Single cell and spatial analysis of immune-hot and immune-cold tumours identifies fibroblast subtypes associated with distinct immunological niches and positive immunotherapy response.

Cancer-associated Fibroblasts (CAFs) have emerged as critical regulators of anti-tumour immunity, with both beneficial and detrimental properties that remain poorly characterised. To investigate this, we performed single-cell and spatial transcriptomic analysis, comparing head & neck squamous cell carcinoma (HNSCC) subgroups, which although heterogenous, can be considered broadly immune-hot and immune-cold (human papillomavirus [HPV]+ve and HPV-ve tumours respectively). This identified six fibroblast subpopulations, including two with immunomodulatory gene expression profiles (IL-11 + inflammatory [i]CAF and CCL19 + fibroblastic reticular cell [FRC]-like).

Meta-analysis: the prophylactic use of tranexamic acid to reduce blood loss during caesarean delivery.

Introduction: The 2022 national guideline on The Prevention and Management of Primary Postpartum Haemorrhage (PPH) recommended consideration of prophylactic tranexamic acid (TXA) for women who are at high PPH risk undergoing caesarean section (CS). This meta-analysis reviews the basis for this recommendation.

Method: PubMed, OVID Medline, EMBASE, Science Citation Index, Scopus, CENTRAL, and ClinicalTrials.

Individual Differences in the Impact of Distracting Environmental Sounds on the Performance of a Continuous Visual Task in Older Adults.

Vulnerability to sound distraction is commonly reported in older adults with dementia and tends to be associated with adverse impacts on daily activity. However, study outcome heterogeneity is increasingly evident, with preserved resistance to distraction also evident. Contributory factors may include individual differences in distractibility in older adulthood per se, and failure to consider the influence of how difficult a person found the test.

Differentiation signals induce APOBEC3A expression via GRHL3 in squamous epithelia and squamous cell carcinoma.

Two APOBEC DNA cytosine deaminase enzymes, APOBEC3A and APOBEC3B, generate somatic mutations in cancer, thereby driving tumour development and drug resistance. Here, we used single-cell RNA sequencing to study APOBEC3A and APOBEC3B expression in healthy and malignant mucosal epithelia, validating key observations with immunohistochemistry, spatial transcriptomics and functional experiments. Whereas APOBEC3B is expressed in keratinocytes entering mitosis, we show that APOBEC3A expression is confined largely to terminally differentiating cells and requires grainyhead-like transcription factor 3 (GRHL3).