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Background In women of reproductive age, polycystic ovary syndrome (PCOS) constitutes the most frequent endocrine disorder. Women with PCOS are considered to typically belong to an age and sex group which is at lower risk for severe COVID-19. Main body Emerging data link the risk of severe COVID-19 with certain factors such as hyper-inflammation, ethnicity predisposition, low vitamin D levels, and hyperandrogenism, all of which have known direct associations with PCOS. Moreover, in this common female patient population, there is markedly high prevalence of multiple cardio-metabolic conditions, such as type 2 diabetes, obesity, and hypertension, which may significantly increase the risk for adverse COVID-19-related outcomes. This strong overlap of risk factors for both worse PCOS cardio-metabolic manifestations and severe COVID-19 should be highlighted for the clinical practice, particularly since women with PCOS often receive fragmented care from multiple healthcare services. Comprehensively informing women with PCOS regarding the potential risks from COVID-19 and how this may affect their management is also essential. Conclusion Despite the immense challenges posed by the COVID-19 outbreak to the healthcare systems in affected countries, attention should be directed to maintain a high standard of care for complex patients such as many women with PCOS and provide relevant practical recommendations for optimal management in the setting of this fast moving pandemic.

(1) Background: Following the discovery of the adipokine/hormone asprosin, a substantial amount of research has provided evidence for its role in the regulation of glucose homeostasis, as well as appetite, and insulin sensitivity. Its levels are dysregulated in certain disease states, including breast cancer. To date, little is known about its role in endometrial cancer (EC). The present study investigated the effects of asprosin on the transcriptome of the Ishikawa and NOU-1 EC cell lines, and assessed the expression of asprosin’s candidate receptors (TLR4, PTPRD, and OR4M1) in health and disease. (2) Methods: tissue culture, RNA extraction, RNA sequencing, reverse transcription-quantitative PCR, gene enrichment and in silico analyses were used for this study. (3) Results: TLR4 and PTPRD were significantly downregulated in EC when compared to healthy controls. TLR4 appeared to have a prognostic role in terms of overall survival (OS) in EC patients (i.e., higher expression, better OS). RNA sequencing revealed that asprosin affected 289 differentially expressed genes (DEGs) in Ishikawa cells and 307 DEGs in NOU-1 cells. Pathway enrichment included apoptosis, glycolysis, hypoxia, and PI3K/AKT/ mTOR/NOTCH signalling for Ishikawa-treated cells. In NOU-1, enriched processes included inflammatory response, epithelial-mesenchymal transition, reactive oxygen species pathways, and interferon gamma responses. Other signalling pathways included mTORC1, DNA repair, and p53, amongst others. (4) Conclusions: These findings underscore the importance of understanding receptor dynamics and signalling pathways in the context of asprosin’s role in EC, and provide evidence for a potential role of TLR4 as a diagnostic biomarker.

Background In patients with cancer, the current gold standard for assessing response to treatment involves measuring cancer lesions on computed tomography (CT) imaging. The percentage change in size of specific lesions determines whether patients have had a complete/partial response or progressive disease, according to RECIST criteria. Dual Energy CT (DECT) permits additional measurements of iodine concentration, a surrogate marker of vascularity. Here we explore the role of changes in iodine concentration within cancer tissue on CT scans to assess its suitability for determining treatment response in patients with high grade serous ovarian cancer (HGSOC). Methods Suitable RECIST measurable lesions were identified from the CT images of HGSOC patients, taken at 2 different time points (pre and post treatment). Changes in size and iodine concentration were measured for each lesion. PR/SD were classified as responders, PD was classified as non-responder. Radiological responses were correlated with clinical and CA125 outcomes. Results 62 patients had appropriate imaging for assessment. 22 were excluded as they only had one DECT scan. 32/40 patients assessed (113 lesions) had received treatment for relapsed HGSOC. RECIST and GCIG (Gynaecologic Cancer Inter Group) CA125 criteria / clinical assessment of response for patients was correlated with changes in iodine concentration, before and after treatment. The prediction of median progression free survival was significantly better associated with changes in iodine concentration (p = 0.0001) and GCIG Ca125 / clinical assessment (p = 0.0028) in comparison to RECIST criteria (p = 0.43). Conclusion Changes in iodine concentration from dual energy CT imaging may be more suitable than RECIST in assessing response to treatment in patients with HGSOC. Trial Registration CICATRIx IRAS number 198179, 14 Dec 2015, https://www.myresearchproject.org.uk/ .

Background Team-based learning (TBL) combines active and collaborative learning, while incorporating aspects of the flipped classroom approach and problem-based learning. The COVID-19 pandemic presented certain challenges in the delivery of TBL in class. In this study, we investigated the impact of TBL on the academic performance of final year Biomedical Sciences’ undergraduate students in the context of an “Endocrine Disorders” study block. We did so by comparing the classical in-person approach and online delivery due to the COVID-19 pandemic. Methods A non-compulsory TBL session was introduced to the curriculum of this block, which followed the traditional 2-h lecture delivery. Comparative analysis was performed for the exam and coursework performance of students who attended the TBL sessions (online and in-person) and those that did not. Results Both cohorts of students who attended either in-person ( n  = 66) or online TBL sessions ( n  = 109) performed significantly better in their exams ( p  < 0.05) and a related coursework ( p  < 0.001 and p < 0.05, respectively) when compared to those that did not attend. For both these cohorts the exam mark distribution was much narrower compared to those that did not attend the TBL sessions where the majority of fails and “no shows” were recorded. Conclusions Online and in-person TBL, can successfully supplement traditional lecture-based teaching and enhance the learning/performance, for complex medical subjects/topics. Our findings demonstrate that it is possible to deliver these sessions online with demonstrable benefit for students suggesting that there is greater flexibility in the use of TBL in higher education.

Ovarian cancer (OvCa) is the sixth most common gynaecological cancer in the UK, accounting for over 200,000 deaths worldwide. Cancerous Inhibitor of Phosphatase 2 A (CIP2A) is an oncoprotein and an endogenous inhibitor of PP2A. CIP2A is a key regulator for cellular processes (e.g. proliferation, DNA damage) and is involved in the progression of many malignancies. In this study we provide a comprehensive overview of its role in OvCa making use of in silico tools, clinical samples and in vitro models. CIP2A is overexpressed in OvCa patients, with metastatic patients having significantly higher expression when compared to patients with malignant and benign ovarian tumours. High CIP2A expression reduces both overall-and progression-free survival, whereas an R530T mutation is predicted to cause structural destabilisation of the CIP2A dimer. We also provide evidence for microRNA (miRNA) and mRNA target interactions with CIP2A . Finally, we have studied the effects of CIP2A inhibition in an in vitro BRCA2 model compared to BRCA2 wild-type OvCa cells, using RNA-sequencing. Gene enrichment pointed towards changes p53 pathway, protein metabolism, transporter activity, DNA replication, and cell cycle. Our data provide a novel insight into the role of CIP2A in OvCa and the potential of drug repurposing for therapeutic interventions.

Glioblastoma multiforme (GBM) is a highly heterogenic and malignant brain tumour with a median survival of 15 months. The initial identification of primary glioblastomas is often challenging. Coronin 1C (CORO1C) is a key player in actin rearrangement and cofilin dynamics, as well as enhancing the processes of neurite overgrowth and migration of brain tumour cells. Different bioinformatic databases were accessed to measure CORO1C expression at the mRNA and protein level in normal and malignant brains. CORO1C expression was observed in brain regions which have retained high synaptic plasticity and myelination properties. CORO1C was also expressed mainly within the hippocampus formation, including the Cornu Ammonis (CA) fields: CA1–CA4. Higher expression was also noticed in paediatric GBM in comparison to their adult counterparts. Pediatric cell populations were observed to have an increased log2 expression of CORO1C. Furthermore, 62 miRNAs were found to target the CORO1C gene. Of these, hsa-miR-34a-5p, hsa-miR-512-3p, hsa-miR-136-5p, hsa-miR-206, hsa-miR-128-3p, and hsa-miR-21-5p have shown to act as tumour suppressors or oncomiRs in different neoplasms, including GBM. The elevated expression of CORO1C in high grade metastatic brain malignancies, including GBM, suggests that this protein could have a clinical utility as a biomarker linked to an unfavorable outcome.

Ovarian cancer is fifth in the rankings of cancer deaths among women, and accounts for more deaths than any other gynecological malignancy. Despite some improvement in overall-(OS) and progression-free survival (PFS) following surgery and first-line chemotherapy, there is a need for development of novel and more effective therapeutic strategies. In this mini review, we provide a summary of the current landscape of the clinical use of tyrosine kinase inhibitors (TKIs) and mechanistic target of rapamycin (mTOR) inhibitors in ovarian cancer. Emerging data from phase I and II trials reveals that a combinatorial treatment that includes TKIs and chemotherapy agents seems promising in terms of PFS despite some adverse effects recorded; whereas the use of mTOR inhibitors seems less effective. There is a need for further research into the inhibition of multiple signaling pathways in ovarian cancer and progression to phase III trials for drugs that seem most promising.

Background: Approximately 50% of ovarian cancer patients harbour homologous recombination repair deficiencies. These deficiencies have been successfully targeted using poly (ADP-ribose) polymerase inhibitors (PARPi) particularly for patients harbouring BRCA1/2 mutations. The aim of this study is to assess the effects of the PARPi rucaparib in vitro using cell lines with BRCA2 mutations in comparison to those with BRCA2 wild type. Methods: Cell proliferation assays, RT-qPCR, immunofluorescence, annexin V/PI assays were used to assess the effects of rucaparib in vitro. Results: The BRCA2 mutant ovarian cancer cell line PEO1 exhibited higher PARP1 activity when treated with H2O2 compared to wild type cell lines. The migratory and proliferative capacity of PEO1 cells was compromised following treatment with rucaparib 10 µM compared to BRCA2 wild-type cell lines via a mechanism involving the mTOR pathway. Rucaparib treatment significantly increased DNA damage primarily in PEO1 cells and SKOV3 cells compared with wild type. Conclusions: Appropriate identification of robust predictive biomarkers for homologous recombination deficiency using ‘liquid’ biopsies would facilitate the identification of patients suitable for PARPi therapy. Preliminary efforts to undertake such testing are described here. This study also demonstrates the mechanisms of action of rucaparib (PARPi) which may involve elements of the mTOR pathway.

Pulmonary surfactant proteins SP-A and SP-D are pattern recognition innate immune molecules. However, there is extrapulmonary existence, especially in the amniotic fluid and at the feto-maternal interface. There is sufficient evidence to suggest that SP-A and SP-D are involved in the initiation of labour. This is of great importance given that preterm birth is associated with increased mortality and morbidity. In this study, we investigated the effects of recombinant forms of SP-A and SP-D (rhSP-A and rhSP-D, the comprising of trimeric lectin domain) on contractile events in vitro, using a human myometrial cell line (ULTR) as an experimental model. Treatment with rhSP-A or rhSP-D increased the cell velocity, distance travelled and displacement by ULTR cells. rhSP-A and rhSP-D also affected the contractile response of ULTRs when grown on collagen matrices showing reduced surface area. We investigated this effect further by measuring contractility-associated protein (CAP) genes. Treatment with rhSP-A and rhSP-D induced expression of oxytocin receptor (OXTR) and connexin 43 (CX43). In addition, rhSP-A and rhSP-D were able to induce secretion of GROα and IL-8. rhSP-D also induced the expression of IL-6 and IL-6 Ra. We provide evidence that SP-A and SP-D play a key role in modulating events prior to labour by reconditioning the human myometrium and in inducing CAP genes and pro-inflammatory cytokines thus shifting the uterus from a quiescent state to a contractile one.