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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.

This study uses spatial proteomic and spatial compartment-based whole-transcriptome profiling to develop predictive models for immunotherapy outcomes in non-small cell lung cancer.

Human papillomavirus (HPV)-associated oropharyngeal cancer is increasing but the natural history of oral HPV infection is not well understood. Here, the authors investigate clearance of oncogenic oral HPV infection in a cohort of men from the US, Brazil, and Mexico.

People living in rural areas of the United States have poorer outcomes from acute COVID-19. Here, the authors show that higher mortality rates among rural dwellers persist for up to two years after the initial infection, even after accounting for baseline risk factors.

A proteotoxic stress response specific to exhausted T cells, governed by AKT signaling and accompanied by increased protein translation, represents a mechanistic vulnerability and a new therapeutic target to improve cancer immunotherapies.

Genetic background, plasma metabolome and dietary data from 4,215 women and 1,490 men reveal 57 metabolites whose associations with dementia risk vary by APOE4 genotype and other risk variants.

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare cancer. Here, the authors develop a NLPHL specific model to identify 34 distinct cell states across 14 cell types that co-occur within 3 lymphocyte predominant ecotypes (LPEs) for 171 cases.

COX-2-mediated prostaglandin E2 (PGE2) release from dying cancer cells contributes to cytotoxic therapy resistance. Here the authors show that cytotoxic drugs induce PGE2 release only in cancer cells with basal COX-2 activity and that pharmacological COX-2 inhibition can boost the efficacy of the combination of chemotherapy and PD-1 blockade.

VRK Serine/Threonine Kinase 2 (VRK2) has shown to play a significant role in apoptosis, cell growth, and immune response. Here the authors report that VRK2 is a key regulator of hepatocellular carcinoma (HCC) which can enhance myelocytomatosis oncogene (MYC) protein stability and transcriptional activity resulting in HCC progression when expressed increased levels

Temporal interference stimulation is thought to act via low-frequency envelope demodulation. Here, the authors demonstrate that stimulation thresholds in TIS follow the same carrier frequency dependence as direct kHz stimulation, indicating a shared biophysical mechanism.

In an integrated analysis of transcriptomic data from the SUBSPACE consortium and public datasets of patients with sepsis, acute respiratory distress syndrome, trauma and burns, dysregulation within four consensus molecular clusters related to myeloid and lymphoid cells is associated with mortality and illness severity.

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 tissue-specific accumulation patterns of pathogenic mtDNA mutations during aging remain incompletely understood. In this study, the researchers developed three mouse models with distinct mitochondrial tRNA mutations, revealing age-dependent accumulation of these mutations in the kidneys, leading to mitochondrial kidney disease.

In atrial fibrillation patients, circulating biomarkers reflecting inflammation, myocardial injury, and coagulation improve prediction of stroke, heart failure, and bleeding, outperforming clinical scores and enhance risk stratification.”.

In this prespecified exploratory biomarker analysis of the placebo-controlled CheckMate 274 trial, a composite model of adaptive immunity biomarkers and clinical parameters was identified and shown to predict benefit from nivolumab treatment in patients with muscle-invasive urothelial cancer.

In multiple sclerosis, smoldering inflammation contributes to clinical progression. Using multi-omics data, here the authors link chronic inflammation to senescence-like processes and cellular network changes, suggesting a potential therapeutic target.

Patients with myelodysplastic syndromes (MDS) have limited therapeutic options. Here the authors show that functionally impaired NK cells contribute to immune escape of pre-malignant clones in early stage MDS and that NK adoptive cell therapy can be considered to prevent or delay the development of MDS.

Chemotherapy is commonly used for the treatment of cancer but resistance often occurs. Here, the authors identify mitochondrial DLAT as driver of chemotherapy resistance via interaction with (MTHFD2) and develop a decoy peptide which blocks this interaction, restoring sensitivity to chemotherapy.

Sehgal et al. report Systems Age as a framework to capture within-person heterogeneity in aging using a single blood-based epigenetic assay that measures aging across 11 body systems and identifies aging subtypes, enabling personalized prediction of disease risk and tailoring of longevity interventions.

In the CheckMate 142 study, nivolumab (anti-PD-1) alone and in combination with ipilimumab (anti-CTLA-4) was shown to induce durable clinical benefit in patients with previously treated microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer. Here, the authors perform exploratory biomarker analysis of the CheckMate 142 study.

This study found higher RSV antibody levels were associated with lower RSV risk in children outside the hospital. An earlier rise in incidence and higher incidence rates were observed among children <5 years compared to older children and adults.

Zhao et al. used single-cell and spatial multiomics data analysis of human and mouse lung adenocarcinoma tumors and cell lines to reveal TP53 mutation-associated changes in cancer cells and their microenvironment.

Using data from six population-scale cohorts involving more than 10 million individuals, a large language model-based aging signature is shown to outperform traditional aging biomarker indices and signatures in predicting multiple health outcomes, at general and organ-specific levels.

Lowering the levels of coagulation factor XII may prevent thrombosis without increasing the risk of bleeding. Here, Haj et al. use a large human dataset to show that this is the case for people carrying mutations that lower the levels of factor XII.

In the secondary endpoint analysis of the phase 3 SONIA trial, circulating tumor DNA (ctDNA) analysis showed that a pretreatment aneuploidy-based high ctDNA level in patients with advanced breast cancer was associated with benefit from first-line treatment with CDK4/6 inhibitors.

Mitochondrial dysfunction contributes to septic cardiomyopathy and poor outcomes. Here, the authors identify a cardiomyocyte-enriched non-coding RNA that preserves mitochondrial function and reduces mortality in septic mice by preventing citrate synthase acetylation.

The location of EGFR exon 20 loop insertions (EGFRex20ins) has been shown to alter sensitivity to lung cancer therapy. Here, the authors report the results of the ZENITH20 clinical trial investigating poziotinib (EGFR TKI) in lung cancer patients and, combining with a similar trial, investigate how structural differences due to location of EGGFRex20ins alters sensitivity to EGFR TKI.

Shigella sonnei is divided into five lineages and most infections are caused by Lineage 3. Here, the authors investigate factors contributing to the epidemiological success of Lineage 3 through comparative genomics and virulence analyses in a zebrafish infection model.

Preeclampsia poses significant risks in pregnancy, and accurately predicting delivery timing is crucial for optimal care. Here, the authors show that deep-learning models, using limited electronic health record features, can effectively predict the time from preeclampsia diagnosis to delivery, potentially offering a tool for better resource allocation.

This prespecified updated survival and exploratory subgroup efficacy analysis of the phase 3 DESTINY-Breast04 trial shows that trastuzumab deruxtecan treatment in patients with HER2-low metastatic breast cancer leads to continuous survival benefit irrespective of estrogen receptor or hormone receptor status.

The treatment potential of psilocybin for postpartum depression was investigated in a preclinical mouse model. Here the authors show both acute and long-term effects of psilocybin in mothers and their offspring who were exposed via lactation.

Here, the authors report that combining Army Liposome Formulation with QS21 saponin (ALFQ) and Alum to formulate the ΔV1gp120 boost decreases the risk of simian immunodeficiency virus (SIV) mac251 acquisition in female macaques.

CAR-T cells engineered with αPD-L1–IL-12 fusion proteins show antitumour activity in mouse models of prostate and ovarian cancer.

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.

Boccella, Yu and colleagues reveal that the transmembrane protein ANTXR1 regulates post-infarction fibrotic remodeling, and its inhibition blocks collagen turnover and improves heart function.

Adult stem cells often reside in specialized niches that they exit upon injury. Here they show that in Drosophila, after damage the gut-associated trachea produces the PDGF-VEGF-related ligand Pvf1, which acts as a guidance cue directing ISC migration toward injury sites.

Here the authors show that chromosomal instability signatures can predict resistance to anthracycline-, taxane- and platinum-based chemotherapeutics in breast, ovarian and prostate cancer and sarcoma. Validation is performed through emulation of phase 2 and 3 clinical trials using real-world data.

TFE3-fusions are known to drive both epithelial and mesenchymal renal tumors. Here, the authors generate a transgenic mouse model of renal tumorigenesis expressing the human SFPQ-TFE3 fusion, showing that the fusion regulates mTORC1 activity and induces lineage plasticity.

The management of ulcerative colitis (UC) remains challenging due to the complexity of its etiology. Here, the authors establish that argininosuccinate synthetase 1 (ASS1) and its metabolite arginine are pivotal inducers of UC, through the triggering of mTOR and iNOS activation, and the induction of gut microbiota dysbiosis by metabolomics and proteomics. Inhibition of ASS1 by C-01 provides a viable strategy for the treatment of UC.

Cellular spatial organisation is crucial for shaping tissue functions and phenotypes. Here, authors present TrimNN, a graph-based deep learning framework to identify conserved cellular community motifs, revealing links between spatially distributed cell-type patterns and diverse phenotypes.