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MedHELM, an extensible evaluation framework including a new taxonomy for classifying medical tasks and a benchmark of many datasets across these categories, enables the evaluation of large language models on real-world clinical tasks.

The anterior cingulate cortex encodes affective pain behaviours modulated by opioids; targeting opioid-sensitive neurons through a new chemogenetic gene therapy replicates the analgesic effects of morphine, providing precise chronic pain relief without affecting sensory detection.

The authors report an integrated triply-resonant superconducting electro-optic transducer combining a 107 GHz NbTiN resonator with a thin-film lithium niobate optical racetrack at telecom wavelengths. Achieving η_OE ≈ 0.82 × 10⁻⁶ and g₀/2π ≈ 0.7 kHz, this work analyzes mm-wave resonator design challenges and proposes strategies for improved quantum transduction.

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

Many premalignant colorectal polyps in familial adenomatous polyposis arise polyclonally rather than from a single mutated cell, showing diverse early evolutionary trajectories that frequently occur without clonal APC or KRAS driver events.

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.

Global Burden of Disease estimates show that between 1990 and 2023, the prevalence and burden of drug use disorders, inclusive of amphetamine, cannabis, cocaine and opioid use, have been increasing in high-income countries, particularly in the USA.

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.

While the connectivity of VTA dopamine neurons is well studied, less is known about the connectivity of VTA glutamate and GABA neurons. Here, authors show that these neurons form local circuits to modulate reward, aversion, feeding and locomotion.

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.

Sleep-active physiological processes enhance overnight glymphatic clearance of Alzheimer’s disease biomarkers into plasma in humans, supporting the critical role of glymphatic function in Alzheimer’s pathophysiology and its potential as a therapeutic target.

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.

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.

A method, RARE-seq, for sensitive detection of cell-free RNAs in blood is demonstrated to have diverse clinical applications including diagnosing and characterizing human cancers, and tracking response to RNA therapeutics.

A flexible micro-electrocorticography brain–computer interface that integrates a 256 × 256 array of electrodes, signal processing, data telemetry and wireless powering on a single complementary metal–oxide–semiconductor substrate can provide stable, chronic in vivo recordings.

A combination of genome-wide functional screening, imaging and chromatin profiling identifies a new class of highly prevalent genomic elements that help retain extrachromosomal DNA copies in dividing cells and persist across generations.

Thomas, Noishiki, Gaddam et al. used thrombotic vascular tissues and iPSC-derived cardiac organoids to show that COVID-19-induced endotheliitis and cytokine release disrupt endothelial–cardiomyocyte crosstalk and contribute to cardiac dysfunction in long COVID.

A human ascending somatosensory assembloid model was developed, which integrates multiple organoids to simulate the spinothalamic pathway, demonstrating functional connectivity and responsiveness to stimuli and revealing insights into pain-related genetic mutations.

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.

Human stem cell-derived cortical organoids transplanted into rats mature and integrate into sensory and motivation circuits to influence behaviour.

Chen et al. show that redox signals activate ADAR1 to fix faulty RNA pieces during DNA copying, ensuring smooth replication and protecting genome stability.

In 1990, I was diagnosed with cerebral palsy. Like many in the community, my parents were told explicitly that the condition has no genetic roots. Now, as research suggests that up to 30% of cases have genetic etiologies, robust community engagement is needed to ensure that the perspectives of the community shape the future of genetic research into cerebral palsy.

Females are more sensitive to social exclusion and loneliness, risk factors for anxiety and stressrelated disorders. Here, the authors identified molecular signals in the amygdala that make females more susceptible to effects of chronic social isolation in mice.

A transcriptomics study demonstrates cell-type-specific responses to differentially aged blood and shows young blood to have restorative and rejuvenating effects that may be invoked through enhanced mitochondrial function.

Dystrophic Epidermolysis Bullosa is an uncurable monogenetic skin disease. Here, Neumayer et al. develop a cGMP-compatible CRISPR- and iPS cell-based approach that produces gene-corrected, autologous skin composite grafts for definitive treatment.

A single-cell transcriptomic atlas across the lifespan of the mouse, denoted Tabula Muris Senis, provides molecular information about the hallmarks of ageing in a range of tissues and cell types.

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.

Dense multi-omics microsampling for the frequent capture and analysis of thousands of molecules in blood alongside physiological information from wearables facilitates the profiling of lifestyle-associated changes in an individual’s health.

This Review outlines the fundamental role of chimeric antigen receptor (CAR) T cell therapy for children, adolescents and young adults (CAYAs) with relapsed and/or refractory B cell acute lymphoblastic leukaemia, emphasizing the crucial need to further exploit CAR T cells and other immunotherapies to improve survival with broadened access across disease states. Opportunities and challenges for expanding CAR T cell therapy to other haematological and non-haematological malignancies in CAYAs are also discussed.

Single-walled carbon nanotubes can be modified into bright and biocompatible agents for high resolution whole-animal imaging at wavelengths in the 1100–1700 nm region.

Using data from a single time point, passenger-approximated clonal expansion rate (PACER) estimates the fitness of common driver mutations that lead to clonal haematopoiesis and identifies TCL1A activation as a mediator of clonal expansion.

The individual roles of default network regions in social thinking remain unclear. Using electrocorticography, the authors show a spatiotemporal hierarchy of neurocognitive specialization across temporoparietal and prefrontal default network regions.

Permafrost locks away the largest reservoir of mercury on the planet, but climate warming threatens to thaw these systems. Here the authors use models to show that unconstrained fossil fuel burning will dramatically increase the amount of mercury released into future ecosystems.

Specific binders to peptide–MHC class II are rapidly generated without laborious screening.

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.

Personalized omics profiling can lead to actionable health discoveries and stimulate lifestyle changes.

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.

Bulk RNA sequencing of organs and plasma proteomics at different ages across the mouse lifespan is integrated with data from the Tabula Muris Senis, a transcriptomic atlas of ageing mouse tissues, to describe organ-specific changes in gene expression during ageing.

T cell activation is a process that requires extra nutrients, which could be difficult to source from the tumor microenvironment in competition with tumor cells. Here authors increase the metabolic fitness of CAR-T cells by stable overexpression of the glucose transporter GLUT1, which allows them to increase their glucose intake and enhances their antitumour function.

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.

Targeted protein degradation of cell-surface glycoproteins suppresses cancer in mice.

This multi-omic longitudinal analysis of the healthy human peripheral immune system constructs the Human Immune Health Atlas and assembles data on immune cell composition and state changes with age, including responses to cytomegalovirus infection and influenza vaccination.

Deep profiling of transcriptomes, metabolomes, cytokines, and proteomes, alongside changes in the microbiome, in samples from individuals with and without prediabetes reveal insights into inter-individual variability and associations between changes in the microbiome and other factors.