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Polygenic scores often underperform in non‑European ancestries. Here, the authors present GPTL, an R package with three transfer‑learning methods that improve cross‑ancestry PGS using either individual‑level data or GWAS summary statistics.

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

Increasing dietary carbohydrate-to-fat ratio in a randomized controlled feeding study altered circulating small molecules (metabolites), including ones associated with diabetes risk, underscoring important metabolic effects of dietary composition.

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.

Rettkowski, Romero-Mulero et al. show that myocardial infarction impacts bone marrow haematopoietic stem cells and leads to inflammatory myelopoiesis, which can be dampened by treatment with 4-oxo-retinoic acid, promoting cardiac recovery.

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.

In a randomized, double-blind, placebo-controlled trial comparing autologous mRNA-engineered BCMA-targeting CAR T cell therapy versus placebo in patients with generalized myasthenia gravis, a significantly higher percentage of patients exhibited a reduction in disease activity in the treatment arm than in the placebo arm.

Myocardial infarction disrupts cardiac repair mechanisms, limiting regeneration. Here, the authors show that extracellular matrix therapies activate spatial and cell-specific pro reparative programs, revealed through spatial transcriptomics and snRNA-seq.

Boccella, Yu and colleagues reveal that the transmembrane protein ANTXR1 regulates post-infarction fibrotic remodeling, and its inhibition blocks collagen turnover and improves heart function.

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.

Multi-omics and genetic models show that CGG repeat toxicity in GABAergic neurons drives FXTAS pathology and identify PRKCG as a critical modifier and potential therapeutic target.

SpatialZ generates virtual single-cell spatial transcriptomics slices between experimentally measured sections, enabling accurate and efficient building of 3D cell atlases of different tissues.

Analysis combining multiple global tree databases reveals that whether a location is invaded by non-native tree species depends on anthropogenic factors, but the severity of the invasion depends on the native species diversity.

It remains uncertain whether genetic variants and day–night cycles affect the efficacy of drugs in acute disease settings. Here, the authors show that metoprolol reduces risk only in patients who carry two Arg389 alleles of the beta-1 adrenoceptor, and specifically when myocardial infarction occurs at the beginning of the light cycle.

Genome-wide association studies incorporating data for populations of African ancestry provide an expanded view of the genetic basis of schizophrenia, which has previously been studied mainly in European and East Asian cohorts.

Myocardial infarction accelerates atherosclerosis through activation of the sympathetic nervous system, and the consequent release of haematopoietic stem and progenitor cells.

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.

The tumour suppressor BRCA1 is mutated in familial breast and ovarian cancer. Now, Shuklaet al.demonstrate that mice lacking BRCA1 in cardiomyocytes are more sensitive to ischaemia than control mice, and that BRCA1 is elevated in human tissues exposed to ischaemia, suggesting a cardioprotective role for BRCA1.

Analysing the causal links of gene expression and protein abundance on type 2 diabetes risk in blood and seven tissues related to the disease from individuals of four ancestries, the authors advance our understanding of the genetic architecture of type 2 diabetes

In a randomized trial of patients with a previous myocardial infarction and with residual inflammation, a monoclonal antibody targeting the LOX-1 receptor, thought to contribute to atherosclerotic plaque progression and inflammation, reduced soluble LOX-1 and interleukin-6 levels but did not lead to a substantial reduction in coronary plaque volume.

Neonatal brain injury from intermittent hypoxemia increases fatty acid oxidation and causes long-term changes in hippocampal lipid profile. Here authors demonstrate oral treatment with glycerol-triacetate restores lipid fatty acid profile and promotes functional recovery.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

Single-cell data analysis is challenging due to inherent noise and sparsity. Here, authors introduce scMINER, a mutual information-based integrative tool to enhance clustering and reveal regulatory networks and hidden biological drivers by transforming scRNA-seq expression into activity profiles.

Kinematic measurements of the Perseus galaxy cluster reveal two drivers of gas motions: a small-scale driver in the inner core associated with black-hole feedback and a large-scale driver in the outer core powered by mergers.

Somatic mutations in blood cells (CHIP) are linked to diseases like heart disease, but the mechanisms are unclear. Here, the authors show that different CHIP driver genes alter unique sets of plasma proteins, some of which are validated in mouse models.

Covalent inhibitors are powerful entities in drug discovery. Now the amino acid selectivity and reactivity of a diverse electrophile library have been assessed proteome-wide using an unbiased workflow. This comparative analysis and the probes described could help guide the discovery and design of covalent ligands targeting residues beyond cysteine.

Zhang et al. show that bone marrow fatty acid metabolism fuels expanded leukocyte production after myocardial infarction and, based on mouse, pig and human data, suggest that lipolysis in marrow adipocytes provides fatty acids to hematopoietic stem cells.

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.

The authors used deep metric learning to characterize 650 neuroactive compounds by zebrafish behavioral profiles. After redesigning a large screen to overcome AI/ML shortcut learning, zebrafish behavioral similarity found compounds acting on the same human receptors as structurally dissimilar drugs.

How various factors dynamically influence neuronal variability is a longstanding question. Here, the authors build an encoding model to partition variability, revealing heterogeneous source contributions to individual units and state-dependent changes of variability across the visual hierarchy.

Huang et al. show that myocardial infarction (MI)-associated vasculature is structurally and functionally abnormal, impeding vessel function and cardiac repair in mice. Analyses of the transcriptome of the cardiac endothelium after MI identify a PDGF–NF-κB–HIF-1α Snail axis responsible for mesenchymal transformation of endothelial cells and show that genetic ablation or targeted disruption of PDGF signaling normalizes vasculature and improves cardiac function recovery after MI.

Endogenous brain states influence perception. In this manuscript the authors use human intracranial recordings to provide mechanistic insight into this process by showing that endogenous brain activity facilitates neural tuning and behavior in a stimulus and circuit specific manner.

Spontaneous coronary artery dissection (SCAD) is a cause of myocardial infarction Here, the authors present a genome-wide association study of SCAD, finding an association at 1q21.2 which potentially affects expression of ADAMTSL4.

This study investigates drivers of redox potential in several salt marsh sites on the basis of time series datasets. Wavelet and mutual information analyses show that the terrestrial groundwater level, rather than the marsh groundwater level, is the dominant control on redox potential.

Neural networks unlock the ability to predict and manipulate noisy light propagation in nonlinear fibres, advancing control strategies for photonic technologies and paving the way for tailored shaping of incoherent optical signals.

Analysis of cancer genome sequencing data has enabled the discovery of driver mutations. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium the authors present DriverPower, a software package that identifies coding and non-coding driver mutations within cancer whole genomes via consideration of mutational burden and functional impact evidence.

Recently published results from a Phase I trial showed the blood brain barrier could be transiently opened in glioblastoma patients using low-intensity ultrasound and microbubbles. Here, the authors develop a microfluidic chip to capture tumour-derived extracellular vesicles and particles in response to paclitaxel treatment.

Climate change can alter when and how animals grow, breed, and migrate, but it is unclear whether this allows populations to persist. This global study shows that shifts in seasonal timing are key to helping vertebrate species maintain population growth under global warming.

Whether prediction errors are encoded by synergistic information across the cortex is unknown. Here, the authors demonstrate that distributed representations of prediction errors across the cortex can be highly synergistic.

Long-distance migration and dispersion is a common characteristic of nearly all classes of telencephalic GABAergic neurons, which diversify extensively after birth in the cortex and striatum, but show limited postnatal changes in the septum, preoptic area and pallidum.

Here, the authors implement a genetic approach grouping fasting insulin-associated genetic variants based on their genetic and phenotypic similarities and highlight specific processes that decouple increased fasting insulin levels from T2D and cardiovascular risk, offering potential avenues for investigating process-specific pathways of disease risk.

The early postnatal roles of dendrite-targeting interneurons in primary visual cortex (V1) remain elusive. Here, the authors find that somatostatin interneurons in mouse V1 exhibit a uniquely delayed developmental trajectory for innervation and sensory responses, highlighting a window for the emergence of a key mechanism for normalization in cortical circuits.

MultiSTAAR provides a general and flexible statistical framework for functionally informed multi-trait rare variant analysis of biobank-scale sequencing studies by jointly analyzing multiple traits and incorporating annotation information.

Noel et al. show aberrant updating of expectations in three distinct mouse models of autism spectrum disorder. Brain-wide neurophysiology data suggest this stems from excess units encoding deviations from prior mean and a lack of sensory prediction errors in frontal areas.

Here the authors provide an explanation for 95% of examined predicted loss of function variants found in disease-associated haploinsufficient genes in the Genome Aggregation Database (gnomAD), underscoring the power of the presented analysis to minimize false assignments of disease risk.

Neo et al. map blood emergence from three hemogenic endothelial (HE) populations biased toward distinct blood fates. HE primed for stem progenitors shows elevated chromatin and RNA splicing gene expression and greater isoform diversity.