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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.

BRCA1 and BRCA2 are well known breast cancer predisposition genes, however, many variants have not yet been classified for their pathogenicity. Here, the authors analyse a large combined cohort to provide evidence of variant pathogenicity.

Polygenic risk scores for Alzheimer’s disease derived from individuals of European ancestry can show improved performance in multiancestry settings after incorporating genome-wide association summary statistics from diverse populations.

The number of ligand binding sites in the dopamine transporter is enigmatic due to conflicting data from structures and molecular pharmacology. Here, force spectra reveal the position and dynamics of a previously invisible transient site.

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.

Fang and colleagues show that the metabolite succinate can inhibit succinylation, and consequently protection from ubiquitin-mediated degradation, of the transcription factor FOXP3, with consequences on T_reg cell-suppressive function and IBD pathology.

Tissue-expansion method compatible with mass-spectrometry imaging (TEMI) enables the profiling of lipids, metabolites, peptides, proteins, and N-glycans in complex tissues with high spatial resolution, advancing spatially resolved multi-omics mapping.

A non-contact wearable device that defines and modulates a microclimate adjacent to the skin can measure incoming and outgoing streams of vapourized substances, offering valuable insights into physiological health, wound healing and environmental exposures.

A millimetre-scale bioresorbable optoelectronic system with an onboard power supply and a wireless, optical control mechanism is developed for general applications in electrotherapy and specific uses in temporary cardiac pacing.

Hutchinson-Gilford Progeria Syndrome is characterized by premature aging with cardiovascular disease being the main cause of death. Here the authors show that inhibition of the NAT10 enzyme enhances cardiac function and fitness, and reduces age-related phenotypes in a mouse model of premature aging.

Extracellular matrices are viscoelastic, yet how matrix viscoelasticity regulates the epigenome remains unclear. Here, the authors show that cells cultured on viscoelastic matrices exhibit changes in the nucleoskeleton and in chromatin that enhance cell reprogramming.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

Genomic studies often lack representation from diverse populations, limiting equitable insights. Here, the authors show that the BIG Initiative captures extensive genetic diversity and reveals ancestry-linked health disparities in a community-based Mid-South cohort.

In this Consensus Statement, the authors outline strategies for processing, analysing and interpreting low-biomass microbiome samples, and provide recommendations to minimize contaminants.

Hollandite structured materials are potentially useful for battery technologies. Here the authors report the unusual lateral transport of lithium ions between lithiated silver manages oxide nanorods where the reaction fronts and kinetics are maintained within the neighbouring nanorods.

The conversational diagnostic artificial intelligence system AMIE (Articulate Medical Intelligence Explorer) has potential as a real-world tool for clinical history-taking and diagnostic dialogue, based on its performance in simulated consultations.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

Allele-preferential transcription factor binding can influence pancreatic ductal adenocarcinoma risk loci function. Here, the authors show allele-specific JunB and JunD binding at chr1p36.33 and propose a role for KLHL17 in protein homeostasis by mitigating inflammation.

This study, together with a companion manuscript, shows that in mice, weight loss as a result of GIP receptor antagonism requires and potentiates functional GLP-1 receptor signalling in the brain, explaining how both GIP receptor agonists and antagonists trigger weight loss through different mechanisms.

In contrast to the conventional wisdom on conversion-driven structural collapse of the host, this work shows that lithium conversion in magnetite resembles the intercalation process, going via topotactic reactions, thereby enabling multi-electron transfer and high reversible capacity.

A genome-wide association meta-analysis study of blood lipid levels in roughly 1.6 million individuals demonstrates the gain of power attained when diverse ancestries are included to improve fine-mapping and polygenic score generation, with gains in locus discovery related to sample size.

The RNA methyltransferase activity of SPOUT1/CENP-32 is crucial for accurate mitotic spindle organization. Here, the authors describe a neurodevelopmental disorder caused by bi-allelic pathogenic SPOUT1 variants with reduced activity and compromised function in spindle organization.

Dense calcium imaging combined with co-registered high-resolution electron microscopy reconstruction of the brain of the same mouse provide a functional connectomics map of tens of thousands of neurons of a region of the primary cortex and higher visual areas.

A consensus cell type atlas for the fly brain provides both an intellectual framework and open-source toolchains for brain-scale comparative connectomics.

An analysis of the Drosophila connectome yields all cell types intrinsic to the optic lobe, and their rules of connectivity.

A unified framework is presented that integrates observed spatial patterns of individual trees in forests with ecological processes into a novel coexistence theory.

Saloner et al. used large-scale cerebrospinal fluid proteomics to uncover molecular signatures in frontotemporal dementia, revealing RNA splicing and synaptic protein candidate markers for genetic and sporadic disease progression.

In a large multinational cohort study, maternal, gestational or pregestational diabetes was associated with only a small-to-moderate risk of ADHD in offspring, contrary to previous estimates that showed stronger effect sizes, attributing the differences in findings to confounding by shared genetic and familial factors.

An integrated analysis of de novo and inherited coding variants in 42,607 individuals with autism spectrum disorder identifies 60 risk genes of which five have not previously been associated with neurodevelopmental disorders.

Reducing particle size of electrode materials to nanoscale dimensions is believed responsible for their enhanced reaction kinetics and electrochemical performance. Here, the authors use in situ transmission electron microscopy to study the dynamic process of the spinel zinc ferrite nanoparticles as a function of size, finding that the intercalation reaction pathway changes below a critical particle size.

Inbreeding depression has been observed in many different species, but in humans a systematic analysis has been difficult so far. Here, analysing more than 1.3 million individuals, the authors show that a genomic inbreeding coefficient (FROH) is associated with disadvantageous outcomes in 32 out of 100 traits tested.

A rare variant burden analytical framework for Mendelian diseases was developed and applied to data from the 100,000 Genomes Project, identifying 69 probable new disease–gene associations.

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

In this Review, we provide an overview of the current state of the field of 3D batteries. We discuss critical performance metrics, the potential for scalability and commercialization, and suggest focused areas for future development.

Genome-wide association studies (GWAS) have improved our understanding of the genetic basis of lung adenocarcinoma but known susceptibility variants explain only a small fraction of the familial risk. Here, the authors perform a two-stage GWAS and report 12 novel genetic loci associated with lung adenocarcinoma in East Asians.

Xie et al. present UnitedMet, a tool that leverages RNA–metabolite covariation to impute metabolite levels from transcriptomic data, and find oxidative phosphorylation associated with both BAP1 status and metastasis or therapy outcome in kidney cancer.

Luo et al. conducted a multinational cohort study examining the trends in mortality risk among 1,272,495 individuals with incident dementia between 2000 and 2018. There is a consistent decline in mortality risk following dementia diagnosis in the UK, Canada, South Korea, Taiwan and Hong Kong, indicating potential advancements in dementia care.

Using ethnically and geographically diverse metagenomic data, the authors identify microbiota alterations associated with inflammatory bowel disease (IBD). They discover universal IBD-associated bacteria, which serve as the basis for a multibacteria biomarker panel that could support a noninvasive tool for IBD diagnosis.

Although the resolution achievable with cryo-EM can now rival crystallography, its application to small protein assemblies remains challenging. Here the authors demonstrate the use of the Volta phase plate for single particle analysis and its potential for the study of small specimens.

Targeting the endothelium across ages and neurodegenerative diseases in 92 donors with single-cell inCITE-seq reveals similar alterations in ~40% of capillaries in AD, ALS and FTD. Endothelial TDP-43 loss coincides with increased nuclear p65/NF-κB activity and reduced Wnt/β-catenin.

A multi-ancestry genome-wide gene–smoking interaction study identifies 13 new loci associated with serum lipids.

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.

The properties of materials can be drastically modified under extreme pressure. Here the authors investigate ramp-compressed sodium to 5 million atmospheres with in situ X-ray diffraction and optical reflectivity, revealing a complex temperature-driven polymorphism and suggesting the formation of a previously predicted electride phase.

In the I-SPY2.2 trial, patients with high-risk stage 2/3 breast cancer received neoadjuvant datopotamab–deruxtecan, followed by sequential chemotherapy with or without targeted therapy, with the option of early surgical resection after each block of therapy. In a subgroup of patients, the sequential treatment strategy was superior to standard of care.