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Cellular niches are highly heterogenous in triple negative breast cancer. Here, the authors utilise imaging mass cytometry and spatial transcriptomics to characterise the microenvironment in Black American and White American patients.

Here the authors use sex-stratified genetic analyses in mice and humans to uncover hidden trait influences, revealing many undetected loci and cautioning against misleading genetic interactions from widespread effects.

The long-term natural history of long-COVID is not well understood. In this population-based cohort study from Scotland, the authors describe symptom prevalence and health-related quality of life up to 18 months after a positive SARS-CoV-2 test and compare with matched test-negative controls.

In a randomized, placebo-controlled, stepwise dose-escalation phase 1 trial evaluating a conjugate vaccine against both typhoid and invasive non-typhoidal Salmonella infections, the vaccine was found to be safe and immunogenic in healthy adults.

Despite improving therapeutic options, the prognosis for patients with metastatic castration-resistance prostate cancer (mCRPC) remains poor. Here, the authors identify MCL1 copy number alterations as a prognostic and predictive biomarker, demonstrating its therapeutic potential as a drug target, either alone or in combination, in patients with mCRPC.

Head and neck squamous cell carcinoma (HNSCC) frequency and risk factors vary considerably across regions and ancestries. Here, the authors conduct a multi-ancestry genome-wide association study and fine mapping study of HNSCC subsites in cohorts from multiple continents, finding susceptibility and protective loci, gene-environment interactions, and gene variants related to immune response.

A study of several longitudinal birth cohorts and cross-sectional cohorts finds only moderate overlap in genetic variants between autism that is diagnosed earlier and that diagnosed later, so they may represent aetiologically different conditions.

Bone marrow adipose tissue accounts for almost 10% of human fat mass, but its roles remain unclear. Here, Xu et al. identify more than 45 diseases linked to marrow adiposity in over 48,000 people, including causal roles in musculoskeletal disease.

The synthesis of organophosphorus compounds from elemental phosphorus is an inefficient process, using multiple steps, stoichiometric metal complexes and/or hazardous reagents such as chlorine gas. Here, a direct photocatalytic route to convert white phosphorus (P₄) into phosphines and phosphonium salts is reported.

Polygenic risk scores can help identify individuals at higher risk of type 2 diabetes. Here, the authors characterise a multi-ancestry score across nearly 900,000 people, showing that its predictive value depends on demographic and clinical context and extends to related traits and complications.

Reduced dependence on wild-caught fish in favour of crop-based ingredients for feeds has supported aquaculture growth. An analysis of ingredient origins versus feed composition shows that origin must be considered to assess the environmental footprint of feed production.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

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.

This study presents FolTAC-dual, a folate receptor-mediated platform for dual degradation of EGFR/HER2 and PD-L1/VISTA, offering a strategy to overcome drug resistance and enhance antitumor immunity for cancer treatment.

Together with an accompanying paper presenting a transcriptomic atlas of the mouse lemur, interrogation of the atlas provides a rich body of data to support the use of the organism as a model for primate biology and health.

Spatial cell distribution within a tissue microenvironment is a rapidly advancing field. Here, authors assess three commercially available single-cell resolution spatial transcriptomics approaches (CosMx, MERFISH, and Xenium) to inform which technology outperforms for immune profiling of solid tumors using patient samples.

An Earth-mass planet is found to have a white dwarf host—the final evolutionary stage of Sun-like stars. This system suggests that terrestrial planets in Earth-like orbits may avoid being engulfed during the red-giant phases of their host stars.

In this study, Jirsaraie et al. analyze data from the Adolescent Brain Cognitive Developmental study and use machine learning to predict both current and future psychological symptoms and to determine rates of change in symptom severity over time.

The cortex fuels essential physiological processes with glucose-derived carbon, while gliomas fuel their aggressiveness by rerouting glucose carbon pathways and scavenging alternative carbon sources such as environmental amino acids, providing a potential therapeutic target.

A report from the first 2,000 newborns enrolled in the Early Check program, which offered genome screening covering 198 genes associated with early-onset diseases, shows the feasibility and potential clinical utility of the approach, leading to 28 true positive results.

Here, the authors find that a benign polygenic predisposition to lower white blood cell counts is associated with multiple clinical endpoints, suggesting that predisposed individuals are susceptible to escalations or alterations in clinical care that may be harmful or of little benefit.

Expanding the complexity of genetically encoded peptides is a long-standing challenge at the intersection of chemistry and biology. Now it has been shown that linear peptides with a reactive N-terminal β- or γ-keto amide can be synthesized ribosomally and elaborated to generate atropisomeric and/or macrocyclic peptides with embedded pharmacophores.

GIANT, a genetically informed brain atlas, integrates genetic heritability with neuroanatomy. It shows strong neuroanatomical validity and surpasses traditional atlases in discovery power for brain imaging genomics.

Following spinal cord injury, gamified physical therapy that incorporates closed-loop vagus nerve stimulation can aid restoration of arm and hand function.

Hominin fossils from the Ledi-Geraru Research Project area, Ethiopia, suggest that early Homo and Australopithecus species co-existed in the region more than 2.5 million years ago.

The genetic susceptibility to breast cancer remains understudied in non-European populations. Here, the authors analyse pathogenic variants associated with breast cancer susceptibility in Hispanic/Latina women using genomics, and find that loss of function variants in FANCM are strongly associated with ER-negative breast cancer risk.

Depletion of a transcriptional factor ZBTB11 using molecular glue degraders can overcome oxidative-phosphorylation-mediated KRAS inhibitor resistance in pancreatic ductal adenocarcinoma with low acute neurotoxicity.

Here the authors show a function for lymph nodes in the maintenance of effector T cell differentiation and function during chronic infection and checkpoint blockade, identifying a spatial component in the regulation of exhausted T cell fitness.

The enzyme ABHD18 is shown to have a key role in cardiolipin metabolism in mitochondria, offering a potential route for a small-molecule treatment of the rare genetic disease Barth syndrome.

Single-cell studies of human white adipose tissue (WAT) provide insights into the specialized cell types in the tissue. Here the authors combine publicly available and newly generated high-resolution and bulk transcriptomic results from multiple human datasets to provide a comprehensive cellular map of white adipose tissue.

State-of-the-art industrial methods for transforming P₄ into useful phosphorus compounds currently rely on indirect, multi-step strategies. It has now been shown that straightforward one-pot reactions can convert P₄ directly into industrially relevant products while requiring only mild conditions and simple, inexpensive reagents—and can also functionalize P₄ catalytically.

Although the number of participants is important for phenotypic prediction accuracy in brain-wide association studies using functional MRI, scanning for at least 30 min offers the greatest cost effectiveness.

Integrated multi-omic analyses using samples from the TRACERx study highlight cross-talk between DNA hypermethylation and genomic lesions in non-small cell lung cancer.

Histone deacetylases, such as HDAC3, have been shown to alter cellular metabolism in various tissues. Here the authors show that HDAC3 regulates WAT metabolism by activating a futile cycle of fatty acid synthesis and oxidation, which supports WAT browning.

Bone marrow adipose tissue accounts for over 10% of human fat mass. Here, Xu et al. use deep learning to measure marrow adiposity in over 45,000 people, and identify genes associated with altered bone marrow adiposity.

Maqdasy, Lecoutre et al. show that increased an phosphocreatine/creatine ratio in white adipocytes drives changes in AMP-activated protein kinase activity and promotes white adipocyte inflammation during obesity.

In an observational study comparing individuals with type 2 diabetes and obesity who underwent metabolic surgery with similar individuals who received GLP-1 receptor agonist treatment, metabolic surgery was associated with a lower risk of macrovascular and microvascular outcomes, including major adverse cardiovascular events, nephropathy, retinopathy and all-cause mortality.

To overcome limitations of previous genome-wide association studies of coronary artery disease, this study incorporates a cohort of individuals containing large fractions of Black and Hispanic individuals to provide a wider view of the genetic landscape of this disease.