabetes treatments is gaining urgency. Here, the authors show patterns of glucose-lowering medication use for diabetes across 62 low- and middle-income countries.

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.

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.

The long-term natural history of long-COVID is not well understood. In this population-based cohort study from Scotland, the authors describe symptom prevalence and health-related quality of life up to 18 months after a positive SARS-CoV-2 test and compare with matched test-negative controls.

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).

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.

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.

A new optical imaging study demonstrates that norepinephrine and the state of arousal influence hemodynamic correlations across cerebral cortex, calling for a conceptual shift in interpreting functional magnetic resonance imaging data.

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.

Gene correction in the lung is achieved with inhalable mRNA lipid nanoparticles containing an amino acid-derived ionizable lipid identified from screening and structure–function optimization studies.

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.

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.

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.

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.

Single-nucleus chromatin and RNA sequencing identifies epigenetic chromatin domains that confer vulnerability to paediatric brain tumours such as ependymomas, providing insight into the development of such tumours despite ‘quiet’ genomes.

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.

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.

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.

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.

Colonic stem cells retain a memory of inflammation following disease resolution and there is a mechanistic link between chronic inflammation and malignancy, suggesting potential strategies to mitigate cancer risk in patients with chronic inflammatory conditions.

In this study, long-read RNA sequencing achieves accurate single-nucleotide polymorphism calling, haplotype phasing and allele-specific expression analysis.

After a heart attack, blood flow restoration often fails in small vessels, worsening outcome. Here, the authors show that remote ischaemic preconditioning releases the gut hormone GLP-1, which relaxes cardiac pericytes via K_ATP channels to reduce capillary constriction and no-reflow.

Robin et al. use dry immersion to assess cardiovascular and metabolic responses to 5 days of simulated microgravity in healthy women and men. They find pronounced but largely similar deconditioning in both sexes, supporting dry immersion as a robust ground-based model for spaceflight-related physiological changes.

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.

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.

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.

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.

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 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.

Disulfide tethering screening is applied to address the challenge of targeting oncogenic KRAS, historically deemed undruggable due to its high nucleotide affinity and perceived lack of binding sites. Here, the authors developed a disulfide library and a set of 83 cysteine KRAS mutants to perform tethering screens towards the oncogenic KRAS, while describing the discovery of fragment-binding pockets in KRAS G12D, identified by this screening approach.