Guidance for Triangulating Data and Estimates of HIV Prevalence Among Pregnant Women and Coverage of PMTCT Using the Spectrum AIDS Impact Module.

Background: Most countries use the Spectrum AIDS Impact Module (Spectrum-AIM), antenatal care routine HIV testing, and antiretroviral treatment data to estimate HIV prevalence among pregnant women. Nonrepresentative program data may lead to inaccurate estimates of HIV prevalence and treatment coverage for pregnant women.

Setting: One hundred fifty-four countries and subnational locations across 126 countries.

Epithelial overexpression of IL-33 induces eosinophilic esophagitis dependent on IL-13.

Background: Eosinophilic esophagitis (EoE) is an increasingly common inflammatory condition of the esophagus; however, the underlying immunologic mechanisms remain poorly understood. The epithelium-derived cytokine IL-33 is associated with type 2 immune responses and elevated in esophageal biopsy specimens from patients with EoE.

Objective: We hypothesized that overexpression of IL-33 by the esophageal epithelium would promote the immunopathology of EoE.

Wilms' tumor 1 (WT1) antigen is overexpressed in Kaposi Sarcoma and is regulated by KSHV vFLIP.

In people living with HIV, Kaposi Sarcoma (KS), a vascular neoplasm caused by KS herpesvirus (KSHV/HHV-8), remains one of the most common malignancies worldwide. Individuals living with HIV, receiving otherwise effective antiretroviral therapy, may present with extensive disease requiring chemotherapy. Hence, new therapeutic approaches are needed.

Cost and affordability of healthy diets in Vietnam.

Objectives: To estimate the cost and affordability of healthy diets recommended by the 2016-2020 Vietnamese food-based dietary guidelines (FBDG).

Design: Cross-sectional analysis. The Cost of a Healthy Diet (CoHD) indicator was used to estimate the lowest cost of healthy diets and compare the cost differences by food group, region and seasonality.

Association Between Aspirin Use and Sepsis Outcomes: A National Cohort Study.

Background: Aspirin has anti-inflammatory and antiplatelet activities and directly inhibits bacterial growth. These effects of aspirin may improve survival in patients with sepsis. We retrospectively reviewed a large national health database to test the relationship between prehospital aspirin use and sepsis outcomes.

Polygenic risk modeling for prediction of epithelial ovarian cancer risk.

Polygenic risk scores (PRS) for epithelial ovarian cancer (EOC) have the potential to improve risk stratification. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could improve predictive performance over standard approaches of PRS construction. Here, we implemented computationally efficient, penalized, logistic regression models (lasso, elastic net, stepwise) to individual level genotype data and a Bayesian framework with continuous shrinkage, "select and shrink for summary statistics" (S4), to summary level data for epithelial non-mucinous ovarian cancer risk prediction.

Measuring the Prevalence of Mental Disorders in Adolescents in Kenya, Indonesia, and Vietnam: Study Protocol for the National Adolescent Mental Health Surveys.

Purpose: In low- and middle-income countries, there are limited data on mental disorders among adolescents. To address this gap, the National Adolescent Mental Health Surveys (NAMHS) will provide nationally representative prevalence data of mental disorders among adolescents in Kenya, Indonesia, and Vietnam. This paper details the NAMHS study protocol.

An in vivo method for diversifying the functions of therapeutic antibodies.

V(D)J recombination generates mature B cells that express huge repertoires of primary antibodies as diverse immunoglobulin (Ig) heavy chain (IgH) and light chain (IgL) of their B cell antigen receptors (BCRs). Cognate antigen binding to BCR variable region domains activates B cells into the germinal center (GC) reaction in which somatic hypermutation (SHM) modifies primary variable region-encoding sequences, with subsequent selection for mutations that improve antigen-binding affinity, ultimately leading to antibody affinity maturation. Based on these principles, we developed a humanized mouse model approach to diversify an anti-PD1 therapeutic antibody and allow isolation of variants with novel properties.

Decreased inflammatory cytokine production of antigen-specific CD4 T cells in NMDA receptor encephalitis.

Anti-N-methyl-D-aspartate-receptor (NMDAR) encephalitis is the most common autoimmune encephalitis with psychosis, amnesia, seizures and dyskinesias. The disease is mediated by pathogenic autoantibodies against the NR1 subunit that disrupt NMDAR function. Antibody infusion into mouse brains can recapitulate encephalitis symptoms, while active immunization resulted also in strong T cell infiltration into the hippocampus.

Genetically Defined, Syngeneic Organoid Platform for Developing Combination Therapies for Ovarian Cancer.

The paucity of genetically informed, immunocompetent tumor models impedes evaluation of conventional, targeted, and immune therapies. By engineering mouse fallopian tube epithelial organoids using lentiviral gene transduction and/or CRISPR/Cas9 mutagenesis, we generated multiple high-grade serous tubo-ovarian cancer (HGSC) models exhibiting mutational combinations seen in patients with HGSC. Detailed analysis of homologous recombination (HR)-proficient ( ), HR-deficient ( ), and unclassified ( ) organoids revealed differences in properties (proliferation, differentiation, and "secretome"), copy-number aberrations, and tumorigenicity.

One-Year Effects of Omega-3 Treatment on Fatty Acids, Oxylipins, and Related Bioactive Lipids and Their Associations with Clinical Lipid and Inflammatory Biomarkers: Findings from a Substudy of the Vitamin D and Omega-3 Trial (VITAL).

Omega-3 (n-3) treatment may lower cardiovascular risk, yet its effects on the circulating lipidome and relation to cardiovascular risk biomarkers are unclear. We hypothesized that n-3 treatment is associated with favorable changes in downstream fatty acids (FAs), oxylipins, bioactive lipids, clinical lipid and inflammatory biomarkers. We examined these VITAL200, a nested substudy of 200 subjects balanced on demographics and treatment and randomly selected from the Vitamin D and Omega-3 Trial (VITAL).

Conditional antibody expression to avoid central B cell deletion in humanized HIV-1 vaccine mouse models.

HIV-1 vaccine development aims to elicit broadly neutralizing antibodies (bnAbs) against diverse viral strains. In some HIV-1-infected individuals, bnAbs evolved from precursor antibodies through affinity maturation. To induce bnAbs, a vaccine must mediate a similar antibody maturation process.

Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer.

To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.

No Evidence That Genetic Variation in the Myeloid-Derived Suppressor Cell Pathway Influences Ovarian Cancer Survival.

The precise mechanism by which the immune system is adversely affected in cancer patients remains poorly understood, but the accumulation of immunosuppressive/protumorigenic myeloid-derived suppressor cells (MDSCs) is thought to be a prominent mechanism contributing to immunologic tolerance of malignant cells in epithelial ovarian cancer (EOC). To this end, we hypothesized genetic variation in MDSC pathway genes would be associated with survival after EOC diagnoses. We measured the hazard of death due to EOC within 10 years of diagnosis, overall and by invasive subtype, attributable to SNPs in 24 genes relevant in the MDSC pathway in 10,751 women diagnosed with invasive EOC.

Shared genetics underlying epidemiological association between endometriosis and ovarian cancer.

Epidemiological studies have demonstrated associations between endometriosis and certain histotypes of ovarian cancer, including clear cell, low-grade serous and endometrioid carcinomas. We aimed to determine whether the observed associations might be due to shared genetic aetiology. To address this, we used two endometriosis datasets genotyped on common arrays with full-genome coverage (3194 cases and 7060 controls) and a large ovarian cancer dataset genotyped on the customized Illumina Infinium iSelect (iCOGS) arrays (10 065 cases and 21 663 controls).