Targeting P4HA1 promotes CD8 T cell progenitor expansion toward immune memory and systemic anti-tumor immunity.

Successful immunotherapy relies on both intratumoral and systemic immunity, which is yet to be achieved for most patients with cancer. Here, we identify P4HA1, encoding prolyl 4-hydroxylase 1, as a crucial regulator of CD8 T cell differentiation strongly upregulated in tumor-draining lymph nodes (TDLNs) and hypoxic tumor microenvironment. P4HA1 accumulates in mitochondria, disrupting the tricarboxylic acid (TCA) cycle through aberrant α-ketoglutarate and succinate metabolism, promoting mitochondria unfitness and exhaustion while suppressing progenitor expansion.

Genomic and transcriptomic profiling of radioresistant prostate and head and neck cancers implicate a BAHD1-dependent modification of DNA damage at the heterochromatin.

Radiotherapy is an integral modality in treating human cancers, but radioresistance remains a clinical challenge due to the involvement of multiple intrinsic cellular and extrinsic tumour microenvironment factors that govern radiosensitivity. To study the intrinsic factors that are associated with cancer radioresistance, we established 4 radioresistant prostate (22Rv1 and DU145) and head and neck cancer (FaDu and HK1) models by irradiating their wild-type parentals to 90 Gy, mimicking the fractionated radiotherapy schema that is often using in the clinic, and performed whole exome and transcriptome sequencing of the radioresistant and wild-type models. Comparative genomic analyses detected the enrichment of mismatch repair mutational signatures (SBS6, 14, 15, 20) across all the cell lines and several non-synonymous single nucleotide variants involved in pro-survival pathways.

Artificial Intelligence and Machine Learning Predicting Transarterial Chemoembolization Outcomes: A Systematic Review.

Background: Major society guidelines recommend transarterial chemoembolization (TACE) as the standard of care for intermediate-stage hepatocellular carcinoma (HCC) patients. However, predicting treatment response remains challenging.

Aims: As artificial intelligence (AI) may predict therapeutic responses, this systematic review aims to assess the performance and effectiveness of radiomics and AI-based models in predicting TACE outcomes in patients with HCC.

Advancing precision medicine through the integration of clinical cardiovascular genetics - An Asian perspective.

Purpose: The integration of cardiovascular genetic (CVG) testing into clinical practice is gaining recognition, but its implementation in the Asian setting has not been widely reported. We present our experience developing a clinical CVG service and analyze its impact on patient care at our center.

Methods: In 2020, the National Heart Centre Singapore collaborated with SingHealth Duke-NUS Genomic Medicine Centre, to establish a comprehensive clinical CVG service.

A nationwide epidemiological study of myasthenia gravis in Turkey.

Background: Variable incidence and prevalence rates of myasthenia gravis (MG) have been reported over time from different geographical regions. We aimed to determine incidence and prevalence of MG in Turkey and contribute to the development of proper national health policies.

Methods: Patients with G70.