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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.

Siglecs are immunoregulatory lectins with very similar architectures. The authors show how the V-set domain of Siglec-6 allows it to select for precise sialylation patterns in specific biological environments, recasting Siglecs as molecular precision tools

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.

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.

The existing ENCODE registry of candidate human and mouse cis-regulatory elements is expanded with the addition of new ENCODE data, integrating new functional data as well as new cell and tissue types.

A new version of nanorate DNA sequencing, with an error rate lower than five errors per billion base pairs and compatible with whole-exome and targeted capture, enables epidemiological-scale studies of somatic mutation and selection and the generation of high-resolution selection maps across coding and non-coding sites for many genes.

Pulmonary type 2 inflammation is associated with type 2 innate lymphoid cells. Here the authors use the Collaborative Cross mouse panel to show that ILC2 abundance during type 2 lung inflammation is different across the panel and identify free-fatty acid receptor 3 (Ffar3) as a gene responsible and show cytokine and ILC2 functional changes.

New hominin fossils from the Grotte à Hominidés at Thomas Quarry I (ThI-GH) in Casablanca, Morocco, dated to around 773 thousand years ago are similar in age to Homo antecessor, yet are morphologically distinct.

Glioblastoma is characterised by high levels of intratumoural heterogeneity and plasticity, hindering treatment. Here, the authors develop an analytical framework, scFOCAL, to predict the sensitivity of glioblastoma cell subpopulations to therapies based on reversal of disease transcriptional signatures to identify synergistic therapeutic combinations.

Accurately predicting the optimal pH level for enzyme activity is challenging due to the complex relationship between enzyme structure and function. Gado and colleagues show that a language model can effectively learn the structural and biophysical features to predict the optimal pH for enzyme activity.

This research developed and compared firearm-specific and method-agnostic machine-learning models using data from 800,579 Army veterans, revealing that model choice and intervention thresholds impact predictive accuracy and fairness, guiding tailored suicide prevention efforts.

Here the authors provide an explanation for 95% of examined predicted loss of function variants found in disease-associated haploinsufficient genes in the Genome Aggregation Database (gnomAD), underscoring the power of the presented analysis to minimize false assignments of disease risk.

Effective early detection and intervention strategies for lung cancer are urgently needed. The authors of this Review summarize the current state of lung cancer screening and provide future directions for optimal implementation, including biomarker development. They also discuss precancer interception strategies that could transform both lung cancer prevention and early intervention.

Reported detections of gases in exoplanet atmospheres, including claims of biosignatures on K2-18 b, disappear when broader models are tested, revealing that such detections often reflect modelling limits rather than real signals.

DNA double-strand breaks endanger genome stability. Here, the authors present cryo-EM structures showing how Ku70/80 and DNA-PK bind DNA ends on nucleosomes, offering a mechanistic model for break recognition within chromatin.

An exploratory analysis of the phase 3 ECOSPOR III trial shows that a higher dosage of the oral microbiome therapeutic VOWST led to enhanced pharmacokinetics, increased species engraftment and altered microbiome and metabolite profiles, providing mechanistic insights into how it may prevent Clostridioides difficile infection recurrence.

The emergence of resistant subpopulations often underlies the development of resistance to cancer therapy. Here, using a DNA barcoding approach, the authors demonstrate EGFR TKI treatment in non-small cell lung cancer enriches for resistant subpopulation which can be prevented by treatment with the multikinase inhibitor sorafenib via inhibition of MKNK, STAT3 and MCL1.

Here, the authors examine the mechanisms behind cheatgrass’s successful invasion of North American ecosystems. Their genetic analyses and common garden experiments demonstrate that multiple introductions and migrations facilitated cheatgrass local adaptation.

Mu opioid receptor agonists with a preference for the non-GTP-bound state of the G protein promote GTP release, thereby potentiating antinociceptive effects of drugs such as morphine and fentanyl without also increasing their respiratory or cardiac effects.

De novo structural variants are an important cause of rare disorders but remain poorly understood. Here, the authors analyse over 12,000 families and reveal the prevalence, diversity, and clinical impact of complex de novo structural variants.

Surface controls nanocrystal growth, but atomic-scale hard-soft interfaces are hard to measure. Here, the authors develop electron microscopy methods to reveal the position of metal adatoms and surfactant counterions on gold nanocuboid surfaces.

Building scalable quantum technologies requires generating robust many-body entanglement in solid-state platforms. This Review highlights how engineered light–matter interactions, optical nonlinearities and coupling to nanophotonic structures enable coherent many-body entangled states that are resilient to disorder and decoherence.

Glioblastoma (GBM) is characterized by a high degree of heterogeneity and plasticity due to interplay with neural developmental programs. Here, the authors develop a model of GBM by introducing sequential oncogenic mutations in human neural stem cells and using this, identify INSM1 as a driver of a neural progenitor gene network promoting tumorigenesis.

When doubly-degenerate band crossings known as Kramers nodal lines intersect the Fermi level, they form exotic three-dimensional Fermi surfaces composed of massless Dirac fermions. Here, the authors present evidence that the 3R polytypes of TaS₂ and NbS₂ are Kramers nodal line metals with open octdong and spindle-torus Fermi surfaces, respectively.

A study of the evolution of the SARS-CoV-2 virus in England between September 2020 and June 2021 finds that interventions capable of containing previous variants were insufficient to stop the more transmissible Alpha and Delta variants.

This study shows that non-invasive ultrasound to the human nucleus accumbens can modulate deep brain activity and enhance reward-guided learning, offering a potential alternative to invasive neuromodulation therapies.

Lung adenocarcinomas bearing the ID2 mutational signature display increased LINE-1 retrotransposon activity, which contributes to their fast evolutionary dynamics and aggressive phenotype.

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.

Here, as part of the Sherlock-Lung study, the authors profile the microbiomes of 940 lung cancers in never smokers finding no significant associations with demographic and clinical features, suggesting lung bacteria are unlikely to have a sizable role in lung cancer.

High-depth sequencing of non-cancerous tissue from patients with metastatic cancer reveals single-base mutational signatures of alcohol, smoking and cancer treatments, and reveals how exogenous factors, including cancer therapies, affect somatic cell evolution.

The authors demonstrate dual-probe multi-messenger imaging of high-energy-density plasmas based on laser-wakefield-accelerated electrons. This enables spatiotemporally resolved simultaneous probing of plasma hydrodynamics and electromagnetic field evolution with both x-ray and electron beams.

The authors develop multimodal machine learning models to infer metastatic recurrence risk for early-stage, hormone receptor-positive breast cancer from H&E images using >6000 cases across three centers, outperforming a nomogram and unimodal methods.

Allogenic mesenchymal stem cells are engineered with three mRNAs to bind to multiple myeloma B cells while activating T cells for cancer therapy.

Genomic analyses applied to 14 childhood- and adult-onset psychiatric disorders identifies five underlying genomic factors that explain the majority of the genetic variance of the individual disorders.

Plasmodium falciparum proteins were engineered to create a nanoparticle vaccine platform capable of displaying multiple antigens at 48 sites. Displaying a designed malaria circumsporozoite protein immunogen on this platform achieves full sterile protection in mice.

High-throughput chemical ligand discovery is challenged by false positives. Here, authors introduce a scalable enantioselective affinity-selection mass spectrometry approach for proteome-wide ligand discovery with high sensitivity and selectivity

As the complexity of synthetic genetic circuits increases for biocomputing applications, there is a need to reduce the footprint of circuits to reduce burden on cells. Here, the authors develop wetware and software to design 3-input Boolean logic circuits that utilize fewer genetic parts.

Authors measure plasma proteins in a cohort of hospitalised patients presenting to the emergency department with suspected infection, revealing six discrete host response clusters that were driven by pathogen exposure and organ dysfunction, and had distinct clinical characteristics, hospital courses, and responses to treatment.

Here, the authors exploit the genetic information encoded in Klebsiella prophages to model the interplay between bacteria, prophages, and their depolymerases, using a directed acyclic graph-model and a sequence clustering-based model.

vConTACT3 enables multirank, large-scale classification of eukaryotic and prokaryotic viruses.