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Here, the authors develop Q4ddPCR, a high-throughput assay to quantify genetically intact HIV reservoirs by targeting four regions, and demonstrate that it reduces assay dropout to 5%, tracks reservoir decay, and closely correlates with viral outgrowth.

While therapies targeting type I BRAF mutations have been developed, there are limited options for those with type II and III mutations. Here, the authors identify a subset of BRAF-mutant non-small cell lung cancer patients and characterise the pan-RAF inhibitor exarafenib, demonstrating efficacy in preclinical models and investigating subsequent resistance mechanisms.

The role of the innate immune system in pancreatic cancer is largely unexplored. Here, the authors reveal a targetable cancer cell-intrinsic axis in pancreatic cancer comprising ASC inflammasome complexes that link innate immunity with mitochondrial function and metabolism.

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

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.

This study introduces a semi-automated, scalable whole-brain mapping workflow that enables unbiased comparisons across cohorts, revealing widespread temporally and sexually distinct regional activation patterns after acute morphine exposure in mice.

Estimates from the Global Burden of Disease study reveal declines in chronic respiratory disease mortality between 1990 and 2023—especially during the COVID-19 pandemic—but the burdens on people affected remain substantial.

Metabolite signatures were identified for subtypes of dietary carbohydrate, including added sugar, whole grain and refined grain, and showed different associations with type 2 diabetes, providing an objective measure of dietary risk.

Post-transcriptional regulation of mRNA translation was explored using Ribo-STAMP and single-cell RNA sequencing to reveal cell-type-specific and isoform-specific translation patterns across hippocampal neuronal and non-neuronal cell types, highlighting functional differences between CA1 and CA3.

Genome-wide association meta-analysis identifies 58 independent risk loci for major anxiety disorders among individuals of European ancestry and implicates GABAergic signaling as a potential mechanism underlying genetic risk for these disorders.

The high-plasticity cell state (HPCS) is a critical hub that enables reciprocal transitions between cancer cell states, and targeting the HPCS may suppress cancer progression and eradicate treatment resistance.

Identifying jets originating from heavy quarks plays a fundamental role in hadronic collider experiments. In this work, the ATLAS Collaboration describes and tests a transformer-based neural network architecture for jet flavour tagging based on low-level input and physics-inspired constraints.

CFAP20 has a key role in rescuing RNA polymerase II complexes that have arrested during DNA transcription, limiting the accumulation of R-loops and preventing collisions between the transcription and replication machinery.

Semaglutide, a GLP-1 receptor agonist, may offer neuroprotective benefits after stroke, but its effects in large vessel occlusion (LVO) are unknown. Here the authors show, in a phase 2 randomized trial, that semaglutide is safe after endovascular therapy and may improve recovery in patients not receiving intravenous thrombolysis.

Chan and colleagues report that tumor ecosystem and microbiome features are associated with response to anti-PD-L1 avelumab plus chemoradiotherapy in patients with locally advanced head and neck cancer.

The PCRCR complex of Plasmodium spp. binds basigin on the erythrocyte surface. While Rh5 of the complex is restricted to P. falciparum, PTRAMP, CSS and Ripr orthologs are present across the genus, for which the authors report common features.

Exploration of the chemistry of allylic, benzylic, propargylic and allenylic oxonium ions is lacking despite the latest developments in onium ion chemistry. Now, a unified approach for the synthesis and NMR spectroscopic characterization of these unusual species is reported, helping to understand their reactivity.

Somatic instability plays a role in Huntington’s disease. Here, the authors show that lowering HTT levels by transcriptional repression suppresses somatic instability. This can also be done without affecting HTT levels by direct CAG repeat binding.

Several recent publications have attempted to detect novel unannotated microproteins using mass spectrometry proteomics. Here, the authors reassess these claimed microprotein detections, finding that many are poorly supported, while a subset represents likely genuine discoveries of novel proteins.

Projected impacts of climate change on malaria burden in Africa by 2050 highlight the urgent need for climate-resilient malaria control strategies and robust emergency response systems to safeguard progress towards malaria eradication.

Newly developed mouse models that enable cell-specific analyses of proteostasis dynamics across the lifespan of the mice reveal key aspects of neuronal proteostasis with ageing.

Dynamic cellular changes within the tumor immune microenvironment inform clinical responses. Two studies now present automated tools that analyze complex spatial patterns to discern prognostic spatial features of triple-negative breast cancer specific to cell interactions at the tumor border or metastatic site.

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.

Vinyard et al. present a generative method to model cell dynamics using neural stochastic differential equations that learn state-dependent drift and diffusion, outperforming existing approaches and enabling perturbation studies of development and disease.

High-throughput chemical ligand discovery is challenged by false positives. Here, authors introduce a scalable enantioselective affinity-selection mass spectrometry approach for proteome-wide ligand discovery with high sensitivity and selectivity

Cheng et al., use non-infectious stable viral replicon cell lines in genome-wide CRISPR KO screens across diverse viral pathogens to identify host factors specifically involved in the intracellular stages of viral replication.

popEVE is a proteome-wide deep generative model to identify and predict pathogenicity of missense mutations causing genetic disorders.

Korobkina et al. show that ACLY in brown fat prevents metabolic overload in the tricarboxylic acid cycle, thus ensuring adequate thermogenesis by avoiding cellular stress.

A 15-year prospective cohort study found that during times of social unrest in Hong Kong, people experienced more conflicts with family and friends and this coincided with the use of social media—these factors were also associated with higher levels of depression.

MultiSTAAR provides a general and flexible statistical framework for functionally informed multi-trait rare variant analysis of biobank-scale sequencing studies by jointly analyzing multiple traits and incorporating annotation information.

Schooley et al. find that mitotically bookmarked loci drive a transient chromosome folding state during G1 entry that is subsequently modulated by factors inherited through the cytoplasm.

NutriSighT, an interpretable AI transformer model, accurately predicts which mechanically ventilated ICU patients are at risk of underfeeding, enabling clinicians to personalize nutritional care

Lam et al. evaluate a self-report scale and eight BERT-family large language models trained on clinical interview transcripts to detect clinician-rated depression in people with and without alexithymia. All models detect depression more accurately than the self-report scales in detecting depression, particularly in those with alexithymia.

This Article details the methods used for rigorous assessment of disease interventions in a multicenter preclinical trial. Using stroke models as proof of concept, it offers adaptable protocols for any field requiring robust preclinical validation.

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.

Plasmid-mediated transmission plays a significant role in the spread of carbapenem-resistant Enterobacterales. Here, analyzing 1,115 carbapenemase-producing plasmids from Singapore, the authors suggest that maintenance of conserved genomes adapted for stable propagation across multiple species, enables evolutionarily successful carbapenemase plasmid genotypes to achieve hyperendemicity in the population.

The authors show that the CD4 mimetic CJF-III-288 stabilizes HIV-1 Env in an asymmetric “open” State-3 conformation, guiding anti-CoRBS antibodies to boost ADCC against infected cells and delay viral rebound in vivo, underscoring therapeutic promise.