Patterns of genomic instability in > 2000 patients with ovarian cancer across six clinical trials evaluating olaparib.

Background: The introduction of poly(ADP-ribose) polymerase (PARP) inhibitors represented a paradigm shift in the treatment of ovarian cancer. Genomic data from patients with high-grade ovarian cancer in six phase II/III trials involving the PARP inhibitor olaparib were analyzed to better understand patterns and potential causes of genomic instability.

Patients And Methods: Homologous recombination deficiency (HRD) was assessed in 2147 tumor samples from SOLO1, PAOLA-1, Study 19, SOLO2, OPINION, and LIGHT using next-generation sequencing technology.

Studying the Pulmonary Endothelium in Health and Disease: An Official American Thoracic Society Workshop Report.

Lung endothelium resides at the interface between the circulation and the underlying tissue, where it senses biochemical and mechanical properties of both the blood as it flows through the vascular circuit and the vessel wall. The endothelium performs the bidirectional signaling between the blood and tissue compartments that is necessary to maintain homeostasis while physically separating both, facilitating a tightly regulated exchange of water, solutes, cells, and signals. Disruption in endothelial function contributes to vascular disease, which can manifest in discrete vascular locations along the artery-to-capillary-to-vein axis.

Enhancing HIV pre-exposure prophylaxis outcomes among Kenyan adolescent girls and young women with a novel pharmacy-based PrEP delivery platform: protocol for a cluster-randomized controlled trial.

Background: In Kenya, 65% of sexually active unmarried women use modern contraceptives, a population at increased risk of HIV acquisition compared to other populations. Anchoring HIV prevention services, including pre-exposure prophylaxis (PrEP), to trusted contraceptive delivery settings offers opportunities to efficiently reach this important population. In Kenya, almost half (40%) of women accessing contraception services do so outside traditional healthcare facilities, such as retail pharmacies.

Occupational therapy practice for post-acute COVID-19 inpatients requiring rehabilitation.

Introduction: COVID-19 caused significant occupational disruption to people's life roles, with some people requiring an inpatient rehabilitation admission. Occupational therapists assessed and treated these patients using previous knowledge of similar conditions due to limited specificity in available guidelines to inform practice. The aim of this study was to investigate current practice with post-acute COVID-19 (PAC) patients within an inpatient rehabilitation setting in Australia, to better understand the role and impact of occupational therapy.

Priorities for contraceptive method and service delivery attributes among adolescent girls and young women in Kenya: a qualitative study.

Introduction: Despite increasing global commitment to meeting the family planning needs of adolescent girls and young women (AGYW), there is limited research on how they prioritize contraceptive method and service delivery characteristics. In this qualitative study, we examine the specific elements that drive the contraceptive choices of Kenyan AGYW, and apply our findings to the development of attributes and levels for a discrete choice experiment (DCE).

Methods: Our four-stage approach included data collection, data reduction, removing inappropriate attributes, and optimizing wording.

Confirmatory Factor Analysis and Validation of the Sexual and Reproductive Empowerment Scale for Adolescents and Young Adults in Kenya.

Understanding the levels of power that adolescent girls and young women exercise in their sexual and reproductive lives is imperative to inform interventions to help them meet their goals. We implemented an adapted version of the Sexual and Reproductive Health Empowerment (SRE) Scale for Adolescents and Young Adults among 500 adolescent girls and young women aged 15-20 in Kisumu, Kenya. We used confirmatory factor analysis (CFA) to assess factor structure, and logistic regression to examine construct validity through the relationship between empowerment scores and ability to mitigate risk of undesired pregnancy through consistent contraceptive use.

Mobile solutions to Empower reproductive life planning for women living with HIV in Kenya (MWACh EMPOWER): Protocol for a cluster randomized controlled trial.

Background: Women living with HIV (WLWH) face unique reproductive health (RH) barriers which increase their risks of unmet need for contraception, contraceptive failure, unintended pregnancy, and pregnancy-related morbidity and mortality and may prevent them from achieving their reproductive goals. Patient-centered counseling interventions that support health care workers (HCWs) in providing high-quality RH counseling, tailored to the needs of WLWH, may improve reproductive health outcomes.

Methods And Design: We are conducting a non-blinded cluster randomized controlled trial (cRCT) of a digital health intervention for WLWH (clinicaltrials.

Individuals' experiences in genetic counseling and predictive testing for familial amyotrophic lateral sclerosis.

As clinical genetic testing in the amyotrophic lateral sclerosis (ALS) diagnostic setting increases, the identification of at-risk family members has also expanded. No practice guidelines specifically for predictive genetic testing exist, and few studies about the psychological impacts of testing in this subgroup have occurred, limiting the ability to tailor recommendations and counseling in this community. We surveyed asymptomatic individuals at risk for inheriting an ALS-associated gene mutation.

Transcriptional profiles of pulmonary artery endothelial cells in pulmonary hypertension.

Pulmonary arterial hypertension (PAH) is characterized by endothelial cell (EC) dysfunction. There are no data from living patients to inform whether differential gene expression of pulmonary artery ECs (PAECs) can discern disease subtypes, progression and pathogenesis. We aimed to further validate our previously described method to propagate ECs from right heart catheter (RHC) balloon tips and to perform additional PAEC phenotyping.

Adaptation of the sexual and reproductive empowerment scale for adolescents and young adults in Kenya.

Measuring empowerment is critical to understanding the level of control adolescents and young adults (AYA) have over their sexual and reproductive health (SRH) behaviors, and could provide a key window into addressing their unique SRH needs. We adapted the Sexual and Reproductive Empowerment (SRE) scale for AYA for use in an East African context. This multi-method qualitative study sampled 15-23 year-old female adolescents and young adults in Kisumu, Kenya.

Acute protein kinase C beta inhibition preserves coronary endothelial function after cardioplegic hypoxia/reoxygenation.

Objective: Protein kinase C (PKC) influences myocardial contractility and susceptibility to long-term cardiac dysfunction after ischemia-reperfusion injury. In diabetes, PKC inhibition has a protective effect in terms of microvascular dysfunction. SK-channel dysfunction also influences endothelial dysfunction in cardioplegic hypoxia-reoxygenation (CP-H/R).

Prevalence and correlates of condom use at last sexual intercourse pre- and post-COVID-19 lockdown among adolescent girls and young women in central and western Kenya.

We investigated condom use at last sexual intercourse among adolescent girls and young women (AGYW) to determine the prevalence and correlates of condom use pre- and post-COVID-19 lockdown. Condom use was compared pre- and post-COVID-19 lockdown using a single group interrupted time series analysis. Multivariable Poisson regression was used to determine the correlates of condom use at last sexual intercourse.

Deletion of the gene increases severity of acute lung injury in obese mice.

Previous studies have shown that atrial natriuretic peptide (ANP) attenuates agonist-induced pulmonary edema and that this effect may be mediated in part by the ANP clearance receptor, natriuretic peptide receptor-C (NPR-C). Obesity has been associated with lower plasma ANP levels due to increased expression of NPR-C, and with decreased severity of acute lung injury (ALI). Therefore, we hypothesized that increased expression of NPR-C may attenuate ALI severity in obese populations.

Impact of DNA damage repair alterations on prostate cancer progression and metastasis.

Prostate cancer is among the most common diseases worldwide. Despite recent progress with treatments, patients with advanced prostate cancer have poor outcomes and there is a high unmet need in this population. Understanding molecular determinants underlying prostate cancer and the aggressive phenotype of disease can help with design of better clinical trials and improve treatments for these patients.

The landscape of BRCA1 and BRCA2 large rearrangements in an international cohort of over 20 000 ovarian tumors identified using next-generation sequencing.

Background: Approximately half of ovarian tumors have defects within the homologous recombination repair pathway. Tumors carrying pathogenic variants (PVs) in BRCA1/BRCA2 are more likely to respond to poly-ADP ribose polymerase (PARP) inhibitor treatment. Large rearrangements (LRs) are a challenging class of variants to identify and characterize in tumor specimens and may therefore be underreported.

Clinical testing panels for ALS: global distribution, consistency, and challenges.

: In 2021, the Clinical Genome Resource (ClinGen) amyotrophic lateral sclerosis (ALS) spectrum disorders Gene Curation Expert Panel (GCEP) was established to evaluate the strength of evidence for genes previously reported to be associated with ALS. Through this endeavor, we will provide standardized guidance to laboratories on which genes should be included in clinical genetic testing panels for ALS. In this manuscript, we aimed to assess the heterogeneity in the current global landscape of clinical genetic testing for ALS.

Impact of blood factors on endothelial cell metabolism and function in two diverse heart failure models.

Role of blood-based factors in development and progression of heart failure (HF) is poorly characterized. Blood contains factors released during pathophysiological states that may impact cellular function and provide mechanistic insights to HF management. We tested effects of blood from two distinct HF models on cardiac metabolism and identified possible cellular targets of the effects.

Commercial human pulmonary artery endothelial cells have in-vitro behavior that varies by sex.

It is unknown whether biological sex influences phenotypes of commercially available human pulmonary artery endothelial cells (HPAECs). Ten lots of commercial HPAECs were used (Lonza Biologics; PromoCell). Five (50%) were confirmed to be genotypically male (+) and five (50%) were confirmed to be female (-).

Olaparib Efficacy in Patients with Metastatic Castration-resistant Prostate Cancer and BRCA1, BRCA2, or ATM Alterations Identified by Testing Circulating Tumor DNA.

Purpose: The phase III PROfound study (NCT02987543) evaluated olaparib versus abiraterone or enzalutamide (control) in metastatic castration-resistant prostate cancer (mCRPC) with tumor homologous recombination repair (HRR) gene alterations. We present exploratory analyses on the use of circulating tumor DNA (ctDNA) testing as an additional method to identify patients with mCRPC with HRR gene alterations who may be eligible for olaparib treatment.

Patients And Methods: Plasma samples collected during screening in PROfound were retrospectively sequenced using the FoundationOne®Liquid CDx test for BRCA1, BRCA2 (BRCA), and ATM alterations in ctDNA.

Patient, Caregiver, and Oncologist Experiences With and Perceptions of Racial Bias and Discrimination in Cancer Care Delivery.

Background: Cancer prevention and treatment systems are significantly impacted by interpersonal, organizational, and structural and systemic racism. A wide body of research has found that racial disparities in access to guideline-adherent cancer care are pervasive throughout the United States and contributing factors include social determinants of health, insurance status, and bias and discrimination in care delivery. Although the existence of racial disparities in cancer care and outcomes is well established, there has been limited research exploring the patient and caregiver experience with bias and discrimination in cancer care.

Deep RNA sequencing of intensive care unit patients with COVID-19.

COVID-19 has impacted millions of patients across the world. Molecular testing occurring now identifies the presence of the virus at the sampling site: nasopharynx, nares, or oral cavity. RNA sequencing has the potential to establish both the presence of the virus and define the host's response in COVID-19.