bluuebunny/crossref_metadata_2025 huggingface dataset:
378 Regulation of renal function by the peroxisome proliferator-activated receptor-alpha: A novel target for treating hypertension
Authors: Hatcher Mark D , Sandberg Kathryn , Lee Dexter
Published: April 2023

OBJECTIVES/GOALS: 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. PPAR-Î±knockout (KO) mice exhibit increased renal inflammation and blood pressure. In this study, we investigated the role of PPAR-Î±in renal function in a mouse model of hypertension. METHODS/STUDY POPULATION: Male 4-month-old wild type (WT) and PPAR-Î±KO mice were instrumented with radio transmitters by artery canulation (Data Science Intl). 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 angiotensin II (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 (3.74Âµl/g body weight) and collected 8 blood samples (20Âµl/sample) over 75 minutes to enable calculation of the glomerular filtration rate (GFR) using [GFR = I/(A/Î±+ B/ÃŸ)]. RESULTS/ANTICIPATED RESULTS: Similar to our prior observations, no significant (ns) differences in baseline MAP were observed between WT and PPAR-Î±KO mice [(mmHg): WT (n=6), 111 ± 20 vs. PPAR-Î±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-Î±KO (n=8) , 156 ± 16#; #p DISCUSSION/SIGNIFICANCE: PPAR-Î±protects mice from worsening hypertension and is critical to preserving GFR during normotensive conditions. Ongoing studies are further investigating how PPAR-Î±regulates renal function. These finding suggest therapeutics designed to increase PPAR-Î±activity could have clinical benefit in chronic kidney disease.
380 The kinesin-like protein Kif11 is essential for the survival of TP53 mutant triple-negative breast cancer cells
Authors: Lanier Amanda , Tahaney William , Mazumdar Abhijit , Brown Powel
Published: April 2023

OBJECTIVES/GOALS: While mutant TP53 is an attractive therapeutic target in TNBC, attempts to target the mutant p53 protein directly have failed. Thus, we aim to identify pathways critical for the survival of TP53 mutant cells that can be targeted in TNBC. We have identified Kif11 as one such target and aim to further investigate its function in TP53 mutant TNBC. METHODS/STUDY POPULATION: We conducted a dual in silico/in vivo screen that identified Kif11 inhibition as preferentially inhibiting the growth of TP53 mutant TNBC. We obtained data on TP53 mutational status, KIF11 mRNA expression levels, and clinical characteristics from TCGA, METABRIC, and CCLE datasets. We treated breast cancer cell lines with the KIF11 inhibitor SB-743921. Cell counts were obtained through staining with DAPI or Hoechst and imaging on the ImageXPress PICO. We detected cell death by DRAQ7 staining and flow cytometry analysis following Annexin V-PI staining. To investigate mitotic spindle organization, we performed immunofluorescent staining with an anti-tubulin antibody and DAPI co-staining. Cell cycle analysis was performed through flow cytometry. RESULTS/ANTICIPATED RESULTS: KIF11 is highly expressed in TP53 mutant and TNBC clinical samples. High KIF11 expression is associated with poorer clinical outcomes. Kif11 inhibition suppresses growth of both TP53 mutant and wild-type breast cancer cells, but preferentially induces the death of TP53 mutant cells as detected by DRAQ7 and Annexin V/PI staining. Kif11 inhibition induces a G2-M block and growth inhibition in TP53 wild-type cells. On the other hand, following treatment with the Kif11 inhibitor SB-743921, TP53 mutant cells undergo mitotic spindle dysfunction leading to the formation of multinucleated cells and cell death. DISCUSSION/SIGNIFICANCE: These results demonstrate that Kif11 is a promising therapeutic target in aggressive, TP53 mutant TNBCs. Kif11 inhibitors, including SB-743921, have been tested in human trials, and are well tolerated, but it is unclear which patients would most benefit. Our studies show that Kif11 inhibitors may be most useful in patients with TP53 mutant TNBCs.
382 The Role of the IL-6-IGF-II Axis in Systemic Sclerosis-Associated Lung Fibrosis
Authors: Adewale Adegboyega Timothy , Feghali-Bostwick Carol
Published: April 2023

OBJECTIVES/GOALS: Interleukin (IL)-6 is produced in excess in Systemic Sclerosis (SSc). Likewise, microarray analysis of Insulin-like Growth Factor (IGF)-II-treated NL fibroblasts revealed increased expression of the basic helix-loop-helix transcription factor, BHLHB2. Our goal is to delineate the role of BHLHB2 in the fibrotic response to IGF-II and IL-6. METHODS/STUDY POPULATION: Primary lung fibroblasts were cultured from human lung tissues at 37oC and 5% CO2. Cell cultures were stimulated with IL-6. Gene expression was measured using quantitative PCR (qPCR). IGF-II mRNA expression levels after IL-6 stimulation were compared with those of the housekeeping gene PPIB (Peptidylprolyl Isomerase B). Western blot was performed on nuclear and chromatin-bound subcellular fractions from treated lung fibroblasts. BHLHB2 protein levels were assayed in response to IGF-II in comparison to PBS as vehicle control. RESULTS/ANTICIPATED RESULTS: Results: Our results show that IL-6 increases IGF-II levels in fibroblasts. In turn, IGF-II increases BHLHB2 nuclear localization. We further show that IL-6 increases BHLHB2 levels and its nuclear localization in lung fibroblasts. Our findings are novel since the role of the transcription factor BHLHB2 in the IL-6 induced/ IGF-II-mediated fibrotic response in SSc lung disease remains unexplored. DISCUSSION/SIGNIFICANCE: Our findings may provide a rationale for combination therapy to block IL-6 and IGF-II function concomitantly and thus halt the progression of SSc pulmonary fibrosis (PF). Our findings may have wide implications for lung fibrosis associated with various diseases, since SSc-PF, is characterized by the activation of common fibrotic pathways.
384 Alterations in the fungal microbiome in ulcerative colitis
Authors: Jangi Sushrut , Hsia Katie , Zhao Naisi , Chung Mei , Algarrahi Khalid , Kouhsari Laleh Montaser , Fu May , Chen Hannah , Singh Siddharth , Michaud S.
Published: April 2023

OBJECTIVES/GOALS: Although gut fungi have been implicated in the immunopathogenesis of inflammatory bowel disease, the fungal microbiome has not been deeply explored across endo-histologic activity and treatment-exposure in ulcerative colitis. METHODS/STUDY POPULATION: Our retrospective cohort was derived from the Study of a Prospective Adult Research Cohort with Inflammatory Bowel Disease. We evaluated the fungal composition of fecal samples from 98 ulcerative colitis patients across endoscopic activity (n=43), endo-histologic activity (n=41), and biologic-exposure (n=98). Across all subgroups, we assessed fungal diversity and differential abundance of specific taxonomic groups. RESULTS/ANTICIPATED RESULTS: We identified 504 unique fungal amplicon sequence variants across the cohort of 98 patients, dominated by phylum Ascomycota. Compared to endoscopic remission, patients with endoscopic activity had an increased global fungus load (p DISCUSSION/SIGNIFICANCE: Endoscopic inflammation in ulcerative colitis is associated with altered fungal diversity driven by expansion of Saccharomyces and Candida compared to remission. The role of these fungal taxa as potential biomarkers and targets for personalized approaches to therapeutics in ulcerative colitis should be evaluated.
386 A novel truncating variant of EBF2 disrupts human adipocyte differentiation in lipodystrophy syndromes: an example of a discovery from a clinical translational pipeline
Authors: Foss-Freitas Maria C. , Wys Noel , Udler Miriam , Pais Lynne , Rocha Andre Monteiro da , MacDougald Ormond A. , Oral Elif A. , Chun Tae-Hwa
Published: April 2023

OBJECTIVES/GOALS: Aiming to better understand the molecular pathogenesis of familial partial lipodystrophy (PL), we initiated whole-exome sequencing for our patients with PL syndromes. A novel variant of early B cell factor 2 (EBF2) was identified. Here we report the biological impact of a novel truncating EBF2 variant. METHODS/STUDY POPULATION: Using 3T3-L1 and human primary subcutaneous preadipocytes, we performed loss-of-function and gene rescue experiments. All cells were cultured in DMEM with 10% bovine calf serum (Invitrogen) at 5% CO2. After lentivirus transfection, cells were grown to confluence and then exposed to adipogenesis induction media containing dexamethasone (0.25ÂµM), insulin (1Âµg/ml) and isobutyl methylxanthine (0.5 mM). Total RNA was extracted using RNeasy Mini Kit (Qiagen) and cDNA was synthesized using IScript (Bio-Rad). Real-time qPCR was performed using TaqMan probes for Pparg and Fabp4, two key adipogenesis markers. RESULTS/ANTICIPATED RESULTS: Patient was found to carry a heterozygous nonsense mutation in exon 6 of EBF2, causing the premature termination of the protein at amino acid position 165. Adipogenesis was significantly suppressed in 3T3L1 cells when endogenous Ebf2 was suppressed with siRNA and lentiviral shRNA. Adipocytes with suppressed Ebf2 expression showed marked reduction of intracellular lipid content and Pparg and Fabp4 expression (>80% reduction). With lentiviral gene transfer, EBF2 fully rescued adipogenic potential, whereas the truncated variant EBF2 did not. Of note, 3T3-L1 cells transfected with the EBF2 variant displayed impaired adipogenesis, suggesting a dominant-negative effect of the EBF2 variant on adipogenesis. We confirmed the dominant effect of the EBF2 variant in human adipocyte differentiation. DISCUSSION/SIGNIFICANCE: Our data suggest that EBF2 is indispensable for adipogenesis. The loss of function and dominant-negative effect of the truncating variant of EBF2 likely plays a pathogenic role in PL. Whole exome sequencing of PL patients and ex-vivo functional analysis help identify novel gene variants and better understand the molecular pathogenesis of PL.
389 Insights into the complex immune environment during pregnancy and association with the developing human connectome
Authors: Aydin Ezra , Rodriguez Raimundo , Monk Catherine , Stockton Thirsten , Murthy Sanjana , Peterson Bradley S. , Scheinost Dustin , Spann Marisa N.
Published: April 2023

OBJECTIVES/GOALS: Maternal health and exposures during pregnancy play a major role in shaping the neurodevelopment of our offspringâ€”one influence is maternal immune activation (MIA). Here we explore the association of MIA during pregnancy and the developing human connectome through analysis of 46 markers of activation. METHODS/STUDY POPULATION: 74 healthy women with singleton pregnancies underwent blood draws between 34-37 weeks gestation. 46 markers of maternal immune activation, both adaptive (e.g., IgG) and innate (e.g., cytokines and acute phase reactants), were collected. In addition, for preliminary analyses of MIA in relation to the newborn brain, we utilized 30 participants with MRIs between the ages of 0-6 months. RESULTS/ANTICIPATED RESULTS: Principal component analysis (PCA) identified the first 5 PCs explains ~68% of the variance and the first 10 explains ~83% (top PC is 42.1%). Using the top PC each edge in the connectome was correlated with the immune profiles. Several regions trended towards significance–one survived correction and included 359 edges, showing. The highest number of edges was observed in the inferior parietal lobe of the left hemisphere–a region associated with functions from basic attention toa social cognition, suggesting that deviations in fetal exposure to MIA can longitudinally impact offspring behavior in areas essential for human interaction. DISCUSSION/SIGNIFICANCE: This is the first study in understanding how interruptions (i.e., MIA) influence later development. Identification of alterations, and long-term outcomes could lead to the development of mechanism-based healthcare, facilitate timely referral for appropriate interventions and provide family support.
391 An Investigation on the Activity of Repurposing Already Marketed Drugs for New Indications from 2015 to 2021.
Authors: Wu Wenchao , Pacifici Eunjoo
Published: April 2023

OBJECTIVES/GOALS: To examine the prevalence of new indications for existing drugs conducted by non-originator companies from 2015 to 2021 and determine how many could qualify for 505(b)(2) under the Food, Drug, and Cosmetics Act. METHODS/STUDY POPULATION: A search within Clinicaltrials.gov was conducted to identify phase 3 drug interventional studies completed from 2015 to 2021. Results were categorized by funding source and industry sponsored studies were further separated into originator- and non-originator companies using dailymed.com. An in-depth review of 2018 was conducted to understand the nature of the studies including indication, dosage form, and route of administration. RESULTS/ANTICIPATED RESULTS: According to clinicaltrials.gov, a total of 7148 phase 3 studies were conducted between 2015 and 2021. Most of these studies were funded by industry (4447, 66.21%), followed by other (2428, 33.97%), NIH (266, 3.72%), and government (62, 0.87%). In-depth examination of the studies completed in 2018 (n=1077) revealed similar pattern in that most were funded by industry (674, 62.58%) followed by other (356, 33.05%), NIH (43, 3.99%), and government (10, 0.93%). Some studies were funded by more than one type. Of the industry-sponsored studies, 623 were funded by originator companies and 51 by non-originator companies. A total of 49/674 of the industry sponsored studies were for new indications, with 42 studies conducted by originator companies and 7 conducted by non-originator companies. DISCUSSION/SIGNIFICANCE: The 505(b)(2) is a way for manufacturers to add new indications to drugs by non-originator companies. In 2018, 49/674 studies were conducted to pursue new indications with few, 7/49, conducted by non-originator companies. The product development landscape reveals few opportunities for entities pursuing the 505(b)(2) pathway for new indications.
393 Disposable Electronic Nicotine Delivery Systems (ENDS) and Underage Nicotine Addiction–A Survey of College Students
Authors: Riggs Griffin , Church Terry David
Published: April 2023

OBJECTIVES/GOALS: To identify factors enabling growing underage consumption of disposable Electronic Nicotine Delivery Systems (ENDS) by understanding young adults’perceptions and patterns of use of disposable ENDS through surveying college students. METHODS/STUDY POPULATION: Disposable ENDS are all-in-one devices with pre-filled nicotine liquid and a built-in battery. Recent data shows increased sales as users, including youth, are switching from pod-based to disposable ENDS. Gaps were identified via a literature review of current survey data revealing unknown information about disposable ENDS. Based on these data gaps, an anonymous survey was developed to gain insight into youth disposable ENDS use. The survey was distributed to college students via social media, university email chains, and flyers with QR codes. Responses were analyzed to identify trends and correlations in disposable ENDS use among college students. The survey was approved by USC IRB, Study ID: UP-22-00023. RESULTS/ANTICIPATED RESULTS: Between March 6 and October 28, 2022, 166 completed survey responses were collected; 158 were students. 80.4% (127/158) of surveys were eligible for analysis with the following criteria: 18-20 years old, under the US legal age to use ENDS. Of respondents aged 18-20, 57.5% (73/127) reported using ENDS at least once. 79.5% (58/73) of underage respondents used disposable ENDS and 72.9% (51/70) reported disposable ENDS as their usual device. 93.0% (53/57) of underage users reported using a flavored product, 56.1% (32/57) reported FlumÂ®as their usual brand, 48.2% (27/56) reported convenience of use as the most attractive aspect of disposable ENDS, and 46.4% (26/56) obtained disposable ENDS from a convenience store. Of all disposable ENDS-using respondents, 98.7% (75/76) used for the first time while under the age of 21. DISCUSSION/SIGNIFICANCE: The survey continues to be open for data collection, with the goal of obtaining additional data. The goal with the additional data will be to create a comprehensive list of identified risk factors influencing underage disposable ENDS use and to suggest specific regulatory and policy reform to better address underage nicotine addiction.
396 Quantitative Analysis of FDA Warning Letters Related to the Use of Social Media Sites in Product Misbranding for the Treatment, Prevention, or Diagnosis of COVID-19
Authors: Ajaj Mahmoud , Cooper Lisa
Published: April 2023

OBJECTIVES/GOALS: Food and Drug Administration (FDA) warning letters regarding misbranding of products intended to treat, prevent, or diagnose COVID-19 were used as a proxy for assessing misinformation on social media. The FDA database of Warning Letters was used to identify the largest misinformation contributor. METHODS/STUDY POPULATION: On November 9, 2022, the full dataset of warning letters dating back to January 1, 2018 was extracted from the FDA website. Separate datasets were also extracted using the search terms: Facebook’, Twitter’, YouTube’, and Instagram’. The data entries were organized by issuing office and subject. The subjects were then filtered to only include letters related to misbranding of products for COVID-19. Letters regarding medical devices, manufacturing practices, and adulterated products were excluded from the analysis. Cumulative totals were collected for the number of letters issued for each search term. These totals were stratified by year and scaled by platform size for relative comparison. RESULTS/ANTICIPATED RESULTS: The FDA’s Center for Drug Evaluation and Research issued the most letters related to misbranding of COVID-19 products, 153 out of the 2798 entries in the complete dataset. Analysis of the datasets by search term show: 53, 18, 24, and 17 letters were related to Facebook, Twitter, YouTube, and Instagram respectively. Forty-one letters were related to other non-social media sources. Facebook had the most letters issued, however when scaled to account for the size of each respective platform’s approximate user base, Twitter had the largest proportional amount of misinformation regarding agents for the management of COVID-19, followed by Facebook, then Instagram. Most letters were issued in 2020. DISCUSSION/SIGNIFICANCE: In light of COVID-19, many social media sites adopted policies to limit inaccurate information. The success of these efforts have been variable. Although Facebook is the largest absolute contributor assessed, greater attention should be given to the policies of other platforms utilized by the industry.
397 Regulations and Marketing of Energy Drinks in the United States: A Survey of University Student Beliefs about Caffeine Consumption
Authors: Chung Christian , Church Terry
Published: April 2023

OBJECTIVES/GOALS: To understand how energy drinks are marketed and regulated and the effects of these policies on adolescent consumption and perceptions of the product. METHODS/STUDY POPULATION: A review of research studies using the PubMed database (PubMed.gov); clinical trials (clinicaltrials.gov); FDA Recall, Market Withdrawals, and Safety Alerts (FDA.gov); and emergency department (ED) visits from reports from the Drug Abuse Warning Network (DAWN) were conducted. A survey is being designed and will be sent to undergraduate and graduate university students through advertised QR codes and university email chains sent out to student organizations and courses. The survey will determine the percentage of respondents who consume caffeine, the frequency in which individuals consume caffeine, and reasons for consuming caffeine. The survey also seeks to understand perceptions and thoughts on energy drinks and caffeine regulation and consumption. RESULTS/ANTICIPATED RESULTS: From January 1st, 2000, to August 5th, 2022, 112 research studies investigated the physiological impact of energy drinks on adolescents, and 13 clinical trials from the age group of 0-17 were conducted. No FDA recalls have been observed for energy drinks or the top 4 brands within the US (by sales; Red Bull, Monster, Bang Energy, Rockstar), though some recalls regarding container manufacturing were made outside the US. ED visits from energy drinks doubled from 2007 to 2011 with 1/10 of them resulting in hospitalization. 58% of the total ED visits were exclusively related to energy drinks. It is anticipated that survey results will indicate trends of frequent caffeine/energy drink consumption among college students for studying, but students will not have a clear understanding of recommended caffeine intake. DISCUSSION/SIGNIFICANCE: Due to the lack of regulations and studies surrounding energy drinks, the dangers (as seen from ER visits) to public health are concerning. Regulatory agencies should invest in developing new protocols or regulations regarding the content of energy drinks as well as find ways to monitor the marketing strategies more closely behind them.
402 Developing a rubric to distinguish translational science from translational research in CTSA pilot projects
Authors: Dillon Pamela , McCoy Renee , Duguid Paul , Sparks Crystal , Thaker Swathi , Xiang Henry , Boerger Lindsie , Hunt Joe , Denne Scott , McCaffree Tim , Lee Jennifer , Schneider Margaret
Published: April 2023

OBJECTIVES/GOALS: The goal of the CTSA consortium is to move scientific discoveries to clinical application. Translational science (TS) focuses on the process by which this happens, and NCATS supports pilot projects that propose TS questions. We are developing a rubric to guide program managers’ability to discriminate between TS and translational research (TR). METHODS/STUDY POPULATION: The CTSA External Review Exchange Consortium (CEREC) and CEREC II are reciprocal review collaborations between CTSA hubs that identify reviewers for each other’s pilot grant applications. CEREC and CEREC II partners developed a 31-item rubric, based on NIH’s Translational Science Principles, for discriminating pilot TS grant applications from those proposing TR. The hubs contributed proposals pre-selected as either TS or TR projects. Then, experienced reviewers and/or program administrators from the hubs used the rubric to score each of the proposals. Reliability of the rubric will be assessed using inter-rater reliability (% agreement and kappa). To identify which of the items in the rubric best discriminate between TS and TR, Item Response Theory analysis will be employed. RESULTS/ANTICIPATED RESULTS: Ten CEREC participating hubs submitted 30 applications: 20 TS proposals and 10 TR proposals. Twenty-two reviewers from 12 CEREC hubs evaluated the applications by using the scoring rubric; at least two reviewers evaluated each proposal. The results of the analyses will describe the reliability of the rubric and identify which of the seven TS Principles are most useful for distinguishing between TS and TR pilot grant proposals. Ultimately, this work will yield a scoring rubric that will be disseminated throughout the CTSA network to facilitate the screening of TS applications. DISCUSSION/SIGNIFICANCE: Optimizing research processes is critical to ensure that scientific discoveries are integrated into clinical practice and public health policy as rapidly, efficiently, and equitably as possible. By appropriately identifying and funding TS projects, CTSA hubs can accelerate the impact of clinical and translational research.
408 Quality by Design: A Framework for Study Success
Authors: Orechwa Allison , Watson-Faulkner Minyan , Buchanan Thomas
Published: April 2023

OBJECTIVES/GOALS: The SC CTSI Quality by Design (QbD) program aims to improve the execution of clinical research studies identifying and addressing possible issues before implementation. The program’s overall goal is to optimize operational design to achieve an 80% on-time completion rate. METHODS/STUDY POPULATION: Adapted from the Clinical Trials Transformation Initiative, our QbD program applies principles of quality management, project management, and team science to SC CTSI-funded studies. The process begins with a Design Studio for systematic review of critical-to-quality factors and a discussion of risks and mitigation plans. Studio attendees generally include the research team, SC CTSI faculty, and at least one community member. Outcomes include mitigation plans, a study project plan, and continued support from the project-tailored advisory board. We will iteratively evaluate satisfaction, quality improvement, and study completion rates. RESULTS/ANTICIPATED RESULTS: In an evaluation of the pilot phase, QbD participants responded that careful planning and expert input added value to their studies. The QbD process improved the quality of their studies, and all participants plan to apply QbD tools and resources to future studies. Beyond quality improvement, other anticipated outcomes include higher on-time study completion rates and uptake of QbD resources by other research teams. We also plan to assess the comparative benefit of QbD by study type. DISCUSSION/SIGNIFICANCE: Broader application of the CTSI QbD program has the potential for widespread benefit on research processes and outcomes. Studies implemented with minimal avoidable errors are more likely to complete on time, helping ensure efficient use of valuable resources and participant time.
409 Raising research awareness through StudyFinder
Authors: Hoffman Megan C , Whitwam Rachel , Hoedeman Michelle , Prich Brenda , Fehrmann Joshua , Vaughn Byron P
Published: April 2023

OBJECTIVES/GOALS: To increase public awareness and access to research opportunities at the University of Minnesota (UMN) utilizing StudyFinder, a public-facing website that features actively enrolling UMN research studies and directly connects website visitors with study teams. METHODS/STUDY POPULATION: Promote the University of Minnesota CTSI’s StudyFinder website to the public via social media ad campaigns and community outreach. Upon completion of the latest StudyFinder enhancement project in 2021, CTSI focused 2022 efforts on marketing and promotion of the site. CTSI created three StudyFinder social media ad campaigns in January, June, and October. CTSI also planned outreach events during the week of Clinical Trials Day, the Minnesota State Fair (1.8M attendees over 12 days), and the UMN’s Urban Research and Outreach-Engagement Center Community Day. RESULTS/ANTICIPATED RESULTS: Website traffic data from Google Analytics indicated a 72.76% increase in StudyFinder sessions from 2021 (Jan 1, 2021 to Nov 1, 2021) to 2022 (Jan 1, 2022 to Nov 1, 2022), with 16,262 sessions to 28,094 sessions, respectively. Direct emails from potential participants to study teams increased 89% in that same timeframe, from 3,082 emails to 5,819 emails. Targeted marketing campaigns and attending community events can improve the visibility of an institution’s research and connections of potential research participants to research teams. DISCUSSION/SIGNIFICANCE: Recruitment remains a main challenge in clinical and translational research. StudyFinder is an important patient-facing tool to connect individuals to specific studies. Future directions include expanding marketing efforts, events, and public feedback.
410 Successful Implementation of a Cross-Institutional Clinical Research Coordinator Pool to Support Georgia Clinical and Translational Science Alliance (Georgia CTSA) Investigators
Authors: Beltran Diana J. , Gulick Dalia , Croyle Stephanie , Rostad Christina
Published: April 2023

OBJECTIVES/GOALS: In 2020 the Georgia CTSA Clinical Research Center site at Emory University developed a highly trained, credentialed research coordinator pool with a goal to expand the pool to include clinical research coordinators from our partner institutions with the ability to work across institutional barriers in support of Georgia CTSA investigators. METHODS/STUDY POPULATION: Fall 2022, an Emory Investigator requested Georgia CTSA Biorepository samples with supporting clinical data for a NIH funded study. This provided a pilot opportunity to utilize clinical research nursing support offered by the UGA Clinical and Translational Research Unit (CTRU). De-identified samples were collected from our Biorepository while Emory’s coordinators and lab collaborated with UGA’s nursing support for data collection. Our obstacle for cross-institutional support was access to Emory Healthcare (EHC) medical records that would be needed by the UGA nurses, but partnerships created with the Georgia CTSA allowed us to overcome this, granting access to the electronic medical records (EMR) needed to complete the study. RESULTS/ANTICIPATED RESULTS: As expected, the process of credentialing and gaining access to the EHC EMR for the UGA team was the most time-consuming in the development of the pool. Discussions began in June 2021 to determine needs to allow the UGA research nurses to support the Emory coordinator pool. Requirements included acquiring an EHC network ID, completion of required Emory research training, letters of support from the Georgia CTSA outlining the collaboration between institutions, and a credentialing application. All steps were completed in May 2022 and the team began to identify studies that could benefit from this collaboration. Given that all credentialing and access needs were in place, the team was able to initiate the study and complete all study requirements, from sample identification to data collection and clean up, in five weeks. DISCUSSION/SIGNIFICANCE: Workforce shortages of experienced clinical research coordinators make it imperative to overcome barriers presented by institutional rules in order to efficiently utilize available resources to conduct high quality research. The CTSAs provide the perfect opportunity for partner institutions to develop processes to allow support across sites.
411 The Hatchery, a Universal Approach for Incubator Space in Academia
Authors: Hale Rena , Rotman Maarten , Sreedhar Anu , Ekker Stephen
Published: April 2023

OBJECTIVES/GOALS: The goal of the Hatchery is a new approach to de-risk innovative life science ideas within an entrepreneurial setting. The Hatchery creates value by vetting the initial potential through experimental testing. METHODS/STUDY POPULATION: In this study we took a functioning wet laboratory space that was vacant due to principle investigator movement, and created a pipeline for its use in life science startup formation. A functioning laboratory can remain unoccupied for a notable period with transitions of research leadership. At the same time, a life science startup company who is testing core principles of their technology need wet lab space at an affordable cost. Our solution called the Hatchery provides startup companies a state-of-the-art wet laboratory space, next to a research hospital, for a very short duration of time and minimal fee. This novel approach allows preliminary validation of a technology for initial NIH SBIRs and STTRs funding pathways. RESULTS/ANTICIPATED RESULTS: Initial findings demonstrated the effectiveness of the Hatchery method. Our pilot study included five different life science startups company tenants. Each company was enabled to de-risk technologies and secure a phase 1 SBIR/ STTR funding or resulted in an exit via acquisition. DISCUSSION/SIGNIFICANCE: Entrepreneurship is a growing approach for testing and expanding new research areas. The Hatchery model makes use of existing space and infrastructure, can scale with an entrepreneurial community, and can serve as critical pilot data for a more permanent space commitment.
415 Impact of Pennsylvania Medicaid payment policy change on rural versus non-rural hospital implementation of immediate postpartum long-acting reversible contraception
Authors: Horvath Sarah , Guare Emma , Fried Grace , Chuang Cynthia
Published: April 2023

OBJECTIVES/GOALS: To apply implementation science strategies to evaluate the impact of the 2016 Pennsylvania (PA) Medicaid payment policy change on hospital-level access to immediate postpartum long-acting reversible contraception (IPP LARC), an evidence-based strategy to increase contraceptive access; to identify differences by rurality and academic status. METHODS/STUDY POPULATION: We conducted a web-based, IRB-exempt survey of Labor and Delivery (L&D) leaders at all PA hospitals in Summer-Fall 2022, assessing hospital characteristics, contraceptive practices, and facilitators/barriers to IPP LARC implementation, using concepts from health services studies of small subsets of implementing hospitals; we translate these concepts into policy evaluation by sampling the complete population of Pennsylvania hospitals with active L&D units. L&D hospitals were characterized as sustainers if they implemented by 2019 and continued to provide IPP LARC, as implementers if they implemented IPP LARC in 2020-22, and non-implementers if they had not started the process. We use the Center for Rural Pennsylvania definition of rural: counties with RESULTS/ANTICIPATED RESULTS: We collected data from 48/74 (64.9%) hospitals with L&D units. Hospitals were heterogenous with 18/48 (37.5%) in rural counties and 15/48 (31.3%) identifying as academic. A minority of hospitals provide IPP LARC, with 17/48 (35.4%) offering implants and 16/48 (33.3%) offering intrauterine devices (IUD) immediately postpartum. Before the PA Medicaid payment policy change, few offered implants [4/48 (8.3%)] or IUDs [1/48 (2.1%)]. Non-rural hospitals implemented IPP LARC more often and on an earlier timeline than rural hospitals: [7/30 (23.3%) v 3/18 (16.7%)] sustainers, [5/30 (16.6%) v 2/18 (11.1%)] implementers. Common facilitators include clinical champions, meeting patient needs, and adequate knowledge. Planned analyses include implementation barriers, and impact of external implementation support. DISCUSSION/SIGNIFICANCE: Despite unmet need in rural populations for evidence-based contraception, rural hospitals were less likely to implement IPP LARC. Implementation support should be designed to meet the needs of rural hospitals. Implementation science methods can be translated to evaluate the impact of healthcare policy on access to care.
416 A Comparison of Bone Stresses in Transtibial and Transfemoral Osseointegrated Prostheses
Authors: Tinsley Jake , Gaffney Denver Brecca , Stoneback Jason
Published: April 2023

OBJECTIVES/GOALS: This investigation aimed to develop and validate a subject-specific finite element analysis (FEA) model with subject-specific mechanical loads during walking and to use this method to compare mechanical stresses between transfemoral and transtibial osseointegrated (OI) implants. METHODS/STUDY POPULATION: One patient with a unilateral transtibial OI prosthesis and one with a unilateral transfemoral OI prosthesis participated in motion analysis to collect kinematics and ground reaction forces during overground walking. Subject-specific musculoskeletal models were created, and static optimization was used to estimate muscle and joint reaction forces throughout walking. 3D FEA models of the tibia, femur, and implants were created using ScanIP and exported into ABAQUS CAE. Muscle forces were applied at corresponding origin/insertion locations, determined from the musculoskeletal models [7]. Fixed boundary conditions were applied at proximal joint centers, and bone stresses throughout gait were calculated. OpenSim and FEA derived estimates of joint reaction forces were compared for validation. RESULTS/ANTICIPATED RESULTS: A maximum stress of 65.53 MPa and 60.70 MPa was observed at the bone-implant interface for the transtibial and transfemoral patients (respectively) in the late stance phase of the walking task, corresponding to terminal stance and heel off. Averaged root mean squared errors of the walking task (in the anterior-posterior, inferior-superior, and medial-lateral directions, respectively) for the transtibial and transfemoral patients were (124, 152, 80) N, (71, 80, 30) N, and (190, 62, 30) N, respectively. DISCUSSION/SIGNIFICANCE: The purpose of the above study was to develop a methodology for determining subject-specific mechanical loads during walking using finite element analysis and compare mechanical stresses in patients with transfemoral and transtibial OI. Similar stresses between the two implant types were found.
417 A CTS Team Approach to Developing an Effective Vaccine for Non-Typhoidal Salmonella
Authors: Emerson Lisa E. , Rainey Andrew L. , Maurelli Anthony T. , Edelmann Mariola J.
Published: April 2023

OBJECTIVES/GOALS: Non-Typhoidal Salmonella causes over 95 million infections globally each year, and no effective vaccine exists to combat infections in humans. The goal of this study is to determine the immune protection provided by a novel extracellular vesicle (EV)-based vaccine generated using lab-strain Salmonella against wastewater-derived Salmonella. METHODS/STUDY POPULATION: We isolated Non-Typhoidal Salmonella (NTS) from raw influent wastewater samples collected from two wastewater reclamation facilities (WRF) in Gainesville, FL. Whole genome sequencing was performed on each isolate and compared to sequences of clinically-derived isolates in FL during our study period to identify a clinical and subclinical isolate for assessing EV based vaccine protection. Mouse serum and stool samples were collected from a cohort of EV-vaccinated mice. Surrogates of protection against Salmonella used anti-Salmonella IgA in the feces of these mice, and anti-Salmonella IgG in serum of the mice, by using ELISAs coated with whole cell lysate collected from the two wastewater-derived isolates. RESULTS/ANTICIPATED RESULTS: We have previously shown that an EV vaccine provides protection against Salmonella enterica Serovar Typhimurium, the serovar used in the generation of the EV vaccine. We anticipate that the EV vaccine generates additional protection against the community-acquired strains, which will be characterized by increases in fecal IgA and serum IgG against two community Salmonella isolates that is similar to responses against the serovar used to generate the EV vaccine (Typhimurium). DISCUSSION/SIGNIFICANCE: This study will improve the translation of our vaccine studies by demonstrating the efficacy of our novel EV vaccine against circulating Salmonella isolates.
418 A CTS Team Approach to Fetal Hyperinsulinemia in Diabetic Pregnancy and its Effects on Vasculature and Early Life Metabolism
Authors: Pruitt Jennifer , Mahadevan Aditya , Jones Helen , Parker Leslie A.
Published: April 2023

OBJECTIVES/GOALS: Fetal glucose dynamics mediate many of the adverse outcomes seen in infants of diabetic mothers (IDM). The goals of this study are to identify: (1) rates of blood glucose change in normoglycemic and hypoglycemic IDM; (2) their relation to in-utero insulin exposure; and (3) their transcriptional impacts on placental and umbilical vasculature. METHODS/STUDY POPULATION: Using a longitudinal prospective study design, placental/umbilical cord tissue and maternal hemoglobin A1c (HbA1c) are being collected from mothers diagnosed with Type 1, Type 2, or gestational diabetes mellitus. Blood glucose levels are also collected from their infants at birth, and every 3-4 hours for up to 9 hours to determine the rate of change. Linear regression modeling will be used to determine associations between placental and umbilical endothelial RNA expression, umbilical cord insulin levels, and maternal HbA1c within each diabetic sub-type. Gene expression from endothelial specimens will be compared between diabetic sub-types and between normoglycemic and hypoglycemic infants via paired t-tests using Benjamini-Hochberg procedure for false discovery rate correction. RESULTS/ANTICIPATED RESULTS: We hypothesize the following; (1) glucose levels will have a steeper rate of change in hypoglycemic infants; (2) maternal HbA1c and in-utero insulin levels will correlate with the level of transcriptional change identified in placental and umbilical endothelial samples; (3) a negative association will exist between cord insulin levels and the rate of change in infant glucose levels; and (4) a positive association will exist between cord insulin level and transcriptional change on the placental and umbilical endothelium. DISCUSSION/SIGNIFICANCE: Identifying gene expression changes in diabetic placental/umbilical endothelium, and the role of insulin/glucose in these changes, is key to managing diabetic vasculopathy and its adverse outcomes. Understanding infant insulin response may also guide management of hypoglycemia and decrease the risk for neonatal intensive care unit admission.
420 A novel mouse model of COVID-19
Authors: Milicic Stanic Branka , Dugal Nisha , Shults Nataliia , Ji Hong , de Souza Aline M.A. , Hawkins Seth , Wu Xie , Saavedra Juan M. , Sandberg Kathryn
Published: April 2023

OBJECTIVES/GOALS: Rodents are the most widely used experimental animals to study disease mechanisms due to their availability and cost-effectiveness. An international drive to investigate the pathophysiology of COVID-19 is inhibited by the resistance of rats and mice to SARS-CoV-2 infection. Our goal was to establish an appropriate small animal model. METHODS/STUDY POPULATION: To recreate the cytokine storm that is associated with COVID-19, we injected angiotensin converting enzyme 2 knockout (ACE2KO) mice (C57BI/6 strain) with lipopolysaccharide (LPS) intraperitoneally and measured the expression of multiple cytokines as a function of time and LPS dose. We then chose a minimum dose (500ug/kg) and time (3h) when multiple cytokines were elevated to measure lung injury scores using a point-counting technique on tissue sections stained with hematoxylin and eosin. The data are expressed as mean percentage of grid points lying within the peribronchial and superficial area in up to 20 fields. Percentage of peribronchial and superficial intrapulmonary hemorrhage, congestion, neutrophil infiltration and area of alveolar space were all assessed. RESULTS/ANTICIPATED RESULTS: Compared to the wildtype group (WT-G), the LPS-injected ACE2KO mice (LPS-G) exhibited a higher percentage of peribronchial intrapulmonary hemorrhage [(%): LPS-G, 10.56 ± 2.06 vs. WT-G, 5.59 ± 0.53; p DISCUSSION/SIGNIFICANCE: Establishing this novel mouse model of COVID-19 will facilitate studies investigating tissue-specific mechanisms of pathogenesis in this disease. This model can also be used to discover novel therapeutic targets and the design of clinical trials focusing on diagnostics, treatments and outcomes in COVID-19.
422 Addressing complex and urgent problems through innovative team science: The University of Miami Laboratory for Integrative Knowledge (U-LINK)
Authors: Das Rosalina , Olivares Eva , Dominguez Sheela , Kobetz Erin
Published: April 2023

OBJECTIVES/GOALS: The goal of U-LINK is to bring together diverse scholars from multiple disciplines to address complex and challenging problems in healthcare, climate change, social equity, and community, through innovative team science, and aligned with the University of Miami’s strategic plans. METHODS/STUDY POPULATION: The U-LINK program has supported developmental and implementation projects through a competitive selection process. Developmental funding was intended for teams to develop and refine ideas and to become established as an effective team. Additional funding was provided to teams to advance their projects by conducting data collection and feasibility testing. In addition, U-LINK has supported fellowship for pre-doctoral and affiliated doctoral trainees. Team science training was provided to all teams through didactic lectures and hands-on training. Teams were tracked longitudinally by using surveys and bibliometrics to measure success and impact including scholarly output and follow on funding. Network analysis was performed to analyze research collaboration networks before and after ULINK funding. RESULTS/ANTICIPATED RESULTS: U-LINK has funded pilot programs and initial phases for 57 projects and 13 fellowships in the last three years. Over 400 individuals on teams from 16 schools/academic units collaborated on these projects on topics such as resilience, climate change, social equity and societal challenges, health, and impact of recent legislation on LGBTQ+ community. While data collection and analysis are ongoing, initial results show successful outcomes from U-LINK projects including publications and $29.5m in follow-on external funding. We anticipate network analysis to demonstrate increased and continued multi-disciplinary collaborations among U-LINK teams through co-authorship networks and increase in collaborative grants being submitted and/or funded. DISCUSSION/SIGNIFICANCE: The University of Miami’s U-LINK program has demonstrated success in forming interdisciplinary teams that have produced real-world solutions to complex problems by harnessing the inherent diversity and strength across UM’s programs.
423 An omega-6-derived eicosanoid negatively regulates platelet reactivity of cardiovascular patients at increased risk for thrombosis
Authors: Yamaguchi Adriana , Prieur Amanda , Holman Theodore R. , Sutton Nadia R. , Holinstat Michael
Published: April 2023

OBJECTIVES/GOALS: This study aimed to investigate the mechanistic effects of the omega-6-derived eicosanoid 12-HETrE on platelets of cardiovascular patients at risk for a recurrent cardiovascular event triggered by thrombosis. 12-HETrE negatively regulates platelet reactivity through binding to the prostacyclin receptor in platelets. METHODS/STUDY POPULATION: Healthy donors were recruited from the Ann Arbor community and the University of Michigan Medicine Center. Cardiovascular patients with elevated cardiovascular risk were recruited from the Cardiac Catheterization Laboratory at Michigan Medicine Hospital. All subjects were recruited under study protocols approved by the University of Michigan IRB. Healthy donors were matched with the cardiovascular patients regarding age, sex, race, and BMI. Whole blood was collected via venipuncture into vacutainers containing sodium citrate. Platelets were isolated via serial centrifugation and treated ex vivo with vehicle control, 12-HETrE, or Iloprost. RESULTS/ANTICIPATED RESULTS: Based on our previous studies, we chose to treat platelets ex vivo with 25uM of 12-HETrE for 10 minutes. Using platelets of healthy donors, we have shown that treatment with 25uM of 12-HETrE for 10 minutes inhibited platelet aggregation and activation, and activated protein kinase A, suggesting activation of the prostacyclin receptor. We conducted a preliminary study to demonstrate that ex vivo treatment of 12-HETrE regulated signaling pathways in platelets such as cell-to-cell interaction, platelet activation and cytoskeleton rearrangements. In this study, we have demonstrated that treatment with 12-HETrE regulated receptors and intraplatelet proteins in platelets of cardiovascular patients. Furthermore, these proteins are involved in critical pathways in the platelet. DISCUSSION/SIGNIFICANCE: Dual antiplatelet therapy has significantly decreased mortality due to thrombotic events. However, cardiovascular events triggered by thrombosis persist as the leading cause of death in the US. This study may uncover key regulators to be targeted for the long-term goal of providing additional protection to reduce future incidence of thrombosis.