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Genome-wide association meta-analyses of waist-to-hip ratio adjusted for body mass index in more than 224,000 individuals identify 49 loci, 33 of which are new and many showing significant sexual dimorphism with a stronger effect in women; pathway analyses implicate adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution.

Artificial intelligence (AI) system is known to improve dermatologists’ diagnostic accuracy for melanoma. This group applies the eye-tracking technology on dermatologists when diagnosing dermoscopic images of melanomas and reports improved balanced diagnostic accuracy when using an X(explainable) AI system comparing to the standard one.

The hippocampus in mammalian brain varies in size across individuals. Here, Hibar and colleagues perform a genome-wide association meta-analysis to find six genetic loci with significant association to hippocampus volume.

BAG3 is found in the serum of pancreatic cancer patients and can be used as a marker of disease, but its role in cancer is unclear. Here, the authors show that BAG3 secreted from tumour cells binds to and activates macrophages, which in turn promotes cell growth, and an antibody blocking BAG3 binding reduces tumour formation in mice.

The species threat abatement and restoration (STAR) metric quantifies the contributions that abating threats and restoring habitats offer towards reducing species’ extinction risk in specific places.

The role of viral Fc-gamma receptors in rhesus cytomegalovirus (RhCMV) infection is unclear. Here, the authors characterized RhCMV vFcγRs and report that their deletion did not affect virus replication, tropism or superinfection in rhesus macaques but increased susceptibility of the virus to antibody control.

Heart failure is a complex syndrome that is associated with many different underlying risk factors. Here, to increase power, the authors jointly analyse cases of heart failure of different aetiologies in a genome-wide association study and identify 11 loci of which ten had not been previously reported.

N-terminal acetylation is a common protein modification in eukaryotes. Here the authors show that in Arabidopsis, N-terminal acetylation is decreased by drought stress, that abundance of an N-terminal acetyltransferase is reduced by abscisic acid and that constitutive downregulation can confer drought resistance.

An exploratory randomized controlled clinical trial of renal cell carcinoma identifies molecular patterns distinguishing responders to immune checkpoint blockade alone or combined with angiogenesis inhibitor versus angiogenesis inhibitor alone.

During the 2022 Hunga Volcano eruption, 10 km³ of seafloor material was removed, fueling long-run out seafloor density currents. These powerful currents damaged seafloor cables over a length of >100 km, reshaped the seafloor, and caused mass-mortality of seafloor life.

Investigation of variation in three cohorts has identified multiple genetic signals associated with the pregnancy-specific liver disorder, intrahepatic cholestasis of pregnancy, giving insight into the disease which can cause preterm birth and stillbirth.

Autophagy is initiated by the Unc-51-like kinase protein kinase complex (ULK1C) and class III phosphatidylinositol 3-OH kinase complex I (PI3KC3-C1). Here, the authors reveal the structure of the 2:1:1 core of ULK1C and its complex with PI3KC3-C1. ULK1C transitions to a 2:2:2 complex in the presence of PI3KC3-C1, suggesting a mechanism for autophagy induction.

Sterylglucosidase 1 (Sgl1) is a virulence factor in Cryptococcus neoformans that modulates fungal pathogenesis and host response. Here, the authors characterize Sgl1 structurally, identify Sgl1 inhibitors, and demonstrate Sgl1 inhibition has efficacy in mouse models of infection.

Reduced glomerular filtration rate (eGFR) is a hallmark of chronic kidney disease. Here, Pattaro et al. conduct a meta-analysis to discover several new loci associated with variation in eGFR and find that genes associated with eGFR loci often encode proteins potentially related to kidney development.

Comparison of genome-wide association studies of HTT CAG repeat expansion in blood to expansion-driven clinical traits in Huntington’s disease identifies shared and distinct modifiers implicating DNA mismatch repair with tissue and cell-type specificity.

He et al. develop a network-based metric of amyloid-β burden by integrating individualized brain connectomes with amyloid-PET imaging. This approach improves prediction of future cognitive decline in older adults and may support earlier identification of individuals at risk of dementia.

An accurate, noninvasive method of imaging the heart and coronary arteries has long been elusive. Multidetector row CT, however, seems a likely candidate to fill this gap. This modality can be safely used to obtain high-quality images in seconds. Michael Poon provides an update on the advances in the development of this technology.

Michael O'Donovan and colleagues present a genome-wide association study of schizophrenia in 479 cases and 2,937 controls, followed by replication in several cohorts. They report evidence for association for a susceptibility allele near ZNF804A.

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.

Remdesivir is under evaluation for treatment of COVID-19 in clinical trials. Here, the authors report results of remdesivir treatment in a patient with COVID-19 and the genetic antibody deficiency XLA. They show a temporally correlated clinical and virological response, suggesting that remdesivir can reduce SARS-CoV-2 replication in patients.

The development of a first-in-class non-covalent small-molecule inhibitor of SARS-CoV-2 replication that targets the viral guanine-N7 methyltransferase NSP14 is reported.

Physical realizations of qubits are often vulnerable to leakage errors, where the system ends up outside the basis used to store quantum information. A leakage removal protocol can suppress the impact of leakage on quantum error-correcting codes.

The heterogeneity of colorectal cancer has important clinical and therapeutic implications. Here the authors analysed the responses of a large biobank of organoids and xenografts derived from colorectal patients to a panel of clinically relevant therapeutic agents to identify genes signatures associated with drug response.

Merz and colleagues perform single-cell multiomic analysis of mononuclear cells isolated from individuals receiving BCMA-directed CAR T cell therapy for myeloma and show that nonresponders are characterized by an immune-suppressive microenvironment.

A human–SARS-CoV-2 protein interaction map highlights cellular processes that are hijacked by the virus and that can be targeted by existing drugs, including inhibitors of mRNA translation and predicted regulators of the sigma receptors.

Lipin/Pah phosphatidic acid phosphatases generate diacylglycerol to regulate triglyceride synthesis and cellular signaling. Here authors determine structures of Tetrahymena thermophila Pah2 and identify an N-terminal amphipathic helix essential for membrane association.

Medulloblastoma in children is a difficult cancer to treat and the immune response to this tumour is not fully understood. Here the authors characterise and validate T cell epitopes from these cancers using an immunopeptidomics approach, comparing different molecular subtypes.

A multi-cohort genome-wide association study of tau PET, a brain imaging-based marker of Alzheimer’s disease, identifies a CYP1B1-RMDN2 locus as associated with higher tau and faster cognitive decline. These results suggest a new genetic contribution to cerebral tau and target for Alzheimer’s disease research.

Coronary artery calcium is an accurate predictor of cardiovascular events but this information is not routinely quantified. Here the authors show a robust and time-efficient deep learning system to automatically quantify coronary calcium on CT scans and predict cardiovascular events in a large, multicentre study.

Kim and colleagues perform a phase 2 clinical trial (ELM-2) of odronextamab monotherapy in patients with relapsed/refractory diffuse large B cell lymphoma and report on the primary analyses of the efficacy and safety profile.

Mucosal-associated invariant T (MAIT) cells are a subset of innate-like T cells, abundant in mucosal tissues, blood and liver. Here, using T-cell cloning and deep sequencing, Lepore et al. analyse the T-cell receptorβ repertoire of MAIT cells and further characterize function and tissue distribution of two semi-invariant subsets of these cells.

In a prespecified interim analysis of a pivotal phase 2 trial, avapritinib, a selective KIT inhibitor, elicited robust clinical and molecular responses, was generally well tolerated and led to improved patient-reported outcomes in patients with advanced systemic mastocytosis.

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.

Genome-wide association analyses of intracranial and nine subcortical brain volumes in 74,898 participants of European ancestry identify 254 independent loci and yield polygenic scores accounting for brain variation across ancestries.

Systematic characterization of longitudinal tau variability in human Alzheimer’s disease using an unbiased subtyping algorithm reveals four trajectories of tau deposition with distinct clinical features.

Tertiary lymphoid structures play important roles during homeostatic but also immunopathological conditions including autoimmune disorders. Here the authors integrate single cell sequencing with spatial proteomics and transcriptomics to define a cellular and spatial map of tertiary lymphoid structures in salivary glands of patients with Sjogren’s syndrome.

Moderately reducing the visibility of renewable energy infrastructure in Germany is found to have a negligible impact on energy system costs and design. Strict visibility restrictions, however, may reduce the system’s resilience and increase costs by 38% in 2045.