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Hepatitis B virus (HBV) infection is associated with hepatitis and hepatocellular carcinoma (HCC). Here, the authors show that HBV promotes HCC formation only in response to environmental carcinogens, involving increased IL-33 signaling and regulatory T cells.

Embryonal tumour with multilayered rosettes (ETMR) is a rare and aggressive paediatric brain tumour. Here, the authors analyse intratumour heterogeneity and the tumour microenvironment in ETMR using single-cell and spatial transcriptomics, in vitro cultures, and a 3D forebrain organoid model, finding important aspects – such as the communication with pericytes – for ETMR development and response to therapy.

A machine learning model for prime editing efficiency prediction takes into account chromatin context.

Plasmonic excitations of electrons in metallic nanostructures are promising for the enhanced conversion of light in semiconductor solar cells. Here, the authors are able to experimentally distinguish the absorption phenomena of plasmonic carrier generation and excitation of carriers by light absorption.

This work introduces engineered TnpBmax proteins with enhanced efficiency and an expanded targeting range. By leveraging an extensive dataset on editing efficiencies, it also integrates a deep learning model to predict guide RNA activity.

Sun et al. report human lifespan changes in the brain’s functional connectome in 33,250 individuals, which highlights critical growth milestones and distinct maturation patterns and offers a normative reference for development, aging and diseases.

Being able to precisely analyse behaviour is essential for the study of motor behaviour in health and disease, but is often time- and labour-intensive. Brattoli et al. develop an automatic approach based on deep learning for analysing motor behaviour and evaluate it on different species and diverse motor functions.

Detecting relevant odours from background odours is important for animal behaviour. Here the authors design a task to study this process in mice.

The invariant chain CD74 is involved in the formation of major histocompatibility complex class II. Jefferies and colleagues show that it also associates with class I in the endolysomal compartment and is important in cross-presentation.

Dysfunction of the deacetylase Sirt1 has been associated with certain metabolic diseases. Abramson and colleagues show that Sirt1 has high expression in the thymus, where it deacetylates the transcriptional regulator Aire and is essential for Aire's ability to switch on the expression of tissue-specific genes.

The lack of generalizability and reproducibility of machine learning models in medical applications is increasingly recognized as a substantial barrier to implementing such approaches in real-world clinical settings. Highlighting this issue, Jie Cao et al. aim to reproduce a recent acute kidney injury prediction model, and find persistent discrepancies in model performance in different subgroups.

ELMO1 is a protein centrally involved in controlling the engulfment of apoptotic cells. Ravichandran and colleagues demonstrate a noncanonical role for ELMO1 in the promotion of neutrophil migration and inflammatory arthritis.

The activation of cleavable organometallic dimers upon exposure to ultraviolet radiation allows air-stable n-type doping of organic materials with electron affinity lower than the expected thermodynamic reducing strength of the dimers.

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.

The design of prime editing guide RNAs is optimized by deep learning.

Information on stellar populations of the grand-design spiral galaxy UGC 3825 is exploited to measure the offset between young stars of a known age and the spiral arm in which they formed. The measured offset is consistent with a quasi-stationary density wave.

Mid-infrared observations of the dusty structures of the galaxy NGC 1068 support the unified model of active galactic nuclei.

Isolation and optimization of antibodies targeting the malaria parasite may offer the potential for immediate protection as a prophylactic intervention to prevent severe disease.

Neurons in the hippocampal formation encode diverse spatial properties. Here, the authors present a hierarchical network model for 3D spatial navigation that accounts for the observed neuronal representations and predict as yet unreported cell types with planar selectivity.

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.

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.

The interplay between amyloid and tau pathology in Alzheimer’s disease is still not well understood. Here, the authors show that amyloid-related increased in soluble p-tau is related to subsequent accumulation of tau aggregates and cognitive decline in early stage of the disease.

The BIN1 SNP rs744373 is associated with higher CSF tau and phosphorylated tau levels. Here the authors show, using PET imaging, that this SNP is associated with tau accumulation in the brain as well as impaired memory in older individuals without dementia.

In Alzheimer’s disease (AD) tau and neurodegeneration have complex regional relationships. Here, the authors show neuronal hypometabolism discordant with tau burden defines functional resilience or susceptibility to Alzheimer’s pathology via limbic/cortical axes. Susceptible groups have faster cognitive decline and evidence of non-Alzheimer’s pathologies.

Whether Alzheimer’s disease originates in basal forebrain or entorhinal cortex remains highly debated. Here the authors use structural magnetic resonance data from a longitudinal sample of participants stratified by cerebrospinal biomarker and clinical diagnosis to show that tissue volume changes appear earlier in the basal forebrain than in the entorhinal cortex.

Late-onset Alzheimer's disease (LOAD) is a complex multi-factorial disorder. Here, the authors perform a data-driven analysis of LOAD progression, including multimodal brain imaging, plasma and CSF biomarkers, and find vascular dysfunction is among the earliest and strongest altered events.

Brain-iron elevation is implicated in Alzheimer’s disease (AD), but the impact of the metal on disease outcomes has not been analysed in a longitudinal study. Here, the authors examine the association between the levels of ferritin, an iron storage protein, in the cerebrospinal fluid (CSF) of AD patients and show that CSF ferritin levels predict AD outcomes.

The KL-VS haplotype of the Klotho gene has been associated with reduced risk of Alzheimer’s disease and dementia. Here the authors show an association between the KL-VS haplotype and amyloid-dependent tau accumulation using PET data.

This study finds that sST2 is a disease-causing factor for Alzheimer’s disease. Higher sST2 levels impair microglial Aβ clearance in APOE4⁺ female individuals. A genetic variant, rs1921622, is associated with a reduction in sST2 level and protects against AD in APOE4⁺ female individuals.

Tau accumulation is associated with disease progression in Alzheimer’s disease. Here the authors use resting state fMRI and tau-PET to demonstrate that baseline connectivity in Alzheimer's disease is associated with tau spreading.

Bicuspid aortic valve (BAV) is the most common human congenital cardiovascular malformation. Here, the authors perform a genome-wide association study for BAV and identify risk variants in the gene region of cardiac-specific transcription factor GATA4 and implicate GATA4 in heart valve development.

Alzheimer’s disease is heterogeneous in its neuroimaging and clinical phenotypes. Here the authors present a semi-supervised deep learning method, Smile-GAN, to show four neurodegenerative patterns and two progression pathways providing prognostic and clinical information.

A recent workshop was convened under the auspices of the US National Institutes of Health (NIH) to examine the relationship of the innate immune system to autoimmune disorders.

Assembly theory conceptualizes objects as entities defined by their possible formation histories, allowing a unified language for describing selection, evolution and the generation of novelty.