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Breast cancer (BC) is the most common malignancy in female patients with Li-Fraumeni Syndrome (LFS). Here, the authors perform a multimodal analysis of LFS breast cancer (LFS-BC) compared to sporadic premenopausal BC, finding important differences in genomic alterations and instability, gene regulation, and the immune microenvironment.

Global analysis of obesity trends from 1980 to 2024 in 200 countries and territories using data from 4,050 population-based studies reveals that framing obesity as a single global epidemic masks the highly varied dynamics across countries and age groups.

Structural analysis reveals that the type VI secretion system effector cargo is enclosed within hexameric Hcp3 rings that form sequentially to enable effector loading and delivery by the Pseudomonas aeruginosa H3-type VI secretion system.

Kancharla, Kelly et al. identify an acridone antimalarial potent across all major parasite life stages. Lead candidate T111 shows oral efficacy, low toxicity, and synergy with tafenoquine, providing a unique mechanism to overcome resistance.

RNA velocity is a widely used method to predict the fate of single cells. Here the authors show that the concept can be adapted to predict the fate of individual human subjects, using RNA velocity of whole blood at a single point in time to predict future clinical outcomes and treatment responses.

In a randomized trial, pasteurized Akkermansia muciniphila improved weight loss maintenance and metabolic health after a low-energy diet, especially in individuals with initially lower Akkermansia levels. The work suggests leveraging gut A. muciniphila as a potential target for weight management.

A large-scale study on the replicability of claims from social and behavioural science journals reports that about half of the results replicate in the same patterns as the original study.

Massively parallel reporter assays promise rapid in vivo characterization of enhancer AAVs. Here, through systematic testing, authors uncover pervasive technical and biological noise, including chimeric AAV species, that exposes fundamental limitations in pooled enhancer screening.

Machine learning is used to understand emissions of the potent greenhouse gas nitrous oxide from the Southern Ocean. Low-pressure storms are found to drive emissions, leading to a revised picture of marine greenhouse gas cycling

This research investigates optimal brain states for predicting autistic traits using connectome-based predictive modeling across four datasets. Findings indicate that a sustained attention task enhances prediction accuracy, generalizing effectively to neurotypical adults and various measures of social responsiveness.

Robustness checks and reproduction of analyses with existing and updated data based on 110 articles in economics and political science journals with data and code-sharing requirements found high levels of robustness and reproducibility and determined that robustness was not dependent on author characteristics or data availability.

A deep learning framework integrates protein language models, protein interactions and domains, medical knowledge graphs and electronic health records to map variants to phenotypes.

The authors report an anti-β-tryptase antibody as a potential therapeutic for asthma with a superior mechanism of action that inhibits both tetrameric and monomeric β-tryptase activity. Structural analysis reveals that the molecular path of allosteric inhibition is due to a single antibody residue.

In four studies, Kelly and Sharot reveal that web-browsing both reflects and affects mental health. Poorer mental health leads to more negative content consumption, which in turn worsens mood. Highlighting webpage emotional impacts reduced negative browsing and improved mood.

Decreased sound tolerance refers to alterations in a person’s ability to cope with everyday sounds that do not bother most people. In this Review, Scheerer et al. synthesize evidence supporting that two frequent subtypes of these alterations, hyperacusis and misophonia, are transdiagnostic to psychopathology.

Transition metal oxides constitute a promising class of catalysts for the oxygen reduction reaction, but they are found generally to be less active than Pt. Now, computational analyses and high-throughput experiments are used to understand the reasons behind the lower activity, and strategies to improve them are proposed.

In a randomized, double-blind, placebo-controlled trial comparing autologous mRNA-engineered BCMA-targeting CAR T cell therapy versus placebo in patients with generalized myasthenia gravis, a significantly higher percentage of patients exhibited a reduction in disease activity in the treatment arm than in the placebo arm.

Pancreatic ductal adenocarcinoma carries a poor prognosis, with pancreatectomy as the only potentially curative option. This Phase II trial assessed distant metastasis-free survival in locally advanced disease using GVAX vaccine, pembrolizumab, and SBRT following chemotherapy.

The first-in-human clinical trial of the LRRK2-targeting antisense oligonucleotide BIIB094 in Parkinson’s disease demonstrates that the treatment is well tolerated and produces dose-dependent reductions in cerebrospinal fluid levels of LRRK2 and phosphorylated Rab10, indicating successful target engagement.

Warren et al. used data from a retrospective cohort of 50,000 women attending breast screening. Arbitration between human and AI decisions was performed in a reader study following normal arbitration workflow. After arbitration, replacing the second human reader with AI in a double-read breast screening workflow was noninferior to two human readers.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

Divergent white matter metabolic patterns reveal a mechanistic basis for cognitive resilience and enhance prediction of future cognitive decline beyond established aging and dementia biomarkers.

A prototypical example of a ‘strategic atom replacement’ approach enables synthesis of N-alkyl pyrazoles from isothiazoles by swapping the sulfur atom with a nitrogen atom and its associated alkyl fragment to deliver the alkylated pyrazole.

Authors analyzed malaria and tuberculosis drugs to create a pharmacometric model. They used an AI pipeline that prioritized pharmacogenetic drug-gene pairs with an emphasis on high variant frequency genes in an African population.

Analysis of clinical trial data suggests that CDK4/6 inhibitors prevent the expansion of TP53-mutant clones in the blood, potentially mitigating the risk of secondary myeloid neoplasms in patients treated with cytotoxic drugs.

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

Turajlic and colleagues assess longitudinal antibody and cellular immune responses against SARS-CoV-2 variants of concern in patients with cancer, following either recovery from SARS-CoV-2 infection or vaccination, in two back-to-back reports from the CAPTURE study.

Analysis of a placebo-controlled trial of a BCMA-targeting CAR-T cell therapy in patients with myasthenia gravis shows that CAR-T cell infusion selectively remodels the systemic immune environment, with elimination of BCMA-high plasma cells and activated plasmacytoid dendritic cells and changes in the autoreactive B cell repertoire.

LARP6 is an EMT-associated RNA-binding protein with diverse RNA targets. Here, the authors show that the N-terminal disordered region of LARP6 promotes RNA-binding selectivity by modulating the adjacent La-module and forming auxiliary contacts with RNA.

Inhibition of ALK is initially effective in patients with ALK-driven lung cancer but resistance often arises. Here, the authors use circulating tumour DNA, collected as part of a phase I trial investigating lorlatinib (ALK inhibitor) in pediatric patients with ALK-driven neuroblastoma, to detect early resistance mechanisms.

In a phase 1 trial testing healthy donor fecal microbial transplantation with immune checkpoint blockade in patients with previously untreated renal cell carcinoma, treatment was safe with an encouraging response signal and microbiome analyses, suggesting specific donor taxa associations with toxicity.

A couple-close approach used to build semisaturated ring systems from dual radical precursors allows sampling of regions of underexplored chemical space, leading to an annulation that can be used for late-stage functionalization of pharmaceutical scaffolds.

Therapies combining chemotherapy and immune checkpoint inhibitors have shown limited efficacy in patients with advanced pancreatic ductal adenocarcinoma (PDAC). Here the authors report the results of a pilot phase 1 trial of neoadjuvant modified Folfirinox plus nivolumab in borderline-resectable PDAC, including safety, efficacy and immunological correlates.

Amorphous films with tunable thermal conductivity are needed for semiconductor/aerospace fields. Amorphous Al(Ti)N nanoparticles have negligible effect on thermal conductivity of Si₃N₄ 2 W m⁻¹K⁻¹, while incorporating crystal TiN phases increases to 15 W m⁻¹K⁻¹.

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.

Newly developed mouse models that enable cell-specific analyses of proteostasis dynamics across the lifespan of the mice reveal key aspects of neuronal proteostasis with ageing.

Identifying jets originating from heavy quarks plays a fundamental role in hadronic collider experiments. In this work, the ATLAS Collaboration describes and tests a transformer-based neural network architecture for jet flavour tagging based on low-level input and physics-inspired constraints.

The use of a thin layer of zinc oxide nanoparticles as an electron-transport layer allows flexible perovskite solar cells to be fabricated with a power conversion efficiency as high as 15.7%.

Using data from the CoVPN 3008 study, the authors show that the neutralizing antibody correlate of risk holds in people living with HIV. However, the nAb correlate was weaker and shorter-lived in a vaccine-immunity versus hybrid-immunity population.