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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.

Acute rheumatic fever (ARF) is a serious sequela of Strep A infection, for which a diagnostic biomarker is still lacking. Here, the authors demonstrate that CXCR3 directs T cells to heart valves in patients with ARF, linking inflammation to tissue damage.

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.

High-resolution satellite data enables a unique verification of national methane emissions worldwide. Global estimates are 63 Tg a⁻¹ for oil-gas, 30% higher than the UNFCCC reports due to under-reporting by four largest emitters, and 33 Tg a⁻¹ for coal, consistent with previous estimates.

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

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.

The microtubule–kinesin system is a well-known active matter system. Now it is shown that a microtubule-based active fluid can assemble adhesive non-thermal fibres into a membrane-like structure.

Recent data has observed sequential, rather than persistent, neural activity during evidence accumulation for decision-making. Here, the authors develop models that accumulate evidence through sequences and relate model predictions to neural recordings in different brain regions.

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.

Li and colleagues show that the transcription factor ZFP148 restrains the differentiation of antigen-specific CD8⁺ T cells toward cytolytic effector cells by repressing the expression of KLF2.

Detailed oxygen maps of spiral galaxy NGC 1365 and cosmological simulations trace when its disk, bar and outer gas formed, showing that chemical fingerprints can reveal the merger and growth history of a galaxy.

In the nonpivotal stage 1 of the randomized phase 3 PRESERVE-003 trial, patients with immunochemotherapy-resistant metastatic squamous non-small cell lung cancer without actionable genomic alterations treated with the next-generation, pH-sensitive anti-CTLA-4 agent gotistobart had encouraging overall survival outcomes compared to docetaxel.

In mice, a circuit between the spinal cord and various regions of the brain, centring on spinal-cord-projecting neurons in the rostral ventromedial medulla, has a key role in driving chronic pain.

The authors consider risks to global biodiversity from wildfire under climate change. They show increased risk to 83.9% of species pre-identified as wildfire vulnerable, with high risks for species with small ranges, high conservation concern and those in South America, Australia and South Asia.

Kelly et al. assessed an artificial intelligence system for breast cancer screening in retrospective datasets, followed by prospective feasibility evaluation, and report its accuracy, fairness and clinical implementation in multiple workflow settings.

Lin et al. investigate the immune response in severely ill H7N9 patients and its link to early-life influenza imprinting. They find that individuals first exposed to H2N2 develop faster, higher-avidity cross-reactive antibodies and tend to experience less severe illness.

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

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.

Connectome-seq allows access to connectomic and transcriptomic information in high throughput, using an RNA barcoding strategy and isolation of synaptosomes, followed by single-nucleus and single-synaptosome RNA sequencing.

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 monolithically integrated photonic ski-jump enables scalable, diffraction-limited 2D beam scanning from photonic chips, achieving ultrahigh spot rates, compact footprints and applications spanning displays, sensing and quantum photonics.

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 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.

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.

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.

Inhibition of the histone methyltransferase NSD2 and the androgen receptor in preclinical models can reverse lineage plasticity to suppress tumour growth and promote cell death in multiple subtypes of castration-resistant prostate cancer.

TREM2 is an important AD risk factor playing essential roles in the microglial response to amyloid pathology. Here, authors show using a TREM2 reporter mouse that TREM2 levels are critical for efficacy of TREM2 agonism informing current clinical efforts.

Wildfire observations reveal that 21% of black carbon aerosols contain multiple cores, and accounting for this morphology increases global absorption by 19%, highlighting a missing source of radiative forcing in current models.

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.

The mitochondrial pathway of apoptosis requires coordinated protein–lipid signals. Here, Gelles et al. show that a BAX lipid-binding cavity for 2-trans-hexadecenal cooperates with BIM to allosterically activate BAX prior to membrane insertion.

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 corpus callosum is essential for coordinating sensorimotor, associative and executive functions. Here, the authors show a GWAS of corpus callosum morphology implicates prenatal growth pathways, immune-driven thinning, and genetic overlap with cortical and neuropsychiatric traits.

Some cancer patients first present with metastases where the location of the primary is unidentified; these are difficult to treat. In this study, using machine learning, the authors develop a method to determine the tissue of origin of a cancer based on whole sequencing data.

A meta-analysis of genome-wide association studies of type 2 diabetes (T2D) identifies more than 600 T2D-associated loci; integrating physiological trait and single-cell chromatin accessibility data at these loci sheds light on heterogeneity within the T2D phenotype.

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

Genome-wide association analyses using data from 19 biobanks identify variants influencing risk of thyroid diseases and yield polygenic risk scores associated with features of aggressive thyroid cancer.

Man-made ammonia emissions have harmful effects on human health and ecosystems, yet global mitigation strategies remain underexploited. A study now finds that emissions could be halved cost-effectively by 2050 through targeted and prioritized measures, with benefits far outweighing costs.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.

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.

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.

Climate limits where insects can live and which species can coexist. Using thermal tolerances of 653 moths on Asian mountains, this study shows warmer temperatures broaden thermal tolerance traits diversity; daily variation has little influence, and strong seasonality mildly weakens this pattern.

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.

Here the authors combine clinical and metabolomics data to identify distinct metabotypes of pediatric metabolic dysfunction-associated steatotic liver disease (MASLD). The results provide information regarding heterogeneity of MASLD presentation, but require validation in independent cohorts.