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Chronic diabetic wounds heal poorly due to impaired tissue repair and persistent inflammation. Here, authors demonstrate that a Smad7-based topical biologic accelerates diabetic wound healing by improving epithelial regeneration and reducing inflammatory neutrophil activity.

Response to vagus nerve stimulation cannot currently be predicted, leaving many children to undergo implantation without benefit. We present a deep representation learning model using preoperative T1-weighted MRI to predict treatment response.

Decreased brain volumes and increased NfL levels can be observed earlier than disease diagnosis in short-tandem-repeat-associated neurological diseases.

When 100 social and behavioural science claims were examined, 34% of reanalyses closely matched the original results, with 74% reaching the same conclusion, revealing limited robustness of single-path analyses and the need to address analytical uncertainty.

The Human Development Multiomic Atlas catalogues single-cell accessibility and gene expression data from human fetal cells across 12 organs, enabling the inference of syntactic rules for motifs that govern cell-type-specific transcription factor binding and chromatin accessibility during human development.

A study of reproducibility in a stratified random sample of 600 papers published from 2009 to 2018 in 62 journals spanning the social and behavioural sciences finds higher reproducibility among more recent papers and papers from journals that require data sharing.

Singi et al. use a multiple instance learning AI system to analyze liquid tissue and blood Samples. Their system outperforms existing models on hematological tasks.

Polymer thin films that emit and absorb circularly polarised light are promising in achieving important technological advances, but the origin of the large chiroptical effects in such films has remained elusive. Here the authors demonstrate that in non-aligned polymer thin films, large chiroptical effects are caused by magneto-electric coupling, not structural chirality as previously assumed.

DNA G-quadruplex (G4) structures can form at regulatory regions of transcriptionally active genes in open chromatin and are abundant in cancer states, but targeting G4-binding proteins in their native chromatin environment is challenging. Now bifunctional molecules that bind naturally occurring G4 sites and recruit ubiquitination machinery facilitate the degradation of G4-specific transcription factors and chromatin remodellers.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

A screen of lung-targeting lipids revealed lipid nanoparticles offering improved delivery of mRNA and genome editors to lungs. Probing structure–activity relationships revealed a unique ‘tripod-like’ shape associated with the improvements.

A multiancestry phenome-wide analysis of copy number variants in the UK Biobank genomes increases power to detect genetic associations with complex traits across human populations.

Greenwald, Nederlof and colleagues developed a computational pipeline analyzing multiplex imaging data and established spatial patterns within breast cancer microenvironment that are predictive of immune checkpoint blockade response across treatment time course.

cellSTAAR advances noncoding rare variant association analysis by integrating single-cell genomics data.

TDP-43 pathology is a key event in ALS/FTD and selectively affects specific neurons in the motor cortex. Here, the authors report which neuron types are affected and demonstrate that transcriptomic changes are cell-type specific.

Biocatalysis of the chemotherapy drug, doxorubicin, relies on the cytochrome P450 DoxA, which is inefficient. Here, the authors ameliorated the biosynthetic limitations by identifying DoxA redox partners and DnrV, which prevents product inhibition, helping improve microbial production.

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 dynamics of breast tissue aging are characterized by imaging mass cytometry of over 500 reduction mammoplasties, revealing nonlinear loss of cellularity and a compositional shift favoring inflammation.

Small cell lung carcinoma (SCLC) neuroendocrine (NE) subtypes often transdifferentiate to the more aggressive non-NE cell state during disease progression. Here, the authors discover that eIF6 is a regulator of SCLC plasticity, driving non-NE transdifferentiation via regulation of the CD104/FAK complex.

Rare coding variants that reduce the activity of a protein can have a beneficial impact on health. Here, researchers identify rare genetic variants in the CHRNB3 gene that associate with reduced cigarette smoking across diverse populations.

Analyses of genome and exome sequencing data identify rare coding and structural variants associated with atrial fibrillation and highlight genetic links between atrial fibrillation and cardiomyopathies.

The APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer’s disease, but it is not deterministic. Here, the authors show that common genetic variation changes how APOE-ε4 influences cognition.

MultiSTAAR provides a general and flexible statistical framework for functionally informed multi-trait rare variant analysis of biobank-scale sequencing studies by jointly analyzing multiple traits and incorporating annotation information.

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.

Disassembly of three-dimensionally ordered materials generates nanoparticles with new structural and physicochemical properties. Here the authors show a fragmentation strategy applied to a perovskite material leading to nanostructures with improved catalytic activity in the methane combustion.

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

A high-bandwidth neuromotor interface offers performant out-of-the-box generalization across people.

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.

Vapour-phase methods are promising for nanomaterial synthesis but the vaporization of different precursors for the synthesis of a broad nanomaterial space is challenging. Here electrified vapour deposition generates ultrahigh-temperature, high-flux atomic vapour at atmospheric pressure to rapidly vaporize diverse precursors, enabling the synthesis of multi-elemental nanomaterials with uniform compositions and tunable structures.

Antigen escape relapse remains a major obstacle when treating B-cell malignancies with immunotherapies. Here, the authors show that IKAROS regulates the surface expression of CD19 and CD22, revealing a mechanism by which B-cell cancers evade targeted immunotherapies.

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.

Vassy, Dornisch and colleagues developed a genomics-based prostate cancer risk model to support a randomized clinical trial of precision screening in a national healthcare system.

Here, the authors demonstrate that the Hand2 transcription factor partitions into the cell nucleolus to activate pacemaker-specific gene programs by accessing specific binding sites residing within repressive nucleolar heterochromatin.

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.

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.

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.

SARS-CoV-2 viruses are known to hijack human proteins in order to facilitate their own virulence and replication. In this study, Liu and colleagues present structural analysis of how this phenomenon occurs between SARS-CoV-2 viral envelope protein and human PALS1. The findings provide insights in to viral-host recognition.

An inherently explainable AI trained on 1,015 expert-annotated prostate tissue images achieved strong Gleason pattern segmentation while providing interpretable outputs and addressing interobserver variability in pathology.

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.

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.

Typical quantum error correcting codes assign fixed roles to the underlying physical qubits. Now the performance benefits of alternative, dynamic error correction schemes have been demonstrated on a superconducting quantum processor.

Radiotherapy induces expression of the EGFR ligand amphiregulin, which promotes metastasis growth at remote sites in mouse models and human patients by shifting myeloid cells towards an immunosuppressive state.

Incorporating membrane-destabilizing zwitterionic lipids into commercially available LNPs boosts mRNA expression in antigen-presenting cells within lymph nodes, enhancing cytotoxic T cell activation, and dampens reactogenicity in mice.

A broad systems-level approach is necessary to understand the intricate etiology of clinical complications from atherosclerotic cardiovascular disease. Here, the authors reconstruct a causal network of circulating proteins and identify subnetworks linked to future risk of myocardial infarction and other cardiometabolic traits.

Magnetic Weyl semimetals in the 2D limit may behave like 2D Chern insulators and host the quantum anomalous Hall effect at high temperatures. Here, the authors report the observation of linearly dispersing topological states confined to the edges of the kagome Co₃Sn terraces in the magnetic Weyl system Co₃Sn₂S₂.

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.

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.

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.