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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.

Genomic analyses of large population-based cohorts uncover the genetic determinants of perivascular space burden, an MRI marker of cerebral small vessel disease, across the lifespan, and reveal potential pathways implicated in the etiology of stroke and dementia.

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.

The development of confined organocatalysts for the enantioselective cyanosilylation of small, unbiased substrates, including 2-butanone, is shown to lead to catalysts that are as selective as enzymes, with excellent levels of control.

XPR1 is the only known protein that exports inorganic phosphate from cells. This study demonstrates that XPR1 uses a channel-like mechanism for phosphate transport, offering insights into potential therapeutic strategies for XPR1-linked diseases.

The ergot alkaloids are a class of natural products known for their pharmacologically privileged molecular structure that are used in the treatment of neurological ailments. Here the authors report on the production of the ergot (fungus)-derived therapeutic precursor, D-lysergic acid (DLA), in baker’s yeast.

Though bound states in the continuum (BICs) in acoustic systems are attractive for acoustic resonators design, acoustic BICs typically show low Q-factor. Here, the authors report a high performance open acoustic resonator that supports symmetry-protected, Friedrich-Wintgen and mirror symmetry-induced BICs.

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.

Transparent photodetectors based on graphene stacked vertically along the optical axis have shown promising potential for light field reconstruction. Here, the authors develop transparent photodetector arrays and implement a neural network for real-time 3D optical imaging and object tracking.

Single crystals of a helical covalent polymer have been obtained from an achiral monomer through spiroborate formation. Polymerization and crystallization occur simultaneously to give a network of pairs of entwined helical strands of the same handedness. No strong non-covalent interactions were observed between the two helical polymers forming a pair; instead, each interacts with neighbouring pairs through hydrogen bonding.

A strategy that preserves stereochemistry in intramolecular Friedel–Crafts alkylation is reported. An iterative synthetic approach to extend spiro-bridged molecular skeletons via C–H activation–annulation is developed, where the stereoretentive one-shot conversion to form multiple spirocarbon-bridged carbocycles resembles a ‘zipping up’ process.

Transition-metal-catalyzed asymmetric multicomponent reactions with two similar substrates often suffer from the lack of strategies to control the chemo-, regio-, and stereoselectivity. Here, the authors report a Cu(I)-catalyzed asymmetric radical 1,2-carboalkynylation of two different terminal alkynes and alkyl halides with chemo-, regio-, and stereoselectivity.

The connection between plasma proteomic and brain structure remains unclear. Here, the authors establish a comprehensive atlas of the patterns of associations between microscale proteome and brain structure, and demonstrate their potential value for studying brain disorders.

Using a large multisite dataset of people with major depressive disorder and healthy controls, the authors show global brain connectivity alterations in the sensorimotor, visual, and default mode networks.

A flat stanene layer can be grown on Cu (111) by MBE growth, exhibiting topological properties as revealed by a combination of ARPES, STM and DFT calculations.

Axial chirality is found in many important compounds, such as bioactive molecules and catalytic components. Now palladium and chiral norbornene cooperative catalysis is reported for the construction of atropisomeric biaryls and chiral fluorenols.

Fibroblasts are found to be heterogeneous in multiple fibrotic diseases, but fibroblast heterogeneity in fibrotic skin diseases is not well characterized. Here the authors employ scRNA-seq to explore fibroblast heterogeneity in keloid, a paradigm of fibrotic skin diseases.

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

Pairing center (PC) on each chromosome are crucial for homolog pairing and initiating synapsis in Caenorhabditis elegans. Here the authors investigate how the meiosis-specific proteins: ZIM/HIM-8 family recognize their cognate PC DNA motifs.

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.

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.

Diagnostic reasoning using an optimized large language model with a dataset comprising real-world medical cases exhibited improved differential diagnostic performance as an assistive tool for clinicians over search engines and standard medical resources.

Inherited retinal diseases are both numerous and diverse, but all arise from genetic mutations leading to retinal degeneration. Through the use of modern diagnostic tools, accurate genotype prediction is now possible using high-resolution imaging techniques alone, facilitating improved screening and genetic variant prioritization.

ARF4 GTPase activity is needed for vesicular trafficking for multiple RNA viruses. Blocking ARF4 using specific peptides redirects viral progeny to lysosomal degradation and decreases influenza and Zika virus infection in mice.

The conversational diagnostic artificial intelligence system AMIE (Articulate Medical Intelligence Explorer) has potential as a real-world tool for clinical history-taking and diagnostic dialogue, based on its performance in simulated consultations.

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.

Methane (CH4) photocatalytic upgrading to value-added chemicals, especially C2 products, is significant yet challenging. Here the authors realize solar-driven CH4 oxidation to ethanol on carbon nitride modified with Cu9S5 and Cu single atoms with a record-high selectivity of ~95%.

The growth of stanene on bismuth telluride has been achieved using molecular beam epitaxy. Photoemission spectroscopy and theoretical calculations are used to investigate the effects of the substrate on the electronic properties of the Sn layers.

The feasibility of satellite-assisted quantum communication is demonstrated by a field test on the ground. To supress noise due to sunlight the wavelength of 1,550 nm is chosen, and spectrum and spatial filtering technology developed.

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.

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.

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.

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.

Psoriasis is a skin disease associated with neurogenic inflammation. Here, the authors activation of ASIC3 on sensory neurons that leads to the release of CGRP, which triggers inflammation through dendritic cells and drives psoriatic inflammation.

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.

Evidence for the treatment of patients with mild-to-moderate COPD is limited. Here, the authors show that long-term treatment with high-dose N-acetylcysteine neither significantly reduced the annual rate of total exacerbations nor improve lung function in patients with mild-tomoderate COPD.

A phased pangenome of potato constructed from 60 wild and cultivated haplotypes shows that substantial hybridization occurred during domestication and enables identification of many putative deleterious variants, providing a basis for the design of improved inbred lines.

Genome-wide studies of 1,916 plasma and urine metabolites from 5,023 participants of the German Chronic Kidney Disease study provide insights into systemic and kidney-specific enzymatic and transport processes.