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.

High performance of the DNA methylation-based WID-qEC test for detecting uterine cancers independent of sampling modalities.

Endometrial cancer (EC) is the most prevalent gynaecological cancer in high-income countries and its incidence is continuing to rise sharply. Simple and objective tools to reliably detect women with EC are urgently needed. We recently developed and validated the DNA methylation (DNAme)-based women's cancer risk identification-quantitative polymerase chain reaction test for endometrial cancer (WID-qEC) test that could address this need.

Objective assessment tools in laparoscopic or robotic-assisted gynecological surgery: A systematic review.

Introduction: There is a growing emphasis on proficiency-based progression within surgical training. To enable this, clearly defined metrics for those newly acquired surgical skills are needed. These can be formulated in objective assessment tools.

Feasibility of Sentinel Lymph Node Biopsy in Early-Stage Epithelial Ovarian Cancer: A Systematic Review and Meta-Analysis.

Sentinel lymph node biopsy (SLNB) has been widely adopted in the management of early-stage gynaecological cancers such as endometrial, vulvar and cervical cancer. Comprehensive surgical staging is crucial for patients with early-stage ovarian cancer and currently, that includes bilateral pelvic and para-aortic lymph node assessment. SLNB allows the identification, excision and pathological assessment of the first draining lymph nodes, thus negating the need for a full lymphadenectomy.

The peritoneal cancer index as a predictor of complete cytoreduction at primary and interval cytoreductive surgery in advanced ovarian cancer.

Objective: The peritoneal cancer index quantitatively assesses cancer distribution and tumor burden in the peritoneal cavity. The aim of this study is to evaluate the association between the peritoneal cancer index and completeness of surgical cytoreduction for ovarian cancer and to identify a cut-off above which complete cytoreduction is unlikely.

Methods: This is a single-center prospective cohort observational study.

Patient decision aids in mainstreaming genetic testing for women with ovarian cancer: A prospective cohort study.

Objective: To evaluate patient preference for short (gist) or detailed/extensive decision aids (DA) for genetic testing at ovarian cancer (OC) diagnosis.

Design: Cohort study set within recruitment to the Systematic Genetic Testing for Personalised Ovarian Cancer Therapy (SIGNPOST) study (ISRCTN: 16988857).

Setting: North-East London Cancer Network (NELCN) population.

Impact of minimally invasive surgery on surgical outcomes for obese women with endometrial cancer following robotic surgery introduction; a single centre study.

Background: The aim was to assess the surgical outcomes in obese women with endometrial cancer following robotic surgery introduction in a London tertiary gynaecological cancer unit.

Methods: Data was prospectively collected for 281 women undergoing endometrial cancer surgery in 2016, 2018 and 2019 (robotic surgery was introduced in November 2017).

Results: The proportion of obese and morbidly obese patients undergoing minimally invasive surgery (MIS) significantly increased following robotic surgery introduction from 43.

Patient outcomes following interval and delayed cytoreductive surgery in advanced ovarian cancer: protocol for a multicenter, international, cohort study (Global Gynaecological Oncology Surgical Outcomes Collaborative).

Background: The Global Gynecological Oncology Surgical Outcomes Collaborative (GO SOAR) has developed a network of gynecological oncology surgeons, surgical departments, and other interested parties that have the long-term ability to collaborate on outcome studies. Presented is the protocol for the GO SOAR2 study.

Primary Objectives: To compare survival following interval and delayed cytoreductive surgery, between delayed cytoreductive surgery and no surgery (chemotherapy alone); and international variations in access to cytoreductive surgery for women with stage III-IV epithelial ovarian cancer.

Unselected Population Genetic Testing for Personalised Ovarian Cancer Risk Prediction: A Qualitative Study Using Semi-Structured Interviews.

Unselected population-based personalised ovarian cancer (OC) risk assessments combining genetic, epidemiological and hormonal data have not previously been undertaken. We aimed to understand the attitudes, experiences and impact on the emotional well-being of women from the general population who underwent unselected population genetic testing (PGT) for personalised OC risk prediction and who received low-risk (<5% lifetime risk) results. This qualitative study was set within recruitment to a pilot PGT study using an OC risk tool and telephone helpline.

AdCOFE: Advanced Contextual Feature Extraction in conversations for emotion classification.

Emotion recognition in conversations is an important step in various virtual chatbots which require opinion-based feedback, like in social media threads, online support, and many more applications. Current emotion recognition in conversations models face issues like: (a) loss of contextual information in between two dialogues of a conversation, (b) failure to give appropriate importance to significant tokens in each utterance, (c) inability to pass on the emotional information from previous utterances. The proposed model of Advanced Contextual Feature Extraction (AdCOFE) addresses these issues by performing unique feature extraction using knowledge graphs, sentiment lexicons and phrases of natural language at all levels (word and position embedding) of the utterances.

Implementation of Multigene Germline and Parallel Somatic Genetic Testing in Epithelial Ovarian Cancer: SIGNPOST Study.

We present findings of a cancer multidisciplinary-team (MDT) coordinated mainstreaming pathway of unselected 5-panel germline and parallel somatic testing in all women with epithelial-OC and highlight the discordance between germline and somatic testing strategies across two cancer centres. Patients were counselled and consented by a cancer MDT member. The uptake of parallel multi-gene germline and somatic testing was 97.

Surgical decision making in premenopausal carriers considering risk-reducing early salpingectomy or salpingo-oophorectomy: a qualitative study.

Background: Acceptance of the role of the fallopian tube in 'ovarian' carcinogenesis and the detrimental sequelae of surgical menopause in premenopausal women following risk-reducing salpingo-oophorectomy (RRSO) has resulted in risk-reducing early-salpingectomy with delayed oophorectomy (RRESDO) being proposed as an attractive alternative risk-reducing strategy in women who decline/delay oophorectomy. We present the results of a qualitative study evaluating the decision-making process among carriers considering prophylactic surgeries (RRSO/RRESDO) as part of the multicentre PROTECTOR trial (ISRCTN:25173360).

Methods: In-depth semistructured 1:1 interviews conducted using a predeveloped topic-guide (development informed by literature review and expert consultation) until informational saturation reached.

Population Study of Ovarian Cancer Risk Prediction for Targeted Screening and Prevention.

Unlabelled: Unselected population-based personalised ovarian cancer (OC) risk assessment combining genetic/epidemiology/hormonal data has not previously been undertaken. We aimed to perform a feasibility study of OC risk stratification of general population women using a personalised OC risk tool followed by risk management. Volunteers were recruited through London primary care networks.

Persistence of fimbrial tissue on the ovarian surface after salpingectomy.

Background: Salpingectomy is recommended as a risk-reducing strategy for epithelial tubo-ovarian cancer. The gold standard procedure is complete tubal excision.

Objective: The purpose of this study was to assess the presence of residual fimbrial/tubal tissue on ovarian surfaces after salpingectomy.

Axin2-expressing cells differentiate into reparative odontoblasts via autocrine Wnt/β-catenin signaling in response to tooth damage.

In non-growing teeth, such as mouse and human molars, primary odontoblasts are long-lived post-mitotic cells that secrete dentine throughout the life of the tooth. New odontoblast-like cells are only produced in response to a damage or trauma. Little is known about the molecular events that initiate mesenchymal stem cells to proliferate and differentiate into odontoblast-like cells in response to dentine damage.

Promotion of natural tooth repair by small molecule GSK3 antagonists.

The restoration of dentine lost in deep caries lesions in teeth is a routine and common treatment that involves the use of inorganic cements based on calcium or silicon-based mineral aggregates. Such cements remain in the tooth and fail to degrade and thus normal mineral volume is never completely restored. Here we describe a novel, biological approach to dentine restoration that stimulates the natural formation of reparative dentine via the mobilisation of resident stem cells in the tooth pulp.

The Role of Ultrasound Simulation in Obstetrics and Gynecology Training: A UK Trainees' Perspective.

Introduction: Ultrasonography is a core skill required by all obstetrics and gynecology trainees; however, training opportunities in clinical ultrasound are declining. Simulation ultrasound training has been proposed as a strategy to overcome this.The study aims were to determine the current availability of clinical and simulation ultrasound training in obstetrics and gynecology in the United Kingdom and to explore the trainees' perspective on the role of ultrasound simulation.

Impact of hypofunctional occlusion on upper and lower molars after cessation of root development in adult mice.

Background: Hypofunctional occlusion is known to lead to changes in the length of roots over time. The mechanisms that drive such changes, however, are poorly understood, with most studies concentrating on juvenile rats prior to the arrest of root development. In this article, we investigated the response of the upper and lower first molar roots to lack of occlusion concentrating on time-points after the development of the roots has ceased using the mouse as a model.

Risk reducing salpingectomy and delayed oophorectomy in high risk women: views of cancer geneticists, genetic counsellors and gynaecological oncologists in the UK.

Risk-reducing-salpingectomy and Delayed-Oophorectomy (RRSDO) is being proposed as a two-staged approach in place of RRSO to reduce the risks associated with premature menopause in high-risk women. We report on the acceptability/attitude of UK health professionals towards RRSDO. An anonymised web-based survey was sent to UK Cancer Genetics Group (CGG) and British Gynaecological Cancer Society (BGCS) members to assess attitudes towards RRSDO.

Comparative in vitro Cytotoxic Studies of Novel 8-(4'/2'-Methoxy/Unsubstituted phenylcarbamoyl)bicyclo[3.3.1]nonane Derivatives on Ehrlich Ascites Carcinoma Cell Line.

Novel bicyclo[3.3.1]nonane derivatives were synthesized by an efficient methodology from acetoacetanilide, 2-methoxy and 4-methoxyacetoacetanilides, 1,3,5-trinitrobenzene and triethylamine.

Inhibitory effects of belatacept on allospecific regulatory T-cell generation in humans.

Background: It is unclear if new costimulatory blockade agents, such as the cytotoxic T lymphocyte-associated antigen 4-Ig molecule belatacept (BEL), promote or inhibit the potential for immunologic tolerance in transplantation. We therefore tested the in vitro effects of BEL on human regulatory T cells (Tregs) in mixed lymphocyte reactions (MLR) alone and in combination with maintenance agents used in transplant recipients.

Methods: BEL, mycophenolic acid (MPA), and sirolimus, either alone or in combination, were added to healthy volunteer Treg-MLR, testing (a) H-TdR incorporation for inhibition of lymphoproliferation and (b) flow cytometry to analyze for newly generated CD4+ CD25(high) FOXP3+ Tregs in carboxyfluorescein succinimidyl ester-labeled MLR responders.

Systemic immunoregulatory and proteogenomic effects of tacrolimus to sirolimus conversion in liver transplant recipients.

Unlabelled: Immunosuppression (IS) withdrawal from calcineurin inhibitors is only possible in ≈ 20% of liver transplant recipients. However, mammalian target of rapamycin inhibitors (e.g.

Favorable effects of alemtuzumab on allospecific regulatory T-cell generation.

We studied the effects of alemtuzumab on T-regulatory cells (Tregs) during alloactivation, first by differences in depletion of various naive versus alloactivated cell subsets in peripheral blood of healthy volunteers, then by adding serial concentrations to human leukocyte antigen (HLA)-DR-matched and -mismatched responding and stimulating cells in mixed lymphocyte reaction (MLR). Lymphoproliferation inhibition and the development of proliferating carboxyfluorescein succinimidyl ester (CFSE)-diluted CD4(+)CD25(high)CD127(-)FOXP3(+) (phenotypic) Tregs by flow cytometry were measured. Also, the ability of alemtuzumab-treated versus nontreated MLR generated CD4(+)CD127(-) cells to allospecifically inhibit MLRs and recruit additional responding Tregs was tested.