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This study mapped normative growth trajectories of 28 fetal brain phenotypes derived from 4,205 3D ultrasound scans collected across 7 international sites. The low variance between sites reinforces the principle that the brain develops similarly when environmental constraints are minimal.

In this study, the authors designed potent Enterovirus D68 capsid inhibitors that block viral binding and show that the lead compounds reduce virus levels, prevent paralysis and improve survival in EV-D68-challenged mice, even when treatment starts days after infection.

Visible-light-mediated intramolecular [2+2] cycloaddition of aza-1,6-dienes gives bridged, not fused, heterocycles, in violation of the ‘rule-of-five’, which dictates that five-membered rings are preferentially formed. This method allows a variety of bridged bicyclic scaffolds to be accessed, enabling drug-relevant properties to be readily tuned.

This manuscript from Choquette and colleagues finds that sclerostin gene expression is up-regulated in bone by β3-adrenergic signaling via an adipose to bone relay and acts as an endocrine factor to inhibit adipose tissue beiging in mice.

Understanding collective behaviour is an important aspect of managing the pandemic response. Here the authors show in a large global study that participants that reported identifying more strongly with their nation reported greater engagement in public health behaviours and support for public health policies in the context of the pandemic.

The APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer’s disease, but it is not deterministic. Here, the authors show that common genetic variation changes how APOE-ε4 influences cognition.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

Convergent mutations in hot spots of the spike proteins of currently circulating SARS-CoV-2 Omicron variants increase the binding affinity for the host receptor and promote more efficient fusion with host cell membranes.

Polygenic scores often underperform in non‑European ancestries. Here, the authors present GPTL, an R package with three transfer‑learning methods that improve cross‑ancestry PGS using either individual‑level data or GWAS summary statistics.

Remote sensed information and population data for continental Africa are used to assess how migration acts as an adaptation response after drought event. The effect on mobility is amplified with drought frequency and poverty.

Prostate cancer incidence and mortality rates vary across males from diverse populations. Here, the authors perform a proteome-wide association study across different populations and establish population-specific genetic prediction models.

cellSTAAR advances noncoding rare variant association analysis by integrating single-cell genomics data.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

Estimates from the Global Burden of Disease study reveal declines in chronic respiratory disease mortality between 1990 and 2023—especially during the COVID-19 pandemic—but the burdens on people affected remain substantial.

Designing monovalent anion-selective membranes is challenging due to the need to balance trade-offs between flux and selectivity, membrane stability, and cost-effective fabrication. Here, the authors synthesized a polymer via superacid polymerization and designed a membrane using in-situ interfacial polymerization to optimize membrane properties.

Single iron atoms on nitrogen-doped carbon catalysts are a promising alternative to platinum for the oxygen reduction reaction on fuel cell cathodes, but commonly suffer from low stability. Here an in situ chemical vapour deposition synthetic approach is presented, enabling high iron active site dispersion and reducing surface porosity, which mitigates demetallation and carbon corrosion, ensuring high activity and stability.

Language models can write human-readable code that captures general design rules, generating whole families of quantum experiments at once. A design strategy described here makes results interpretable and scalable, as well as accelerates discovery.

A juvenile iguanodontian from the Lower Cretaceous of China preserves both spikes and scales in its skin that are different from integumentary structures in either non-avian dinosaurs or extant squamates and may have had a defensive function.

Anti-phased changes in Antarctic Circumpolar Current strength between the Indian and Pacific sectors of the Southern Ocean occurred on orbital timescales over the past one million years, linked to glacial cycles and obliquity forcing, according to proxy records and modelling.

Carbon dioxide removal (CDR) plays an important role in decarbonization pathways to meet climate goals, but some methods are land-intensive. Multimodel analysis reveals conflicts between biodiversity and CDR that are distributed unevenly, and shows that synergies are crucial to meet climate and conservation goals.

Engineered mucus-tethering bispecific nanobodies neutralize and entrap viruses to enhance mucosal immunity, preventing influenza infection and limiting SARS-CoV-2 transmission.

A comprehensive atlas platform integrating transcriptional and epigenetic data enables more precise engineering of T cell states, accelerating the rational design of more effective cellular immunotherapies.

Ribas and colleagues report the results of a phase 2 clinical trial of neoadjuvant PD-1 blockade in patients with surgically resectable desmoplastic melanoma.

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.

A CRISPR screen reveals that loss of structural components of the SAGA complex derails hematopoiesis by decoupling epigenetic control. This halts stem cell maturation, triggers a pathogenic interferon program and boosts human MDS-L cell growth.

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.

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.

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.

Here the authors perturb genes linked to schizophrenia risk in human neurons. They find that single perturbations share common downstream effects on gene networks, while joint perturbations result in downstream effects being saturated.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

In this study the authors consider the structural variants (SVs) present within cancer cases of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. They report hundreds of genes, including known cancer-associated genes for which the nearby presence of a SV breakpoint is associated with altered expression.

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.

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.

Some cancer patients first present with metastases where the location of the primary is unidentified; these are difficult to treat. In this study, using machine learning, the authors develop a method to determine the tissue of origin of a cancer based on whole sequencing data.

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.

Many tumours exhibit hypoxia (low oxygen) and hypoxic tumours often respond poorly to therapy. Here, the authors quantify hypoxia in 1188 tumours from 27 cancer types, showing elevated hypoxia links to increased mutational load, directing evolutionary trajectories.

There is an unmet medical need for endometrial cancer patients with mismatch-repair proficient disease. Here, the authors report the primary analysis of the FRUSICA-1 phase Ib/II trial evaluating fruquintinib plus sintilimab in this population, showing an ORR of 32.7%, a median PFS of 8.6 months, and manageable toxicity.

Murphy et al. reveal a unifying pathogenetic mechanism according to which diverse mutations in the muscle-specific ribosomal protein RPL3L cause severe neonatal dilated cardiomyopathy, establishing a framework for interpreting the growing spectrum of RPL3L variants.

A pan-cancer genomic analysis reports the effects of structural variations on chromatin domains (TADs). Most TAD disruptions do not result in appreciable changes in expression of nearby genes.

Large-effect variants in autism remain elusive. Here, the authors use long-read sequencing to assemble phased genomes for 189 individuals, identifying pathogenic variants in TBL1XR1, MECP2, and SYNGAP1, plus nine candidate structural variants missed by short-read methods.

Early life RSV infection contributes to risk of childhood asthma. Here, the authors develop a statistical model to predict age at first RSV infection in the United States based on birthdate, demographics, and RSV surveillance data which could be used to identify groups at risk of chronic respiratory sequalae like asthma.

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.

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

The authors consider the future risks of warming and drying to water-sensitive anuran species. They show that increased aridity of anuran habitats and drought exposure under climate change, combined with warming, can substantially reduce anuran activity.

An analysis of 2,954 genomes from 38 cancer subtypes identified 19,166 retrotransposition events in 35% of samples. Aberrant LINE-1 retrotranspositions can lead to the deletion of tumor-suppressor genes as well as the amplification of oncogenes.

Newly developed mouse models that enable cell-specific analyses of proteostasis dynamics across the lifespan of the mice reveal key aspects of neuronal proteostasis with ageing.

In somatic cells the mechanisms maintaining the chromosome ends are normally inactivated; however, cancer cells can re-activate these pathways to support continuous growth. Here, the authors characterize the telomeric landscapes across tumour types and identify genomic alterations associated with different telomere maintenance mechanisms.