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The Taiwan Precision Medicine Initiative (TPMI) has built a cohort of more than half a million individuals with Han Chinese ancestry, providing a rich resource of genetic and medical data for this group.

Monitoring charge carrier dynamics and photocatalytic reaction rates in individual photocatalyst particles is a challenging task that can help us to understand structure–reactivity relationships. Here single-molecule fluorescence imaging is coupled with femtosecond interferometric scattering microscopy to investigate these properties in 2D InSe flakes.

Here the authors reveal a study of 486,956 Han Chinese individuals showing that most people with genetic variants affecting drug response do not have the predicted adverse events, highlighting the challenges of implementing pharmacogenetics in clinical practice.

A cell-autonomous role for the COUP-TFII transcription factor in prostate cancer cells is identified, in which COUP-TFII inhibits TGF-β signalling by binding to SMAD4; COUP-TFII promotes prostate tumorigenesis and metastasis in a mouse model, and is associated with more aggressive disease in human prostate cancers.

Infection with SARS-CoV-2 causes interstitial pneumonia and viral replication in the lungs of transgenic mice that express a human version of ACE2, confirming the pathogenicity of the virus in this model.

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 this phase 3 trial, first-line treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma with anti-PD-1 finotonlimab plus cisplatin plus 5-fluorouracil (C5F) prolonged overall survival compared with placebo plus C5F.

Metallic molybdenum disulfide is a metastable phase of the material. Here, the authors synthesize two-dimensional metallic molybdenum disulfide nanosheets, stabilized by adsorbed aqueous monolayers, and evaluate their catalytic hydrogen evolution activity.

Integrating the Pancharatnam–Berry phase with integrated resonant nanoantennas in a metalens design produces an achromatic device capable of full-colour imaging in the visible range in transmission mode.

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.

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.

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.

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.

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.

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.

This study demonstrated that different types of HC-Pros from potyviruses exhibit varying capacities to inhibit HEN1. This results in distinct levels of autophagic AGO1 degradation, which in turn leads to differences in RNA silencing suppression efficiency.

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.

Analyses of the genome sequences and expression data for two closely related mycoheterotrophic orchid species provide insights into the genomic basis underlying the evolution of mycoheterotrophy.

Benzylic oxygenation of methylarenes is a direct but challenging method for aldehyde synthesis from simple starting materials. Here, the authors show an electrochemical, site-selective method for the oxidation of methyl benzoheterocycles to aromatic acetals without using chemical oxidants or transition metal catalysts.

Multimodal large language models (MLLMs) hold promise for a range of medical applications. Here, the authors use MLLMs for 3D brain CT radiology report generation, demonstrating that combining anatomy-aware model fine-tuning with robust evaluation metrics establishes a comprehensive and effective framework.

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.

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.

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.

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.

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.

The development of exciplex-type hosts for thermally activated delayed fluorescence organic light-emitting diodes is hindered by a lack of structural information for these donor:acceptor blends. Here, the authors report the pump-probe Step-Scan Fourier transform IR spectra for a D:A exciplex host.

Transcription factor COUP-TFII is elevated in the hearts of non-ischaemic cardiomyopathy patients, but the nature of this correlation is unknown. Here the authors show that forced cardiac expression of COUP-TFII in mice causes dilated cardiomyopathy because of altered mitochondrial function and impaired metabolic remodelling.

Pulmonary fibrosis is a major public health problem with unclear mechanism and limited therapeutic options. Here the authors show that a fibroblast-enriched endoplasmic reticulum protein, TXNDC5, promotes pulmonary fibrosis by stabilizing TGFBR1 and show the potential of TXNDC5 as a therapeutic target against pulmonary fibrosis.

Thymic epithelial tumours represent a heterogenous group of malignancies with varied immune cell infiltration and prognosis. Here authors systematically analyze the phenotypes of both epithelial and immune cells that form these tumours, and identify three major subtypes with different T cell involvement that might affect prognosis.

A pangenome analysis of 76 wild and domesticated barley accessions in combination with short-read sequence data of 1,315 barley genotypes indicates that allelic diversity at structurally complex loci may have helped crop plants to adapt to agricultural ecosystems.

In the multicenter, phase 3 DAWNA-1 trial, the combination of dalpiciclib, a new cyclin-dependent kinase 4 and 6 inhibitor, with fulvestrant, in patients with HR⁺HER2⁻ advanced breast cancer who progressed or relapsed on endocrine therapy, improved progression-free survival with manageable safety and may represent a new treatment option.

Adult human hearts exhibit restricted regenerative ability, where cardiomyocyte loss leads to dysfunction, while neonatal hearts can regenerate, though the molecular mechanisms remain poorly understood. Here, the authors show that N-cadherin plays a crucial role in driving cardiomyocyte self-renewal by stabilizing β-catenin, representing a unique opportunity to promote cardiac regeneration and restore contractile function in the injured adult heart

The in vitro characterization of a key event in the early stages of meiosis—the induction of double-strand DNA breaks by the SPO11–TOP6BL complex—provides insight into the catalytic mechanism and evolution of SPO11.

Domestic ducks are descended from the Mallard and have been bred for several purposes. Here the authors present three high-quality duck genome assemblies which recover previously missing genes and provide a rich resource of variants potentially related to domestication.

The metastatic tumour microenvironment in pancreatic ductal adenocarcinoma (PDAC) remains to be explored. Here, the authors perform single cell RNA sequencing analysis for synchronously resected PDAC primary tumours and matched liver metastases and find differences in cellular composition.

Advances in beta cell differentiation have propelled cell therapies for diabetes into the clinic; this Review outlines the lessons learned from early-phase trials and discusses the clinical, manufacturing and regulatory challenges that must now be overcome.

2D semiconductors are promising candidates for next-generation electronics, but the realization of competitive 2D p-type transistors remains challenging. Here, the authors report the characterization of nitric-oxide-doped monolayer and bilayer WSe₂ p-type transistor arrays, showing on-state currents up to 300–448 μA/μm, contact resistance down to 390–875 Ω·μm and on/off ratios of ~ 10⁶−10⁹.