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Mesothelioma is a highly lethal cancer that remains challenging to diagnose. Here, the authors curate a histomorphological atlas of resected mesothelioma and map it using self-supervised AI endorsed by human pathological assessment, revealing patterns that generate highly interpretable predictions.

Propane oxidative dehydrogenation offers a promising path for propylene production, but selective propylene formation with minimal COx remains challenging. Here, the authors introduce dual-atom catalysts achieving just 5.2% COx selectivity at 46.1% propane conversion (520 °C) with stable performance for over 1000 hours.

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.

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.

Postpartum involution of the mammary gland is a recognized risk factor for breast cancer. This report identifies a mechanism that could be at least partially responsible for the increased risk, involving both the elevated expression of COX-2 and its interaction with extracellular collagen, the deposition of which occurs during postpartum involution. Both these factors promote tumor growth and invasion in mice and correlate with poor prognosis in young women with breast cancer. The data suggest that ibuprofen treatment during involution is a safe and effective approach to diminish pregnancy-associated cancer.

Whether paternal pre-conceptual SARS-CoV-2 infection impacts sperm RNA content, or effects offspring phenotypes, has not been previously investigated. Here authors report changes in sperm noncoding RNAs in SARS-CoV-2 infected sires and increased anxiety-like behaviors in offspring.

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.

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.

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.

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.

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.

In the randomized phase 3 AMPLITUDE trial, patients with HRR-deficient mCSPC experienced longer progression-free survival when they were treated with niraparib and AAP compared to placebo and AAP.

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.

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.

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.

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.

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.

Native state proteomics of PV interneurons revealed unique molecular features of high translational and metabolic activity, and enrichment of Alzheimer’s risk genes. Early amyloid pathology exerted unique effects on mitochondria, mTOR signaling and neurotransmission in PV neurons.

Cell state plasticity of neuroblastoma cells is linked to therapy resistance. Here, the authors develop a transcriptomic and epigenetic map of indisulam (RBM39 degrader) resistant neuroblastoma, demonstrating bidirectional cell state switching accompanied by increased NK cell activity, which they therapeutically enhance by the addition of an anti-GD2 antibody.

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 they perform a systematic dissection of OCT4 and reveal how intrinsically disordered regions can be used to serve specific functions during reprogramming and embryonic development. This can be exploited to engineer more efficient and specific reprogramming factors.

Enrichment for efferocytic macrophages in the islets of Langerhans promotes the accumulation of anergic-like CD4⁺ T cells and dampens autoimmune diabetes.

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.

Glioblastoma—the deadliest form of brain cancer—alters the calvarial bone and its marrow components, pushing it toward producing more myeloid cells and contributing to an immunosuppressive environment.

Glioblastoma (GBM) is an aggressive tumor characterized by an immunosuppressive microenvironment. Here, the authors present a therapeutic approach based on the implantation of a biodegradable scaffold for the sustained, local release of a TLR7/8 agonist at the time of tumor resection, to achieve anti-tumor immunity and protection from future tumor challenge.

Currently, the biological and clinical implications of copy number alteration (CNA) size heterogeneity and co-occurrence are incompletely understood. Here, the authors use 691 meningiomas and 29 cancer types from The Cancer Genome Atlas to develop size-dependent CNA and CNA co-occurrence models to optimize individualized pan-cancer risk stratification.

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.

The gut microbiota can influence the severity of pneumonia through the production of metabolites. In this translational study, the authors investigate the effects of tryptophan metabolites, specifically indole-3-acetic acid (IAA), on pneumonia.

The prognostic and diagnostic roles of DNA methylation in acute myeloid leukemia remains to be explored. Here, the authors develop DNA methylation-based models for the prediction of five-year survival and clinical molecular subtypes in both pediatric and adult test cohorts.

In vivo loss-of-function CRISPR screens were performed to identify genes influencing CAR T cell persistence and function in human multiple myeloma, highlighting CDKN1B as a promising target.

UCHL5 is a deubiquitinating enzyme that cleaves Lys-48-linked polyubiquitin chains. Here, the authors discover through in-vivo CRISPR-Cas9 screens that Uchl5 is involved in immune evasion and modulation of extracellular matrix deposition in head and neck squamous cell carcinoma.

Comprehensive pan-cancer analysis of loss of the Y chromosome (LOY) in benign and malignant cells establishes a new model linking LOY in circulating and tumour-infiltrating immune cells to LOY in malignant cells.

The tumor environment is nutrient deficient. Here the authors show that early availability of methionine is critical for optimal T cell activation and prevents T cell dysfunction, and that dietary methionine can improve the efficacy of cancer immunotherapy in mice.

Few genome-wide association studies have explored the genetic architecture of age-of-onset for traits and diseases. Here, the authors develop a Bayesian approach to improve prediction in timing-related phenotypes and perform age-of-onset analyses across complex traits in the UK Biobank.

Heart failure can be caused by cardiac fibroblasts replacing myocytes. Here, the authors use functional genomic data from fibroblasts, genetic signals enriched in people with heart disease, and gene perturbation analyses to link disease-associated regulatory elements to protein-coding genes.

Chimeric antigen receptor (CAR)-T cell is a promising therapy for hematological malignancy, but further optimization is still desirable. Here the authors show that incorporating CD99, a membrane protein expressed on activated T cells, transmembrane and juxtamembrane domains into CAR design helps improve CAR-T efficacy in vitro and in vivo in mice.

CAR-T cells have been found to be less effective as treatment for solid tumours. Here the authors, utilising B7H3 as an antigen, consider how changes in B7H3 binders lead to functional changes of CAR-T cells and differences in tumour outcomes in humanised mouse tumour models.

Epstein-Barr virus is associated with increased cancer risk. Here, the authors analysed two population-based prospective cohorts in Southern China to examine the association between increased seropositivity and the risk of multiple cancer types.

The Cox’s Bazar area of Bangladesh has received a large number of Forcibly Displaced Myanmar Nationals. Cholera outbreaks have been detected in the area, and here, the authors perform genomic surveillance of cholera in the refugee and non-refugee population to infer the risk of epidemic spread.

Tan and colleagues conducted a single-cell multiomic analysis of T cell acute lymphoblastic leukemia and identified a treatment-resistant subpopulation of bone marrow progenitor-like blasts associated with poor outcomes.

Basal cells, rather than neuroendocrine cells, have been identified as the probable origin of small cell lung cancer and other neuroendocrine–tuft cancers, explaining neuroendocrine–tuft heterogeneity and offering new perspectives for targeting lineage plasticity.

Five-year follow-up and prespecified exploratory biomarker analysis from the phase 3 KEYNOTE-426 trial show that pembrolizumab plus axitinib compared to sunitinib as first-line therapy continues to show overall and progression-free survival benefits in patients with advanced clear cell renal cell carcinoma and indicate that a T-cell-inflamed gene expression profile is predictive of response.