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This scoping review examines previous experience in performing silent evaluations of clinical AI applications, collecting evidence from 75 studies on implementation features and the sociotechnical context.

A 3D soft electronic mesh allows high-resolution electrical recording and stimulation across the full surface of neural organoids, enabling long-term studies, drug testing and optogenetic control without compromising their viability owing to its porous design.

Synthetic cells have huge potential in model systems. Here, the authors engineer synthetic–living hybrid tumoroids that replicate tumour-immune interactions in 3D, study synthetic cells integration, and demonstrate systematic studies of immune evasion and T cell engager therapies.

Melting ice and associated sea-level change will expose new land in Antarctica. Here the authors quantify this change and combine it with our understanding of known Antarctic mineral occurrences, showing that substantial mineral deposits may become accessible over the next few centuries in Antarctica.

A wearable that continuously measures the concentration of a drug is demonstrated in humans.

Sabatino and colleagues examine expanded CD8⁺ T cell clonotypes from a small cohort of multiple sclerosis patients. They identified several cognate peptide epitopes that derive from Epstein–Barr virus, suggesting EBV reactivation may drive pathogenesis in these patients.

Over the past 40 years, 42% of tropical and subtropical ecosystems have experienced an increase in plant reliance on past precipitation, consistent with greening during the late growing season in drylands and drying during the wet-to-dry period in non-drylands.

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.

Variation in responses to bacterial and viral stimuli between Batwa rainforest hunter-gatherers and Bakiga agriculturalists from Uganda suggests population-level divergence under natural selection, with hunter-gatherers disproportionately showing signatures of positive selection.

Symmetry breaking is key to tissue formation. Now it is shown that symmetry breaking of epithelial spheroids is controlled by an interplay of collective migration with curvature and matrix remodelling.

Understanding self-replication and persistence in an out-of-equilibrium state is key to designing systems with new properties mimicking “living systems”. Here, the authors developed a synthetic small molecule system in which a transient surfactant replicator is responsible for both an autocatalytic aggregation pathway and a destructive pathway.

Phototrophic bacteria could be used for chemical manufacturing from various carbon sources. This Review discusses the pathways, engineering and potential application of solar chemical biosynthesis.

The fabrication self-sorting supramolecular gels, containing co-existing homomolecular assemblies with similar physical and chemical properties, is challenging. Here pH-controlled self-sorting gelators are reported, where the order of assembly of each component is predetermined by gelator pK_a.

Mitochondrial DNA heteroplasmy associates with context-specific nuclear CpG methylation, supported by a cell model. Heteroplasmy–CpG scores relate to mortality and cardiovascular risk, though direction and mechanisms remain unclear.

Researchers studied the blood-based metabolome of over 23,000 people from ten ethnically diverse cohorts. They identified 235 metabolites associated with future risk of type 2 diabetes (T2D). By integrating genetic and modifiable lifestyle factors, their findings provide insights into T2D mechanisms and could improve risk prediction and inform precision prevention.

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.

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.

Vassy, Dornisch and colleagues developed a genomics-based prostate cancer risk model to support a randomized clinical trial of precision screening in a national healthcare system.

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

Polymerization-inducing chimeras are a novel bifunctional modality that uses protein symmetry to sequester targets by forming insoluble supramolecular assemblies. This approach overcomes reliance on accessory proteins and differs functionally from conventional inhibitors.

Neville, Ferguson et al. show that non-canonical Polycomb repressive complex 1.1-mediated gene silencing is antagonized by DOT1L and is required for the therapeutic efficacy of Menin and DOT1L inhibitors in mixed-lineage leukaemia.

Stem-cell-derived islet cells could transform type 1 diabetes by removing the need for injected or infused insulin and improving quality of life. But evaluation of these therapies must center on the voices of people living with type 1 diabetes and examine meaningful outcomes.

RNAi therapy has huge potential but effective delivery to target location is a major issue. Here, the authors report on the delivery of RNAi to tumors using self-agglomerating nanohydrogels that can overcome the different delivery barriers and supply multiple RNAi payloads.

Maurice et al. examine how cytokines regulate antigen-independent activation of memory CD8⁺ T cells. They show that IL-4 signaling changes the quality of the bystander T cell response by antagonizing IL-18 sensing and subsequent IFNγ production, but increasing granzyme B expression without changing perforin, thereby limiting bystander-mediated protection.

The Earth’s continents amalgamated into the supercontinent Pangaea 320 million years ago. After the supercontinent formed, structural deformation continued, which eventually resulted in the subduction of the ocean margin of Pangaea beneath the continental edge at the other end of the same plate.

The protospacer-adjacent motif specificity of several Cas enzymes is customized using protein language models.

In a randomized phase 2 trial in patients with acute coronary syndrome and high levels of the inflammation biomarker C-reactive protein, treatment with low-dose interleukin-2 increased the numbers of regulatory T cells and reduced arterial inflammation, compared to placebo.

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.

Hexim regulates transcription by sequestering kinase P-TEFb in the 7SK RNP. Here, the authors show that Hexim autoinhibition dictates its specificity for 7SK RNA and safeguards against premature P-TEFb inactivation, coupling transcriptional control to RNP assembly.

A prospective nationwide genomic screening pilot for ten genes in young adults in Australia detected pathogenic variants in 2% of the population, most of whom were ineligible for government-funded genomic testing.

“This randomized controlled trial in adults with central obesity found that high-intensity interval training, performed once or thrice weekly, reduced body fat mass compared with control, highlighting the benefits of “weekend warrior” interventions.”

Intracellular redox state orchestrates a self-reinforcing circuit connecting hypoxia inducible factor 1α-dependent signalling with post-translational regulation of the metabolic enzyme isocitrate dehydrogenase 1 to govern intestinal stem cell fate.

The R21/Matrix-M vaccine, but not the ME-TRAP vaccine, was protective against intradermal challenge with Plasmodium falciparum sporozoites, while neither was protective against direct venous inoculation, potentially explaining previously observed differences in protection.

Membrane ion channels can be responsive to a variety of stimuli such as pressure, temperature, or pH. Here, the authors show that simply shining 365 nm light activates a native potassium channel in rodent pain-sensing neurons, delivering powerful analgesia without drugs or genetic manipulations.

De novo and inherited dominant variants in genes encoding U4 and U6 small nuclear RNAs are identified in individuals with retinitis pigmentosa. The variants cluster at nucleotide positions distinct from those implicated in neurodevelopmental disorders.

The lowest-frequency gravitational wave background may be shaped by supermassive black hole binaries that scatter nearby stars or dark matter. In this case, the NANOGrav 15-year dataset favours dense galactic centres with 10⁶ solar masses per cubic parsec.

Using chemical photoswitchable reagents to exert purely wavelength-dependent control over biological systems in deep tissue and in vivo requires a concentration-independent design paradigm. Here, such photoswitchable ligands are realized by ensuring that E/Z isomers have opposing efficacies yet similarly high affinity, allowing them to probe transient receptor potential C4 and C5 channel functions up to the tissue level.

One of three back-to-back papers to show that dosage of BACH2 can modulate T cell differentiation and function and how we might apply this to enhance CAR T cell therapies for cancer.

Serapio-García, Safdari and colleagues develop a method based on psychometric tests to measure and validate personality-like traits in LLMs. Large, instruction-tuned models give reliable personality measurement results, and specific personality profiles can be mimicked in downstream tasks.

Using two-photon intravital imaging, the authors show that mechanical stress in skin triggers fluid-filled “stress vesicles” in epidermal cells, altering Piezo1-dependent calcium signals to drive stem cell differentiation and protect tissue integrity.

Affinity-proteomics platforms often yield poorly correlated measurements. Here, the authors show that protein-altering variants drive a portion of inter-platform inconsistency and that accounting for genetic variants can improve concordance of protein measures and phenotypic associations across ancestries.

Radiation reaction (RR) on particles in strong fields is the subject of intense experimental research, but previous efforts lacked statistical significance due to the extreme regimes required. Here, the authors report a 5σ observation of RR and obtain strong, quantitative evidence favouring quantum models over classical, using an all-optical setup where electrons are accelerated by a laser in a gas jet before colliding with a second, intense pulse.

The Taiwan Precision Medicine Initiative recruited and genotyped more than half a million Taiwanese participants, almost all of Han Chinese ancestry, and performed comprehensive genomic analyses and developed polygenic risk score prediction models for numerous health conditions.

In this Viewpoint, actor, author, and broadcaster Stephen Fry describes his prostate cancer journey alongside the same story from his surgeon, Ben Challacombe, enabling us to consider “both sides of the scalpel”.

Barcoding aids in the optimization of lipid nanoparticles. Here, the authors report on multiplexed mRNA barcoding that enables high-resolution spatiotemporal profiling of lipid nanoparticles, linking accumulation kinetics to functional delivery and revealing zonal liver targeting.

The literature assumes that intergroup contact is naturally occurring, positive and consistently associated with positive outcomes, but these premises are inconsistent with everyday intergroup contact experiences. In this Perspective, Paolini et al. propose that variations in contact valence and environmental affordances for self-selection influence segregation dynamics, leading to stable trajectories of contact and intergroup bias.

Harmonizing data from 2390 participants across four diverse reaching studies, this work quantifies how age, sex/gender, and everyday experience influence reaction time, movement speed, and precision—establishing a robust normative benchmark for human motor control.

Many clinically relevant pathogens enter the body through mucosal surfaces, yet conventional parenteral immunization is insufficient to elicit robust mucosal immunity. This Review examines the unique anatomical and immunological features of the mucosal surfaces of the body and how this knowledge can be used to develop protective mucosal vaccines.