Predictive modelling of the UK physician associate supply: 2014-2038.

Introduction: The NHS Long Term Workforce Plan aims for 10,000 physician associates (PAs, formerly physician assistants) by 2036/7. This article uses three modelling approaches to project the UK PA supply from a baseline of 2014-2021 through to 2038 to forecast the profession's growth.

Methods: The number of cClinically available PAs' (cPAs; qualified PAs either working clinically or seeking clinical employment) was estimated using raw data from the 2014-2021 Faculty of Physician Associates censuses.

Intratumor microbiota as a novel potential prognostic indicator in mesothelioma.

Introduction: Despite increased attention on immunotherapy, primarily immune checkpoint blockade, as a therapeutic approach for mesothelioma (MMe), its efficacy and tolerability remain questioned. One potential explanation for different responses to immunotherapy is the gut and intratumor microbiota; however, these remain an underexplored facet of MMe. This article highlights the cancer intratumor microbiota as a novel potential prognostic indicator in MMe.

Protein disulfide isomerase A1‑associated pathways in the development of stratified breast cancer therapies.

The oxidoreductase protein disulfide isomerase A1 (PDIA1) functions as a cofactor for many transcription factors including estrogen receptor α (ERα), nuclear factor (NF)‑κB, nuclear factor erythroid 2‑like 2 (NRF2) and regulates the protein stability of the tumor suppressor p53. Taking this into account we hypothesized that PDIA1, by differentially modulating the gene expression of a diverse subset of genes in the ERα‑positive vs. the ERα‑negative breast cancer cells, might modify dissimilar pathways in the two types of breast cancer.

Molecular Mechanisms of PD-1 and PD-L1 Activity on a Pan-Cancer Basis: A Bioinformatic Exploratory Study.

Immune checkpoint blockade targeting PD-1 (PDCD1)/PD-L1 (CD274) is increasingly used for multiple cancers. However, efficacy and adverse-related events vary significantly. This bioinformatic study interrogated molecular differences pertaining to PDCD1/CD274 and their correlated genes on a pan-cancer basis to identify differences between cancer types.

Differential regulation of cell death pathways by the microenvironment correlates with chemoresistance and survival in leukaemia.

Glucocorticoids (GCs) and topoisomerase II inhibitors are used to treat acute lymphoblastic leukaemia (ALL) as they induce death in lymphoid cells through the glucocorticoid receptor (GR) and p53 respectively. Mechanisms underlying ALL cell death and the contribution of the bone marrow microenvironment to drug response/resistance remain unclear. The role of the microenvironment and the identification of chemoresistance determinants were studied by transcriptomic analysis in ALL cells treated with Dexamethasone (Dex), and Etoposide (Etop) grown in the presence or absence of bone marrow conditioned media (CM).