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In this Stage 2 Registered Report, Buchanan et al. show evidence confirming the phenomenon of semantic priming across speakers of 19 diverse languages.

The transcription factor COUP-TFII plays a critical role in regulating endothelial cell (EC) identity. Here the authors report that the ectopic expression of COUP-TFII in endothelial cells induces molecular programs of post-capillary venules in tumor EC, associated with enhanced recruitment of anti-tumour T cells, inhibition of tumour growth, and sensitized responses to immune checkpoint blockade and adoptive T cell transfer therapies.

The authors use surface acoustic waves, focused in a Gaussian geometry, to manipulate the spin state of divacancy defects in silicon carbide via mechanical driving. They demonstrate that shear strain is important in controlling the spin transitions.

Here the authors characterize the evolutionarily conserved role of the Arp2/3 actin nucleation complex in double-strand break mobility in budding yeast. Arp2/3 has important roles in end resection and Mec1-mediated DNA damage checkpoint activation.

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.

Shoals of fish can more quickly solve a two-stage foraging task when individuals experienced in only one stage of each task are combined, demonstrating that pooling experiences can aid collective problem-solving in animal groups.

A free-living trial in people with overweight or obesity found that minimally processed diets led to greater weight loss and cardiometabolic improvements than ultraprocessed diets following UK healthy eating guidelines at 8 weeks.

Assessing the degree to which medical large language models reliably convey existing, trustworthy knowledge is crucial. This study introduces SourceCheckup, an automated framework revealing that large language models frequently cite medical references that do not fully support, or even contradict, their responses, showing significant gaps in reliability for clinical use.

Pocock et al. reveal that transient activation of 5′ AMP-activated protein kinase and estrogen-related receptor drives robust maturation of multicellular human cardiac organoids, enabling modeling of desmoplakin cardiomyopathy dysfunction, which could be rescued using the bromodomain and extra-terminal inhibitor INCB054329.

The epigenetic changes underlying the heterogeneity of RA disease presentation have been the subject of intense scrutiny. In this study, the authors use multiple single-cell sequencing datasets to define ‘chromatin superstates’ in patients with RA, which associate with distinct transcription factors and disease phenotypes.

A genome-wide study by the Long COVID Host Genetics Initiative identifies an association between the FOXP4 locus and long COVID, implicating altered lung function in its pathophysiology.

The way of things.

Apolipoprotein L1 genetic variants contribute to a subtype of proteinuric kidney disease referred to as APOL1-mediated kidney disease (AMKD). Here the authors report the discovery and characterization of potent and selective APOL1 ion channel inhibitors for the potential treatment of AMKD.

Mucosal melanoma (MM) is a cancer with poor prognosis derived from mucosal melanocytes. Here, the authors implement a combination of genetic changes that occur in MM patients in a zebrafish model, revealing the potential MM cell of origin and showing that patient and zebrafish MMs share a gene signature that is more metastatic and immune-evasive.

Aggregates of misfolded proteins are sequestered in the aggresome via dynein transport in an aggregate size-dependent manner. Here, authors find episodic transport kinetics mediated by aggresome-dynein adapters are central to this size-filter effect.

In vivo chimeric antigen receptor (CAR)-T cell engineering uses targeted delivery systems to generate CAR-T cells directly in patients, bypassing ex vivo manufacturing. This Review examines emerging viral and lipid nanoparticle platforms, early clinical proof of concept and potential applications beyond cancer.

Despite the availability of chromatin conformation capture experiments, discerning the relationship between the 1D genome and 3D conformation remains a challenge. Here, the authors propose a method that produces low-dimensional latent representations that summarize intra-chromosomal Hi-C contacts.

Melting experiments with planetary materials show that oxidized core formation occurred via percolation of molten sulfide at low igneous temperatures.

Acquiring biomarkers from blood or sweat is limited by invasiveness or biofouling. Skin gas emissions bypass these issues, offering rich biosignals. Authors present passive sensing strategies capturing water vapor (Sweat rate), CO2, and VOCs, enabling real-time tracking of physiological changes.

In a comprehensive dataset from 3,652 patients across 20 centers in eight countries, an ultrasound-based AI model shows robust performance across centers, ultrasound systems, 58 histological diagnoses and patient age groups and reduced referral to experts by 63% in a retrospective triage simulation.

Bilateral vestibular schwannomas (VS) are the main feature of NF2-related schwannomatosis, but the immunological landscape of VS is poorly understood. By performing imaging mass cytometry, the authors assess the cellular heterogeneity in VS tumours and reveal niche-dependent modes of T-cell regulation in these neoplasms.

Das et al. show that the correct editing activity of the methionyl tRNA synthetase, regulated by AIMP3, is required to prevent the accumulation of homocysteine and the resulting cardiomyocyte cell death and cardiac dysfunction.

Kevin Boehnke and Richard E. Harris introduced a course in meditation, yoga and mindfulness to the neuroscience programme at their institution.

Cohesin plays a crucial role in both chromosome organization and DNA repair. Here the authors find that cohesin mediated genome architecture prevents interactions between damaged chromatin. In contrast cohesin phosphorylation  appears to primarily impact DNA repair speed.

In a post hoc multiomics analysis of a trial comparing a plant-based, low-fat diet to an animal-based, ketogenic diet, the diets have differential effects on peripheral immune cell frequencies and immune-related gene expression.

Microglia mediate the early and selective degeneration of corticostriatal synapses and the development of cognitive deficits in presymptomatic Huntington’s disease via the complement cascade.

Electron-electron interactions in many-body systems may manifest themselves through the fractional quantum Hall effect. Here, the authors perform transport measurements in bilayer graphene, and observe particle-hole symmetric fractional quantum Hall states in theN=2 Landau level.

With an improved framework for model development and evaluation, a large language model is shown to provide answers to medical questions that are comparable or preferred with respect to those provided by human physicians.

InstaNovo, a transformer-based model, and InstaNovo+, a multinomial diffusion model, enhance de novo peptide sequencing, enabling discovery of novel peptides, improved therapeutics sequencing coverage and detection of unreported organisms in proteomics studies

The function of single-nucleotide variants can now be tested in a base editor mouse model.

Brucella melitensis is a zoonotic bacterial pathogen of livestock that can infect humans and causes brucellosis. Here, the authors sequence an ancient specimen of B. melitensis and show that the species emerged in the Neolithic period, around the time of development of animal management practices.

Ventricular arrhythmias after heart attack are a leading cause of death. Here the authors show, in a porcine model, that KCNE3 and KCNE4 upregulation and a unique pattern of repolarization heterogeneity in the scar facilitate reentrant ventricular tachycardia.

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.

An analysis of 38 ancient genomes from the aurochs, the extinct ancestor of modern cattle, provides insight into the population ancestry and domestication of this species.

This study challenges the prevailing paradigm that wetness drives peat carbon accumulation, by showing that increased catchment water and nutrient inputs to high-latitude peatlands reduce recent carbon accumulation because of enhanced peat decay.

A major challenge in coronavirus vaccination and treatment is to counteract rapid viral evolution and mutations. Here the authors show that CRISPR-Cas13d can be used as a broad-spectrum antiviral to inhibit human coronaviruses, including new SARS-CoV-2 variants, combined with small molecule drugs for an enhanced antiviral effect in human primary cells.

Though it is the most common joint disease, osteoarthritis has no molecular biomarkers or disease-modifying therapies. Here, the authors show miR-126-3p is a mechanistic biomarker that regulates angiogenesis and mitigates knee osteoarthritis severity.

Bacterial biofilms rely on shared extracellular polymeric substances (EPS) and are often highly tolerant to antibiotics. Here, the authors show in in vitro experiments that Salmonella does not evolve resistance to EPS inhibition because such strains are outcompeted by a susceptible strain under inhibitor treatment.

Dinosaur relatives called pterosaurs are the earliest known flying vertebrates. The branch of the evolutionary tree from which pterosaurs evolved has been unclear, but new fossil discoveries offer a solution to the mystery.

The role of IFN signaling in SARS-CoV-2 infection and outcome is still debated. Here, the authors longitudinally profiled plasma samples from hospitalized patients and show that a persistent inflammatory response is linked to delayed generation of adaptive immunity and increased risk of death when coupled with severe infection.

δ-Opioid receptors (δOR) are promising targets for pain management with reduced side effects. Here, the authors use a structure-based approach to design and characterize C6-Quino, a selective δOR partial agonist, highlighting its potential therapeutic relevance.

Azacitidine (AZA) response in myelodysplastic neoplasms is unpredictable. Here, the authors show in a phase 2 trial that while global methylation changes did not differ by response, baseline and initial CpG methylation differences in HSPCs predicted AZA response.

This study investigates the protection provided by mRNA COVID-19 vaccine booster doses against Omicron-associated severe disease in adults aged 50 and older. The authors use data from Ontario, Canada, and find that booster doses provide strong protection but that it declined during the period of BA.4/BA.5 predominance.

Astrocyte activation may contribute to neurodegenerative disease. Here the authors show that the combined knockout of three factors known to promote astrogliosis, IL-1α, TNFα and C1qa, leads to improved survival in the SOD1^G93A mouse model of ALS.

Jeppesen, Sanchez et al. identify blebbisomes as large membrane-enclosed vesicles containing organelles and secreted by cells. Blebbisomes can both secrete and internalize exosomes and microvesicles.