Screening a living biobank identifies cabazitaxel as a strategy to combat acquired taxol resistance in high-grade serous ovarian cancer.

The anti-mitotic agent taxol (paclitaxel) remains a cornerstone of ovarian cancer treatment. To tackle drug resistance and toxicity, second-generation targeted anti-mitotic agents and combination strategies are being explored but have yet to demonstrate meaningful clinical benefits. A limitation is the lack of a platform to compare strategies in models that capture disease heterogeneity.

Mental health services in jail: Identifying and quantifying barriers to implementation.

Although jails are the largest provider of mental health care nationally, access to treatment in U.S. jails is limited.

Germline BRCA1/2 status and chemotherapy response score in high-grade serous ovarian cancer.

Background: High-grade serous ovarian cancer (HGSOC) can be treated with platinum-based neoadjuvant chemotherapy (NACT) and delayed primary surgery (DPS). Histopathological response to NACT can be assessed using Böhm's chemotherapy response score (CRS). We investigated whether germline BRCA1/2 (gBRCA1/2) genotype associated with omental CRS phenotype.

Family Members Grieving the Loss of a Person to Incarceration: A Scoping Review.

This scoping review examined grief related to the incarceration of a family member in order to establish a theoretical framework. A comprehensive search of PubMed, Social Sciences Citation Index, Embase, PsycInfo, Psychology & Behavioral Sciences, CINAHL, Cochrane Central Register of Controlled Trials & Cochrane Database of Systematic Reviews, PILOTS, and Psychiatry Online was conducted. We extracted data on sample characteristics, study design, purpose of the study, grief measure used, grief term and definition used, and key qualitative and quantitative findings.

Confirmatory information seeking is robust in psychologists' diagnostic reasoning.

Objective: Across two experiments, we examined three cognitive biases (order effects, context effects, confirmatory bias) in licensed psychologists' diagnostic reasoning.

Hypotheses: Our main prediction was that psychologist-participants would seek confirming versus disconfirming information after forming an initial diagnostic hypothesis, even given multiple opportunities to seek new information in the same case. We also expected that individual differences would affect diagnostic reasoning, such that psychologists with lower (vs.

British Gynaecological Cancer Society/British Association of Gynaecological Pathology consensus for genetic testing in epithelial ovarian cancer in the United Kingdom.

Standard of care genetic testing has undergone significant changes in recent years. The British Gynecological Cancer Society and the British Association of Gynecological Pathologists (BGCS/BAGP) has re-assembled a multidisciplinary expert consensus group to update the previous guidance with the latest standard of care for germline and tumor testing in patients with ovarian cancer. For the first time, the BGCS/BAGP guideline group has incorporated a patient advisor at the initial consensus group meeting.

Extended panel testing in ovarian cancer reveals BRIP1 as the third most important predisposition gene.

Purpose: The prevalence of germline pathogenic variants (PVs) in homologous recombination repair (HRR) and Lynch syndrome (LS) genes in ovarian cancer (OC) is uncertain.

Methods: An observational study reporting the detection rate of germline PVs in HRR and LS genes in all OC cases tested in the North West Genomic Laboratory Hub between September 1996 and May 2024. Effect sizes are reported using odds ratios (ORs) and 95% confidence intervals (95% CI) for unselected cases tested between April 2021 and May 2024 versus 50,703 controls from the Breast Cancer Risk after Diagnostic Gene Sequencing study.

Intrinsic PARG inhibitor sensitivity is mimicked by haploinsufficiency and rescued by nucleoside supplementation.

A subset of cancer cells are intrinsically sensitive to inhibitors targeting PARG, the poly(ADP-ribose) glycohydrolase that degrades PAR chains. Sensitivity is accompanied by persistent DNA replication stress, and can be induced by inhibition of , a replisome accelerator. However, the nature of the vulnerability responsible for intrinsic sensitivity remains undetermined.

Cost-Effectiveness of Unselected Multigene Germline and Somatic Genetic Testing for Epithelial Ovarian Cancer.

Background: Parallel panel germline and somatic genetic testing of all patients with ovarian cancer (OC) can identify more pathogenic variants (PVs) that would benefit from PARP inhibitor (PARPi) therapy, and allow for precision prevention in unaffected relatives with PVs. In this study, we estimate the cost-effectiveness and population impact of parallel panel germline and somatic BRCA testing of all patients with OC incorporating PARPi therapy in the United Kingdom and the United States compared with clinical criteria/family history (FH)-based germline BRCA testing. We also evaluate the cost-effectiveness of multigene panel germline testing alone.

Breast cancer after ovarian cancer in BRCA1 and BRCA2 pathogenic variant heterozygotes: Lower rates for 5 years post chemotherapy.

Purpose: The identification of germline BRCA1/BRCA2 pathogenic variants (PV) infer high remaining lifetime breast/ovarian cancer risks, but there is paucity of studies assessing breast cancer risk after ovarian cancer diagnosis.

Methods: We reviewed the history of breast cancer in 895 PV heterozygotes (BRCA1 = 541). Cumulative annual breast cancer incidence was assessed at 2, 5, 10, and >10 years after ovarian cancer diagnosis date.

Once daily cediranib and weekly paclitaxel to prevent malignant bowel obstruction in at-risk patients with platinum-resistant ovarian cancer (CEBOC): a single-arm, phase II safety trial.

Objective: Cytotoxic chemotherapy for ovarian cancer can be augmented by co-administration of vascular endothelial growth factor inhibitors but these are contraindicated in patients with bowel obstruction due to the risk of gastrointestinal perforation. We evaluated the safety and feasibility of paclitaxel plus cediranib to treat patients with platinum-resistant ovarian cancer at risk of malignant bowel obstruction.

Methods: A phase II trial included eligible patients between March 2018 and February 2021, identified by clinical symptoms and radiographic risk factors for malignant bowel obstruction.

Implementing a Treatment for People with Serious Mental Illness in Jail: A Mixed-Methods Study of Stakeholder Perspectives on Feasibility and Acceptability.

People with mental illness are over-represented in the U.S. criminal legal system.

Real-World Concordance between Germline and Tumour Status in Epithelial Ovarian Cancer.

Patients diagnosed with epithelial ovarian cancer may undergo reflex tumour / testing followed by germline testing in patients with a positive tumour test result. This testing model relies on tumour / tests being able to detect all types of pathogenic variant. We analysed germline and tumour test results from patients treated for epithelial ovarian cancer at our specialist oncological referral centre.

Exploiting a living biobank to delineate mechanisms underlying disease-specific chromosome instability.

Chromosome instability (CIN) is a cancer hallmark that drives tumour heterogeneity, phenotypic adaptation, drug resistance and poor prognosis. High-grade serous ovarian cancer (HGSOC), one of the most chromosomally unstable tumour types, has a 5-year survival rate of only ~30% - largely due to late diagnosis and rapid development of drug resistance, e.g.

Multi-Maintenance Olaparib Therapy in Relapsed, Germline BRCA1/2-Mutant High-Grade Serous Ovarian Cancer (MOLTO): A Phase II Trial.

Purpose: A single maintenance course of a PARP inhibitor (PARPi) improves progression-free survival (PFS) in germline BRCA1/2-mutant high-grade serous ovarian cancer (gBRCAm-HGSOC). The feasibility of a second maintenance course of PARPi was unknown.

Patients And Methods: Phase II trial with two entry points (EP1, EP2).

Is Reflex Germline Testing Necessary in Women Diagnosed with Non-Mucinous High-Grade Epithelial Ovarian Cancer Aged 80 Years or Older?

Women diagnosed with non-mucinous high-grade epithelial ovarian cancer (EOC) in England are often reflex-tested for germline and tumour / variants. The value of germline testing in women diagnosed aged ≥80 is questionable. We performed an observational study of all women diagnosed with non-mucinous high-grade EOC who underwent germline and tumour testing by the North West of England Genomic Laboratory Hub.

Multiple-low-dose therapy: effective killing of high-grade serous ovarian cancer cells with ATR and CHK1 inhibitors.

High-grade serous ovarian cancer (HGSOC) is an aggressive disease that typically develops drug resistance, thus novel biomarker-driven strategies are required. Targeted therapy focuses on synthetic lethality-pioneered by PARP inhibition of -mutant disease. Subsequently, targeting the DNA replication stress response (RSR) is of clinical interest.

Tried and True? A Psychometric Evaluation of the Psychological Inventory of Criminal Thinking Styles-Short Form.

The Psychological Inventory of Criminal Thinking Styles-Short Form (PICTS-SF) is an abbreviated 35-item version of the PICTS, a measure of cognitions that support a criminal lifestyle. Despite use in research and clinical work, the PICTS-SF's psychometric properties have not been tested. Using two archival datasets, we analyzed the PICTS-SF's reliability and structural validity in multiply imputed data from adult males and females on probation in a residential treatment facility ( = 514).

Predicting the likelihood of a pathogenic variant being somatic by testing only tumour DNA in non-mucinous high-grade epithelial ovarian cancer.

Aims: Clinical guidelines recommend testing both germline and tumour DNA for pathogenic variants (PVs) in non-mucinous high-grade epithelial ovarian cancer (NMEOC). In this study, we show that some tumour PVs are highly likely to be somatic based on certain clinical and variant characteristics, meaning it may not be necessary to test all NMEOC cases for germline PVs.

Methods: An observational study that included all tumour PVs detected in cases of NMEOC in the Northwest of England between July 2017 and February 2022.

Changing criminal thinking: An examination of heterogeneity in treatment effects in a sample of justice-involved persons with dual diagnoses.

Recent studies have indicated variable reductions in criminal thinking for justice-involved persons with mental illness exposed to cognitive-behavioral treatments. To date, however, no studies have identified risk factors for limited response or modeled observed disparities in responsivity to interventions aimed at reducing criminal thinking. Using an archival data set of 162 probationers with a dual diagnosis who were exposed to a latent profile analysis modeled unobserved heterogeneity in treatment response per observed changes in criminal thinking.

The relation between the working alliance on mental illness and criminal thinking among justice-involved people with co-occurring mental illness and substance use disorders.

Objective: The therapeutic working alliance is an important factor in producing treatment change and positive therapeutic outcomes for people with mental illness, yet little is known about the working alliance's role in treatment change in people with mental illness that is justice involved. In addition to treating the mental illness symptoms of justice-involved people with mental illness, addressing factors known to predict criminal behavior (including criminal thinking) could optimize posttreatment outcomes and reduce future justice involvement. This study examines the role of the working alliance in treatment change in a clinical treatment sample of 265 adult male and female justice-involved people with mental illness and substance use disorders completing probation sentences in a residential treatment facility.

BRCA1/2 in non-mucinous epithelial ovarian cancer: tumour with or without germline testing?

National guidelines recommend testing all cases of non-mucinous epithelial ovarian cancer (NMEOC) for germline (blood) and somatic (tumour) BRCA1/2 pathogenic variants (PVs). We performed paired germline and somatic BRCA1/2 testing in consecutive cases of NMEOC (n = 388) to validate guidelines. Thirty-four somatic BRCA1/2 (sBRCA) PVs (9.

c-MET/VEGFR-2 co-localisation impacts on survival following bevacizumab therapy in epithelial ovarian cancer: an exploratory biomarker study of the phase 3 ICON7 trial.

Introduction: Bevacizumab improves survival outcomes in women diagnosed with epithelial ovarian cancer (EOC). Pre-clinical data showed that the c-MET/VEGFR-2 heterocomplex negates VEGF inhibition through activation of c-MET signalling, leading to a more invasive and metastatic phenotype. We evaluated the clinical significance of c-MET and VEGFR-2 co-localisation and its association with VEGF pathway-related single nucleotide polymorphisms (SNPs) in women participating in the phase 3 trial, ICON7 (ClinicalTrials.