Aberrant SWI/SNF Complex Members Are Predominant in Rare Ovarian Malignancies-Therapeutic Vulnerabilities in Treatment-Resistant Subtypes.

SWI/SNF (SWItch/Sucrose Non-Fermentable) is the most frequently mutated chromatin-remodelling complex in human malignancy, with over 20% of tumours having a mutation in a SWI/SNF complex member. Mutations in specific SWI/SNF complex members are characteristic of rare chemoresistant ovarian cancer histopathological subtypes. Somatic mutations in , encoding one of the mutually exclusive DNA-binding subunits of SWI/SNF, occur in 42-67% of ovarian clear cell carcinomas (OCCC).

Metronomic and single high-dose paclitaxel treatments produce distinct heterogenous chemoresistant cancer cell populations.

More than 75% of epithelial ovarian cancer (EOC) patients experience disease recurrence after initial treatment, highlighting our incomplete understanding of how chemoresistant populations evolve over the course of EOC progression post chemotherapy treatment. Here, we show how two paclitaxel (PTX) treatment methods- a single high dose and a weekly metronomic dose for four weeks, generate unique chemoresistant populations. Using mechanically relevant alginate microspheres and a combination of transcript profiling and heterogeneity analyses, we found that these PTX-treatment regimens produce distinct and resilient subpopulations that differ in metabolic reprogramming signatures, acquisition of resistance to PTX and anoikis, and the enrichment for cancer stem cells (CSCs) and polyploid giant cancer cells (PGCCs) with the ability to replenish bulk populations.

A Survey of Cancer Risk Behaviors, Beliefs, and Social Drivers of Health in New Hampshire and Vermont.

Unlabelled: Compared with urban areas, rural areas have higher cancer mortality and have experienced substantially smaller declines in cancer incidence in recent years. In a New Hampshire (NH) and Vermont (VT) survey, we explored the roles of rurality and educational attainment on cancer risk behaviors, beliefs, and other social drivers of health. In February-March 2022, two survey panels in NH and VT were sent an online questionnaire.

Systematic profiling of conditional degron tag technologies for target validation studies.

Conditional degron tags (CDTs) are a powerful tool for target validation that combines the kinetics and reversible action of pharmacological agents with the generalizability of genetic manipulation. However, successful design of a CDT fusion protein often requires a prolonged, ad hoc cycle of construct design, failure, and re-design. To address this limitation, we report here a system to rapidly compare the activity of five unique CDTs: AID/AID2, IKZF3d, dTAG, HaloTag, and SMASh.

Phosphate dysregulation via the XPR1-KIDINS220 protein complex is a therapeutic vulnerability in ovarian cancer.

Despite advances in precision medicine, the clinical prospects for patients with ovarian and uterine cancers have not substantially improved. Here, we analyzed genome-scale CRISPR-Cas9 loss-of-function screens across 851 human cancer cell lines and found that frequent overexpression of SLC34A2-encoding a phosphate importer-is correlated with sensitivity to loss of the phosphate exporter XPR1, both in vitro and in vivo. In patient-derived tumor samples, we observed frequent PAX8-dependent overexpression of SLC34A2, XPR1 copy number amplifications and XPR1 messenger RNA overexpression.

Estimating US Background Ozone Using Data Fusion.

US background (US-B) ozone (O) is the O that would be present in the absence of US anthropogenic (US-A) emissions. US-B O varies by location and season and can make up a large, sometimes dominant, portion of total O. Typically, US-B O is quantified using a chemical transport model (CTM) though results are uncertain due to potential errors in model process descriptions and inputs, and there are significant differences in various model estimates of US-B O.

Significant contrasts in aerosol acidity between China and the United States.

Aerosol acidity governs several key processes in aerosol physics and chemistry, thus affecting aerosol mass and composition and ultimately climate and human health. Previous studies have reported aerosol pH values separately in China and the United States (USA), implying different aerosol acidity between these two countries. However, there is debate about whether mass concentration or chemical composition is the more important driver of differences in aerosol acidity.

Synthetic Lethal Interaction between the ESCRT Paralog Enzymes VPS4A and VPS4B in Cancers Harboring Loss of Chromosome 18q or 16q.

Few therapies target the loss of tumor suppressor genes in cancer. We examine CRISPR-SpCas9 and RNA-interference loss-of-function screens to identify new therapeutic targets associated with genomic loss of tumor suppressor genes. The endosomal sorting complexes required for transport (ESCRT) ATPases VPS4A and VPS4B score as strong synthetic lethal dependencies.

Associations between reliable changes in depression and changes in BMI, total body fatness and visceral adiposity during a 12-month weight loss trial.

We investigated associations between changes in depression and body composition over a 12-month weight loss trial. Of the 298 adults (BMI > 27 m/kg), 219 with complete depression and body composition data were included. A 10-item Center for Epidemiologic Studies Depression Scale measured depression; dual-energy X-ray absorptiometry measured body composition.

Identifying subgroups of care providers participating in a telehealth educational intervention: hierarchical cluster analysis of evaluation data.

Unlabelled: Health care providers (HCPs) serving HIV-infected patients, especially in rural and underserved areas, have limited access to continuing medical education.

Objectives: To identify subgroups of HCPs who might benefit from a telehealth training program focusing on HIV/AIDS care based on HCPs' objective for attending the training.

Methods: Hierarchical cluster analysis combined with thematic analysis identified the subgroups.

Navigation: process of building relationships with kaumātua (Māori leaders).

In the article the authors depict relations in sociocultural navigation by Māori researchers conducting research embedded in mutual trust; rather than instrumental navigation in linear time. A longitudinal study of Māori and non Māori men and women ageing successfully was planned; this feasibility stage tested whether engaging with kōroua/older Māori men and kuia/older Māori women was possible. We document the process undertaken with Ngā Pae o te Maramatanga New Zealand's Indigenous Centre of Research Excellence (hosted by the University of Auckland) to involve Māori people in the research, engaging with kōroua and kuia aged 75 to 79 years old, developing focus groups to discuss questions specific to te reo Māori me ngā tikanga/Maori language and culture, and building research capacity in Māori tribal and primary health organisations in the Bay of Plenty.

Utilization management: a rehabilitation approach to cost control.

Santa Rosa Rehabilitation Hospital in San Antonio, TX, not unlike many healthcare facilities throughout the nation, was faced with several issues: (a) increased cost, (b) lower reimbursement, (c) high length of stay, and (d) low staff morale. The management team was responsible for developing a system to control these issues, the most noticeable and measureable of which was length of stay. In 1987, the facility reached a high length of stay of 43 days.