Preclinical Models and Resources to Facilitate Basic Science Research on Malignant Mesothelioma – A Review

Malignant mesothelioma is an aggressive cancer with poor prognosis, predominantly caused by human occupational exposure to asbestos. The global incidence of mesothelioma is predicted to increase as a consequence of continued exposure to asbestos from a variety of sources, including construction material produced in the past in developed countries, as well as those currently being produced in developing countries. Mesothelioma typically develops after a long latency period and consequently it is often diagnosed in the clinic at an advanced stage, at which point standard care of treatment, such as chemo- and radio-therapy, are largely ineffective. Much of our current understanding of mesothelioma biology, particularly in relation to disease pathogenesis, diagnosis and treatment, can be attributed to decades of preclinical basic science research. Given the postulated rising incidence in mesothelioma cases and the limitations of current diagnostic and treatment options, continued preclinical research into mesothelioma is urgently needed. The ever-evolving landscape of preclinical models and laboratory technology available to researchers have made it possible to study human disease with greater precision and at an accelerated rate. In this review article we provide an overview of the various resources that can be exploited to facilitate an enhanced understanding of mesothelioma biology and their applications to research aimed to improve the diagnosis and treatment of mesothelioma. These resources include cell lines, animal models, mesothelioma-specific biobanks and modern laboratory techniques/technologies. Given that different preclinical models and laboratory technologies have varying limitations and applications, they must be selected carefully with respect to the intended objectives of the experiments. This review therefore aims to provide a comprehensive overview of the various preclinical models and technologies with respect to their advantages and limitations. Finally, we will detail about a highly valuable preclinical laboratory resource to curate high quality mesothelioma biospecimens for research; the biobank. Collectively, these resources are essential to the continued advancement of precision medicine to curtail the increasing health burden caused by malignant mesothelioma.

Research Productivity and Citation Impact of Indian institutes of Science Education and Research

The paper’s main objective is to investigate the trends of basic science research in India using a combination of qualitative and quantitative approaches. It examines the publication patterns and impact of research productivity of five basic science institutions, i.e., “Indian Institutes of Science Education and Research” (IISER), namely IISER Kolkata, IISER Pune, IISER Mohali, IISER Bhopal, and IISER Thiruvananthapuram. The research output indexed in the SCOPUS bibliographic database of these five established IISERs was obtained from 2015 to 2019. A total number of 7329 research publications were analysed using various scientometric dimensions. This paper makes a concerted effort to present a comprehensive picture of the assessment of research outcomes at the five older IISERs, which are ostensibly India’s most active and prominent basic science research institutions. The findings reveal that these institutions are accountable for important research outcomes, such as a high number of citations, preferences towards open access (OA) publications, a rise in research publication year over year, a strong author network, a high degree of collaboration, and a high impact in terms of other scientometrics indicators. This paper discusses the findings of the research publications on the position of IISERs in basic sciences research and draws some conclusions about their effects.

CLRM-11. BENCH TO BEDSIDE NEURO-ONCOLOGY: ADVOCATING FOR A CLINICALLY RELEVANT STRATEGY AS UNDERSCORED BY THE PANDEMIC

INTRODUCTION The basic science research endeavor has been abundantly and astonishingly successful in the last three decades in elucidating the mechanisms of neuro-oncologic disease and in suggesting therapeutic strategies. Clinical successes have lagged behind, and translation of promising laboratory findings into clinical practice is rare. We hypothesize that one important reason for this discordance is the use of different paradigms for designing laboratory and clinical trials, and that utilizing clinically relevant procedures could improve laboratory study impact. METHODS We identified all pre-clinical neuro-oncology therapeutic trials published in four high-impact journals between 11/2018 and 4/2019 and assigned a level of evidence (LOE) to each study using the American Academy of Neurology evidence classification system. We then identified all phase III trials of therapeutics for COVID and performed the same analysis on all preclinical studies preceding the trials. RESULTS Of the 26 neuro-oncology articles identified, 85% had a LOE of IV and 15% were class III. An analysis of successful human trials showed significantly more high quality laboratory studies supporting “successful” compared to “unsuccessful” trials (p=0.048). This same pattern was identified in phase III trials of COVID. Twenty antiviral studies failed to meet the primary endpoint; all were preceded by class III or IV LOE preclinical studies. Eight evaluable phase three studies of COVID vaccines were identified, all of which met their primary endpoints. These were supported with a mix of Class I/II (n=4) and III/IV (n=4) preclinical studies. Higher LOE by AAN criteria is associated with successful COVID therapeutic trials (p=0.0034). CONCLUSIONS Despite rigorous, elegant, and enlightening laboratory experiments, successful translation to human therapeutics remains rare. Envisioning basic science research through the lens of clinical therapeutics represents a challenging but surmountable paradigm shift that may reverse this pattern and create a more successful research enterprise in neuro-oncology and beyond.

Changing Demographics of NIDDK-Funded Physician-Scientists Doing Kidney Research

BACKGROUND AND OBJECTIVES: While U.S. physician scientists have made enormous contributions to biomedical research, this workforce is thought to be getting smaller. However, among kidney researchers, changes have not been fully quantified. DESIGN: We mined NIH RePORTER to explore demographic changes of early career and established, physician and non-physician principal investigators doing kidney-focused research. We searched for NIDDK-funded K series and R01 awards focused on the kidney that were active between 1990 and 2020 and determined if their focus was basic or clinical science. We then used public databases available on the internet to determine if these funded investigators were physicians or non-physicians, the year in which received either their M.D. (physicians) or their terminal graduate degree (non-physicians), their sex and whether they received their terminal degree from a U.S. or an international institution. RESULTS: Kidney-focused R01-funded PIs are aging, particularly among physicians. Moreover, the relative representation of physicians among both early career and established PIs is falling, particularly among those doing basic science research. In contrast, the number and relative representation of non-physician scientists is increasing. There is also greater representation of women and international graduates among physician and non-physician R01-funded, kidney-focused NIDDK investigators. However, while there are greater numbers of women physician PIs doing both basic as well as clinical research, women physician PIs are increasingly more likely to do clinical rather than basic science research. CONCLUSIONS: The physician-scientist workforce is increasingly made up of women and international medical graduates. However, this workforce is older, and represents a smaller proportion of the total PI workforce, particularly among those doing basic science research.