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In the CheckMate 142 study, nivolumab (anti-PD-1) alone and in combination with ipilimumab (anti-CTLA-4) was shown to induce durable clinical benefit in patients with previously treated microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer. Here, the authors perform exploratory biomarker analysis of the CheckMate 142 study.

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.

A super-pangenome analysis incorporating 123 newly sequenced bryophyte genomes reveals that bryophytes exhibit a larger number of unique and lineage-specific gene families than vascular plants.

Charge transport and extraction in polycrystalline perovskite films are often hindered by inefficient carrier transfer across grain domain boundaries (GDBs). Here, authors employ supramolecular assisted Rb+ delivery for in-situ GDB bridging, achieving efficiency of 26.02% for perovskite solar cells.

People living in rural areas of the United States have poorer outcomes from acute COVID-19. Here, the authors show that higher mortality rates among rural dwellers persist for up to two years after the initial infection, even after accounting for baseline risk factors.

Controlling the reactivity of the propagating chain end in polymerization reactions is crucial for achieving well-defined polymers. Here, the authors present a strategy for processive catalytic polymerization by encapsulating catalysts for ring-opening metathesis polymerization into the sub-surface cages of a metal-organic framework.

Natural hydrogen is generated through chemical and radioactive processes in the Earth’s crust, and could be an important future clean chemical feedstock and energy resource. This Review examines the processes of geological hydrogen generation, migration, accumulation and preservation that enable the development of exploitable reserves.

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.

Electrochemical CO₂ capture is hindered by the oxidation of redox-active organic molecules by O₂, affecting energy efficiency and capacity. Here the authors develop a flow cell in which the O₂-sensitive components are isolated from O₂, achieving 99% coulombic efficiency with low energy requirements.

The outflow pathway of cerebrospinal fluid into lymph nodes in the neck and how non-invasive mechanical stimulation can enhance drainage and restore impaired outflow in aged mice are explored.

Artificial photosynthesis systems offer a sustainable solution to energy and environmental challenges, with significant improvements in efficiency. Here, the authors report a single light absorber system that achieves a solar-to-hydrogen efficiency of 1.7 %, with potential for future improvements.

A reinforcement learning-based virtual reality system, implementing a series of sport sessions with coaching, was as effective as standard physical activity in reducing fat mass in adolescents, with positive effects on cognition.

CRISPR-Cas9-based screens have allowed the study of gene-drug interactions. Here, the authors develop CRISPR-Cas9 knock-out, activation and repression screens in human gastric 3D organoids, also integrating single-cell CRISPR screens, to identify genes involved in the response to cisplatin in gastric cancer.

A modelling study based on satellite observations, machine learning and a chemical transport model quantifies the global and regional exposure to particulate-matter pollution and the human health impacts related to the 2023 Canadian wildfires.

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.

In most metals the optical Hall effect is very small at visible wavelengths, and usually can only be observed at low frequencies. Here, Am-Shalom et al present a technique involving a large amplitude modulation of the external magnetic field, allowing for the measurement of the optical Hall effect in a range of metals at visible wavelengths.

A meta-analysis of genome-wide association studies of type 2 diabetes (T2D) identifies more than 600 T2D-associated loci; integrating physiological trait and single-cell chromatin accessibility data at these loci sheds light on heterogeneity within the T2D phenotype.

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.

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.

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 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.

Bedload can dominate river sediment flux after a major earthquake for a prolonged time period.

Electrification is a promising way to decarbonize the chemical industry but could also have important effects on power systems. Here the authors assess the impact of electrifying the production of methanol and ammonia on the Chinese power system in terms of emissions and potential security risks.

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.

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.

This study reveals how pre-mRNA processing factors in Arabidopsis distinctly coordinate cleavage and transcription termination, highlighting complex roles of CPSF, CstF, PAPS1, BORDER proteins, and FPA in efficient mRNA maturation.

A preclinical covalent compound, CMX410, contains a aryl fluorosulfate warhead that targets the acyltransferase domain of Mtb Pks13, an essential enzyme in cell-wall biosynthesis, making it a promising candidate for tuberculosis treatment regimens.

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.

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.

The largest harmonized proteomic dataset of plasma, serum and cerebrospinal fluid samples across major neurodegenerative diseases reveals both disease-specific and transdiagnostic proteomic signatures, including a robust plasma profile associated with the APOEε4 genotype.

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.

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

Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.

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.

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.

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.

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.

Biomimetic membranes can be used for various applications such as sensors and separations. Here, Chen et al. report the assembly of lipid-like peptoids into stable and self-repairing 2D membrane nanomaterials that change in thickness when under external stimuli.

This work demonstrates an efficient electrochemical exfoliation approach to achieve high recovery rate for few-layered halogenated MXenes by leveraging gaseous propylene molecules as ‘physical scissors’, to enable advanced tribovoltaic nanogenerators.

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.

Finding optimal multi-drug combinations for pancreatic cancer remains a complex task. Here, authors across three different groups apply machine learning approaches to predict synergy across 1.6 million combinations of drugs for pancreatic cancer, 307 of which are validated experimentally.

Adriaenssens et al. show that unlike soluble cargo receptors, transmembrane cargo receptors initiate autophagosome biogenesis by recruiting the FIP200/ULK1 or WIPI–ATG13 complex, revealing unexpected flexibility in the selective autophagy machinery.