Worse Wilms' Tumor Outcomes Associated With Chemical Complementarity for Multiple T-Cell Receptor CDR3-CMV Epitope Pairs.

BACKGROUND/AIM: Wilms' tumors are pediatric renal tumors that generally have a good prognosis and outcomes. Viral illnesses have been linked to development of neoplasms and should be considered as a factor that could modulate overall survival. MATERIALS AND METHODS: We considered recently developed adaptive immune receptor, genomics and bioinformatics approaches to assess the potential impact of cytomegalovirus (CMV) infections in Wilms' tumor. RESULTS: T-cell receptor (TCR) complementarity determining region-3 (CDR3) amino acid sequences from Wilms' tumor specimens represented by the Therapeutically Applicable Research to Generate Effective Treatments dataset were compared with known anti-CMV TCR CDR3s, indicating that cases representing the anti-CMV TCR CDR3s had worse outcomes. Then, a chemical complementarity scoring approach for the Wilms' tumor, TCR CDR3s and a series of CMV antigens further indicated that cases representing a higher chemical complementarity to the CMV antigens had worse outcomes. CONCLUSION: Overall, we present a potentially novel method to assess CMV infections and identify patients who could benefit from therapies that address such infections.

Transcriptome-Derived Ligand-Receptor Interactome of Major PitNET Subgroups.

Introduction Pituitary neuroendocrine tumors (PitNETs) are rare skull base tumors which can impart significant disability owing to their locally invasive potential. To date, the gamut of PitNET subtypes remains ill-understood at the ligand-receptor (LR) interactome level, potentially limiting therapeutic options. Here, we present findings from in silico analysis of LR complexes formed by PitNETs with clinical presentations of acromegaly, Cushing's disease, high prolactin production, and without symptoms of hormone hypersecretion. Methods Previously published PitNET gene expression data was acquired from ArrayExpress. These data represented all secretion types. LR interactions were analyzed via a crosstalk score approach. Results Cortisol (CORT) ligand was significantly involved in tumor-to-tumor signaling across all PitNET subtypes but prolactinomas, which evidenced active CORT depletion. Likewise, CCL25 ligand was implicated in 20% of the top LR complex interactions along the tumor-to-stroma signaling axis, but silent PitNETs reported unique depletion of the CCL25 ligand. Along the stroma-to-tumor signaling axis, all clinical PitNET subtypes enriched stromal vasoactive intestinal polypeptide ligand interactions with tumor secretin receptor. All clinical PitNET subtypes enriched stromal DEFB103B (human ß-defensin 103B) ligand interactions with stromal chemokine receptors along the stroma-to-stroma signaling axis. In PitNETs causing Cushing's disease, immune checkpoint ligand CD274 reported high stromal expression, and prolactinomas reported low stromal expression. Moreover, prolactinomas evidenced distinctly high stromal expression of immune-exhausted T cell response marker IL10RA compared with other clinical subtypes. Conclusion Relative crosstalk score analysis revealed a great diversity of LR complex interactions across clinical PitNET subtypes and between solid tumor compartments. More data are needed to validate these findings and exact clinical importance.

Artificial Intelligence for Mohs and Dermatologic Surgery: A Systematic Review and Meta-Analysis.

BACKGROUND: Over the past decade, several studies have shown that potential of artificial intelligence (AI) in dermatology. However, there has yet to be a systematic review evaluating the usage of AI specifically within the field of Mohs micrographic surgery (MMS). OBJECTIVE: In this review, we aimed to comprehensively evaluate the current state, efficacy, and future implications of AI when applied to MMS for the treatment of nonmelanoma skin cancers (NMSC). MATERIALS AND METHODS: A systematic review and meta-analysis was conducted following PRISMA guidelines across several databases, including PubMed/MEDLINE, Embase, and Cochrane libraries. A predefined protocol was registered in PROSPERO, with literature search involving specific keywords related to AI and Mohs surgery for NMSC. RESULTS: From 23 studies evaluated, our results find that AI shows promise as a prediction tool for precisely identifying NMSC in tissue sections during MMS. Furthermore, high AUC and concordance values were also found across the various usages of AI in MMS, including margin control, surgical recommendations, similarity metrics, and in the prediction of stage and construction complexity. CONCLUSION: The findings of this review suggest promising potential for AI to enhance the accuracy and efficiency of Mohs surgery, particularly for NMSC.

Exome sequencing identifies HELB as a novel susceptibility gene for non-mucinous, non-high-grade-serous epithelial ovarian cancer.

Rare, germline loss-of-function variants in a handful of genes that encode DNA repair proteins have been shown to be associated with epithelial ovarian cancer with a stronger association for the high-grade serous hiostotype. The aim of this study was to collate exome sequencing data from multiple epithelial ovarian cancer case cohorts and controls in order to systematically evaluate the role of coding, loss-of-function variants across the genome in epithelial ovarian cancer risk. We assembled exome data for a total of 2,573 non-mucinous cases (1,876 high-grade serous and 697 non-high grade serous) and 13,925 controls. Harmonised variant calling and quality control filtering was applied across the different data sets. We carried out a gene-by-gene simple burden test for association of rare loss-of-function variants (minor allele frequency < 0.1%) with all non-mucinous ovarian cancer, high grade serous ovarian cancer and non-high grade serous ovarian cancer using logistic regression adjusted for the top four principal components to account for cryptic population structure and genetic ancestry. Seven of the top 10 associated genes were associations of the known ovarian cancer susceptibility genes BRCA1, BRCA2, BRIP1, RAD51C, RAD51D, MSH6 and PALB2 (false discovery probability < 0.1). A further four genes (HELB, OR2T35, NBN and MYO1A) had a false discovery rate of less than 0.1. Of these, HELB was most strongly associated with the non-high grade serous histotype (P = 1.3×10-6, FDR = 9.1×10-4). Further support for this association comes from the observation that loss of function variants in this gene are also associated with age at natural menopause and Mendelian randomisation analysis shows an association between genetically predicted age at natural menopause and endometrioid ovarian cancer, but not high-grade serous ovarian cancer.

Digital roots: harnessing digital platforms in advancing traditional and complementary medicine for cancer care in Sub-Saharan Africa.

The rise in cancer rates in Sub-Saharan Africa (SSA), combined with limited access to Western pharmaceuticals, has sparked growing adoption of traditional and complementary medicine (T&CM) for cancer treatment in the region. However, many challenges exist, including the lack of reliable evidence-based research on these products, scarcity of standardized documentation as part of cancer registries, limited physician expertise, and negative effects on mortality. Nonetheless, herbal medicines also present opportunities for further research, development, and stakeholder education, potentially benefiting the regional healthcare systems in SSA countries and global health as whole. Recent trends highlight the willingness of patients to use mobile-based applications that provide accurate information on herbal therapeutics, reflecting the increasing adoption of internet and smart/mobile phone services in SSA. To maximize the potential benefits of traditional and complementary medicine, it is necessary to bridge the trust gap between the public, local practitioners, and Western healthcare providers. Sustained funding and policy support are needed to complement these initiatives. Our preliminary survey hopes to inspire the community and policymakers to embrace innovative solutions, fostering a forward-looking approach to cancer care in SSA.