Academic Integrity, Moral Courage, and Whistleblowing in Student Research

Academic integrity, moral courage, and whistleblowing are interrelated concepts in higher education. This chapter explores these concepts and inter-relationships in the context of medical student research. Producing robust research requires an ethical values foundation, stimulated and enhanced by training and mentoring. Unique to higher education is the relationship between academic integrity and research integrity due to the fact that research outputs such as abstracts, manuscripts, and theses are often curricular requirements with formal summative assessment. Accordingly, research integrity issues such as fabrication, falsification, plagiarism, deception, and conflict of interest automatically become academic integrity issues for medical school teachers and administrators to adjudicate. Medical students who witness research misconduct can feel morally distressed about the observations and their duty to report the behavior during their already stressed academic pursuit of graduation and medical practice. Accordingly, this chapter discusses student struggles with moral courage, courage building, and students as whistleblowers, providing guidance to trainees and the higher education system. Overall, a system which trains, models ethical behavior, and supports and protects students is a system which builds moral courage and promotes academic and research integrity. A net benefit for medical students and newly graduated physicians is the ability to use their moral courage skills when faced with clinical dilemmas. Student researchers in other fields also benefit as they, too, are better prepared for future professional practice.</p

The effect of the COVID-19 pandemic on deceased and living organ donors in the United States of America

Abstract A life-saving treatment, solid organ transplantation (SOT) has transformed the survival and quality of life of patients with end-organ dysfunction. The coronavirus disease (COVID-19) pandemic has impacted the practice of deceased and living donations worldwide by various resource shifting, including healthcare personnel and equipment such as ventilators and bed space. Our work explores the COVID-19 pandemic and global transplant data to create a statistical model for deducing the impact of COVID-19 on living donor and deceased donor transplants in the United States of America (USA). In severely impacted regions, transplant centers need to carefully balance the risks and benefits of performing a transplant during the COVID-19 pandemic. In our statistical model, the COVID cases are used as an explanatory variable (input) to living or deceased donor transplants (output). The model is shown to be statistically accurate for both estimation of the correlation structure, and prediction of future donors. The provided predictions are to be taken as probabilistic assertions, so that for each instant where the prediction is calculated, a statistical measure of accuracy (confidence interval) is provided. The method is tested on both low and high frequency data, that notoriously exhibit a different behavior

<i>HOTAIR</i> levels are decreased in BAVs and stretched AVICs.

<p>A. qPCR demonstrates that BAV leaflets have 69.3% lower levels of <i>HOTAIR</i> as compared to normal aortic valve leaflets (p = 0.08) n = 4. B. Cyclic stretch reduced <i>HOTAIR</i> levels by 67% (p<0.05) n = 3.</p

The Long Non-Coding <i>HOTAIR</i> Is Modulated by Cyclic Stretch and WNT/β-CATENIN in Human Aortic Valve Cells and Is a Novel Repressor of Calcification Genes

<div><p>Aortic valve calcification is a significant and serious clinical problem for which there are no effective medical treatments. Individuals born with bicuspid aortic valves, 1–2% of the population, are at the highest risk of developing aortic valve calcification. Aortic valve calcification involves increased expression of calcification and inflammatory genes. Bicuspid aortic valve leaflets experience increased biomechanical strain as compared to normal tricuspid aortic valves. The molecular pathogenesis involved in the calcification of BAVs are not well understood, especially the molecular response to mechanical stretch. <i>HOTAIR</i> is a long non-coding RNA (lncRNA) that has been implicated with cancer but has not been studied in cardiac disease. We have found that <i>HOTAIR</i> levels are decreased in BAVs and in human aortic interstitial cells (AVICs) exposed to cyclic stretch. Reducing <i>HOTAIR</i> levels via siRNA in AVICs results in increased expression of calcification genes. Our data suggest that <b>β</b>-CATENIN is a stretch responsive signaling pathway that represses <i>HOTAIR</i>. This is the first report demonstrating that <i>HOTAIR</i> is mechanoresponsive and repressed by WNT <b>β</b>-CATENIN signaling. These findings provide novel evidence that <i>HOTAIR</i> is involved in aortic valve calcification.</p></div

Calcification Genes upregulated in <i>HOTAIR</i> siRNA microarray dataset.

<p>Calcification Genes upregulated in <i>HOTAIR</i> siRNA microarray dataset.</p

<i>HOTAIR</i> levels are decreased in BAVs and stretched AVICs.

<p>A. qPCR demonstrates that BAV leaflets have 69.3% lower levels of <i>HOTAIR</i> as compared to normal aortic valve leaflets (p = 0.08) n = 4. B. Cyclic stretch reduced <i>HOTAIR</i> levels by 67% (p<0.05) n = 3.</p

AVICs exposed to cyclic stretch or <i>HOTAIR</i> siRNA have increased expression of <i>ALPL</i> and <i>BMP2</i>.

<p>A and B. Human AVICs exposed to 14% stretch for 24 h have increased <i>ALPL</i> and <i>BMP2</i> mRNA levels, 50% and 77% respectively, as compared to static controls. N = 6. C and D. AVICs transfected with <i>HOTAIR</i> siRNA have more <i>ALPL</i> and <i>BMP2</i>, 6.06 fold, and 66% increase respectively, as compared to AVICs transfected with scramble control. N = 3. #P<0.005, ∧p<0.0001.</p

Proposed mechanism by which stretch-mediated repression of <i>HOTAIR</i> is involved in aortic valve calcification.

<p>Proposed mechanism by which stretch-mediated repression of <i>HOTAIR</i> is involved in aortic valve calcification.</p

WNT/β-CATENIN signaling modulates <i>HOTAIR</i>, <i>ALPL</i>, and <i>BMP2</i> levels.

<p>A. AVICs exposed to cyclic stretch have 39% increased <b><i>β</i></b><i>-CATENIN</i> mRNA levels as compared to static controls. N = 6. B. <i>Cyclin D1 (CCND1)</i> levels were examined in stretched AVICs since it is a known WNT<b>/β</b>-CATENIN target gene. Stretched AVICs have 91% increased <i>CCND1</i> expression as compared to static controls. N = 4. C. Treatment with WNT agonist is sufficient to repress <i>HOTAIR</i> by 50% as compared to DMSO treated controls. N = 3. D and E. AVICs treated with WNT agonist have increased <i>ALPL</i> and <i>BMP2</i>, 87% and 9.5 fold respectively. N = 3. *</p