Prostate Cancer and Sleep Disorders: A Systematic Review.

Prostate cancer (PCa) treatment involves multiple strategies depending on the disease's stage. Androgen deprivation therapy (ADT) remains the gold standard for advanced and metastatic stages. Sleep quality has been suggested as being additionally influenced also by local radiotherapy, prostatectomy and androgen-receptor (AR)-targeted agents. We performed a systematic review exploring the landscape of studies published between 1 January 1990 and 31 July 2021, investigating sleep disturbances in PCa patients receiving active treatments, including the influence of hormonal therapy on sleep quality as a factor affecting their quality of life. Out of 45 articles identified, 16 studies were selected, which recruited patients with PCa, undergoing active treatment in either a prospective longitudinal or cross-sectional study. Development of sleep disorders or changes in sleep quality were reported in 14 out of 16 trials included. Only five trials included objective measurements such as actigraphy, mostly at one time point and without a baseline assessment. Limitations to be addressed are the small number of existing trials, lack of randomized trials and heterogeneity of methodologies used. This systematic review outlines the lack of prospective trials investigating sleep disorders, with a rigorous methodology, in homogeneous cohorts of PCa patients. Future trials are needed to clarify the prevalence and impact of this side effect of PCa treatments

Deconstructing synthetic biology across scales: A conceptual approach for training synthetic biologists

Synthetic biology allows us to reuse, repurpose, and reconfigure biological systems to address society’s most pressing challenges. Developing biotechnologies in this way requires integrating concepts across disciplines, posing challenges to educating students with diverse expertise. We created a framework for synthetic biology training that deconstructs biotechnologies across scales—molecular, circuit/network, cell/cell-free systems, biological communities, and societal—giving students a holistic toolkit to integrate cross-disciplinary concepts towards responsible innovation of successful biotechnologies. We present this framework, lessons learned, and inclusive teaching materials to allow its adaption to train the next generation of synthetic biologists

P1245 Polymorphic Variants of HSD3B1 Gene Confer Different Outcome in Specific Subgroups of Patients Infected With SARS-CoV-2

Introduction: Severe respiratory syndrome coronavirus 2 (SARS-CoV-2) uses the androgen receptor (AR), through ACE2 receptor and TMPRSS2, to enter nasal and upper airways epithelial cells. Genetic analyses revealed that HSD3B1 P1245C polymorphic variant increases dihydrotestosterone production and upregulation of TMPRSS2 with respect to P1245A variant, thus possibly influencing SARS-CoV-2 infection. Our aim was to characterize the HSD3B1 polymorphism status and its potential association with clinical outcomes in hospitalized patients with COVID-19 in Southern Switzerland. Materials and Methods: The cohort included 400 patients hospitalized for COVID-19 during the first wave between February and May 2020 in two different hospitals of Canton Ticino. Genomic DNA was extracted from formalin-fixed paraffin-embedded tissue blocks, and HSD3B1 gene polymorphism was evaluated by Sanger sequencing. Statistical associations were verified using different test. Results: HSD3B1 polymorphic variants were not associated with a single classical factor related to worse clinical prognosis in hospitalized patients with SARS-CoV-2. However, in specific subgroups, HSD3B1 variants played a clinical role: intensive care unit admission was more probable in patients with P1245C diabetes compared with P1245A individuals without this comorbidity and death was more associated with hypertensive P1245A>C cases than patients with P1245A diabetes without hypertension. Discussion: This is the first study showing that HSD3B1 gene status may influence the severity of SARS-CoV-2 infection. If confirmed, our results could lead to the introduction of HSD3B1 gene status analysis in patients infected with SARS-CoV-2 to predict clinical outcome. Keywords: HSD3B1 gene polymorphism; Likelihood-ratio tests; SARS-CoV-2; androgen receptor; direct sequencing

Prognostic value of KRAS G12C in advanced non-small cell lung cancer with high PD-L1 expression treated with upfront immunotherapy: a systematic review and meta-analysis

AIM: This study aims to evaluate the prognostic role of the KRAS G12C mutation in patients with advanced non-small cell lung cancer and PD-L1 expression ≥50% who are treated with immune checkpoint inhibitor monotherapy. METHODS: We conducted a systematic review of clinical studies fulfilling the following criteria: (1) enrolling patients with advanced/metastatic non-small cell lung cancer with high PD-L1 tumour expression receiving first-line therapy with anti-PD-(L)1 immune checkpoint inhibitors; (2) comparing the outcomes of patients with the KRAS G12C mutation to those without this mutation, and (3) reporting overall survival and progression-free survival (PFS). The electronic databases Medline, EMBASE, Cochrane and Google Scholar, along with reference lists, were systematically searched. RESULTS: We identified four publications that fulfilled the inclusion criteria, comprising a total of 469 patients. Of these, two studies reported hazard ratios (HR) for PFS, resulting in a final pooled patient sample of 163 for the meta-analysis. In patients with non-small cell lung cancer who received anti-PD-(L)1 monotherapy, the presence of a KRAS G12C mutation was associated with improved PFS compared to patients with KRAS wild-type tumours, with a pooled hazard ratio of 0.39 and a 95% Confidence Interval (CI) of 0.25–0.63. Among all patients with KRAS mutations, those harbouring a KRAS G12C mutation had improved PFS compared to patients with any other KRAS mutation (pooled HR 0.33, 95% CI 0.19–0.57). CONCLUSIONS: Patients with non-small cell lung cancer who have the KRAS G12C mutation and high PD-L1 expression demonstrate favourable PFS with first-line PD-(L)1 immune checkpoint inhibitor monotherapy compared to patients with KRASwt or other KRAS mutations and high PD-L1 expression