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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.

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.

Dietary restriction promotes the expansion of effector T cells via ketone bodies, which enhances anti-tumour immunity and synergizes with immunotherapy in mice.

Using a mouse model enabling an inducible ‘switch’, Golden et al. show that an astrocyte-specific replacement of the Alzheimer’s risk gene APOE4 with protective APOE2 alters metabolism and gene expression, reducing amyloid pathology and gliosis.

Disparities in risk and outcomes of pediatric acute lymphoblastic leukemia (ALL) are apparent between different ancestries. Here the authors identify genetic variants with African ancestry-specific risks for developing pediatric B-cell ALL that are also linked to greater 5-year mortality risk.

It remains poorly understood how the onset of Alzheimer’s disease affects spatial cognition. Here, the authors report that spatial coding in grid cells deteriorates over time in a mouse model of Alzheimer’s disease during the early stages of pathology while place cell and head direction coding remain intact.

A study of several longitudinal birth cohorts and cross-sectional cohorts finds only moderate overlap in genetic variants between autism that is diagnosed earlier and that diagnosed later, so they may represent aetiologically different conditions.

Large impacts can create deep lying porosity far away from the crater. This result explains GRAIL’s findings and suggests impacts could support widespread fluid circulation, which has implications for habitable environments on early Earth and Mars.

Observations of the shape, topography, crustal thickness and surface composition of the South Pole–Aitken impact basin on the Moon suggest a southward impact trajectory and the excavation of a discontinuous remnant magma ocean from beneath the crust.

Whole-genome sequences and field experiments focusing on the global invasive forage crop, Trifolium repens, show high levels of genetic variation across continents and parallel signatures of selection in five haploblocks.

Plastic additives can hinder the mechanical recycling of plastics; a similar issue arises in chemical deconstruction, where plastic additives can deactivate catalysts. Here the authors compare hydroconversion and catalytic pyrolysis to identify specific criteria needed to mitigate the effects organic additives on the deconstruction of polyolefins.

Genome-wide association analyses identify new risk loci for heart failure and its subtypes, extending understanding of the underlying biological pathways and disease mechanisms.

Here the authors perform a trans expression quantitative trait locus meta-analysis study of over 3,700 people and link a USP18 variant to expression of 50 inflammation genes and lupus risk, highlighting how genetic regulation of immune responses drives autoimmune disease and informs new therapies.

Using multi-ancestry genome-wide association study and fine-mapping, 298 loci and 36 credible genes are identified in the aetiology of bipolar disorder.

The origin of most chondrules (small, previously molten spherules inside meteorites) is shown to be impact jetting; chondrules form from the shock-melted material ejected from a protoplanet on impact, making meteorites a byproduct of planet formation.

This study used fine-mapping to analyze genetic regions associated with bipolar disorder, identifying specific risk genes and providing new insights into the biology of the condition that may guide future research and treatment approaches.

Targeting CD8⁺ T cell exhaustion is a strategy to enhance immune checkpoint inhibition and to fight cancer. Here the authors show a NRF2-dependent role for the prostaglandin I₂ receptor PTGIR in controlling T cell exhaustion.

Multi-ancestry genome-wide analyses identify 95 loci associated with post-traumatic stress disorder and implicate candidate genes, pathways and neurobiological systems underlying its pathophysiology.

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.

The goals, resources and design of the NHLBI Trans-Omics for Precision Medicine (TOPMed) programme are described, and analyses of rare variants detected in the first 53,831 samples provide insights into mutational processes and recent human evolutionary history.

Although progress in the coverage of routine measles vaccination in children in low- and middle-income countries was made during 2000–2019, many countries remain far from the goal of 80% coverage in all districts by 2019.

Geospatial estimates of the prevalence of anemia in women of reproductive age across 82 low-income and middle-income countries reveals considerable heterogeneity and inequality at national and subnational levels, with few countries on track to meet the WHO Global Nutrition Targets by 2030.

Jayavelu, Samaha et al., apply machine learning models on hospital admission data, including antibody titers and viral load, to identify patients at high risk for Long COVID. Low antibody levels, high viral loads, chronic diseases, and female sex are key predictors, supporting early, targeted interventions.

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.

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.

Initialization and operation of spin qubits in silicon above 1 K reach fidelities sufficient for fault-tolerant operations at these temperatures.

Federated ML (FL) provides an alternative to train accurate and generalizable ML models, by only sharing numerical model updates. Here, the authors present the largest FL study to-date to generate an automatic tumor boundary detector for glioblastoma.

Bringing together multiple models and databases on nature’s contributions to people, the authors map these contributions globally and determine the critical areas where their magnitude is the highest and where they provide the highest potential human benefit.

G protein-coupled receptors (GPCRs) are important targets for drug discovery. Here, the authors develop a Virion Display array of 315 functional non-odorant GPCRs, providing a platform for high-throughput, unbiased screening for small molecule drugs, affinity reagents, and microbial interactions.

Isotopic analysis reveals that the samarium/neodymium ratio of the Earth–Moon system is higher than that of chondrites, and that the neodymium composition of Earth is similar to that of enstatite chondrites.

New data on brain-wide circuits centred around two interconnected hypothalamic neuron populations provide significant mechanistic insights into the emergence of social need during social isolation and the satiation of social need during social reunion.

Genome-wide analyses identify common variants associated with 11 distinct neuropathology endophenotypes, providing insights into the mechanisms underlying the genetic risk of Alzheimer’s disease and related dementias.

Study shows PTSD predisposition shares distinct genes and genomic regions with several cardiovascular conditions. Here the findings reveal neuronal, immune, and metabolic pathways, and repurposed drug targets that further the understanding of the comorbidity.

Controlling substrate elasticity during physical vapour deposition allows access to high-density stable glasses that would otherwise be formed under prohibitively slow deposition conditions on rigid substrates.

Preparing two-dimensional heterolayers by vertically stacking chemically different layers with multiple anions remains challenging. Now, a general approach for the synthesis of heterolayered oxychalcogenides using molten hydroxides as unconventional solutions for the rapid stacking of oxide and chalcogenide layers with precise composition control is demonstrated.

Highly crystalline BaTiS₃ has been shown to exhibit record-breaking birefringence of 0.76 in the wavelength range of 7–16 μm. The large anisotropy is a result of its quasi-one-dimensional structure.

Genome-wide association analyses of 41,917 bipolar disorder cases and 371,549 controls of European ancestry provide new insights into the etiology of this disorder and identify novel therapeutic leads and potential opportunities for drug repurposing.

Alzheimer’s disease has been associated with increased structural brain aging. Here the authors describe a model that predicts brain aging from resting state functional connectivity data, and demonstrate this is accelerated in individuals with pre-clinical familial Alzheimer’s disease.

The role of IgG glycosylation in the immune response has been studied, but less is known about IgM glycosylation. Here the authors characterize glycosylation of SARS-CoV-2 spike specific IgM and show that it correlates with COVID-19 severity and affects complement deposition.

This study shows how including different ancestry groups in a genome-wide association study for prostate-specific antigen levels can improve prostate cancer risk prediction, with implications for population screening.

Armstrong and colleagues discover that combined targeting of IKAROS and MENIN is a therapeutic strategy for acute myeloid leukemia through disruption of essential leukemogenic transcriptional programs.

Nonlinear optical processing devices are not yet fully practical as they are single channel. Here the authors demonstrate all-optical regeneration of up to 16 channels by one device, employing a group-delay-managed nonlinear medium where strong self-phase modulation is achieved without nonlinear inter-channel crosstalk.

Factors underlying the effects of gastric bypass surgery on glucose homeostasis are incompletely understood. Here the authors developed and applied high-throughput mediation analysis to identify proteome/metabolome mediators of improved glucose homeostasis after to gastric bypass surgery, and report that improved glycemia was mediated by the growth hormone receptor.

Fine-scale geospatial mapping of overweight and wasting (two components of the double burden of malnutrition) in 105 LMICs shows that overweight has increased from 5.2% in 2000 to 6.0% in children under 5 in 2017. Although overall wasting decreased over the same period, most countries are not on track to meet the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025.

A genetic study identifies hundreds of loci associated with risk tolerance and risky behaviors, finds evidence of substantial shared genetic influences across these phenotypes, and implicates genes involved in neurotransmission.

Large-scale sequence-based analyses identify novel risk variants and susceptibility genes for Crohn’s disease, and implicate mesenchymal cell-mediated intestinal homeostasis in disease etiology.