Translational Science Center Research Articles

Altered transcriptomic immune responses of maintenance hemodialysis patients to the COVID-19 mRNA vaccine.

End-stage renal disease (ESRD) patients experience immune compromise characterized by complex alterations of both innate and adaptive immunity, and results in higher susceptibility to infection and lower response to vaccination. This immune compromise, coupled with greater risk of exposure to infectious disease at hemodialysis (HD) centers, underscores the need for examination of the immune response to the COVID-19 mRNA-based vaccines. The immune response to the COVID-19 BNT162b2 mRNA vaccine was assessed in 20 HD patients and cohort-matched controls. RNA sequencing of peripheral blood mononuclear cells was performed longitudinally before and after each vaccination dose for a total of six time points per subject. Anti-spike antibody levels were quantified prior to the first vaccination dose (V1D0) and 7 d after the second dose (V2D7) using anti-spike IgG titers and antibody neutralization assays. Anti-spike IgG titers were additionally quantified 6 mo after initial vaccination. Clinical history and lab values in HD patients were obtained to identify predictors of vaccination response. Transcriptomic analyses demonstrated differing time courses of immune responses, with prolonged myeloid cell activity in HD at 1 wk after the first vaccination dose. HD also demonstrated decreased metabolic activity and decreased antigen presentation compared to controls after the second vaccination dose. Anti-spike IgG titers and neutralizing function were substantially elevated in both controls and HD at V2D7, with a small but significant reduction in titers in HD groups (p<0.05). Anti-spike IgG remained elevated above baseline at 6 mo in both subject groups. Anti-spike IgG titers at V2D7 were highly predictive of 6-month titer levels. Transcriptomic biomarkers after the second vaccination dose and clinical biomarkers including ferritin levels were found to be predictive of antibody development. Overall, we demonstrate differing time courses of immune responses to the BTN162b2 mRNA COVID-19 vaccination in maintenance HD subjects comparable to healthy controls and identify transcriptomic and clinical predictors of anti-spike IgG titers in HD. Analyzing vaccination as an in vivo perturbation, our results warrant further characterization of the immune dysregulation of ESRD. F30HD102093, F30HL151182, T32HL144909, R01HL138628. This research has been funded by the University of Illinois at Chicago Center for Clinical and Translational Science (CCTS) award UL1TR002003.

515 Implementation of a Translational Science Research Center in a high education level institution in Colombia - Latin America: Unisabana Center for Translational Science (UCTS)

OBJECTIVES/GOALS: To establish and develop a high-level, dynamic, and self-sustainable Translational Science – research center in Colombia that promotes and articulates collaborative participation among different disciplines at Universidad de La Sabana to generate impactful solutions in health to transfer the knowledge to the local community. METHODS/STUDY POPULATION: With the support of core units of the University, internal funding was given for the establishment of the Research Center. An internal call was performed for recruiting researchers for multiple disciplines interested in joining the UCTS. After the researchers were selected, training of the research community in translational science and funding acquisition was performed towards the objective of interdisciplinary projects with impact in the local community. Project management strategies have been used for the follow-up of the advancements of the implementation of the UCTS. Operational structure and business plan for future self-sustainability are being designed. UCTS is proposed as an articulating party among different actors in clinics, research, and industry, for science and funding management. RESULTS/ANTICIPATED RESULTS: As an starting point, 8 research groups of different disciplines of the University have been integrated with the UCTS, increasing the research capacity in translational science. Internal administrative processes have been articulated within the institution and unified processes for international grants applications have been established in order to optimize the funding acquisition and management. Training programs for the research community, and community engagement activities have been offered as well. Networking relationships have been strengthened among the researchers enhancing international collaborations. Novel research projects are being designed towards real solutions in health for the local community, promoting the transference of knowledge from the benchside to the community. DISCUSSION/SIGNIFICANCE: The implementation of the UCTS led to the integration of disciplines within the University, towards new research projects with common interests for the local community. It has been an enriched experience using the project management approach, fulfilling a huge milestone for the University, aligned with the internal strategic priorities

Abstract 3558: An integrated data platform to support the international alliance for cancer early detection

Abstract Cancer early detection is one of the most critical areas of cancer research, as it offers the greatest potential for improving patient outcomes. The International Alliance for Cancer Early Detection (ACED) is a global partnership of world-leading cancer research institutions in the UK and US, established in 2019 to accelerate and revolutionize research in this field. ACED brings together the expertise of the Canary Center at Stanford University, the University of Cambridge, the Knight Cancer Institute at Oregon Health and Sciences University, University College London, and the University of Manchester, together with Cancer Research UK, with the goal of catalyzing new collaborations and research in the field of early detection. One of the major challenges to enabling international collaborations across different institutions is the ability to collect, share and discover datasets between researchers and institutions. To enable collaboration on innovative data science, fundamental functions include, 1) controlled data sharing mechanisms; 2) structured metadata to enable data exploration and data discovery; and 3) enabling easy computational access to that data. To advance researchers' collaboration, ACED began development of an Integrated Data Platform (IDP). The ACED-IDP is based on the Gen3 software platform developed by the University of Chicago's Center for Translational Data Science. Based on software systems originally developed for the NCI's Genomic Data Commons, Gen3 has been used in several other data projects including The Blood Profiling Atlas in Cancer (BloodPAC), Australian BioCommons and numerous other research data platforms. The unique nature of ACED required unique innovations to be made for the development of the IDP. Each of the member institutions within the alliance has different existing computer infrastructures, separate authentication platforms and heterogeneous data types forming the basis of their research. The IDP sought a cloud-ready strategy, while still being cognizant of the extreme costs associated with cloud egress fees that hamper researchers' ability to download data. Additions were made to the Gen3 platform to allow for hybrid cloud support, allowing on-premises as well as cloud object storage systems to be linked to the platform. This innovation permits each institution to share files using the mechanisms that they see fit. To unify the various datasets, the standard Gen3 schema was replaced with one derived from the Fast Healthcare Interoperability Resources (FHIR) standard. To support import from clinical data sets, tooling to enable import and export Observational Medical Outcomes Partnership (OMOP) data has been integrated. With this platform in place, we hope to advance international collaborations and accelerate early cancer detection research. Citation Format: Brian Walsh, Liam Beckman, JD Burchett, Matthew Peterkort, Jordan Lee, Michael Fitzsimons, Peter Vassilatos, Binam Bajracharya, Craig Barnes, Jawad Qureshi, Robert Grossman, Carrie Yakura, Yaozhi Lu, Sarah Burge, Daniel Kelberman, Erin Watson, Kyle Ellrott. An integrated data platform to support the international alliance for cancer early detection [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3558.

"Join the team" clinical research workforce development model: A new paradigm in healthcare career opportunities.

The University of California (UC) Davis Clinical and Translational Science Center has established the "Join the Team" model, a Clinical Research Coordinator workforce pipeline utilizing a community-based approach. The model has been extensively tested at UC Davis and demonstrated to generate a viable pathway for qualified candidates for employment in clinical research. The model combines the following elements: community outreach; professional training materials created by the Association for Clinical Research Professionals and adapted to the local environment; financial support to trainees to encourage ethnic and socioeconomic diversity; and internship/shadowing opportunities. The program is tailored for academic medical centers (AMCs) in recognition of administrative barriers specific to AMCs. UC Davis's model can be replicated at other locations using information in this article, such as key program features and barriers faced and surmounted. We also discuss innovative theories for future program iterations.

582-P: Exercise Training Reverses NAFLD in Mice with Obesity Independent of Changes in Hepatic Mitochondrial Oxidative Capacity

Obesity is a primary cause of hepatic lipid accumulation, leading to nonalcoholic fatty liver disease (NAFLD). As there are no FDA-approved therapies for NAFLD treatment, weight loss through lifestyle intervention is the first-line therapy. Exercise improves hepatic function in patients with obesity related NAFLD. However, the mechanisms whereby exercise mediates the enhancement of liver function are largely unknown. This study evaluated the impact of exercise training on NAFLD in mice with obesity. At 8 weeks of age, mice were randomized to low-fat (LFD) or high-fat diet (HFD). After 4 weeks of dietary intervention, mice were randomized to either control (SED) or exercise training (ExT) with experimental diet for 10 weeks. ExT mice completed 45 minutes of moderate-intensity treadmill running 4 days/week. Body weight was measured weekly, and body composition and maximal treadmill running were evaluated at weeks 0, 4, and 14. Blood lactate accumulation was measured during the final treadmill test. Mice were euthanized 48 hours after the last exercise session for liver histopathology, blood chemistry, and ex vivo mitochondrial function analysis. Liver function was assessed via serum liver panel and quantification of hepatic lipids. High-resolution respirometry was used to determine maximal hepatic fatty acid oxidation, NADH- and succinate-linked oxidative phosphorylation (OXPHOS), and electron transfer capacity in tissue homogenates. HFD increased body mass, which was reduced with ExT. ExT increased maximal running time independent of diet. HFD worsened lactate metabolism, which was improved with ExT. HFD increased liver weight, which was decreased with ExT. HFD-induced increases in hepatic lipid and serum ALT and ALP were reversed with ExT. Hepatic mitochondrial OXPHOS and electron transfer were reduced with HFD relative to LFD. These data suggest that exercise-induced reversal of NAFLD is not mediated by hepatic mitochondrial oxidative capacity. Disclosure E.C. Heintz: None. W.S. Dantas: None. J.E. Stampley: None. G.M. Davis: None. B.A. Irving: None. C.L. Axelrod: None. J.P. Kirwan: None. Funding Nutrition Obesity Research Center (P30DK072476); Louisiana Clinical and Translational Science Center (U54GM104940); Centers of Biomedical Research Excellence (P20GM103528)

Regulation of renal function by the peroxisome proliferator-activated receptor-alpha: A novel target for treating hypertension

Approximately 37 million people in the U.S. have chronic kidney disease, which is a major risk factor for cardiovascular and end stage renal diseases. We have identified a nuclear receptor, peroxisome proliferator-activated receptor – alpha (PPAR-α), that plays a major role in regulating renal glomerular filtration rate in an experimental model of hypertension. Targeting PPAR-α signaling provides novel therapeutic strategies for reducing hypertension associated chronic kidney disease. PPAR-α knockout (KO) mice exhibit increased renal inflammation and blood pressure response to Angiotensin II (Ang II). In this study, we investigated the role of PPAR-α in renal function in a mouse model of hypertension. Male 4-month-old wild type (WT) and PPAR-α KO mice were instrumented with radio transmitters by artery canulation (Data Science International). This method minimizes stress and artifacts by avoiding the use of tethering, restraining, or anesthetizing the mice during data sampling. After recovery from surgery, we continuously measured mean arterial pressure (MAP) via radio telemetry in conscious ambulatory mice. After baseline MAP was established, vehicle (Veh; saline) or Ang II were infused using an osmotic minipump at a slow pressor dose (400 ng/kg/min) for 12 days. On day 12, we injected an intravenous bolus of fluorescin-sinistrin (3.74 ml/g body weight) and collected 8 blood samples (20 μl/sample) during a 75-minute period to enable calculation of the glomerular filtration rate (GFR) using [GFR = I/(A/a + B/b]. Similar to our prior observations, no significant (ns) differences in baseline MAP were observed between WT and PPAR-α KO mice [(mmHg): WT (n=6), 111±20 vs. PPAR-α KO (n=6), 113 ± 10; ns] whereas after 12 days of the slow pressor effect of Ang II, MAP was increased in both strains [(mmHg): WT (n=8), 138 ± 11# vs. PPAR-α KO (n=8), 156 ± 16#; #p&lt;0.05 vs. basal, same strain]; however, the increase in MAP was greater in the PPAR-α KO (43 mmHg) compared to WT (27 mmHg) mice. The absence of PPAR-α reduced GFR by 24% under basal conditions [(μl/min): WT (n=3), 346 ± 20 vs. PPAR-α KO (n=3), 275 ± 27*, *p&lt;0.05 vs WT]. After 12 days of Ang II infusion, GFR was reduced in WT mice by 27% and did not further reduce GFR in PPAR-α KO mice [(μl/min): WT (n=6), 251 ± 11# vs. PPAR-α KO (n=6), 277 ± 61; #p&lt;0.05 vs. basal, same strain]. PPAR-α protects mice from worsening hypertension and is critical to preserving GFR during normotensive conditions. Ongoing studies are further investigating how PPAR-α regulates renal function. These finding suggest therapeutics designed to increase PPAR-α activity could have clinical benefit in chronic kidney disease. Howard University Research Centers at Minority Institutions, Georgetown-Howard Universities Center for Clinical and Translational Science, Howard University Aging Grant, K01HL092593 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

0828 Greater sleep variability is associated with higher systemic inflammation in type 2 diabetes

Abstract Introduction Circadian misalignment increased systemic inflammation in sleep experiments and in those performing shift work. Milder degree of circadian misalignment such as day-to-day shift in sleep timing, i.e. sleep variability, was related to inflammation in population studies. Further, other sleep disturbances and glycemic control can contribute to inflammation. This pilot study explored if sleep variability was associated with inflammation in type 2 diabetes (T2D). Methods Subjects included 35 non-shift working T2D patients with and without diabetic retinopathy (DR) who were participating in a clinical study (NCT04547439). Sleep pattern was assessed by 14-day actigraphy, yielding sleep duration and efficiency. Standard deviation of sleep duration across the night was used to represent sleep variability. Sleep apnea severity was assessed by an overnight home monitor. Neuropathy pain, statin use, serum creatinine, low-density lipoprotein (LDL), HbA1C and by high-sensitivity c-reactive protein (hs-CRP) were collected. Spearman’s correlation analyses and multiple regression analysis (using natural-log transformed values) were performed to establish an independent association between sleep variability and hs-CRP. Results Mean (SD) age was 54.3 (6.4) years, 54.3% were female and 62.9% had DR. Median (interquartile range) of sleep variability was 69 (56,84) minutes. Median A1C was 7.5 (6.6, 8.7)% and hs-CRP was 2.4 (1.4, 4.6) mg/L. Higher hs-CRP was significantly associated with higher sleep variability (r=0.342, p=0.04), HbA1c (r=0.431, p=0.01) and LDL (r=0.379, p=0.03), but not with sleep duration, sleep efficiency, sleep apnea severity, DR status or other variables. Multiple regression analysis showed that higher sleep variability (B = 0.91, p=0.034) and higher HbA1c (B = 1.51, p=0.035), but not LDL, contributed to higher hs-CRP. Conclusion Higher sleep variability in non-shift working T2D patients was shown to be independently associated with higher systemic inflammation, conferring higher cardiovascular risk. This data supports the role of even a mild degree of circadian misalignment on systemic inflammation. Further investigations are needed to determine whether sleep intervention to increase sleep regularity can reduce systemic inflammation and improve cardiometabolic health. Support (if any) NEI R01EY029782 The University of Illinois Chicago Center for Clinical and Translational Science, which is supported by the National Center for Advancing Translational Sciences (NCATS), National Institutes of Health, through Grant Award Number UL1TR002003.”

The catabolism of bilirubin to urobilin might be a leading factor in obesity-induced insulin resistance: New findings in human studies

For unknown reasons, plasma bilirubin levels are lower in obese humans and rodents. One possible explanation is that the hepatic expression of enzymes that regulate its half-life, such as the UGT1A1 UDP-glucuronosyltransferase, is higher in the obese compared to lean persons. Bilirubin is marked for excretion within the liver by the conjugation of two glucuronyl groups by UGT1A1, where it is then transported to the intestines by the biliary system. Once in the intestines, the gut microbiota containing bilirubin reductase remove the glucornyl groups and modify the structure to produce urobilin which can be absorbed via the hepatic portal vein and enter the systemic circulation. Previous correlation studies indicate that urobilin might be a factor that induces visceral obesity and cardiovascular disease. However, the physiological function of urobilin is unknown. The purpose of our study was to determine if there is a correlation between bilirubin and urobilin compared to adiposity and insulin resistance in lean and obese women and men. We hypothesized that bilirubin would be lower and urobilin higher in the plasma of obese humans compared to lean. We found that the plasma levels of urobilin and bilirubin are inversely correlated in women and men. Urobilin levels were positively associated with adiposity (BMI R 2 =0.29 and body fat percentage R 2 =0.25) and insulin resistance (blood glucose R 2 =0.05, insulin R 2 =0.22, and HOMA IR R 2 =0.18) in obese women. Urobilin was only correlated with adiposity in males (BMI R 2 =0.025 and body fat percentage R 2 =0.03). However, the males were not insulin resistant and had no significant difference in HOMA IR compared to lean men. In both women (BMI R 2 =0.065 and body fat percentage R 2 =0.05) and men (BMI R 2 =0.24 and body fat percentage R 2 =0.13), plasma bilirubin levels were negatively associated with adiposity. We observed that plasma bilirubin levels are negatively associated with adiposity, which has been previously reported. The new findings in our study indicate that urobilin is positively associated with adiposity and insulin resistance. Based on these data, we propose that bilirubin and urobilin are maintained at inverse levels in humans via the UGT1A1 axis and that activity is higher in the obese, reducing plasma bilirubin and providing more substrates to produce urobilin in the gut. These events cause an elevation in plasma urobilin levels that commence obesity-associated comorbidities. Future work to determine the role of urobilin in obesity-associated comorbidities such as insulin-resistant diabetes is warranted and may provide a biomarker for the early This work was supported by the National Institutes of Health R01DK121797 (T.D.H.J.). The sample collection was supported by the Center for Clinical and Translational Science (CCTS) grant UL1TR001998 at the University of Kentucky. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

86 A summer research experience to encourage URM students’ participation in health sciences research

OBJECTIVES/GOALS: To increase the diversity of the health sciences research workforce, students from a variety of backgrounds must have the opportunity to participate in hands-on research experiences that highlight translating science to treating human disease. We developed a mentored translational research program for students from VCU and central Virginia HBCUs. METHODS/STUDY POPULATION: The Wright Regional Center for Clinical and Translational Science collaborated with the existing VCU Honors’ Summer Undergraduate Research Program (HSURP) to expand their summer research experience to URM students from our partner HBCUs. For 10 weeks, students worked with faculty mentors to learn research techniques and engage in research projects. Students also participated in career development sessions like developing a CV and choosing graduate programs, and at the end of HSURP, they shared formal presentations of their research with peers and mentors. HSURP students were provided housing and a stipend, and mentors were provided a stipend. A post-program assessment gathered feedback on research and personal skills gained, the program’s influence on their career goals, and overall experiences with HSURP. RESULTS/ANTICIPATED RESULTS: Nine students, 7 from VCU and 2 from Virginia State University participated in HSURP. Students were rising sophomores, juniors, and seniors, and 5 had previous research experience. Students worked on projects ranging from basic to social behavioral, community-placed research. All students rated the program as good or excellent. Post-program assessments showed all students believed they had a better understanding of ethical responsibilities of researchers, relevance of community-engaged and clinical/translational research, and interpreting journal articles after participating in the program. Four students reported they plan to continue working on their research projects during the academic year, and all students strongly agreed or agreed that HSURP prepared them for graduate or professional schools. DISCUSSION/SIGNIFICANCE: A program that combines hands-on research training and career development opportunities provides a robust research foundation for URM students, which can increase their participation in the translational science workforce. Future program development will include preprogram training modules to better prepare students for research experiences.

190 Filling the Gap: Perspectives from a long-standing Community Engagement Advisory Board on conducting community-engaged research that emphasizes the needs of communities

OBJECTIVES/GOALS: Community Engagement Advisory Boards (CEAB) serve as a vital resource for engaging and partnering with communities in research. The purpose of this project is to describe the perspectives of members of a long-standing CEAB in providing input and promoting research that aligns with the needs, experiences, and concerns of the communities they represent METHODS/STUDY POPULATION: Three 90-minute focus groups were conducted with a subset of a CEAB(n=17)(M years spent with CEAB =7.3) affiliated with the Center for Clinical and Translational Science at the University of Illinois-Chicago. Members areas of expertise include perspectives from faith-based organizations, community organizing, public health and working with diverse populations. Transcribed audio recordings of the focus groups were coded using thematic analysis wherein two authors coded independently, followed by audited discussion and final consensus codes. Main themes were identified after reviewing final codes. RESULTS/ANTICIPATED RESULTS: CEAB members described the bi-directional nature of their role serving as a conduit between research institutions and their communities, identified strategies to promote research literacy in communities, called for researchers to take a proactive approach in forming and sustaining community partnerships, and helped identify opportunities to promote community engagement in more creative and feasible ways. Additionally, CEAB members identified perceived opportunities for the board as a whole to be more involved in Chicago communities to further their role as a liaison between the university and the community. DISCUSSION/SIGNIFICANCE: These findings may have implications for investigators to better address community priorities in research by understanding unique local realities as well as help other CTSA hubs’ to leverage their communities’ expertise.

146 A Community Engagement Advisory Board’s 22 Years of Contributions to Translational Research

OBJECTIVES/GOALS: CTSIs around the country rely on Community Engagement Advisory Boards (CEABs) to bridge research and communities. The history of this 22-year-old board offers insight on 1) how it was created and has been sustained over time 2) its evolution, and 3) members’views of their contributions to translational research at UIC. METHODS/STUDY POPULATION: As founding members began to step down from this long-standing board, we started to document its history and members’ narratives and perspectives of the work conducted at UIC since its inception. Using an Oral History methodology, we conducted three virtual focus groups with 13 short and long-term members (n=6, n=4, n=3) to learn about changes within CEAB and in members’ roles, and individual semi-structured interviews with three long-standing members to expand on the origin and evolution of CEAB. Focus group data was coded and analyzed. We also extracted data on key events from archived files including grant proposals and CEAB meeting notes. A steering committee of three CEAB members helped guide this process. RESULTS/ANTICIPATED RESULTS: The CEAB was founded at the UIC College of Nursing in 2001 under the Center for Research on Cardiovascular Respiratory Health, with a grant from the National Institutes of Nursing Research (NINR). It was established as college-wide advisory board of community experts to help engage underserved communities and to contribute to research beyond recruitment and retention. In 2009, upon receipt of a Clinical Translational Science award that established the Center for Clinical Translational Science (CCTS), the CEAB became a campus-wide board. Over 30 community organizations and many non-affiliated community members have contributed to translational research at UIC throughout the board’s history. DISCUSSION/SIGNIFICANCE: Over twenty years later, the CEAB continues to help bridge researchers and communities, and to raise awareness about community needs, the importance of cultural relevance, and the inclusion of underserved communities in research. Long-term members have played a key role in providing continuity over the years.

Bayesian penalized likelihood PET reconstruction impact on quantitative metrics in diffuse large B-cell lymphoma.

Evaluate the quantitative, subjective (Deauville score [DS]) and reader agreement differences between standard ordered subset expectation maximization (OSEM) and Bayesian penalized likelihood (BPL) positron emission tomography (PET) reconstruction methods. A retrospective review of 104 F-18 fluorodeoxyglucose PET/computed tomography (CT) exams among 52 patients with diffuse large B-cell lymphoma. An unblinded radiologist moderator reviewed both BPL and OSEM PET/CT exams. Four blinded radiologists then reviewed the annotated cases to provide a visual DS for each annotated lesion. Significant (P < .001) differences in BPL and OSEM PET methods were identified with greater standard uptake value (SUV) maximum and SUV mean for BPL. The DS was altered in 25% of cases when BPL and OSEM were reviewed by the same radiologist. Interobserver DS agreement was higher for OSEM (>1 cm lesion = 0.89 and ≤1 cm lesion = 0.84) compared to BPL (>1 cm lesion = 0.85 and ≤1 cm lesion = 0.81). Among the 4 readers, average intraobserver visual DS agreement between OSEM and BPL was 0.67 for lesions >1cm and 0.4 for lesions ≤1 cm. F-18 Fluorodeoxyglucose PET/CT of diffuse large B-cell lymphoma reconstructed with BPL has higher SUV values, altered DSs and reader agreement when compared to OSEM. This report finds volumetric PET measurements such as metabolic tumor volume to be similar between BPL and OSEM PET reconstructions. Efforts such as adoption of European Association Research Ltd accreditation should be made to harmonize PET data with an aim at balancing the need for harmonization and sensitivity for lesion detection.

Knowledge of legal rights as a factor of refugee and asylum seekers’ health status: a qualitative study

ObjectivesTo examine health behaviours of refugees and asylum seekers, in relation to their knowledge of public benefits and legal rights.DesignQualitative study, utilising an open-ended, semi-structured interview guide to ensure information-rich...

Decentralized clinical trials in the trial innovation network: Value, strategies, and lessons learned.

New technologies and disruptions related to Coronavirus disease-2019 have led to expansion of decentralized approaches to clinical trials. Remote tools and methods hold promise for increasing trial efficiency and reducing burdens and barriers by facilitating participation outside of traditional clinical settings and taking studies directly to participants. The Trial Innovation Network, established in 2016 by the National Center for Advancing Clinical and Translational Science to address critical roadblocks in clinical research and accelerate the translational research process, has consulted on over 400 research study proposals to date. Its recommendations for decentralized approaches have included eConsent, participant-informed study design, remote intervention, study task reminders, social media recruitment, and return of results for participants. Some clinical trial elements have worked well when decentralized, while others, including remote recruitment and patient monitoring, need further refinement and assessment to determine their value. Partially decentralized, or "hybrid" trials, offer a first step to optimizing remote methods. Decentralized processes demonstrate potential to improve urban-rural diversity, but their impact on inclusion of racially and ethnically marginalized populations requires further study. To optimize inclusive participation in decentralized clinical trials, efforts must be made to build trust among marginalized communities, and to ensure access to remote technology.

Building an infrastructure to support the development, conduct, and reporting of informative clinical studies: The Rockefeller University experience.

Clinical trials are a vital component of translational science, providing crucial information on the efficacy and safety of new interventions and forming the basis for regulatory approval and/or clinical adoption. At the same time, they are complex to design, conduct, monitor, and report successfully. Concerns over the last two decades about the quality of the design and the lack of completion and reporting of clinical trials, characterized as a lack of "informativeness," highlighted by the experience during the COVID-19 pandemic, have led to several initiatives to address the serious shortcomings of the United States clinical research enterprise. Against this background, we detail the policies, procedures, and programs that we have developed in The Rockefeller University Center for Clinical and Translational Science (CCTS), supported by a Clinical and Translational Science Award (CTSA) program grant since 2006, to support the development, conduct, and reporting of informative clinical studies. We have focused on building a data-driven infrastructure to both assist individual investigators and bring translational science to each element of the clinical investigation process, with the goal of both generating new knowledge and accelerating the uptake of that knowledge into practice.

Abstract 11679: Simple Text-Messaging and Social Support to Increase Hypertension Medication Adherence in Non-Hispanic Black Adults in New Orleans, LA

Introduction: Non-Hispanic Black adults (NHB) have the highest US CVD risk, the leading cause of mortality. Medication nonadherence predicts suboptimal HTN control. Self-measured blood pressure (SMBP) effectively tracks BP changes and medication response. Purpose: This New Orleans, LA predominantly NHB single cohort pilot study examined uncontrolled HTN utilizing bidirectional electronic messaging (BEM) with an interdisciplinary healthcare team assessing medication adherence, quality of life (QOL), and BP, without pharmacotherapeutic change. Methods: Participants were screened from Tulane Cardiology Clinic and community sources. Eligibility criteria included: uncontrolled HTN (BP &gt;130/80 mmHg), low Krousel-Wood (KW) adherence score, and smartphone access. Participants (n=36) were provided validated bluetooth-enabled BP devices synced to smartphones via a cloud-based BP recording app. Demographic information included: age, self-identified race (91.7% NHB), and sex. Pre- and post-study KW adherence scores, CDC Health Related QOL surveys, BMI and BP were obtained. Participants were followed with BEM for 8 weeks with SMBP and daily text reminders. Results: Mean age was 58.7±12.8 years; mean BMI was 34.8±7.8; 63.9% were female; 25.7 % with previous diabetes diagnosis; 72% with obesity. Nonadherence significantly improved with mean KW adherence composite score change from 2.19 to 1.58 (p = 0.0001). Mean baseline SBP/DBP was 142.19/81.19; SBP decreased significantly by mean 10.5±20.0 mmHg (p = 0.0027) with no significant change in DBP. There was a non-significant decline in the average summary index of unhealthy days during the previous 30 days from 9.1 days to 6.8 days, change -2.3 ± 10.7 (p = 0.21). Conclusions: A novel approach combining cloud-based bluetooth SMBP transmission with BEM health communication significantly improved medication adherence and systolic BP in a predominantly NHB urban cohort without modifying existing pharmacotherapy. “Supported in part by U54 GM104940 from the National Institute of General Medical Sciences of NIH, which funds the LA Clinical and Translational Science Center. Content is solely the responsibility of the authors and does not necessarily represent official views of the NIH.”

Graduate programs related to acoustics at the University of Minnesota

The University of Minnesota (UMN) has graduate programs that span the areas of Animal Bioacoustics, Psychological and Physiological Acoustics, and Speech Communication. Degrees are offered in Psychology (PhD), Speech-Language-Hearing Sciences (MA in speech-language pathology, AuD, and PhD in speech-language-hearing sciences), Biomedical Engineering (MS and PhD), Ecology, Evolution, and Behavior (PhD), and Neuroscience (PhD). Faculty across departments have a shared interest in understanding how the ear and brain work together to process sound and in developing new technologies and approaches for improving hearing disorders. Located on campus is the Center for Applied and Translational Sensory Science (CATSS), which provides opportunities for interdisciplinary collaborations across departments and industry to understand how sensory impairments work. Within CATSS is the Multi-Sensory Perception Lab, which houses shared equipment, including eye trackers and electroencephalography. The Center for Magnetic Resonance Research houses several ultrahigh field magnets, while the Center for Neural Engineering and affiliated faculty labs also house multiple neuromodulation and neurorecording devices to interact with and monitor neural activity in humans and animals.

P019 Validation of a Smartphone-Based App for Assessing Energy Intake: A Pilot Study

<h3>Background</h3> Smartphone-based methods are innovative and promising tools to accurately quantify energy intake (EI). The PortionSize^TM app measures dietary intake using embedded templates and provides real-time feedback. PortionSize also sends food images to a server where they can be analyzed using the Remote Food Photography Method (RFPM). The RFPM accurately measures EI; however, it requires human raters to analyze food images; therefore, the RFPM does not provide dietary feedback in real-time. <h3>Objective</h3> To compare the validity of EI estimates from PortionSize and RFPM to weighed meals (WM). <h3>Study Design, Setting, Participants</h3> Fifteen adults used the PortionSize app during covertly-weighed simulated meals in a laboratory setting. Trained personnel also quantified EI from the images captured from the PortionSize using the RFPM. <h3>Measurable Outcome/ Analysis</h3> Demographics and body mass index (BMI). Dependent t-tests were performed to investigate whether EI measured with templates in PortionSize or using the RFPM differed to EI from WM. <h3>Results</h3> Mean (± SD) age and BMI of participants were 28 (± 12) years and 24.1 ± 6.6 kg/m2, respectively, and 73.3% were female. PortionSize estimated EI was 743 ± 328 kcal, EI RFPM-estimated intake was 660 ± 196 kcal, and weighed intake was 659 ± 191 kcal. The mean differences of EI estimation between PortionSize and WM (84 ± 288 kcal) and between RFPM and WM (1 ± 32 kcal) were not significant (<i>P</i> > .05). The mean difference in EI estimation (83 ±284 kcal) between PortionSize and RFPM was not significant (<i>P</i> > .05). <h3>Conclusions</h3> RFPM produced very close estimates of EI to WM but requires a human rater and is not easily scalable. These findings are important as PortionSize provides real-time feedback on dietary intake, which may assist with timely behavior change. Improvements to make PortionSize more scalable are ongoing. This work warrants future well-powered trials. <h3>Funding</h3> NIH; Pennington Biomedical (PBRC)/Louisiana Nutrition Obesity Research Center; Louisiana Clinical and Translational Science Center

Abstract CT158: Use of 4-demethyl-4-cholesteryloxycarbonyl-penclomedine (DM-CHOC-PEN) as therapy for advanced non-small cell lung cancer (NSCLC) involving the CNS

Abstract Background: 4-Demethyl-4-cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) is a poly-chlorinated pyridine cholesteryl carbonate that was designed to penetrate the blood brain barrier and be useful as therapy for brain tumors (IND 68,876). A 3-stage mechanism is proposed for drug entry into the CNS and into cancer cells via reversible binding with sialic acid on the surface of RBC’s; and transported into cancer cells with L-glutamine. DM-CHOC-PEN has a MOA via bis-alkylation of DNA @ N7-guanine and N4-cytosine. DM-CHOC-PEN has completed clinical trials involving sixty-four (64) adults and nineteen (19) adolescent/young adult subjects with advanced cancers. Long term survival, good qualities of life and minimal toxicities [AACR #1185, 2013; AACR #CT 129, 2019; AACR #CT152, 2021] have been reported. This update provides affirmation that the drug, previously described as a treatment for non-small cell lung cancer (NSCLC) involving the CNS, is well tolerated with continued durations of responses, no new toxicities, good survival and good quality of life. Primary aims of the previously reported DM-CHOC-PEN clinical trials were to assess clinical response and monitor toxicities/safety and verify the maximum tolerated doses (MTD) for the drug administered IV to subjects with cancer. Here is an update on the long term responses, tolerance and quality of survival in subjects with NSCLC involving the CNS. Subjects &amp; Methods: DM-CHOC-PEN was administered to adults (&amp;gt; 18 y/o) with NSCLC involving the CNS that lacked genetic rearrangements or tumor targets and/or had failed standard therapies as a 3-hr IV infusion once every 21 days employing a verified 2-tiered MTD schedule: 85.8 mg/m2 for subjects with liver involvement and 98.7 mg/m2 for subjects with normal livers. Results: Sixteen (16) adult subjects with NSCLC have been treated to date, which 11 had NSCLC (adeno/large cell carcinomas) involving the CNS that lacked genetic rearrangements, had no tumor targets, and/or had failed standard therapies. Seven of the 11 subjects with NSCLC involving the CNS also possessed cerebellar metastases. The drug was well tolerated with no Gr-3 toxicities. The most common Gr-2 adverse effects were reversible fatigue (17%), reversible vasogenic edema (9%) and nausea (9%). No drug associated neuro/psychological, hematological, cardiac or renal toxicities have been observed, nor have there been any drug associated deaths reported. The pK modelling and properties for the drug have been previously reported [AACR #1185, 2013] and continue to be confirmed. Eight (8) subjects with NSCLC involving the CNS responded to DM-CHOC-PEN with documented CR/PR (RECIST 1.1) and improved OS/QOL/PFS (Kaplan-Meier) lasting 8 - 82+ mos. with survivals of 25% at 34 mos., 50% at 10 mos. and 8% at 84+ mos. Conclusion: DM-CHOC-PEN is a bis-alkylator of DNA that is safe at the dose levels described and has produced long term objective responses with manageable toxicities and improved quality of life in subjects with NSCLC involving the CNS lacking genetic rearrangements or tumor targets and/or had failed standard therapies. Complete data on subject responses and observed toxicities will be presented. Supported by NCI/SBIR grants - R43/44CA132257 and NIH NIGMS 1 U54 GM104940 - the latter supports the Louisiana Clinical and Translational Science Center, New Orleans, LA Citation Format: Lee Roy Morgan, Roy S. Weiner, T. Mahmood, C. Gordon, M. Bhandari, AH Rodgers, ML Ware, Marc Matrana, Thomas M. Cosgriff, Philip Friedlander, J-J Zou. Use of 4-demethyl-4-cholesteryloxycarbonyl-penclomedine (DM-CHOC-PEN) as therapy for advanced non-small cell lung cancer (NSCLC) involving the CNS [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT158.

A Novel Method to Assess Dietary Intake and Obtain Real-Time Dietary Adherence Data: A Pilot Study

ObjectivesWe developed the PortionSizeTM app (PS) to estimate food intake and dietary adherence based on images of meals captured before and after eating occurs. The PS app provides real-time feedback to users about their dietary intake (energy, nutrients, and food groups) and adherence to specific diets. This pilot study provided initial tests of the validity of the PS app at assessing energy and nutrient intake from simulated meals in a laboratory setting. We also explored participants’ satisfaction with the PS app. MethodsFifteen adult participants (aged 18–65 years) were trained to use the app. Participants then used the app to estimate food intake during simulated meals, where participants were provided with a plate of food to represent food provision as well as a plate of leftovers. The amount of food provided as food provision and waste was covertly weighed. Participants completed a six-point user satisfaction survey ranked from 1 (‘extremely dissatisfied’) to six ‘very much satisfied’. Dependent t-tests were performed to compare intake of energy, macronutrients, and food groups (fruits, vegetables, grain, dairy, and protein) from the 15 meals, where intake was estimated with the PS app and compared to directly weighed food. Alpha was set at 0.05. ResultsOf the 15 participants, 73.3% (11) were female, and the mean (± SD) age and body mass index of the participants was 28.0 ± 12.2 years and 24.1 ± 6.6 kg/m2, respectively. Energy intake estimated by PS at the meal level (742.9 ± 328.2 kcal) was similar to directly weighed values (659.3 ± 190.7 kcal) and the difference (83.5 ± 287.5 kcal) was not significant (P > .05). No significant differences were found between the two methods (PS and weigh back) for macronutrients (protein, total fat, and carbohydrate), and four food group servings (all P values > .05) except total grains (P value < .05). About 71% of the participants rated the app as a five or six in terms of satisfaction and ease of using the PS app. ConclusionsResults from this pilot provide preliminary support for the validity of, and user satisfaction with, the PS app. The pilot study identified ways to improve PS. Larger validation studies and further app refinement are ongoing. Funding SourcesNational Institute of Diabetes and Digestive and Kidney Diseases; Nutrition Obesity Research Center: PBRC; Louisiana Clinical and Translational Science Center.