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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.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

Ghatbale et al. adapted a co-evolutionary technique to develop Klebsiella pneumoniae phages to be highly active longitudinally against K. pneumoniae clinical isolates, including drug resistant isolates.

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.

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.

This Resource provides a detailed atlas of morphogen-induced responses in human neural organoids.

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.

Across species, how aging leads to progressive spatial memory decline is not fully understood. This study reports dysfunctional spatial coding by aged entorhinal grid cells and networks related to impaired spatial memory and identifies implicated neuronal gene expression changes.

This study presents an analytic framework to link imaging-derived brain phenotypes to gene expression. In the future, this approach may facilitate in vivo pharmacotranscriptomics and the development of personalized (pharmacological) interventions.

Patients with myeloma multiple treated with BCMA CAR T cells often relapse with BCMA-negative disease or antigen escape. Here the authors describe the design of TACI-directed single and dual CAR T cells with in vitro and in vivo activity against multiple myeloma, overcoming BCMA antigen loss.

Meta-analysis of genome-wide association studies on Alzheimer’s disease and related dementias identifies new loci and enables generation of a new genetic risk score associated with the risk of future Alzheimer’s disease and dementia.

Cross-species transcriptomics on vulnerable neuronal populations unravels the transcription factor CREB3 and its regulatory network as resilience markers of ALS. Genetics and epidemiology further identify the protective rare variant CREB3R119G.

IL-33 induces tertiary lymphoid structures.

Federated learning (FL) algorithms have emerged as a promising solution to train models for healthcare imaging across institutions while preserving privacy. Here, the authors describe the Federated Tumor Segmentation (FeTS) challenge for the decentralised benchmarking of FL algorithms and evaluation of Healthcare AI algorithm generalizability in real-world cancer imaging datasets.

This Consensus Statement presents the standards for technical reporting in environmental and host-associated microbiome studies (STREAMS) guidelines.

Using well-calibrated statistical methods the authors jointly analyze Undiagnosed Diseases Network genomes, identifying known and novel disease genes. Software is publicly available to support future cross-cohort rare disease discovery efforts.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.

Atmospheric oxygen levels on Earth rose in at least six distinct steps and an examination of the timing of the steps suggests that they coincided with the formation of supercontinents and supermountains. This leads to the hypothesis that increased erosion of these supermountains released large amounts of nutrients to the oceans, stimulating productivity and the release of oxygen to the atmosphere. The subsequent burial of organic carbon along with the mountain sediments would have sustained the increased oxygen levels.

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.

Mutations in TREM2 alter risk for Alzheimer’s disease, though the mechanisms underlying risk in human cells are unclear. Here, the authors use iPS-microglia and chimeric mice to highlight altered survival, phagocytosis, migration, and transcriptional programs in microglia lacking TREM2.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

A global multi-taxon extinction risk assessment of freshwater fauna for The IUCN Red List of Threatened Species finds one-quarter of species to be at high risk of extinction.

Synthetic mouse embryos assembled from embryonic stem cells, trophoblast stem cells and induced extraembryonic endoderm stem cells closely recapitulate the development of wild-type and mutant natural mouse embryos up to embryonic day 8.5.

Charlotte Sumner and colleagues report that mutations in the ankyrin repeat region of TRPV4 cause Charcot-Marie-Tooth disease type 2C. Their functional studies indicate that the mutations result in increased channel activity.

Siew et al. using multi-omic, physiological & imaging approaches have demonstrated that spaceflight causes kidney remodelling, suggesting a contribution to kidney stone formation, & that space radiation causes kidney damage & early signs of dysfunction.

Non-human primates are important animal models for studying SARS-CoV-2 infection. Here, Salguero et al. directly compare rhesus and cynomolgus macaques and show that both species represent COVID-19 disease of mild clinical cases, and provide a lung histopathology scoring system.

EEL FISH profiles spatial transcriptomes in single cells in large, complex tissue samples.

Black and white fonio are two small indigenous grain cereals grown in West Africa. Here, the authors reveal their independent domestication and cultivation histories through population genetics and demographic history analyses.

Pycytominer is a user-friendly, open-source Python package that carries out key bioinformatics steps in image-based profiling.

In mice, prolonged consumption of a high-fat diet decreases interest in calorie-rich foods as a result of reduced neurotensin expression and signalling, which uncouples hedonic feeding behaviour linked to neurons projecting from lateral nucleus accumbens to ventral tegmental area.

Here, the authors look at present day and medieval genome samples from Northern France to piece together demographic history and population structure across Brittany and the Loire basin.

Genomic analysis of Plasmodium DNA from 36 ancient individuals provides insight into the global distribution and spread of malaria-causing species during around 5,500 years of human history.

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

A genome-wide association study including over 76,000 individuals with schizophrenia and over 243,000 control individuals identifies common variant associations at 287 genomic loci, and further fine-mapping analyses highlight the importance of genes involved in synaptic processes.

An investigation using various methods reports an association between adeno-associated virus 2 and paediatric hepatitis of unknown aetiology.

Openshaw and colleagues find myeloid inflammation and complement activation signatures in patients with long COVID who were previously hospitalized.

Here, the authors identify a frontostriatal circuit that is involved in regulating social interactions based on learned hierarchical relationships.

The CNS has limited ability to regenerate following injury, Here, the authors show that a single injection of AAV-hyper-interleukin-6 in the sensory motor cortex results in corticospinal and raphe spinal tracts regeneration in the injured spinal cord as well as functional recovery in mice.

Circadian clocks are a fundamental biological system which orchestrate various physiological and behavioral processes in response to daily environmental changes. Here, the authors utilize a multipronged approach to generate a comprehensive neural connectome of an animal circadian clock.

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.

Whole-genome sequencing analysis of individuals with primary immunodeficiency identifies new candidate disease-associated genes and shows how the interplay between genetic variants can explain the variable penetrance and complexity of the disease.