Interferon response and epigenetic modulation by mutations drive ovarian tumor immunogenicity.

Cell-intrinsic mechanisms of immunogenicity in ovarian cancer (OC) are not well understood. Damaging mutations in the SWI/SNF chromatin remodeling complex, such as (BRG1), are associated with improved response to immune checkpoint blockade; however, the mechanism by which this occurs is unclear. We found that loss in OC models resulted in increased cancer cell-intrinsic immunogenicity, characterized by up-regulation of long-terminal RNA repeats, increased expression of interferon-stimulated genes, and up-regulation of antigen presentation machinery.

Diabetes and all-cause mortality among middle-aged and older adults in China, England, Mexico, rural South Africa, and the United States: A population-based study of longitudinal aging cohorts.

Objective: There is a need for comparable worldwide data on the impact of diabetes on mortality. This study assessed diabetes and all-cause mortality among middle-aged and older adults in five countries.

Research Design And Methods: We analyzed adults aged 51 years or older followed between 2010 and 2020 from population-based cohorts in China, England, Mexico, rural South Africa, and the United States.

Ongoing genome doubling promotes evolvability and immune dysregulation in ovarian cancer.

Whole-genome doubling (WGD) is a critical driver of tumor development and is linked to drug resistance and metastasis in solid malignancies. Here, we demonstrate that WGD is an ongoing mutational process in tumor evolution. Using single-cell whole-genome sequencing, we measured and modeled how WGD events are distributed across cellular populations within tumors and associated WGD dynamics with properties of genome diversification and phenotypic consequences of innate immunity.

Basket study of oral progesterone antagonist onapristone extended release in progesterone receptor-positive recurrent granulosa cell, low-grade serous ovarian cancer, or endometrioid endometrial cancer.

Objective: To determine the safety and efficacy of the oral progesterone antagonist onapristone extended release (onapristone-XR) in patients with recurrent progesterone receptor (PR)-positive adult-type granulosa cell tumor (aGCT), low-grade serous ovarian cancer (LGSOC), or endometrioid endometrial cancer (EEC).

Methods: This single-institution phase II study included patients with PR-positive aGCT, LGSOC, or EEC who received ≥1 prior line of chemotherapy. Patients were enrolled from 5/2019-5/2020.

Nivolumab for mismatch-repair-deficient or hypermutated gynecologic cancers: a phase 2 trial with biomarker analyses.

Programmed death-1 (PD-1) inhibitors are approved for therapy of gynecologic cancers with DNA mismatch repair deficiency (dMMR), although predictors of response remain elusive. We conducted a single-arm phase 2 study of nivolumab in 35 patients with dMMR uterine or ovarian cancers. Co-primary endpoints included objective response rate (ORR) and progression-free survival at 24 weeks (PFS24).

Anemia, hemoglobin concentration and cognitive function in the Longitudinal Ageing Study in India-Harmonized Diagnostic Assessment of Dementia (LASI-DAD) and the Health and Retirement Study.

Background: In India, anemia is widely researched in children and women of reproductive age, however, studies in older populations are lacking. Given the adverse effect of anemia on cognitive function and dementia this older population group warrants further study. The Longitudinal Ageing Study in India - Harmonized Diagnostic Assessment of Dementia (LASI-DAD) dataset contains detailed measures to allow a better understanding of anaemia as a potential risk factor for dementia.

Reaching underserved South Africans with integrated chronic disease screening and mobile HIV counselling and testing: A retrospective, longitudinal study conducted in Cape Town.

Background: Community-based, mobile HIV counselling and testing (HCT) and screening for non-communicable diseases (NCDs) may improve early diagnosis and referral for care in underserved populations. We evaluated HCT/NCD data and described population characteristics of those visiting a mobile clinic in high HIV disease burden settings in Cape Town, South Africa, between 2008 and 2016.

Methods: Trained counsellors registered patients ≥12 years old at a mobile clinic, which offered HCT and blood pressure, diabetes (glucose testing) and obesity (body mass index) screening.

Partner notification and treatment for sexually transmitted infections among pregnant women in Cape Town, South Africa.

Curable sexually transmitted infections (STIs) including (CT), (NG), and (TV) are associated with adverse pregnancy outcomes. Partner notification is an important component of STI control as it has been shown to prevent re-infection and reduce infectious burden. Between October 2017 and February 2019, we conducted a cohort study of women attending antenatal care in Cape Town, South Africa.

Defining heat waves and extreme heat events using sub-regional meteorological data to maximize benefits of early warning systems to population health.

Background: Extreme heat events have been consistently associated with an increased risk of hospitalization for various hospital diagnoses. Classifying heat events is particularly relevant for identifying the criteria to activate early warning systems. Heat event classifications may also differ due to heterogeneity in climates among different geographic regions, which may occur at a small scale.

Prevalence and incidence of in a cohort of HIV-infected and HIV-uninfected pregnant women in Cape Town, South Africa.

Objective: (MG) is a sexually transmitted organism associated with cervicitis and pelvic inflammatory disease in women and has been shown to increase the risk of HIV acquisition and transmission. Little is known about the prevalence and incidence of MG in pregnant women. Our study sought to evaluate the prevalence and incidence of MG infection in HIV-infected and HIV-uninfected pregnant women.

Impact of heat on mortality and morbidity in low and middle income countries: A review of the epidemiological evidence and considerations for future research.

Heat waves and high air temperature are associated with increased morbidity and mortality. However, the majority of research conducted on this topic is focused on high income areas of the world. Although heat waves have the most severe impacts on vulnerable populations, relatively few studies have studied their impacts in low and middle income countries (LMICs).

Sympathetic nerve fibers in human cervical and thoracic vagus nerves.

Background: Vagus nerve stimulation (VNS) therapy has been used for chronic heart failure and is believed to improve imbalance of autonomic control by increasing parasympathetic activity. Although it is known that there is neural communication between the VN and the cervical sympathetic trunk, there are few data regarding the quantity and/or distribution of the sympathetic components within the vagus nerve (VN).

Objective: To examine the sympathetic components within the human VN and correlate them with the presence of cardiac and neurologic diseases.