Cancer-wide in silico analyses using differentially expressed genes demonstrate the functions and clinical relevance of JAG, DLL, and NOTCH.

Notch ligands [jagged (JAG) and, delta-like (DLL) families] and receptors [NOTCH family] are key regulators of Notch signaling. NOTCH signaling contributes to vascular development, tissue homeostasis, angiogenesis, and cancer progression. To elucidate the universal functions of the JAG, DLL, and NOTCH families and their connections with various biological functions, we examined 15 types of cancer using The Cancer Genome Atlas clinical database. We selected the differentially expressed genes (DEGs), which were positively correlated to the JAG, DLL, and NOTCH families in each cancer. We selected positive and negative hallmark signatures across cancer types. These indicated biological features associated with angiogenesis, hypoxia, KRAS signaling, cell cycle, and MYC targets by gene ontology and gene set enrichment analyses using DEGs. Furthermore, we analyzed single-cell RNA sequencing data to examine the expression of JAG, DLL, and NOTCH families and enrichment of hallmark signatures. Positive signatures identified using DEGs, such as KRAS signaling and hypoxia, were enriched in clusters with high expression of JAG, DLL, and NOTCH families. We subsequently validated the correlation between the JAG, DLL, and NOTCH families and clinical stages, including treatment response, metastasis, and recurrence. In addition, we performed survival analysis to identify hallmark signatures that critically affect patient survival when combining the expression of JAG, DLL, and NOTCH families. By combining the DEG enrichment and hallmark signature enrichment in survival analysis, we suggested unexplored regulatory functions and synergistic effects causing synthetic lethality. Taken together, our observations demonstrate the functions of JAG, DLL, and NOTCH families in cancer malignancy and provide insights into their molecular regulatory mechanisms.

Analysis of Clinical Characteristics of Tuberculosis Patients with Dementia in Gyeongsangbuk-do, Republic of Korea.

(1) Background: Among Korean research papers there have been studies on the correlation between tuberculosis-hypertension and diabetes and the correlation between dementia-hypertension and diabetes, but there were no analysis data specifically on tuberculosis and dementia. (2) Methods: A total of 2992 tuberculosis patients in the Gyeongbuk region were analyzed through a final analysis of integrated disease and health management system data collected from 2021 to 2022. In this selection, patients with tuberculosis under 50 years of age and 368 people diagnosed with tuberculosis were excluded. (3) Results: From 2021 to 2022, among the 2992 tuberculosis patients in Gyeongsangbuk-do aged 50 or older, 2722 (91.0%) belonged to the general tuberculosis patient group, while 270 (9.0%) belonged to the dementia-tuberculosis patient group. The average age in the dementia-tuberculosis group was 81.4 years, significantly higher than the general group's average of 75.7 years. Within the dementia-tuberculosis patient group, 235 patients (87.0%) had underlying medical conditions in addition to dementia and tuberculosis. The tuberculosis treatment cure rate was 56.3% (1477 patients) in the general group and 38.9% (105 patients) in the dementia-tuberculosis patient group. (4) Conclusions: The cure rate was notably higher in the general group. Similarly, the mortality rate (deaths due to tuberculosis) was significantly higher in the dementia-tuberculosis patient group (7.0%, 19 patients) compared to the normal group (3.0%, 81 patients). The mortality rate in the dementia group was more than twice that of the general group.