Search

In a randomized study involving 9 general cardiologists and 107 real-world patient cases, assistance from a specifically tailored large language model resulted in preferable responses on complex case management compared to physicians alone, as rated by specialist cardiologists using a multidimensional scoring rubric.

A comprehensive atlas platform integrating transcriptional and epigenetic data enables more precise engineering of T cell states, accelerating the rational design of more effective cellular immunotherapies.

Transcriptomic and clinical data analyses from multiple cohorts of patients with cancer receiving immunotherapy find that PD-1 blockade potentiates tumor-specific IgG1 plasma cell responses that complement cellular immunity and contribute to clinical benefit.

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.

Genome-wide association studies (GWAS) have improved our understanding of the genetic basis of lung adenocarcinoma but known susceptibility variants explain only a small fraction of the familial risk. Here, the authors perform a two-stage GWAS and report 12 novel genetic loci associated with lung adenocarcinoma in East Asians.

RNA G-quadruplexes (rG4s) are structures formed in guanine-rich regions of RNA that can serve as crucial regulatory elements in gene expression. Here the authors present an RNA language model for transcriptome-wide prediction of rG4s and genetic variants that disrupt or create them.

Telomere maintenance by telomerase depends on the correct assembly and the recruitment of the enzyme complex. Here, the authors reveal that the RNA/DNA binding proteins NONO, SFPQ, and PSPC1 interact with telomerase via the hTR RNA template, facilitating telomerase trafficking out of Cajal bodies and recruitment to the telomere.

Federated learning (FL) algorithms have emerged as a promising solution to train models for healthcare imaging across institutions while preserving privacy. Here, the authors describe the Federated Tumor Segmentation (FeTS) challenge for the decentralised benchmarking of FL algorithms and evaluation of Healthcare AI algorithm generalizability in real-world cancer imaging datasets.

The authors find that TDP-43 loss of function—the pathology defining the neurodegenerative conditions ALS and FTD—induces novel mRNA polyadenylation events, which have different effects, including an increase in RNA stability, leading to higher protein levels.

A light-induced spin voltage is demonstrated that arises from a spin-dependent excitation and diffusion of photo-excited electrons near heavy-metal/magnetic-insulator interfaces.

By carefully dispersing small amounts of Ir into the RuO₂ lattice, a Ru₆IrOₓ catalyst reduces Ir usage by 80% while still running stably for over 1,500 h at 2 A cm⁻² in both laboratory- and industrial-scale proton-exchange membrane water electrolysers.

Central serous chorioretinopathy is an eye disease whose etiology is not well known. Here, the authors performed genetic association studies and identified vascular endothelial protein tyrosine phosphatase (VE-PTP) as a likely regulator of the risk of central serous chorioretinopathy, as well as other eye and vascular diseases.

A phase I trial of a neoantigen-targeting personalized cancer vaccine led to durable and polyfunctional T cell responses and antitumour recognition, and was associated with no recurrence in patients with high-risk clear cell renal cell carcinoma.

A multi-ancestry genome-wide association meta-analysis of kidney cancer identifies 63 regions associated with disease susceptibility including one locus that was associated with increased risk in individuals with African ancestry.

A genome-wide association study including over 76,000 individuals with schizophrenia and over 243,000 control individuals identifies common variant associations at 287 genomic loci, and further fine-mapping analyses highlight the importance of genes involved in synaptic processes.

Multi-ancestry genome-wide analyses identify new risk loci for age-related macular degeneration. Ancestry-specific analyses identify distinct effects at major risk loci, including smaller effect sizes for CFH risk alleles in haplotypes of African ancestry.

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).

Neuroinflammation is observed in Alzheimer’s disease. Here the authors show that 15 proteins related to inflammation found in CSF can potentially be used as a prognostic biomarker.

Ghosh et al study transcriptional diversification in the human-adapting zoonotic pathogen, Bordetella hinzii, as it evolved during the course of a chronic infection, revealing plasticity and niche-specific functional adaptation to the blood and gastrointestinal compartments.

A survey of the CD4⁺ T cells in human melanomas indicates that immune evasion is mediated through direct stimulation of neoantigen-specific tumour-reactive regulatory T cells by HLA class II-positive melanoma cells.

Here, the authors use computational screening and a chemogenetic analysis of transgenic mice to show that Gα_s-coupled G-protein-coupled receptors on exhausted CD8⁺ T cells are involved in suppression of effector functions and inhibition of the protective effects of immune checkpoint immunotherapy.

Hydroxyl-carboxylic acid receptor 2 (HCA2) functions as a high-affinity receptor for nicotinic acid (vitamin B3). Here, authors report the cryo-EM structure of the HCA2-G_i complex with the agonist MK-6892 and inactive state crystal structures of mutation stabilized HCA2, to describe the mechanism of HCA2 signaling.

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.

Circulating cell-free DNA (cfDNA) assays for monitoring individuals with cancer typically use tumor-specific mutations that may not be detected in many patients. Here, the authors develop a tumor-independent and mutation-independent approach (DELFI-TF) to estimate tumor burden in cfDNA for treatment response monitoring and clinical outcome prediction.

This overview of the ENCODE project outlines the data accumulated so far, revealing that 80% of the human genome now has at least one biochemical function assigned to it; the newly identified functional elements should aid the interpretation of results of genome-wide association studies, as many correspond to sites of association with human disease.

Configuration control of non-conservative multi-body systems is challenging. Here, the authors develop a general method using parametric pumping to selectively excite and destroy undesired structures to populate a targeted one, and demonstrate it with acoustically levitated particle systems.

A high-resolution, global atlas of mortality of children under five years of age between 2000 and 2017 highlights subnational geographical inequalities in the distribution, rates and absolute counts of child deaths by age.

High-quality diploid assemblies of potato genomes from 24 wild and 20 cultivated potatoes provide insights into the complex evolution and diversity of potatoes, and could have applications in the breeding of hybrid potatoes.

Whether multimorbidity accelerates brain Aβ deposition in humans remains largely unknown. Here, the authors demonstrate that higher self-reported multimorbidity burden predicts increased brain Aβ accumulation rates in the ADNI cohort.

Samples of different body regions from hundreds of human donors are used to study how genetic variation influences gene expression levels in 44 disease-relevant tissues.

Screening in Escherichia coli and biochemical experiments show that in Arabidopsis thaliana, OSCA2.1 and OSCA2.2 function as plant sensors of hypo-osmolarity, utilize Ca²⁺ oscillations as second messengers and have crucial roles in pollen germination.

Purifying C₂H₂ by removing trace CO₂ is needed but challenging due to their analogous physical properties. Herein, the authors report the pilot-scale production of a commercial resin adsorbent loaded with polyethyleneimine for the selective capture of CO₂ traces and exclusion of C₂H₂.

John Chambers, Jaspal Kooner, Pim van der Harst, Shyong Tai, Paul Elliott, Jiang He, Norihiro Kato and colleagues performed a genome-wide association study of blood pressure phenotypes in individuals of European, East Asian and South Asian ancestry. They find trait-associated SNPs at 12 loci, some of which are associated with methylation at nearby CpG sites.

A comprehensive analysis of the cell-specific molecular regulatory mechanisms underlying post-traumatic stress disorder in the human prefrontal cortex.

Population-based surveys are the gold standard for estimating seroprevalence but are expensive and often only capture a small geographic area or window of time. This study describes a new platform, SCALE-IT, for serosurveillance based on algorithmic sampling of electronic health records, and uses it to estimate the seroprevalence of SARS-CoV-2 in San Francisco.

The paper reveals areas of common and differentiated SDG priority at the national and subnational levels in China considering synergy and trade-off. The findings suggest that provincial governments should formulate more targeted policy aligning with national priority to achieve SDGs.

Highly pathogenic avian influenza virus subtype H5 is an important pathogen of wild birds and poultry that has also caused infection in humans and other mammals. Here the authors use wild bird movement tracking data and virus genome sequences to quantify how seasonal bird migration facilitates global dispersal of the virus.

This study finds that sST2 is a disease-causing factor for Alzheimer’s disease. Higher sST2 levels impair microglial Aβ clearance in APOE4⁺ female individuals. A genetic variant, rs1921622, is associated with a reduction in sST2 level and protects against AD in APOE4⁺ female individuals.

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.

Qing Lan and colleagues report the results of a genome-wide association study of lung cancer in never-smoking women from Asia. They identify three new susceptibility loci and confirm three other previously reported associations.

Germline variants may pre-dispose patients to an increased risk of developing anthracycline-induced cardiotoxicity. This report provides insights into the mechanism by which a common genetic variant, rs28714259, may confer an increased risk of cardiac damage.

Experimental warming of the active layer in permafrost tundra increased ecosystem respiration ~30%. Shoulder-season warming caused rapid snow melt and 100-fold higher methane emissions. Warming promotes greenhouse gas emissions, potentially contributing to arctic amplification of climate change

Rhombohedral-stacked molybdenum disulfide with sliding ferroelectric behaviour can be used to create atomically thin ferroelectric transistors for computing-in-memory device applications.

This study reports on biologically sourced polymuconate polymers with weakened C–C backbone bonds, designed for closed-loop chemical recycling to monomers. Synthesized via free-radical polymerization, these materials achieve tunable mechanical properties comparable to those of commercial plastics. A techno-economic analysis shows that recycling significantly reduces costs and environmental impacts, enhancing the competitiveness of these polymers in the sustainable plastics market.

Slide-tags enables multiomic sequencing of single cells and their localization within tissues.

The authors develop a new oxide-dispersion-strengthened NiCoCr-based alloy using a model-driven alloy design approach and laser-based additive manufacturing, showing how such designs can provide superior compositions using far fewer resources than previous methods.

Roland et al. report the results of a randomized, non-comparative phase 2 trial of neoadjuvant nivolumab or a combination of nivolumab and ipilimumab in patients with resectable retroperitoneal dedifferentiated liposarcoma and extremity/truncal undifferentiated pleomorphic sarcoma.

Disruption of mucin-domain glycoprotein expression and function in the endothelial glycocalyx are associated with ageing and Alzheimer’s disease, leading to dysregulated blood–brain barrier function.