Comorbid conditions and survival among Black women with ovarian cancer.

Background: Black women with epithelial ovarian cancer (EOC) have worse survival and a higher burden of comorbid conditions compared with other racial groups. This study examines the association of comorbid conditions and medication use for these conditions with survival among Black women with EOC.

Methods: In a prospective study of 592 Black women with EOC, the Charlson comorbidity index (CCI) based on self-reported data, three cardiometabolic comorbidities (type 2 diabetes, hypertension, and hyperlipidemia), and medication use for each cardiometabolic comorbidity were evaluated.

Replacing rifampicin with minocycline increases the activity of the treatment regimen for Mycobacterium avium complex pulmonary disease in a dynamic hollow-fibre system.

Mycobacterium avium complex bacteria cause chronic pulmonary disease (MAC-PD) in susceptible patients [1]. The recommended treatment regimen (rifampicin, ethambutol and azithromycin) achieves 65% cure rates but with considerable toxicity and drug-drug interactions [2,3]. Minocycline proved active in monotherapy experiments using the hollow-fibre model [4].

Advances in tuberculosis biomarkers: unravelling risk factors, active disease and treatment success.

Tuberculosis (TB) is a major global health threat and demands improved diagnostic and treatment monitoring methods. Conventional diagnostics, such as sputum smear microscopy and culture, are limited by slow results and low sensitivity, particularly in certain patient groups. Recent advances in biomarker research offer promising solutions in three key areas: risk of disease, diagnosis of active disease and monitoring of treatment response.

Diet and Survival in Black Women With Epithelial Ovarian Cancer.

Importance: Ovarian cancer survival among Black women is the lowest across all racial and ethnic groups. Poor dietary quality also disproportionately affects Black populations, but its association with ovarian cancer survival in this population remains largely unknown.

Objective: To examine associations between dietary patterns and survival among Black women diagnosed with epithelial ovarian cancer (EOC).

The role of multiple mediation with contextual neighborhood measures in ovarian cancer survival.

Background: Mediation by multiple agents can affect the relation between neighborhood deprivation and segregation indices and ovarian cancer survival. In this paper, we examine a variety of potential clinical mediators in the association between deprivation indices (DIs) and segregation indices (SIs) with all-cause survival among women with ovarian cancer in the African American Cancer Epidemiology Study (AACES).

Methods: We use novel Bayesian multiple mediation structural models to assess the joint role of mediators (stage at diagnosis, histology, diagnostic delay) combined with the DIs and SIs (Yost, ADI, Kolak's URB, ICE-income) and a set of confounders with survival.

Concurrent RB1 Loss and BRCA Deficiency Predicts Enhanced Immunologic Response and Long-term Survival in Tubo-ovarian High-grade Serous Carcinoma.

Purpose: The purpose of this study was to evaluate RB1 expression and survival across ovarian carcinoma histotypes and how co-occurrence of BRCA1 or BRCA2 (BRCA) alterations and RB1 loss influences survival in tubo-ovarian high-grade serous carcinoma (HGSC).

Experimental Design: RB1 protein expression was classified by immunohistochemistry in ovarian carcinomas of 7,436 patients from the Ovarian Tumor Tissue Analysis consortium. We examined RB1 expression and germline BRCA status in a subset of 1,134 HGSC, and related genotype to overall survival (OS), tumor-infiltrating CD8+ lymphocytes, and transcriptomic subtypes.

Molecular Subtypes of High-Grade Serous Ovarian Cancer across Racial Groups and Gene Expression Platforms.

Background: High-grade serous carcinoma (HGSC) gene expression subtypes are associated with differential survival. We characterized HGSC gene expression in Black individuals and considered whether gene expression differences by self-identified race may contribute to poorer HGSC survival among Black versus White individuals.

Methods: We included newly generated RNA sequencing data from Black and White individuals and array-based genotyping data from four existing studies of White and Japanese individuals.

Integrative multi-omics analyses to identify the genetic and functional mechanisms underlying ovarian cancer risk regions.

To identify credible causal risk variants (CCVs) associated with different histotypes of epithelial ovarian cancer (EOC), we performed genome-wide association analysis for 470,825 genotyped and 10,163,797 imputed SNPs in 25,981 EOC cases and 105,724 controls of European origin. We identified five histotype-specific EOC risk regions (p value <5 × 10) and confirmed previously reported associations for 27 risk regions. Conditional analyses identified an additional 11 signals independent of the primary signal at six risk regions (p value <10).

Cis- and trans-eQTL TWASs of breast and ovarian cancer identify more than 100 susceptibility genes in the BCAC and OCAC consortia.

Transcriptome-wide association studies (TWASs) have investigated the role of genetically regulated transcriptional activity in the etiologies of breast and ovarian cancer. However, methods performed to date have focused on the regulatory effects of risk-associated SNPs thought to act in cis on a nearby target gene. With growing evidence for distal (trans) regulatory effects of variants on gene expression, we performed TWASs of breast and ovarian cancer using a Bayesian genome-wide TWAS method (BGW-TWAS) that considers effects of both cis- and trans-expression quantitative trait loci (eQTLs).

Emergency Preparedness Drills for Active and Mass Shootings in Schools.

Purpose Of Review: There is widespread use of emergency preparedness drills in public K-12 schools across the US, but considerable variability exists in the types of protocols used and how these practices are conducted. This review examines research into both "lockdown drills" and "active shooter drills" as it relates to their impact on participants across different outcomes and evaluations of their procedural integrity.

Recent Findings: A number of studies on lockdown drills yielded largely consistent findings about their impacts, whereas findings related to the effects of active shooter drills are less uniform.

Large-scale genome-wide association study of 398,238 women unveils seven novel loci associated with high-grade serous epithelial ovarian cancer risk.

Background: Nineteen genomic regions have been associated with high-grade serous ovarian cancer (HGSOC). We used data from the Ovarian Cancer Association Consortium (OCAC), Consortium of Investigators of Modifiers of (CIMBA), UK Biobank (UKBB), and FinnGen to identify novel HGSOC susceptibility loci and develop polygenic scores (PGS).

Methods: We analyzed >22 million variants for 398,238 women.

Mapping inherited genetic variation with opposite effects on autoimmune disease and cancer identifies candidate drug targets associated with the anti-tumor immune response.

Background: Germline alleles near genes that encode certain immune checkpoints () are associated with autoimmune/autoinflammatory disease and cancer but in opposite directions. This motivates a systematic search for additional germline alleles which demonstrate this pattern with the aim of identifying potential cancer immunotherapeutic targets using human genetic evidence.

Methods: Pairwise fixed effect cross-disorder meta-analyses combining genome-wide association studies (GWAS) for breast, prostate, ovarian and endometrial cancers (240,540 cases/317,000 controls) and seven autoimmune/autoinflammatory diseases (112,631 cases/895,386 controls) coupled with follow-up.

Molecular subtypes of high-grade serous ovarian cancer across racial groups and gene expression platforms.

Introduction: High-grade serous carcinoma (HGSC) gene expression subtypes are associated with differential survival. We characterized HGSC gene expression in Black individuals and considered whether gene expression differences by race may contribute to poorer HGSC survival among Black versus non-Hispanic White individuals.

Methods: We included newly generated RNA-Seq data from Black and White individuals, and array-based genotyping data from four existing studies of White and Japanese individuals.

The role of rifampicin within the treatment of pulmonary disease.

Rifampicin is recommended for the treatment of complex pulmonary disease alongside azithromycin and ethambutol. We evaluated the azithromycin-ethambutol backbone with and without rifampicin in an intracellular hollow fiber model and performed RNA sequencing to study the differences in adaptation. In an hollow fiber experiment, we simulated epithelial lining fluid pharmacokinetic profiles of the recommended 3-drug (rifampicin, ethambutol, and azithromycin) or a 2-drug (ethambutol and azithromycin) treatment.

The tumor multi-omic landscape of endometrial cancers developed on a germline genetic background of adiposity.

High body mass index (BMI) is a causal risk factor for endometrial cancer but the tumor molecular mechanisms affected by adiposity and their therapeutic relevance remain poorly understood. Here we characterize the tumor multi-omic landscape of endometrial cancers that have developed on a background of lifelong germline genetic exposure to elevated BMI. We built a polygenic score (PGS) for BMI in women using data on independent, genome-wide significant variants associated with adult BMI in 434,794 women.

Menopausal hormone therapy use and risk of ovarian cancer by race: the ovarian cancer in women of African ancestry consortium.

Background: Most studies examining post-menopausal menopausal hormone therapy (MHT) use and ovarian cancer risk have focused on White women and few have included Black women.

Methods: We evaluated MHT use and ovarian cancer risk in Black (n = 800 cases, 1783 controls) and White women (n = 2710 cases, 8556 controls), using data from the Ovarian Cancer in Women of African Ancestry consortium. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association of MHT use with ovarian cancer risk, examining histotype, MHT type and duration of use.

The Association between Mediated Deprivation and Ovarian Cancer Survival among African American Women.

Background: Deprivation indices are often used to adjust for socio-economic disparities in health studies. Their role has been partially evaluated for certain population-level cancer outcomes, but examination of their role in ovarian cancer is limited. In this study, we evaluated a range of well-recognized deprivation indices in relation to cancer survival in a cohort of self-identified Black women diagnosed with ovarian cancer.

Association of inflammation-related exposures and ovarian cancer survival in a multi-site cohort study of Black women.

Background: An association was observed between an inflammation-related risk score (IRRS) and worse overall survival (OS) among a cohort of mostly White women with invasive epithelial ovarian cancer (EOC). Herein, we evaluated the association between the IRRS and OS among Black women with EOC, a population with higher frequencies of pro-inflammatory exposures and worse survival.

Methods: The analysis included 592 Black women diagnosed with EOC from the African American Cancer Epidemiology Study (AACES).