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In this phase 2 trial, combination treatment with elraglusib, a cell-permeable ATP-competitive inhibitor of glycogen synthase kinase-3β, and gemcitabine plus nab-paclitaxel (GnP), in patients with previously untreated metastatic pancreatic ductal adenocarcinoma led to prolonged overall survival compared with GnP only.

A deep learning model using smartwatch data was shown to predict peak oxygen uptake and unplanned healthcare events in the TRUE-HF prospective cohort of patients with heart failure, as well as unplanned healthcare utilization in patients with heart failure in the All of Us Research Program.

Heinen et al. show that the mitochondrial import complex recruits lipid droplets to the mitochondrial outer membrane. The mitochondrial import complex binds to the lipid metabolism enzyme Ayr1 and contributes to lipid-droplet biogenesis and homeostasis.

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.

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.

Dysregulation of H3K4 methylation is associated with neurodevelopmental disorders. Here, the authors perturb H3K4 methylation in the MGE and hypothalamus, resulting in altered gene expression and cell fate as well as changes in behavior that mimic NDD symptoms.

XRISM spectroscopy of the nucleus of the Circinus galaxy indicates elemental abundances suggestive of a dominant enrichment from core-collapse supernovae with progenitors below 20 solar masses; more massive stars may directly collapse into black holes.

Analysis of nuclear and mitochondrial genomes from archaeological canid remains found across Europe and Anatolia shows that a genetically homogeneous dog population was already widely distributed across the region by 15,000 years ago.

Researchers employ machine learning-driven simulations to investigate the behavior of oxygen under extreme pressures up to 1,000 TPa. They identify stable phases and obtain information on the melting line and thermal properties of oxygen, improving our understanding of the structure and evolution of white dwarfs.

Climate and land-use change are transforming biodiversity, yet national futures remain uncertain. The study projects growing extinction debts, but suggests that sustainable low-emission pathways can limit the worst impacts on British biodiversity.

Scabies is a parasitic skin disease with limited treatment options and major global impact. Here, the authors describe structures of a pH sensitive ion channel from the scabies mite, identify residues likely involved in pH sensing, and show pH-dependent ivermectin action and gating impact.

HORMAD1 expression is typically restricted to germline cells where it has an important role in meiotic recombination but has been shown to be upregulated in triple negative breast cancer (TNBC). Here, the authors report that aberrant HORMAD1 expression weakens the spindle assembly checkpoint, driving sensitivity to AURORA kinase inhibition.

Genome-wide analysis shows European dogs existed by 14,200 years ago, were already genetically distinct, received less Neolithic Southwest Asian admixture than humans did and contributed substantially to later European dogs.

In one-shot perceptual learning, what we see can be dramatically altered by a single past experience. Using psychophysics, fMRI, iEEG, and DNNs, the authors identify neural and computational mechanisms underlying this remarkable ability in humans.

Manipulating chemical interactions is crucial in protein assembly. Here, the authors highlight the importance of accounting for solvent forces mediated by interfacial hydration structures when designing protein assemblies at liquid-crystal interfaces.

Prediction of tumour recurrence in anal squamous cell carcinoma can be challenging. Here, the authors use a tumour-informed ctDNA assay to show concordance with relapse in patients following failed definitive-intent chemoradiation.

CD44 expressed by fibroblastic reticular cells in secondary lymphoid organs regulates trafficking of dendritic cells, and thus has an essential role in the priming of T cells and the adaptive immune response.

Nature captures the anxiety, and jubilation, of this mission milestone.

Starburst galaxies are seen to host galaxy-scale winds, which are super-fast and could be powered entirely by the thermal pressure of gas heated by supernovae.

The source of pre-Inca agriculture in the Atacama Desert of Chile has been the subject of multiple theories, but this Article uses preserved maize remains to deduce that coastal guano deposits were utilized in an impressive display of social and ecological sophistication.

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.

This research developed and compared firearm-specific and method-agnostic machine-learning models using data from 800,579 Army veterans, revealing that model choice and intervention thresholds impact predictive accuracy and fairness, guiding tailored suicide prevention efforts.

Tau:αSyn condensates change from pathological to physiological by redirecting interactions toward microtubules. Here, the authors show that tubulin-rich condensates suppress toxic oligomer and amyloid formation, whereas tubulin loss drives aggregation and neurite degeneration.

High-throughput proteomics reveals shared and distinct protein signatures of cerebral small-vessel disease, linking vascular, immune and neuronal pathways to its pathophysiology, and identifying plasma proteins predicting cerebrovascular events.

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.

Juvenile idiopathic arthritis (JIA) associated uveitis can cause vision loss in children, but mechanisms remain unclear. The authors here identify elevated CD19⁺IgD^-CD27^- double negative type 1 B cells in JIA-uveitis and show that targeting B-T cell interactions suppresses disease in mouse models of uveitis.

Early life RSV infection contributes to risk of childhood asthma. Here, the authors develop a statistical model to predict age at first RSV infection in the United States based on birthdate, demographics, and RSV surveillance data which could be used to identify groups at risk of chronic respiratory sequalae like asthma.

This study uncovers a mechanism for innate immune memory in neurons, demonstrated by a more silent epigenetic structure of the Herpes Simplex Virus genome, resulting in a deep form of latent infection that is restricted for reactivation of the virus.

Understanding the mechanisms underlying the survival of drug tolerant persister cells following chemotherapy remains elusive. Here, multi-omics analysis and experimental approaches show that the germ-cell-specific H3K4 methyltransferase PRDM9 promotes metabolic rewiring in glioblastoma stem cells.

Analysis of 37 genomes together with more than 140 phenotypic traits links genomic features to ecological fitness and lifestyle diversity in Trichoderma fungi.

SCEP3 is a new synaptonemal complex protein that prevents clustering of crossovers during meiosis in Arabidopsis, so that every pair of homologous chromosomes receives at least one ‘obligate’ crossover.

ApoE4 is a risk factor for small vessel disease, which can lead to cognitive impairment. Here the authors assess the microvasculature of the corpus callosum using 3-photon microscopy and find that mice expressing the ApoE4 allele are more susceptible than wild-type to white matter injury and cognitive impairment in a model of hypoperfusion-induced hypoxia.

The UK government last week published a White Paper (Cmnd. 6820) in response to the Flowers Commission report on nuclear power and the environment. Chris Sherwell reports

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.

Cellular imaging studies can generate large volumes of complex phenotypic data; however, presenting this information in a form that quickly conveys trends in the data set remains a challenge. Sailem et al.present a tool which translates such data into easily interpretable cell-like glyphs.

Stroke affects the brain in complex, highly individual ways. Here, the authors show that applying generative and causal AI methods to routinely collected brain scans may enable more closely personalized treatment recommendations.

Ward et al. utilise electronic health records to identify groups of adults (who had received a second booster dose of a COVID-19 vaccine) at elevated risk of COVID-19 death.

Kinematic measurements of the Perseus galaxy cluster reveal two drivers of gas motions: a small-scale driver in the inner core associated with black-hole feedback and a large-scale driver in the outer core powered by mergers.

Evolutionarily related ‘proto-point’ centromeres providing resolution to the evolutionary origins of point centromeres are identified in yeast, and comparison shows they evolved in an ancestor with retrotransposon-rich centromeres and that long-terminal-repeat retrotransposons are the genetic substrate.

Men outnumber and out-earn women, and white people take up more posts and are more likely to be in the highest pay grades than people from minority ethnic groups.

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).

Polygenic risk scores can help identify individuals at higher risk of type 2 diabetes. Here, the authors characterise a multi-ancestry score across nearly 900,000 people, showing that its predictive value depends on demographic and clinical context and extends to related traits and complications.

As presented at the ESMO Congress 2025: Results of the phase 2/3 AGITG DYNAMIC-III trial show that de-escalated chemotherapy based on ctDNA-negative status in patients with stage III colon cancer did not meet non-inferiority for 3-year recurrence-free survival when compared to standard of care, although it enables better informed treatment decisions.