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The Global Flourishing Study provides a comprehensive view of the distribution and determinants of well-being by assessing domains such as health, happiness, meaning, character, relationships and financial security. Initial findings reveal significant variations in flourishing across countries and demographic groups, with factors such as age, marital status and religious service attendance showing strong associations with well-being.

Aarrestad et al. show that, in contrast to psychedelics, the nonhallucinogenic psychoplastogen tabernanthalog promotes neuroplasticity through 5-HT_2AR activation without immediately increasing extracellular glutamate levels or immediate early gene expression.

Repetitive shallow resonances provide a pathway to unravelling episodic magma transport deep in the magma plumbing system. Episodic deformation of ~1 nanoradian over ~100 s beneath Aso volcano potentially provides a link between long-term volcanic output and short-term eruption dynamics.

Here the authors perform a trans expression quantitative trait locus meta-analysis study of over 3,700 people and link a USP18 variant to expression of 50 inflammation genes and lupus risk, highlighting how genetic regulation of immune responses drives autoimmune disease and informs new therapies.

In this study, Aggarwal and colleagues perform prospective sequencing of SARS-CoV-2 isolates derived from asymptomatic student screening and symptomatic testing of students and staff at the University of Cambridge. They identify important factors that contributed to within university transmission and onward spread into the wider community.

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

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

Bosonic qubits can be engineered to feature intrinsic protection against certain kinds of errors, which makes quantum error correction across many bosonic qubits possible with less overhead.

With the generation of large pan-cancer whole-exome and whole-genome sequencing projects, a question remains about how comparable these datasets are. Here, using The Cancer Genome Atlas samples analysed as part of the Pan-Cancer Analysis of Whole Genomes project, the authors explore the concordance of mutations called by whole exome sequencing and whole genome sequencing techniques.

There’s an emerging body of evidence to show how biological sex impacts cancer incidence, treatment and underlying biology. Here, using a large pan-cancer dataset, the authors further highlight how sex differences shape the cancer genome.

The US COVID-19 Scenario Modeling Hub produced medium to long term projections based on different epidemic scenarios. In this study, the authors evaluate 14 rounds of projections by comparing them to the epidemic trajectories that occurred, and discuss lessons learned for future similar projects.

In a cluster-randomized trial conducted across 70 medical centers in six countries, a 16-week structured educational program for healthcare providers improved adherence to guidelines for rhythm control but not for stroke prevention in individuals with atrial fibrillation.

The authors construct a time-calibrated phylogeny spanning >90% of spiny-rayed fishes to explore patterns of body shape disparity within acanthomorphs. They find a trend of steady accumulation of lineages from the Cenozoic, with an increase in morphological disparity following the Cretaceous–Palaeogene event, facilitating the radiation of diverse morphotypes that characterize acanthomorphs’ widespread ecological success today.

Polygenic risk scores can help identify individuals at higher risk of type 2 diabetes. Here, the authors characterise a multi-ancestry score across nearly 900,000 people, showing that its predictive value depends on demographic and clinical context and extends to related traits and complications.

Gupta, Johnson et al. quantify the turnover rates of ~3200 E. coli proteins, demonstrating that cytoplasmic proteins are recycled when nitrogen is limited and that protein degradation rates are generally uncoupled from cell division rates.

Here, the authors use passenger mutations to quantify expansion rate in ~6,000 people with mosaic chromosomal alterations in the NHLBI TOPMed cohort, finding associations between growth rate and blood counts along with germline genetic modulators of growth rate.

Post-international travel quarantine has been widely implemented to mitigate SARS-CoV-2 transmission, but the impacts of such policies are unclear. Here, the authors used linked genomic and contact tracing data to assess the impacts of a 14-day quarantine on return to England in summer 2020.

Analysis of cancer genome sequencing data has enabled the discovery of driver mutations. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium the authors present DriverPower, a software package that identifies coding and non-coding driver mutations within cancer whole genomes via consideration of mutational burden and functional impact evidence.

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.

Multi-omics datasets pose major challenges to data interpretation and hypothesis generation owing to their high-dimensional molecular profiles. Here, the authors develop ActivePathways method, which uses data fusion techniques for integrative pathway analysis of multi-omics data and candidate gene discovery.

Multi-ancestry genome-wide analyses identify 95 loci associated with post-traumatic stress disorder and implicate candidate genes, pathways and neurobiological systems underlying its pathophysiology.

The synthesis of a tricoordinate antimony cation is reported by the removal of two chlorides from Tp^Me2SbCl₂, where Tp^Me2 is tris(3,5-dimethylpyrazolyl)borate. The multiple binding sites present in [Tp^Me2Sb]²⁺ bring an amine and an olefinic bond in proximity to enable an intermolecular hydroamination reaction.

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

A newly developed genetically engineered mouse model enables the analysis of specific antigen presentation in vivo, providing insights into the tumour immunopeptidome and cancer progression.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

Spatial transcriptomics aims to pair omic data with tissue structure. Here the authors report Spatially PhotoActivatable Colour Encoded Cell Address Tags (SPACECAT) to track and isolate live cells by location; this enables spatially informed downstream assays like scRNA-seq and flow cytometry.

A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.

The activity of multiple enzymes is dysregulated in cancer, but this cannot always be measured through enzyme expression. Here, the authors develop methods to measure protease activity across the organism, tissue, and single cell scales, and identify protease dysregulation in lung cancer and its response to targeted therapy.

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

The beta variant (B.1.351) is to date the most resistant to neutralization of the SARS-CoV-2 variants. Using nonhuman primates, Seder and colleagues demonstrate that double vaccination with a high dose of the lipid nanoparticle vaccine mRNA-1273 protects against infection with the beta variant.

A base-editing approach optimized to target the retina shows high editing rates in a mouse model of Stargardt disease, as well as in nonhuman primates and ex vivo human retinal explants, paving the way for potential clinical applications.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

Whole-genome sequencing data for 2,778 cancer samples from 2,658 unique donors across 38 cancer types is used to reconstruct the evolutionary history of cancer, revealing that driver mutations can precede diagnosis by several years to decades.

Here, Johnson et al show that bacterial pneumonia induces an interaction between the ubiquitin E3 ligase subunit FBX024 and the mitochondrial protein DARS2 to modulate host immune responses.

The characterization of 4,645 whole-genome and 19,184 exome sequences, covering most types of cancer, identifies 81 single-base substitution, doublet-base substitution and small-insertion-and-deletion mutational signatures, providing a systematic overview of the mutational processes that contribute to cancer development.

Mendelian randomization (MR) identifies causal relationships from observational data but has increased error rates when the genetic variants used as instruments come from a single region, a typical scenario when assessing molecular traits like protein or metabolite levels as risk factors. Here the authors introduce a single-region pleiotropy-robust MR method, validating the method on three ground truth sources, showing its capability to identify disease-causing molecular traits.

Fine-mapping of causal variants and integration of epigenetic and chromatin conformation data identify likely target genes for 150 breast cancer risk regions.

Single-atom catalysts consisting of isolated iron sites on a nitrogen-doped carbon matrix (Fe–N–C) are very promising cathode catalysts for proton exchange membrane fuel cells (PEMFC), but it is challenging to achieve a high density of single iron sites. Now, a synthetic approach is introduced to afford high-density Fe–N–C catalysts with a high PEMFC performance.

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.