ETD -- Graduate theses

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    Exploring the Impact of Patient Race on Cancer Genetic Counselors’ Use of Polygenic Risk Scores for Risk Assessments and Prevention Strategy Discussions
    (Johns Hopkins University, 2023-12-15) Lin, Yifei Sylvia; Helzlsouer, Kathy J; Persky, Susan; Jamal, Leila
    Background: Polygenic risk scores (PRS) are clinically available for risk stratification to guide prevention and screening management in oncology, but the impact of PRS on genetic counselors’ clinical judgments remains unknown. Most data used to generate PRS come from populations of European descent, raising concerns about the contribution of PRS to existing health disparities. The conflation of race, a social construct, with ancestry, a biological construct, adds to the complication and confusion of the information carried by race in clinical genomics. Method: A randomized trial was conducted to explore the influence of patient race and provision of PRS on risk assessments and management decisions. From June to July 2023, 170 cancer genetic counselors were presented with one of two sets of vignettes of cancer genetic counseling via an online survey, using breast cancer as the example, with the only difference of patient race (White vs Black). Results: PRS that elevated or lowered risk relative to the standard of care model, Tyrer-Cuzick, were associated with corresponding increases and decreases in risk assessments and levels of support for prevention strategies, respectively. Patient race did not impact pre- and post-PRS assessment or levels of support for prevention strategies except for prophylactic mastectomy. Few genetic counselors recommended prophylactic mastectomy, but some genetic counselors were slightly more likely to recommend prophylactic mastectomy to Black rather than White patients regardless of whether PRS predicted higher or lower lifetime risk than Tyrer-Cuzick model, but the statistically significant differences have complex patterns. Participants with higher ratings of confidence and beliefs of the utility of PRS were more likely to change their risk assessments and level of support for prevention strategies after access to PRS information. Conclusions: It is critically important to further investigate how PRS influence the interpretation of risk and clinical management and to demonstrate the clinical utility prior to widespread adoption. This study emphasizes the need to inform considerations for the development of PRS educational resources, practice guidelines, and workforce preparation.
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    Exploring the Nature and Outcomes of Genetic Counseling Students' Nonverbal Behaviors During Simulated Telehealth Visits
    (Johns Hopkins University, 2023-12-14) Stearns, Emily; Lowe, Chenery; Roter, Debra; Persky, Susan; Erby, Lori
    Objective: To examine the relationships between nonverbal communication, verbal communication, and patient satisfaction during telehealth sessions with standardized patients and genetic counseling students. Methods: From 2021-2022, 59 genetic counseling students from the U.S. and Canada completed video-recorded standardized patient sessions via Zoom. Session recordings were coded using the Roter Interaction Analysis System (RIAS) and standardized patients completed post-session satisfaction questionnaires. Nonverbal communication coding methods were developed to measure several nonverbal behaviors (nodding, smiling, hand gesturing, eye gaze, forward lean, distance from the camera, camera angle, and use of screensharing). Twelve “thin slices” were systematically sampled from moments throughout each baseline session, for a total of five minutes and 45 seconds sampled from each session. Behaviors were coded for each thin slice sample. Multiple linear regression models assessed relationships between the students’ nonverbal behaviors, students’ verbal behaviors, and standardized patients’ satisfaction with session communication. Results: Increased screensharing was associated with decreased use of facilitating statements (p<0.05), decreased patient-centeredness (p<0.01), and increased verbal dominance (p<0.05). Nodding was negatively correlated with verbal dominance (p<0.05). Forward lean was positively correlated with standardized patient satisfaction with communication (p<0.05). Conclusion: Screensharing, nodding, and forward lean may affect patient-provider communication via telehealth in ways that are analogous to in-person clinical interactions. Practice implications: The possible negative consequences of screensharing suggest a need for additional research to inform best practices for providing patient-centered care in the telehealth setting.
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    Exploring Patient Perceptions of Emerging Gene Therapies for Arrhythmogenic Right Ventricular Cardiomyopathy
    (Johns Hopkins University, 2023-12-11) Schopp, Emma Marie; James, Cynthia; Jamal, Leila; Turriff, Amy
    No disease-specific therapy currently exists for arrhythmogenic right ventricular cardiomyopathy (ARVC), a progressive cardiogenetic condition conferring elevated risk for sudden cardiac death. Emerging gene therapies for ARVC have the potential to fill this gap. However, little is known about how adults with ARVC, or any other inherited cardiomyopathy or arrhythmia syndrome, appraise the risks and benefits of gene therapy research and which considerations influence their decisions about clinical trial participation. Twenty adults with clinically diagnosed and gene positive ARVC participated in semi-structured interviews that explored perceptions of gene therapy and hypothetical decision making around gene therapy clinical trial participation. Transcripts of these interviews were qualitatively coded and abductively analyzed. Participants exhibited enthusiasm for gene therapy with varied levels of interest in research participation. Patients considered perceived disease severity, level of adaptation to disease, level and nature of personal ARVC community involvement, coping styles, and life stage as relevant to decision making about trial enrollment. Clinical severity metrics had little association with interest in participation. Potential ethical concerns included patient vulnerability and extreme trust in clinical teams collaborating on industry-led trials. These findings are relevant for the informed consent process, particularly as some community expectations were at odds with those of researchers. Trial characteristics that mattered to participants included trial stage, perceived participation burden, degree of clinician and researcher trust, and anticipated future cost of gene therapy. Insights from this study may affect trial planning and communication with participants who have inherited cardiac conditions.
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    THE ELICITATION OF AND RESPONSE TO GUILT AND SHAME IN GENETIC COUNSELING COMMUNICATION
    (Johns Hopkins University, 2023-12-11) Jain, Ananya; Erby, Lori; Roter, Debra; Lowe, Chenery
    Guilt and shame are emotions that may arise in genetic counseling sessions; however, little is known about the way genetic counselors elicit and respond to client disclosure of guilt and shame. The purpose of this mixed methods study was to qualitatively describe the context and communication dynamics of guilt and shame in simulated genetic counseling sessions and quantitatively assess session-level simulated client and genetic counselor communication patterns associated with the disclosure and depth of conversation surrounding guilt and shame. Finally, we qualitatively characterized dialogue preceding disclosure. This study was informed by the social cognitive processing model (SCPM), emotion theory and a sequential approach to studying patient-provider interactions. The data for this secondary analysis was drawn from genetic counseling session transcripts from the Genetic Counseling Video Project and Genetic Counseling Student Video Project. Coding and subsequent thematic analysis of the transcripts containing instances of guilt and shame were used to address the qualitative aims of the study. To address the quantitative aim of the study, linear and logistic regressions assessed the relationship between quantitative measures of communication and the disclosure of shame and guilt. Simulated clients disclosed guilt or shame in 14 of the GCSVP sessions and 15 of the GCVP sessions, totaling 29 out of the 311 (9.32%) analyzed sessions. Qualitative analyses showed a variety of approaches taken by genetic counselors to elicit and respond to guilt and shame. In many cases, there were indicators of therapeutic relationship building prior to the disclosure. Genetic counselors and genetic counseling (GC) students' responses to the disclosure varied, with some genetic counselors providing little to no direct response and others attempting multiple interventions to address the simulated client's guilt. Quantitative analyses suggested that verbal dominance and the patient centeredness were significantly associated with the elicitation of guilt or shame and the length of discussion around these emotions in a session. This study is a first step towards identifying communication practices that facilitate disclosure and exploration of feelings of shame and guilt in simulated genetic counseling sessions, which may ultimately help to inform guidelines for guilt and shame counseling for genetic counselors and students.
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    MEASURING GENETIC COUNSELOR GOAL ADAPTATION AT THE INITIATION OF THE GENETIC COUNSELING SESSION
    (Johns Hopkins University, 2023-12-07) Guille, Liam Joseph; Jamal, Leila; Benjamin Neelon, Sara
    As demand for genetic counseling services continues to rise, there is an increasing need to develop models of practice to enable genetic counselors to practice at the top of their scope. To this end, the Reciprocal Engagement Model (REM) and its associated 17 genetic counseling goals have been developed to define genetic counselor practices and support the development of genetic counseling outcomes. The REM and its goals emphasize the need for genetic counselors to dynamically tailor their interactions to patient needs. However, the limited research that exists suggests genetic counselors may only marginally change their communication strategies to adapt to expressed patient needs. In this cross-sectional mixed-methods study, genetic counselors responded to simulated referrals and patient vignettes, ranking REM goals and providing recorded responses to assess goal adaptation to patient distress. Participants also provided debriefing responses to generate context and elaborate strategies they utilized in reranking these goals. Participation was open to currently practicing genetic counselors in the United States and Canada between June 1st to October 31st, 2023. 38 responses were included in the quantitative ranking analysis while 34 qualitative responses were analyzed. Counselors exhibited ranking differences in 5 of the REM goals with two goals having significant pairwise comparisons between specific arms of the study. Qualitative analysis of contracting responses showed more emotionally resonant language used by counselors to address the distressed patient, while debriefing responses provided additional context to reranking strategies and potential future directions for development of the REM. These results indicate genetic counselors recognize the need to adapt to stated patient needs while also suggesting further development opportunities for the REM.
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    Association between same-sex experience and prevalence of subclinical cardiovascular disease among U.S. adults, 1999 – 2004
    (Johns Hopkins University, 2023-12-11) Hwahng, Sel J; Rooney, Mary; Selvin, Elizabeth
    Background: Previous literature has indicated higher levels of cardiometabolic risk factors and cardiometabolic-associated biomarkers among sexual minorities than heterosexuals. It is thus important to examine if there is a corresponding higher prevalence of subclinical cardiovascular disease among sexual minorities. No previous studies have examined the prevalence of subclinical cardiovascular disease among a representative population of adult sexual minorities. We hypothesized that persons reporting any lifetime same-sex experience (SSE) would have higher burden of subclinical cardiovascular disease than heterosexuals. Methods: We conducted a cross-sectional study of 5,938 participants aged 20 to <60 years without cardiovascular disease in the National Health and Nutrition Examination Survey 1999-2004. We used multivariable logistic regression to evaluate the association of any lifetime SSE with elevated high-sensitivity cardiac troponin T (hs-cTnT), high-sensitivity cardiac troponin I (hs-cTnI), and N-terminal B-type natriuretic peptide (NT-proBNP), biomarkers of cardiovascular disease. Results: The prevalence of SSE was 5%. After adjustment for confounders, we found no statistically significant associations between SSE and elevated levels of hs-cTnT, hs-cTnI, or NT-proBNP. Effect estimates for hs-cTnT were attenuated from the unadjusted model after adjusting for demographics (Model 1 OR 95% CI: 0.48 [0.23, 1.00]) and additional behavioral and cardiometabolic risk factors (Model 2 OR 95% CI: 0.48 [0.23, 1.02]). For hs-cTnI and NT-proBNP, respectively, there were no notable patterns from the unadjusted (OR 95% CI: 0.76 [0.34, 1.69]) to the adjusted models (Model 1 OR 95% CI: 0.78 [0.35, 1.73]; Model 2 OR 95% CI: 0.76 [0.33, 1.74]) and from the unadjusted (OR 95% CI: 0.68 [0.40, 1.15]) to the adjusted models (Model 1 OR 95% CI: 0.68 [0.42, 1.09]; Model 2 OR 95% CI: 0.66 [0.41, 1.05]). Conclusion: Counter to our hypothesis, we did not find evidence to suggest that persons reporting SSE had a higher burden of subclinical cardiovascular disease. Future research is needed to characterize the burden of subclinical cardiovascular disease among sexual minorities using contemporary data collected from a sizable sample of older adults.
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    Using Metaphor Analysis to Understand Individuals’ Personal and Familial Experiences with Behavioral Variant Frontotemporal Dementia
    (Johns Hopkins University, 2023-12-07) May, Makenna Lauren; Owczarzak, Jill; Cho, Megan
    Frontotemporal dementia (FTD) is a disease that causes changes in behavior, personality, and language. As researchers better understand the genetic component of FTD, rates of asymptomatic and symptomatic genetic testing are increasing, making it more important to understand the impact of genetic diagnosis on lived experience. Individuals with genetic conditions often use metaphors when they describe their illness experiences. This qualitative study explores how individuals use metaphors to describe personal and familial experiences with behavioral variant FTD (bvFTD) in order to understand what themes may arise in genetic counseling sessions and to accordingly tailor clinical care. The data for this analysis comes from two study populations: asymptomatic individuals with a confirmed genetic risk for bvFTD (n=16) and diagnosed individuals (n=9). Secondary analysis of 25 semi-structured interviews was completed. Abductive analysis and metaphor analysis were used to identify the primary metaphors participants used to describe their experiences with bvFTD. Two of the main themes expressed by metaphors, lack of control over the disease and uncertainty of inheritance and symptoms, consistently conveyed that participants were grappling with how to understand their pasts, presents, and futures. This study suggests that metaphors can provide valuable insight into how patients are revising their life stories when bvFTD causes biographical disruption. These findings have important implications for clinical and research genetic counselors working with individuals with neurodegenerative conditions.
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    Genetic Diagnosis, Bodies, and Envisioned Family: Assemblage Perspectives on Reproductive Planning Within Inborn Errors of Immunity
    (Johns Hopkins University, 2023-12-04) Davidson, Hannah Rochelle; Owczarzak, Jill L; Jamal, Leila; Mueller, Rebecca; Similuk, Morgan N
    Incompletely penetrant and variably expressive conditions expand our understanding of living with a disease-causing genetic variant and potentially complicate patients’ reproductive and family planning processes. The experience of living with a heritable condition, or experiential knowledge, can itself inform reproductive decisions. However, accounts of experiential knowledge and reproductive planning fail to adequately describe the uncertainties experienced by people living with incompletely penetrant and variably expressive conditions. To address this gap, we conducted a qualitative, cross-sectional study that used assemblage theory to render the impacts of experiential knowledge on reproductive planning more visible for individuals living with Inborn Errors of Immunity (IEI) that exhibit incomplete penetrance and variable expressivity. By emphasizing the distribution of agency and action across systems, processes, and relationships, assemblage theory invites novel ways of understanding the role of experiential knowledge on reproductive planning. Eligible participants were between ages 18 and 48, with a diagnosis of either GATA2 deficiency, PIK3CD gain-of-function disorder, or CTLA4 deficiency. Using an abductive thematic approach, attention was paid to the people, ideas, and non-human objects embedded within participants’ accounts of disease experience and reproductive planning. This analysis presents three key findings, namely that: 1) genetic diagnosis invited renegotiation and revision of illness in family context; 2) the body was understood as an uncertain resource from which to plan reproductive futures, including consideration of artificial reproductive technologies (ART), and 3) participants reconciled conflicts between experiential knowledge and their reproductive hopes through considering “hypothetical children”. By provoking renegotiation, uncertainty, and imagination in reproductive planning, these objects illustrate how disease experience can be conceptualized as an assemblage of human and non-human objects.
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    Challenging the American Mental Health Paradigm: Acknowledging Collective Experience
    (Johns Hopkins University, 2023-12-12) Camitan, Maria; Rieder, Travis; Geller, Gail
    Mental health remains one of the most neglected areas of American healthcare. By now, many are aware that the COVID-19 pandemic led to a sharp increase in cases of anxiety and depression, thereby exacerbating the outcomes of a long-standing mental health crisis. In this thesis, I address a pressing concern: racial and ethnic minority populations are experiencing disproportionately worse mental health outcomes, yet are less likely to have access to, seek out, and utilize effective resources. Modern mental health care has had devastating consequences on the health of minority populations. Although it is well documented that structural racism underlies the inequities experienced across all areas of healthcare, the current mental health paradigm is not meeting the needs of communities disproportionately affected by the mental health crisis. The purpose of this thesis is to reframe mental health from a sociopolitical lens and address the unique barriers that prevent people of color from utilizing mental health resources. In this paper, I argue that we ought to rethink the current mental health care paradigm by shifting from an individualistic to collective understanding of mental health, and challenging traditional roles of psychotherapists where I offer the view that psychotherapy can serve as a form of social activism.
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    Evaluating Improvements and Challenges in Affinity Chromatography for AAV Purification
    (Johns Hopkins University, 2023-07-31) Dachenko, Alexandra; Betenbaugh, Michael; Hadidi, Mahsa
    Purification process development is crucial to the Research and Development (R&D) sector in the biotechnology industry by designing and optimizing downstream unit operations capable of manufacturing safe treatments for clinical trials. Purification is crucial in manufacturing therapeutics such as monoclonal antibodies (mAbs), mRNA, viral vectors, and non-viral vectors. Recently, viral vector gene therapy modalities using adeno-associated viruses (AAVs) have been shown to be an effective therapeutic agent for both rare and common diseases in humans. One of the key polishing steps in the downstream manufacturing process of AAVs is affinity chromatography, where a ligand with specific binding affinity to an AAV serotype is coupled to a base matrix that separates AAVs from host cell contaminants produced in the cell culture process. Column resin is the most common affinity chromatography matrix, but it possesses mass transfer limitations. This report evaluated a prototype affinity membrane device coupled with AVB ligand designed to overcome these mass transfer limitations and decrease process times, while yielding comparable AAV recovery and purity to column resin. The evaluations included dynamic binding capacity (DBC) studies, ligand lifetime studies, and buffer optimizations. The performance of the device was compared to control experiments using two common column resins with the same ligand as the device. The novel membrane device can bind at least 2e14 vg/mL_membrane and can undergo at least 3 cycles without a major binding capacity drop. The recovery of AAV is comparable to column resins; additional process development studies were required to increase recovery values because process parameters used for resin with the same ligand were not effective. A comparison of AAV product purity cannot be made because impurity profiles were not tested. Some recommendations for future work with the availability of more devices include more DBC studies, buffer optimization studies, and testing of the device performance with different AAV serotypes and load material. The prototype membrane device offers unique benefits over column resin for affinity chromatography in its fast flow rates, reusability, and potentially lower costs due to its “prepacked” design; however, the evaluations demonstrated the device does not provide significant enough process improvements that would favor its implementation in place of column resin for the tested material.
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    Assessing the Effectiveness of U.S. Financial Regulations: A Comparative Analysis with E.U. Responses
    (Johns Hopkins University, 2023-09-12) Fassas, Vassilios A.; Wolfson, Dorothea; Rosenthal, Alexander; Harris, Doug
    This paper assesses the effectiveness of US financial regulation in carrying out its intended purpose, namely, to adequately protect investors from industry abuse, insider advantages, and fraud. Reviewing recent financial crises, the role of the SEC, high profile Supreme Court cases, and legislation, such findings call into question the legitimacy of the financial system as a whole and is worrying due to Americans’ sheer reliance on banks and securities markets. Furthermore, this paper then compares the U.S. regulatory response with that of the E.U. as a result of the Global Financial Crisis and found that E.U. regulations are more clear, more potent, and more effective in handling and preventing financial crises. This paper uses statistical data, legislative analysis, and testimonial evidence to conclude that there are severe ways in which the US regulatory regime is lacking. Particularly, through vague laws that do not take proper measures to adequately protect against a future crisis, along with the evaluation of the capacity of the SEC to enforce the financial laws in question, US financial regulation does not effectively carry out its intended purpose.
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    PROJECTING LEADERSHIP: THE INTERPLAY OF PERSONALITY AND POLICY IN U.S. PRESIDENTIAL CAMPAIGNS
    (Johns Hopkins University, 2023-08-31) Broadus, Twais; Wolfson, Dorothea; Rosenthal, Alexande
    This study delves into the intricate nexus between personality traits in politics and their influence on electoral outcomes, specifically within the context of U.S. presidential elections from 2000 to 2020. The research utilizes a three-pronged approach: a content analysis of presidential debates to discern strategic trait-mentions, an examination of American National Election Study (ANES) data to capture voter evaluations of candidates based on specific traits, and an exploration of candidates' foreign policy emphasis, reflecting their projection of leadership. Key findings suggest Republicans consistently emphasize traits more than Democrats in debates, and there is noticeable variability in trait preference across partisan lines, particularly among Independents. A shift from domestic to foreign policy considerations was also observed over the years, indicating an electorate more cognizant of international influences on domestic policy. This change allows candidates to demonstrate their leadership skills through their stance on international matters. The culmination of these insights presents a comprehensive view, underscoring the dynamic interplay of candidate personality portrayals, voter preferences, and policy considerations in shaping electoral dynamics. The research emphasizes the imperative for political transparency and robust representation, aiming to demystify leadership roles and promote informed electoral choices for the greater societal benefit.
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    WHERE DO POLITICAL AND CORPORATE CAMPAIGNS CONVERGE AND DIVERGE?
    (Johns Hopkins University, 2023-08-16) Farrow, Monica R; Wolfson, Dorothea; Rosenthal, Alexander
    Abstract This review identifies specific articles and literature that provide insights into the history of and correlations between current political and corporate campaign strategies. The findings suggest that corporations should and do adopt some of the more refined campaign techniques used by political entities and that scholarly attention should be expanded to include more extensive reviews of corporate requirements in this area. The overarching goal of this study is to: (1) convey the history of both corporate and political marketing strategies, (2) summarize where political and corporate marketing constructs diverge, and (3) demonstrate the increasing converging entanglement of corporate and political marketing campaign tactics. This examination particularly highlights the more advanced methodologies utilized by campaign teams to galvanize the passions of the masses. While those in the political arena have accumulated considerable experience with these methodologies, corporations have made less use of certain types, and have, thus, failed to reap the benefits of their advanced techniques. The strategic parallels these institutions have shared for promoting acceptance and growth deserve intense analysis and reflection to determine how the tactics peculiar to their structures can be optimized to promote the success of each individually and both collectively. From the British East India Company’s take on lobbying to the corporate marketing campaigns of Bud Light, Chick Fil A, Delta, and Target, corporations and political factions have assumed vital roles in the development and continuing existence of our institutions, both public and private. This review will consider how the evolution and impact of societal sways have both informed and molded campaign strategies in both sectors. As a result, this analysis will, hopefully, help fill the void of academic information that is available in this area. Additionally, this examination will identify the parallels that exist between how the government achieves support of the population on the one hand with how corporations reel in clients on the other, (e.g., lobbying, PAC fundraising, targeting, messaging, third-party activists, and storytelling). This study will then concurrently seek to address insufficient research as relates to the importance of polling a population to assess the impact of corporate campaign messaging.
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    UNDERSTANDING AND IMPROVING DIVERSITY IN CLINICAL RESEARCH FOR BLACK PATIENTS: A QUALITATIVE META-ANALYSIS STUDY
    (Johns Hopkins University, 2023-08-14) Yogi, Sara Aiko; Kantor, Jeffrey
    Black patients remain underrepresented in clinical research, representing 5% of patients enrolled United States clinical trials (Alegria et al., 2021). Lack of diversity in clinical research creates blind spots about the effectiveness of treatments in underrepresented populations, resulting in substandard downstream care. Through analysis of available literature on Black patient engagement in clinical trials, proposals can be made to increase trial enrollment and equity. A qualitative meta-analysis was conducted to interpret research completed to date on increasing clinical research diversity for Black patients. A PubMed literature search yielded 720 possible articles, 35 were used for meta-analysis. Each article underwent multiphasic review to identify research characteristics; generate enrollment promotors and barriers, identify themes; identify significant findings across multiple articles; identify under-investigation and contradictory findings; and review solutions applicable for future research. Enrollment promotors included thorough explanation and information provision on study design, possible downstream beneficiaries; strong/longitudinal researcher-participant relationships and researcher-participant racial concordance; higher income and socioeconomic status of participants; research institution accessibility; compensation and increased study funding; community outreach and personal contact; and personal connections to research for both participants and researchers. Enrollment barriers included low income/socioeconomic status, low education, unfeasible time commitments, lack of transportation; lack of trust in medicine and clinical research teams; inadequate information on clinical research; studies requiring medical record review, blood samples, novel pharmaceutical interventions, and invasive procedures; and studies with comorbidities as exclusion criteria. Themes in research conducted to date include cancer research, investigations into Black women, and historical, structural, and personal factors. Historical factors that affect enrollment for Black patients include mistrust of the medical establishment, research institutions, and researchers. Structural barriers include income, socioeconomic status, time commitment and lack of transportation as well as exclusionary study designs and lack of resources for better clinical research engagement. Personal factors showcase the need for nuanced engagement around personal connections to research subjects, and benefits and pitfalls of utilizing religious institutions as partners depending on the research study subject. Solutions from current literature included better research explanation, improving diversity of clinical research teams, increasing interactive instruction, and using unique methods of increasing community around clinical research.
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    PERCEIVED COMPETITION, JOB PERFORMANCE, AND SENSE OF BELONGING AMONG RESEARCH ADMINISTRATORS
    (Johns Hopkins University, 2023-08-22) Hammett, Lauren Nicole; Woods, Marianne R; Kantor, Jeffrey
    Research administrators are personnel in the highly collaborative and ever-changing research enterprise. The focus on competition as a means to promote productivity has the potential to work against a perception of belonging that can motivate non-task-specific job performance that benefits the organization. This study investigated the perspectives of research administrators regarding the level of competition amongst coworkers in their work environments in relation to their level of perceived insider status and contextual performance. A sample of 112 adult research administrators employed in the United States from Johns Hopkins University and an online platform for research administrators, NCURA’s Collaborate, was used for hypothesis testing. Data were collected through a self-report survey hosted in Qualtrics. The results of Pearson’s correlation analyses found a significant positive association between competition influenced by coworkers and contextual performance. The simple linear regression analysis of competition influenced by coworkers and contextual performance indicated a statistically significant positive relationship.
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    SURVIVAL AND GROWTH OF NONPROFIT ORGANIZATIONS: A MIXED METHODS STUDY ON SMALL, RESEARCH FOCUSED NONPROFITS IN WASHINGTON, DC.
    (Johns Hopkins University, 2023-08-11) Howard, Rebecca; Kantor, Jeffrey
    Nonprofit organizations (NPOs) are created to carry out a beneficent purpose. Unlike the private sector, nonprofit organizations are purpose-driven so that profit is not the primary goal. Nevertheless, nonprofits require financial resources to operate and carry out their mission. The more financial resources a nonprofit has at its disposal the more mission-oriented success it can achieve. Nonprofits fundraise from a variety of sources and methods, including individual donations, government contracts, corporate giving, and many other sources. Although an abundance of literature exists on nonprofit management and governance, there is little on fundraising management, revenue optimization, and the drivers of financial success for nonprofits. This is surprising given the wealth of research focused on growing revenue and income in the private sector. The goal of this study was to investigate small, research-focused nonprofits based in Washington D.C. that significantly increased revenue in a short time. Qualitative and quantitative data was utilized in combination with mixed methods. Financial data alone was not enough to understand how nonprofits with substantial increases in annual revenue were able to achieve such fundraising success. Semi-structured interviews with nonprofit leaders were conducted to learn about fundraising strategies and best practices for income growth. The mixed methods of this two-part study revealed several common strategies and best practices among small, research-focused nonprofits in Washington, D.C. However, it was also apparent that each nonprofit required an individualized approach to fundraising based on the unique needs and structure of the organization.
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    THE ROLE OF PROJECT MANAGEMENT IN SPONSORED RESEARCH
    (Johns Hopkins University, 2023-08-09) Roig Vitali, Alexandra N; Qureshi, Saiqa A
    Project management provides guidance, direction, and tools for projects ranging in scope and complexity. The role of applying project management principles to sponsored research planning is a crucial factor in the success of most research, as well as an effective method to remain within the scope, schedule, and budget of the project. Project management techniques may be allusively applied to research as informal practice by the Principal Investigators (PI), rather than a Project Manager (PM). It is critical to understand that project management principles may not be applicable to all research ventures as the ambiguity and undefined goals surrounding some research are not conducive to the practices and procedures of project management. This study evaluates the role of project management in research through an in-depth literature review, as well as a survey questionnaire to the research community to evaluate to what extent is project management presently applied to research. The evidence gathered shows that project management is currently being applied by research professionals to a great extent for research projects leading to better results, and with better impact on timelines, and budgets. Consequently, researchers face a number of challenges such as administrative burdens, and lack of resources in staffing, capital, and technology. Two principal approaches to implementing a sound research management strategy are flexibility and an analysis of the requirements to identify the best approach. It is found that PIs are mostly taking on this decision, and ultimately driving the research planning, execution, and oversight, as well as conducting the research and evaluating results. PIs are overburdened, and applying project management principles may help alleviate project planning and execution.
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    THE RELATIONSHIP BETWEEN NIH PANDEMIC FUNDING AND RESEARCH PRODUCTIVITY
    (Johns Hopkins University, 2023-08-03) Clark, Tyler Bradford; Kantor, Jeffrey
    The COVID-19 pandemic has had a lasting effect on all aspects of society and required a quick response to stem the spread of the virus and mitigate its effects. In its efforts to combat the pandemic, the United States federal government appropriated research funding to the National Institutes of Health (NIH) to research the disease, its effects, and possible treatments. The NIH allocated this funding to its constituent institutes according to its mission, goals, and responsibilities in relation to the pandemic. This thesis utilized data from the NIH RePORTER website to analyze the overall changes in NIH funding for fiscal years 2017-2022. Additionally, an analysis of publication data for the same years was conducted to find a measure of research productivity over the course of the pandemic. The two analyses were then used to calculate the cost per publication for the NIH and its 27 constituent institutes. This study found that while the pandemic funding did result in a shift in NIH appropriations to its institutes, the publication costs were only indicative of a trend in research productivity for the NIH overall. A trend in publication costs could only be identified for specific institutes based on the relation of their focus of study to the pandemic.
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    CHARACTERIZING THE STRUCTURE OF THE TYPE III-B CRISPR-CAS CMR COMPLEX USING CRYO-EM
    (Johns Hopkins University, 2023-08-25) Durecki, Brynn; Bailey, Scott; Kavran, Jennifer
    CRISPR-Cas systems are adaptive immune systems found in prokaryotes. Since their discovery, many CRISPR-Cas systems have been characterized biochemically and structurally, and they are divided into two main classes based on their components. Class 1 CRISPR-Cas systems consist of multi-subunit effector complexes (Makarova et al., 2015). Within Class 1, Type III systems are among the most ancient and prevalent CRISPR-Cas complexes found in bacteria and archaea. Consisting of multiple protein subunits and a CRISPR RNA (crRNA), type III effectors specifically bind complementary target RNA, which activates both RNA and DNA cleavage activity to provide defense against invading nucleic acids (Hale et al., 2009; Samai et al., 2015). The subtype III-B complex structure has been solved in many organisms, but little is known about the structural and mechanistic details of type III-B CRISPR-Cas mediated immunity in the system Thermotoga maritima. Previous work in the lab has established the biochemical basis for RNA-activated DNA cleavage by a particular type III-B complex known as the Cas RAMP module (Cmr) in T. maritima, as well as the tolerance of mismatches between the crRNA and the target RNA to elicit this cleavage (Estrella et al., 2016; Johnson et al., 2019). The objective of this thesis was to characterize the structure of the Cmr complex using cryo-EM to validate this biochemical data. The complex was purified by affinity chromatography and analytical gel filtration, the samples were frozen at cryogenic temperature, the complex was imaged, and the resulting images were averaged and processed to obtain a 3D density map of the target unbound complex. We hoped to elucidate the precise catalytic mechanism of target RNA cleavage by the Cmr complex; however, due to low resolution, particle-limited maps and the formation of a sub-stoichiometric subcomplex, we were unable to see the molecular basis for the Cmr complex’s interference activity. Future experiments will focus on optimizing purification protocols and obtaining higher resolution target unbound and target bound structures to investigate specific interactions between the target RNA and key amino acid residues of the complex’s catalytic subunit, Cmr4. This work will not only provide the structural basis for CRISPR-Cas interference in an understudied organism, but it may also give insights that can inform the development of genetic engineering tools.
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    EXPLORATION OF CELL-BASED METHODS TO DISSECT LNCRNA-PROTEIN INTERACTIONS
    (Johns Hopkins University, 2023-08-23) Huang, Yuzhou; Hwang, Taeyoung; Leung, Anthony K. L.
    Long noncoding RNAs (lncRNAs) have been increasingly important in understanding regulations of gene expressions, thanks to the discovery of non-protein-coding genes and transcripts with the advent of high-throughput sequencing. It is known that most of the lncRNA functioning mechanisms involve interactions with RNA-binding proteins. Various in vitro experiments, such as in vitro transcribed RNA pulldown and electrophoretic mobility shift assay (EMSA), have been applied to study lncRNA-protein binding. However, the mechanisms of their interactions in the cell environment remain mysterious for most lncRNAs. Our goal is to explore cell-based methods to explore lncRNA-protein interactions. These include MPRNA-IP (Massively Parallel RNA Assay-Immunoprecipitation), a high throughput experiment developed by our lab, and CLIP-qPCR (Crosslinking Immunoprecipitation and qPCR) with RNA deletion mutants or RNase treatment. We focused on two lncRNA-protein interactions, cytosolic interaction NORAD-PUM2 and intranuclear interaction HOTAIR-EZH2. We detected a well-known PUM2-binding RNA sequence motif in NORAD, validating our methods for RNA-protein interactions. Regarding EZH2-HOTAIR interaction, our experiments showed that the EZH2 protein interacts with the 5’ end of lncRNA HOTAIR, as previous in vitro assays showed. But we unexpectedly identified that EZH2 also has a binding affinity with the middle region of HOTAIR while inside the cell nucleus. Taken together, our results present representative examples of applying multiple methods to study lncRNA-protein interactions inside the cells and provide new insights into the mechanism of lncRNA-protein interactions.