A PSMA-targeted theranostic approach is unlikely to be efficient in serous ovarian cancers

Purpose Until now, results evaluating the expression of PSMA in ovarian cancer were sparse and contradictory. The aim was to reinvestigate the feasibility of a PSMA targeted theranostic approach in epithelial ovarian cancers with data from the tumour bank of a referring cancer centre. Materials and methods The OvaRessources Biological Resources Center database was screened from January 2004 to December 2017 to seek patients referred for the initial management of a serous epithelial ovarian cancer and for whom peritoneal histological samples were available in the tumour bank. Immunodetection of PSMA was performed to assess its cellular and neovascular expression. Slides were controlled by a certified pathologist, recorded as tiled tiff images and processed to compute the proportion of DAB stained surface. Results Of the 51 patients identified by the database screening, 32 patients were included resulting in 57 samples (32 pre-chemotherapy and 25 post-chemotherapy histological samples). Nine patients were chemo-sensitive, 10 were partially chemo-sensitive and 13 were chemo-resistant/refractory. In the entire dataset, the expression of PSMA was quasi-inexistent: %DABPSMA = 0.04 (± 0.12) %. There was no significant difference in the %DABPSMA of sensitive, partially sensitive and resistant/refractory patients. There was also no significant difference in %DABPSMA in tumours before and after chemotherapy in the 25 patients for whom both samples were available. Conclusion The present work demonstrates that PSMA expression is negligible and a fortiori non-sufficient to ensure its usefulness as a prognosticator or a target for a theranostic strategy in ovarian cancers.

Non-covalent TMPRSS2 inhibitors identified from virtual screening

The SARS-CoV-2 pandemic has prompted researchers to pivot their efforts to finding anti-viral compounds and vaccines. In this study, we focused on the human host cell transmembrane protease serine 2 (TMPRSS2), which plays an important role in the viral life cycle by cleaving the spike protein to initiate membrane fusion. TMPRSS2 is an attractive target and has received significant attention for the development of drugs against SARS and MERS. Starting with comparative structural modeling and binding model analysis, we developed an efficient pharmacophore-based approach and applied in a large-scale in silico database screening for small molecule inhibitors against TMPRSS2. A number of novel inhibitors were identified, providing starting points for further development of drug candidates for the treatment of COVID-19.

Effectiveness of Structured Physical Activity (PA) Interventions through the evaluation of PA levels, Adoption, Retention, Maintenance and Adherence Rates – A Systematic Review

Background: Structured physical activity (PA) interventions can potentially be implemented in a variety of facilities, and therefore can reach a large proportion of the population. The effectiveness of interventions is historically evaluated through examination of group differences in outcome measures. Often the proportions of individuals meeting thresholds for PA outcomes related to intervention implementation are not considered. Our aim was to summarise the effectiveness of structured interventions through reported group differences in outcomes, adoption and maintenance rates, and adherence and retention rates, providing information on intervention feasibility. Methods: Database screening resulted in the inclusion of 12 interventions. Results: There was a tendency for structured programmes to result in a significantly greater increase in PA levels than the control conditions in the short-term, with more varying results in the long-term. Only 3 studies published adoption and maintenance rates. On average 67±16% of participants were reported as adopting PA, with only 29±13% maintaining this effect. A mean retention rate of 75±13% was observed, and 61±21% of intervention sessions were attended as described through adherence rates. Conclusion: Structured interventions were classified as overall effective in short-term on the basis of group differences in PA levels; however, adoption and maintenance rates were rarely reported.

VP54 Digital Tools For More Efficient Conduct Of RCTs: Trials Unit Survey

IntroductionRecruitment of participants to, and their retention in, Randomized Controlled Trials (RCTs) is a key determinant of research efficiency, but is challenging. Digital tools and media are increasingly used to reduce costs, waste and delays in the conduct and delivery of research. The aim of this UK Clinical Trials Unit (CTU) survey was to identify which digital recruitment and retention tools are being used to support RCTs, their benefits and success characteristics.MethodsA survey was sent to all UK Clinical Research Collaboration (UKCRC)-registered CTUs with a webinar to help increase completion. A logic model and definitions of a “digital tool” were developed by iterative refinement by project team members, the Advisory Board (NIHR Research Design service, NHS Trust, NIHR Clinical Research Networks and patient input) and CTUs.ResultsA total of 24/52 (46%) CTUs responded, 6 (25%) of which stated no prior use. Database screening tools (e.g. CPRD, EMIS) were the tool most widely used (45%) for recruitment and were considered very effective (67%). The most mentioned success criteria were saving GP time and reaching more patients. Social media was second (27%), but estimated effectiveness varied considerably, with only 17% stating very effective. Fewer retention tools were used, with SMS / email reminders reported most (10/15 67%), but certainty about effectiveness varied. A detailed definition on what constitutes a digital tool with examples and a logic model showing relationships between the resources, activities, outputs and outcomes for digital tools was developed.ConclusionsDatabase screening tools are the most commonly used digital tool for recruitment, with clear success criteria and certainty about effectiveness. Our detailed definition of what constitutes a digital tool, with examples, will inform the NIHR research community about choices and help them identify potential tools to support recruitment and retention.

Virtual Database Screening Algorithm for the Detection of Practically Valuable Proteins of Bovine and Pig Lungs

Abstract-The algorithm of the virtual database screening for the detection of proteins with the practical significance for the pharmaceutical and biotechnological industries has been developed. The Pythom programming language v. 3.6.5 in Notepad++ framework was used to develop the algorithm. The UniProt database served as a source of the information about the structure of the proteins comprising the bovine and pig lung proteome, and the open DrugBank database was used to the subsequent search for matches in the protein structures. The virtual screening allowed to detect more than 5,500 proteins which are present in the proteome of bovine and pig lungs; the assessment of the practical significance was absent in 99% of the proteins, although it resulted from the manual search in the DrugBank database that some of them were parts of drags. The algorithm also made it possible to find out target proteins for drags in the human lung proteome, which were similar with those contained in the bovine (46) and pig (84) lung proteome. Paired alignment of amino acid sequences was used to compare the human and animals' target proteins. In the end, the developed algorithm for virtual screening allowed to identify in the first approximation the proteins with practical significance that are in varying degrees included in the farm animals' lung proteome. In the future, the more detailed screening will be possible due to the algorithm optimization and use of closed databases, which will provide more complete information about practically valuable proteins for biotechnology and medicine. proteome, database, DragBank, UniProt, virtual screening, Python, lungs The work was carried out with financial support by Russian Foundation for Fundamental Research and the administration of the Volgograd region within the framework of the scientific project No. 18-44-343003