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Flores et al. show that brain-penetrant eIF2B agonists suppress ISR activation in cellular and mouse models of ALS and reduce ISR biomarkers in humans, enabling further clinical studies of ISR inhibition in individuals with neurological diseases

The quark structure of the f₀(980) hadron is still unknown after 50 years of its discovery. Here, the CMS Collaboration reports a measurement of the elliptic flow of the f₀(980) state in proton-lead collisions at a nucleon-nucleon centre-of-mass energy of 8.16 TeV, providing strong evidence that the state is an ordinary meson.

Primary angle-closure glaucoma is a leading cause of blindness. Here, the authors identify rare deleterious variants in UBOX5 as risk factors and implicate BIP ubiquitination as a potential disease mechanism.

In a prospective study including 2,300 pediatric and adult patients with liquid and solid tumors, RNA sequencing provided actionable molecular information in 87% of cases, with applications in diagnostics and therapy matching.

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.

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.

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.

The International Brain Laboratory presents a brain-wide electrophysiological map obtained from pooling data from 12 laboratories that performed the same standardized perceptual decision-making task in mice.

Zaman, Yang and Huang et al. demonstrate MDK’s suppressive effect on amyloid-β and its impact on amyloid burden and microglial activation in Alzheimer disease mice, highlighting its protective role in pathogenesis.

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.

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

Cancers evolve as they progress under differing selective pressures. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, the authors present the method TrackSig the estimates evolutionary trajectories of somatic mutational processes from single bulk tumour data.

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.

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.

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 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.

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 from more than 2,500 cancers of 38 tumour types reveal 16 signatures that can be used to classify somatic structural variants, highlighting the diversity of genomic rearrangements in cancer.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

Here, the authors present cryoEM structures of AftB, a key mycobacterial enzyme that adds terminal arabinose residues to the cell wall. In concert with functional assays and MD simulations, mechanistic insights are presented.

Vaults are massive, cytoplasmic, cage-like ribonucleoprotein assemblies. Here, authors describe cryo-EM structures of human vault encapsulating PARP4 & nucleotide ligands, as well as proteomic data showing that depleting PARP4 alters the vault interactome.

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.

The efficacy of CAR-T cells against solid tumors is still limited by immunosuppressive factors. Here, the authors show that engineering of CAR T cells with A1R enhances their efficacy against solid tumors in vitro and in vivo.

Wildfires are becoming increasingly frequent in several regions around the world due to climate change, posing serious health risks, especially for respiratory diseases. This study examines the respiratory health risk and burden of wildfire-specific PM_2.5 pollution across eight countries and territories.

The impact of land-use and cover-change (LUCC) on ecosystem carbon stock in China is poorly known due to large biases in existing databases. Here the authors develop a new LUCC database with corrected false signals and reveal that forest expansion is the dominant driver of China’s recent carbon sink.

Understanding how global changes affect both aboveground plants and belowground soil organisms is essential for preserving ecosystem functions and biodiversity. This study synthesizes extensive data, revealing decoupled responses in plant and soil biota to global changes across different biomes.

Geospatial estimates of the prevalence of anemia in women of reproductive age across 82 low-income and middle-income countries reveals considerable heterogeneity and inequality at national and subnational levels, with few countries on track to meet the WHO Global Nutrition Targets by 2030.

Cosmic rays flying through superconducting quantum devices create bursts of excitations that destroy qubit coherence. Rapid, spatially resolved measurements of qubit error rates make it possible to observe the evolution of the bursts across a chip.

Highly pathogenic avian influenza is an increasing global concern but its distribution in remote regions is not known. Here, the authors conduct an environmental influenza surveillance study in remote, uninhabited regions of the Global South by sampling fresh bird guano.

Acute lymphoblastic leukemias (ALL) with an ETV6::RUNX1 fusion comprise the largest subtype of this cancer, and their optimal treatment strategy remains unclear. Here, the authors perform genomic profiling of 194 ETV6::RUNX1-rearranged pediatric ALL cases, finding two molecular subtypes associated with distinct drug sensitivities.

Miniaturized components have significant potential for portable applications. Here, the authors demonstrate a spectrometer and hyperspectral imager based on photonic-crystal slabs which can enable single-shot imaging on a compact chip.

All-solid-state batteries face practical challenges such as sustainable fabrication and low-stack pressure operation. Here, authors develop a modified dry-process technique to yield robust solid electrolyte-electrode interface for practical fabrication and operation of all-solid-state batteries.

Spatially resolved images of M87 obtained at a wavelength of 3.5 mm in 2018 show a ring-like accretion structure, the inner (outer) edge of which connects the black hole (jet).

Analysis of whole-genome sequencing data across 2,658 tumors spanning 38 cancer types shows that chromothripsis is pervasive, with a frequency of more than 50% in several cancer types, contributing to oncogene amplification, gene inactivation and cancer genome evolution.