Screening Methods to Discover the FDA-Approved Cancer Drug Encorafenib as Optimally Selective for Metallothionein Gene Loss Ovarian Cancer.

Background/objectives: All 11 metallothionein protein-coding genes are located on human chromosome 16q13. It is unique among human genetics to have an entire pathway's genes clustered in a short chromosomal region. Since solid tumors, particularly high-grade serous ovarian cancer (HGSC), exhibit high rates of monoallelic aneuploidy, this region is commonly lost.

Colorectal carcinogenesis in the Lynch syndromes and familial adenomatous polyposis: trigger events and downstream consequences.

Carcinogenesis encompasses processes that lead to increased mutation rates, enhanced cellular division (tumour growth), and invasive growth. Colorectal cancer (CRC) carcinogenesis in carriers of pathogenic APC (path_APC) and pathogenic mismatch repair gene (path_MMR) variants is initiated by a second hit affecting the corresponding wild-type allele. In path_APC carriers, second hits result in the development of multiple adenomas, with CRC typically emerging after an additional 20 years.

Intimate Partner Violence Among LGBTQ+ Adults in Latin America and the Caribbean: A Systematic Review and Meta-Analysis.

We present the first systematic review and meta-analysis of the literature on intimate partner violence (IPV) among LGBTQ+ adults in Latin America and the Caribbean (LAC). Of 1,234 articles, 22 met inclusion criteria, and data were extracted for 4 key research areas: prevalence, measurement, risk and protective factors, and interventions. LGBTQ+ adults in LAC experience IPV at similar or higher rates than those documented among cisgender heterosexuals, with estimates ranging from 0.

Onchocerciasis is not a major cause of blindness in two endemic villages in Sierra Leone.

Objective: Sierra Leone, a country where onchocerciasis is endemic in 14 of the 16 districts, was the focus of our investigation. Despite 17 rounds of annual ivermectin treatment since 2005, a report circulated by a local politician indicated an increase in cases of suspected onchocerciasis-related vision impairment in two villages (Mangobo and Petifu) in Tonkolili district. In response, the National Neglected Tropical Disease Program conducted a comprehensive investigation.

Somatic mutation as an explanation for epigenetic aging.

DNA methylation marks have recently been used to build models known as epigenetic clocks, which predict calendar age. As methylation of cytosine promotes C-to-T mutations, we hypothesized that the methylation changes observed with age should reflect the accrual of somatic mutations, and the two should yield analogous aging estimates. In an analysis of multimodal data from 9,331 human individuals, we found that CpG mutations indeed coincide with changes in methylation, not only at the mutated site but with pervasive remodeling of the methylome out to ±10 kilobases.