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Transcriptomic and clinical data analyses from multiple cohorts of patients with cancer receiving immunotherapy find that PD-1 blockade potentiates tumor-specific IgG1 plasma cell responses that complement cellular immunity and contribute to clinical benefit.

The study combines bulk, single-cell, and spatial transcriptomics of human carotid plaques. It identifies immune– stromal cell diversity, spatial macrophage gradients, smooth muscle cell heterogeneity, and morphology-defined plaque subtypes.

Here, the authors find that relative abundances of stress-sensitive gastrointestinal microbes at age 2 years predicts internalizing symptoms in middle childhood through altered emotion-related brain network connectivity.

Therapeutic gene editing in vivo is an ongoing challenge. Here, authors demonstrate Cas9 nickase guided DNA ligation as a nonviral method for installing permanent genomic corrections with favorable on target edit profiles in model animal cell types and adult mice.

Glioblastoma (GBM) is characterized by a high degree of heterogeneity and plasticity due to interplay with neural developmental programs. Here, the authors develop a model of GBM by introducing sequential oncogenic mutations in human neural stem cells and using this, identify INSM1 as a driver of a neural progenitor gene network promoting tumorigenesis.

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.

Lee et al. use an aggregation-prone CLN4 mutant that causes lysosomal damage in neurons and show that in non-neurons, the ubiquitin ligase CHIP prevents CLN4-dependent lysotoxicity via microautophagy.

Research on sustainable diets has primarily focused on human and planetary health, neglecting workers in food value chains. This study quantifies the risk of forced labour embedded in five different diets in the USA, underscoring the need to integrate such risk in sustainable diet transition efforts.

Effective government partly depends on effective communications to citizens. Over six studies in three different policy contexts, Linos et al. identify a counter-intuitive formality effect: citizens are more likely to respond to formal government communications than informal ones.

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.

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.

Computational models can help to explain the dynamics of cellular infection with pathogens. Here the authors use computational models to assess the single cell infection parameters of human macrophage infection with Legionella pneumophila and the effects on immunometabolism at a single cell and population level.

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.

To investigate inequalities in energy access, Kersey and co-authors conducted a mixed-method study with 25 informal settlements in Kampala, Uganda. They found that despite the expansion of electrical grids in Sub-Saharan Africa, users are connecting to the grid through a range of service arrangements that are highly differentiated and provide inequitable levels of electricity access.

Uechi et al. found that a small-molecule lipoamide dissolves stress granules (SGs) by targeting SFPQ, a redox-sensitive disordered SG protein, alleviating pathological phenotypes caused by amyotrophic lateral sclerosis-associated FUS and TDP-43 mutants.

In this Stage 2 Registered Report, Buchanan et al. show evidence confirming the phenomenon of semantic priming across speakers of 19 diverse languages.

When learning new tasks, both humans and artificial neural networks face a trade-off between reusing prior knowledge to learn faster and avoiding the disruption of earlier learning. This study shows that people and artificial neural networks have similar patterns of transfer and interference and vary in how they balance this trade-off.

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.

BPTF is known to regulate chromatin accessibility and self-renewal in mammary epithelial stem cells. Here, the authors discover that BPTF inhibition delays tumor formation, re-activates ERα expression, increases sensitivity to tamoxifen treatment, and inhibits metastatic development.

This systematic review and meta-analysis of 53 randomized controlled trials finds that educational interventions can help students reduce cognitive biases, with a small but statistically significant overall effect.

An understanding of the molecular mechanisms promoting the generation of immunoregulatory and tumour-promoting monocytes and macrophages is key to breaking the cycle of tumour myelopoiesis and developing more effective myeloid-targeting therapies.

Safely opening university campuses has been a major challenge during the COVID-19 pandemic. Here, the authors describe a program of public health measures employed at a university in the United States which, combined with other non-pharmaceutical interventions, allowed the university to stay open in fall 2020 with limited evidence of transmission.

Smoke PM_2.5 could result in 71,420 excess deaths per year in the USA by 2050 under the SSP3-7.0 high-warming scenario.

Hyperinsulinemia, glucose and fatty acids induce hepatic triglyceride accumulation, proinflammatory cytokine release and predispose to insulin resistance, while resmetirom treatment normalized fat but paradoxically induced higher cytokine expression.

Here, the authors identify distinct gut microbiome and metabolome signatures in microscopic colitis, a condition causing chronic diarrhea, highlighting pro-inflammatory species and metabolites as potential non-invasive biomarkers and therapeutic targets.

A comprehensive single-cell RNA sequencing study delineates cell-type-specific transcriptomic changes in the brain associated with normal ageing that will inform the investigation into functional changes and the interaction of ageing and disease.

Melting experiments with planetary materials show that oxidized core formation occurred via percolation of molten sulfide at low igneous temperatures.

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.

Here the authors reveal that a neomorphic mutation in chromatin protein SMCHD1 enhances SMCHD1-mediated gene silencing, including at the FSHD disease-relevant locus, while depleting SMCHD1-mediated chromatin interactions, suggesting these SMCHD1 functions are unlinked.

Perochon et al. show in Drosophila that gut-derived reactive oxygen species and FGF induce tracheal remodelling after intestinal damage, which in turn promotes intestinal regeneration by activating intestinal stem cells.

A study of the evolution of the SARS-CoV-2 virus in England between September 2020 and June 2021 finds that interventions capable of containing previous variants were insufficient to stop the more transmissible Alpha and Delta variants.

Genomic analyses, performed by Carey-Ewend et al., reveal that Plasmodium ovale curtisi and wallikeri in sub-Saharan Africa show similar low complexity of infection, relatedness by geography, and signatures of selection. However, P. ovale wallikeri harbors lower nucleotide diversity.

A soft mesh microelectrode array can seamlessly integrate in developing brains, enabling long-term, stable mapping of how single-neuron activity and population dynamics emerge and evolve during brain development.

Repeated vaccination is needed to maintain high levels of SARS-CoV-2 immunity in vulnerable populations, but there is concern that it could lead to immune exhaustion. Here, the authors assess the evidence for immune exhaustion following multiple SARS-CoV-2 vaccination three vulnerable population cohorts in Canada.

The authors show pro-inflammatory responses are needed for Marburg virus control in its natural bat reservoir, and that if reduced, humanlike disease and shedding results, suggesting that natural immunomodulatory stressors may increase spillover risk.

Different functional variants in ADH1B (and elsewhere) in Europeans and Africans strongly affect risk for alcohol dependence. Dependence only partly genetically correlates with consumption, with strong correlations to other psychiatric disorders.

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.

The authors present SVclone, a computational method for inferring the cancer cell fraction of structural variants from whole-genome sequencing data.

Brough et al. find that speakers exhibit a ‘like me’ bias, mentioning people who are more like them first and thus highlighting the perspectives of their own social groups.

Viral pathogen load in cancer genomes is estimated through analysis of sequencing data from 2,656 tumors across 35 cancer types using multiple pathogen-detection pipelines, identifying viruses in 382 genomic and 68 transcriptome datasets.

Large-scale combination drug screens in cancer are extremely challenging because of the immense number of possible combinations. Here, the authors develop BATCHIE, a Bayesian active learning platform to design scalable and maximally informative drug combination screening assays; this is validated in retrospective and prospective cancer studies.

The archaeological site Shinfa-Metema 1 in the lowlands of northwest Ethiopia provides early evidence of intensive riverine-based foraging aided by the likely adoption of the bow and arrow.

A genome-wide association study and Metabochip meta-analysis of body mass index (BMI) detects 97 BMI-associated loci, of which 56 were novel, and many loci have effects on other metabolic phenotypes; pathway analyses implicate the central nervous system in obesity susceptibility and new pathways such as those related to synaptic function, energy metabolism, lipid biology and adipogenesis.

This manuscript evaluates forecasts of laboratory-confirmed influenza hospital admissions, a new target for influenza forecasting in the United States. Across two influenza seasons, the FluSight ensemble is robust compared to submitted models.

Bacterial–fungal interactions are studied using a combination of random barcode transposon-site sequencing, RNA sequencing, bacterial cytological profiling and metabolomics. Fungi cause widespread changes in the fitness of bacterial mutants and have both conserved and species-specific impacts on bacteria.

How a lasso cyclase ties a lasso peptide into its characteristic knot has remained poorly understood. Here the authors identify key molecular interactions that guide lasso peptide folding and cyclase substrate tolerance to inform cyclase engineering for expanded lasso peptide diversity.