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Prenatal stress triggers molecular dysregulations in fetal neuroimmune circuits, leading to altered mast cell and sensory neuron function, which predisposes offspring to develop eczema in response to otherwise harmless mechanical friction after birth.

Uranium oxo groups are very inert, in contrast with many transition metal oxo compounds that can carry out reactions that are difficult to achieve with other reagents. Now, the controlled lithiation of a ‘Pacman’ complex is shown to activate the uranium oxo group towards functionalization and single electron transfer.

Both environmental factors and genetic factors influence human immunity. Albert and colleagues leverage data from the Milieu Intérieur Consortium to comprehensively describe the effects of lifestyle, environment and genetics on human innate and adaptive immunity.

External Control Arm methods for clinical trials were developed to compare the efficacy of a treatment to a control group that is built with data from external sources. Here, the authors present FedECA, a privacy-enhancing method for analyzing treatment effects across institutions, streamlining multi-centric trial design and thereby accelerating drug development while minimizing patient data exposure.

Innate lymphoid cells (ILC) are an important modulator of immunity in many tissues, including lymphoid tissues, but their spatial information is still scarce. Here, the authors use multiplexed and multispectral imaging methods to provide a spatial map of ILCs in human thymus, spleen, lymph nodes, intestinal lymphoid tissue, and lymphoma, and observe ILC/T helper cells colocalization.

In oxygen-redox intercalation cathodes, voltage hysteresis can be avoided by forming cathode materials with a ‘ribbon’ superstructure in the transition metal layers that suppresses transition metal migration.

The energy that can be stored in lithium-ion batteries is typically limited by the redox chemistry of the transition metals within the cathodes. Now it is shown that for Li_1.2[Ni²⁺_0.13Co³⁺_0.13Mn⁴⁺_0.54]O₂, a 3d-transition-metal oxide that breaks this limit, Li-ion extraction is charge compensated not just by transition-metal oxidation but also through the generation of localized electron-holes on oxygen.

Disproportion of uranium(IV) is rare, as it is usually the stable product of uranium(III) or (V) disproportionation. Here, the authors report uranium(IV) disproportionation to uranium(III) and (V) revealing ligand and solvent control over a key thermodynamic property of uranium

Magic state distillation is achieved with logical qubits on a neutral-atom quantum computer using a dynamically reconfigurable architecture for parallel quantum operations.

Alkali-metal-rich compositions (for example, Li[Li_xM_1–x]O₂) are promising battery cathode materials that exhibit oxygen redox, which provides additional charge capacity. It is thought to occur in compounds containing alkali ions in the transition metal layers and featuring Li⁺–O(2p)–Li⁺ interactions; however, now it is observed in Na_2/3[Mg_0.28Mn_0.72]O₂, in which Mg²⁺ ions are present in the transition metal layer.

Early and accurate clinical assessment of disease severity in COVID-19 patients is essential for planning the allocation of scarce hospital resources. An explainable machine learning tool trained on blood sample data from 485 patients from Wuhan selected three biomarkers for predicting mortality of individual patients with high accuracy.

The isolation of compounds featuring an actinide–actinide bond is challenging. Now a well-defined Th(III) dimer with a Th–Th two-centre one-electron (2c-1e) σ bond and a 2c-1e π bond is synthesized. Theoretical and magnetic studies show that the open-shell singlet ground state and the two formal Th(III) centres exhibit strong antiferromagnetic coupling.

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 heterogenous nature of rheumatoid arthritis renders the prediction of responsiveness to biological treatments difficult. Here the authors analyze bulk RNA-seq data from the STRAP trial (n = 208) to build a machine-learning model for predicting responses to etanercept, tocilizumab and rituximab with AUCs around 0.75 to potentially assist in therapy planning.

Here Ramanan and colleagues provide an analysis of mammary T cells during late pregnancy and lactation. This revealed an increase in intraepithelial lymphocytes in the lactating mammary gland, which was driven by thymic and intestinal inputs and was sensitive to changes in the microbiota

A wearable device measures parenchymal resistance and its dynamic relationship with sleep MRI measures of glymphatic function, EEG features and cardiovascular parameters in humans.

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.

Human TNF is required for respiratory-burst-dependent immunity to Mycobacterium tuberculosis in macrophages but seems to be largely redundant physiologically.

The antiviral protein SP140 negatively regulates Ifnb1 mRNA stability by directly repressing the expression of the immune regulator RESIST.

The Ly49 gene family mainly encodes inhibitory or activating surface receptors on natural killer cells. Here the authors show that in mice, inhibitory and activating Ly49 genes are regulated by two distinct sets of cis-regulatory elements, and that different Ly49 genes can be cross-regulated.

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.

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.

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.

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.

Kim and colleagues perform a phase 2 clinical trial (ELM-2) of odronextamab monotherapy in patients with relapsed/refractory diffuse large B cell lymphoma and report on the primary analyses of the efficacy and safety profile.

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.

How to achieve ideal antiferroelectricity with sharp switching in nanoscale thin films remains challenges. The authors here unveil the selective stepwise transition, achieve ideal antiferroelectricity with large digital electrostrain in PbZrO₃ epitaxial thin films.

Population differences in immune responses to SARS-CoV-2 can be explained by environmental exposures, but also by local adaptation acting through genetic variants acquired after admixture with archaic hominin forms.

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.

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.

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.

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.

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.

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.

An analysis of 38 ancient genomes from the aurochs, the extinct ancestor of modern cattle, provides insight into the population ancestry and domestication of this species.