bluuebunny/crossref_metadata_2025 huggingface dataset:
190 Filling the Gap: Perspectives from a long-standing Community Engagement Advisory Board on conducting community-engaged research that emphasizes the needs of communities
Authors: Morales Sandra , Gore Devyani , Cua Grace , Segovia David , Rusch Dana , Mehta Tara , Atkins Marc ,   Community Engagement Advisory Board Steering Committee
Published: April 2023

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.
199 M-REACH: The Process of Discovering How the Academy and Community Connect to Partner in Translational Research
Authors: Piechowski Patricia , Spiroff Meghan , Doshi Aalap , Woolford Susan J. , McKay Athena , Calhoun Karen , Gipson Polly Y. , Marsh Erica E.
Published: April 2023

OBJECTIVES/GOALS: To identify insights and challenges in community engaged research for the academy and community. To develop an online platform to match academic and community partners; promote networking; and provision of key resources. METHODS/STUDY POPULATION: Using a human-centered design approach, 19 interviews were conducted with academics, community organizations and members, and other CTSAs. The interviews focused on understanding CEnR challenges and processes in partnership formation. RESULTS/ANTICIPATED RESULTS: Findings revealed the following 10 challenges to and insights about CEnR: (1) time intensive; (2) lack of knowledge; (3) differing motivations; (4) connections occur through networking; (5) topic area, proximity, and readiness influence partnerships; (6) organizational turnover; (7) promotion pressure; (8) collaboration throughout; (9) navigator for partnership; and (10) lack of shared language. Also, a CEnR system flowchart revealed the following five phases of an effective partnership: 1) generating interest; 2) learning process; 3) connecting with the right partner; 4). Defining the research question; and 5) implementing research as a partnership. DISCUSSION/SIGNIFICANCE: In conclusion, input from academicians and community members support the need for an online platform like M-REACH to facilitate CEnR partnerships, networking, and resources to address significant public health issues through translational research.
201 Neighborhood socioeconomic deprivation is not an independent predictor of cardiovascular reactivity during static exercise in young adults
Authors: Linder Braxton A. , Hutchison Zach J. , Barnett Alex M. , Tharpe McKenna A. , Culver Meral N. , Jeong Soolim , Nichols Olivia I. , Fuller-Rowell Thomas E. , Robinson Austin T.
Published: April 2023

OBJECTIVES/GOALS: Greater blood pressure (BP) reactivity and socioeconomic deprivation (e.g., area deprivation index; ADI) are associated with poor vascular health [1-3]. However, it is unclear if ADI is associated with BP reactivity. Thus, we sought to examine if ADI is associated with BP reactivity in young adults. METHODS/STUDY POPULATION: Participants completed questionnaires used to derive lifetime ADI averaged from early-, mid-childhood, and adolescence. Participants completed a handgrip (HG) exercise protocol including 10 minutes of rest, 2 minutes of static HG at 40% of their maximal voluntary contraction, 3 minutes of post-exercise ischemia (PEI), and 2 minutes of recovery (REC). Beat-to-beat BP (photoplethysmography) and heartrate (HR; electrocardiogram) were continually assessed. We used the Shapiro-Wilk test to assess data for normality. We examined associations between ADI, BP reactivity, and HR using unadjusted and body mass index (BMI), sex, and race-adjusted Pearson’s correlation (set a priori to 0.05). RESULTS/ANTICIPATED RESULTS: This study included 53 (27Males/26Females; 21 ± 1 years; 24Black/29White; BP 107 ± 9/64 ± 9 mmHg) participants. There were racial differences (Black compared to White adults) for several BP reactivity metrics (e.g., PEI minute 3 diastolic BP: 96 ± 15 vs. 84 ± 19 mmHg, p=0.014) and lifetime ADI (p0.050). DISCUSSION/SIGNIFICANCE: Our data suggest racial differences exist in socioeconomic deprivation in a modestly sized young adult sample living in the southeast. While additional data are needed for other stressors, socioeconomic deprivation was not independently associated with BP or HR reactivity during acute exercise.
227 The History of PACER (Partners for the Advancement of Community Engaged Research) as a Special Interest Group of ACTS
Authors: Millay Tamara A. , Eder Milton , Cottler Linda B.
Published: April 2023

OBJECTIVES/GOALS: To outline the successes of Partners for the Advancement of Community Engaged Research (PACER), a Special Interest Group (SIG) of ACTS, created to bring together academic and community researchers to promote best practices, contribute to science and form collaborative networks to improve public health through community research and dissemination. METHODS/STUDY POPULATION: Developed from the CTSA Key Function Committee, PACER began monthly meetings in early 2015. Zoom replaced teleconference technology for the initial email list of about 100 people from 50 institutions which has grown to 225 members from 88 affiliates. Meeting attendance is 40 to 50. PACER meetings start with operational updates and member announcements (15 minutes), proceed to presentations (20-25 minutes), followed by Q & A and discussion (20 minutes). A subset of members functions as an Operations Workgroup, meeting monthly to discuss emerging issues and guide the group’s activities. Email traffic is intentionally limited to one or two messages a month, including meeting announcements. RESULTS/ANTICIPATED RESULTS: PACER meetings have included 65 presentations. Featured speakers have described local community engaged research, explored methodology, and talked about diversifying the workforce, ethics, programs and partnerships. PACER members have collaborated on three manuscripts published in the Journal of Clinical and Translational Science; one with 50 members and 20 institutions contributing. Additionally, PACER members obtained two federal grants, including a network to recruit underrepresented scientists and diverse participants for the All of Us precision medicine effort. These projects totaled $23.5M in funding and involved 9 CTSA hubs. Measuring the value of ongoing dialogue and promulgation of successful practices through presentations has proven challenging. DISCUSSION/SIGNIFICANCE: ACTS support helps PACER SIG members share research interests, develop papers and proposals, and archive meeting materials on the SIG webpage. Beginning with Translational Science 2018, the in-person PACER meeting is a much-anticipated opportunity to meet colleagues and foster new collaborations, and is a critical addition to the PACER calendar.
231 Training Medical Interns and Graduate and Professional Students on Community Engaged Research: Lessons Learned from Implementing a Community Scholars Program
Authors: Kas-Osoka Chioma , Lipham Lexie , Murry Velma McBride , Wilkins Consuelo , Miller-Hughes Stephania , Ahonkhai Aima
Published: April 2023

OBJECTIVES/GOALS: 1. Describe the development and implementation of a Community Scholars Program to train graduate and professional students on principles of community engagement and its application to their research. 2. Evaluate lessons learned and overall impact implementing a Community Scholars Program. METHODS/STUDY POPULATION: After identifying a need to train scholars on the principles of community engagement, the Community Engagement Research Core’s (CERC) Community Advisory Council (CAC) developed the Community Scholars Program (CSP) in 2014. The CSP was designed to educate scholars on community engaged research and how it can be applied to their research projects. The program is currently in its ninth cohort with 19 graduate and professional students having participated in the program to date. Prospective scholars identify a community partner and faculty mentor and apply to conduct a community engaged research project over the course of an academic year. The purpose of this project is to describe the development and implementation of a CSP and identify lessons learned throughout the process. RESULTS/ANTICIPATED RESULTS: Five lessons learned have been identified: five major lessons learned from implementing the CSP: (1) establish partnership agreements between the scholars and their community partners and faculty mentors, setting expectations to avoid conflict and increase mutual understanding; (2) expand and implement more creative outreach approaches to cultivate a more diverse pool of applicants; (3) increase networking between current and past scholars to share experiences and serve as a resource for each other; (4) provide formal CE training for scholars to develop a better understanding of the principles of CE and CE research; and (5) document progress of the program through formal feedback and evaluations. DISCUSSION/SIGNIFICANCE: The CSP was constructed to fill a gap in CE research training for graduate and professional scholars. Over the course of the program, the identified lessons learned have created program clarity and increased accountability for scholars, mentors, and community partners alike.
236 Using Learning Health System Principles to Improve Cancer Research: The Citizen Scientist Cancer Research Curriculum
Authors: Brishke Janet , Jones Zachary , Shenkman Elizabeth
Published: April 2023

OBJECTIVES/GOALS: Team science is a focus of the University of Florida Clinical and Translational Science Institute (UF CTSI) Learning Health System Initiative. Citizen Scientists (CSs) are integral research partners who provide pragmatic feedback. The UF Health Cancer Center (UFHCC) aspired to adopt a similar approach to research, starting with onboarding CSs. METHODS/STUDY POPULATION: To understand the content with which they would be engaging through the CTSI, CSs first became certified through a self-paced online curriculum focused on clinical research basics. UFHCC envisioned their onboarding as a companion piece to this first course, and CSs must complete both courses to work in cancer-focused research. The new CS Cancer Curriculum consists of a mix of didactic lessons with quizzes, case studies, a behind-the-scenes look at a research lab meeting, and interviews with CSs. As with the clinical research course, the cancer course was co-developed alongside the CSs and utilized the ADDIE (Analysis, Design, Development, Implementation, Evaluation) instructional design model. The course was implemented with UF CSs from July to September 2021 through Canvas. RESULTS/ANTICIPATED RESULTS: For the nine CSs completing this pilot test, scores for all didactic quizzes across the course were mostly high. Two CSs scored a perfect 100%, three missed only one question (98%), and two CSs missed two questions (96%). A course evaluation was completed by eight of the CSs and determined that most (86%) felt that they were capable of applying what they had learned. An additional 75% felt the course empowered them to advocate for the needs of all stakeholders involved in cancer research. Qualitative responses on the evaluation found that the course helped CSs better relate to the challenges faced by other stakeholders (patients, clinicians, caregivers) and helped them conceptualize how they could contribute to cancer research. DISCUSSION/SIGNIFICANCE: The partnerships within the UF CTSI have a direct impact on patient care through research studies in Florida and nationwide. CSs can be overlooked by researchers unfamiliar with concepts of a learning health system, including those in cancer research. By engaging these stakeholders, we may soon see similar impacts to cancer-related patient care.
241 Examining Relationships between and Experiences of Patient and Provider Factors and Access to, Use of and Disparities in Postpartum Care: A Mixed Methods Study
Authors: Rattan Jesse , Turan Janet , Bartlett Robin , Sinkey Rachel
Published: April 2023

OBJECTIVES/GOALS: Alabama has the 3rd highest maternal mortality ratio in the U.S., with more than 50% of deaths occurring postpartum. There is little evidence on the prevalence or equity of postpartum care use in Alabama. This mixed methods study examines relationships between patient and provider factors and access to, use of, and racial disparities in postpartum care. METHODS/STUDY POPULATION: I will use a sequential explanatory mixed methods design. In the quantitative phase I will analyze an integrated electronic health record and human resource dataset to identify patient and provider factors that have a relationship with receipt of at least one postpartum visit within 12 weeks of delivery in a cross-sectional, retrospective cohort of 30,000 obstetric patients in Alabama. In the qualitative phase I will describe the postpartum experiences of obstetric patients who identify as Black or African American who received or did not receive at least one postpartum visit within 12 weeks of childbirth. In the integration phase I will draw synthesized conclusions about how the results of both phases describe predictors of and barriers and facilitators to postpartum care for Black birthing people in Alabama. RESULTS/ANTICIPATED RESULTS: I will identify relationships between patient factors (e.g., race, racial concordance with primary provider, insurance status, age, parity, type of delivery, Area Deprivation Index, presence of a chronic condition or severe morbidity) and patient receipt of postpartum care. I will also explore whether health care provider factors (e.g., race, racial concordance with the patient, age, gender, provider type, years of experience) predict patient receipt of postpartum care in this retrospective cohort. In the qualitative phase, I will explore the experiences and perceptions of birthing people who identify as Black or African-American that help explain the relationships between patient and provider factors and receipt of postpartum care identified in the quantitative phase. DISCUSSION/SIGNIFICANCE: More than 50% of maternal death occurs after childbirth. Postpartum care is critical to birthing people’s survival, especially in states with high maternal mortality. This study will fill a gap in knowledge about factors that have a relationship with equitable postpartum care in Alabama.
256 Addressing the Underdiagnosis of Familial Hypercholesterolemia
Authors: Kalia Isha , Shope Ronald , Reilly Muredach , Schwartz Lisa
Published: April 2023

OBJECTIVES/GOALS: Familial Hypercholesterolemia (FH) is a common disorder that is vastly underdiagnosed and causes an increased risk for sudden cardiac death. Cardiology providers (CHCPs) are in an ideal position to care for patients with FH. This research aimed to understand the practice behaviors of CHCPs in the screening, diagnosis, and management of FH. METHODS/STUDY POPULATION: An explanatory mixed methods design was utilized for this study. Adaptation of an existing FH knowledge tool guided survey development. The results of the quantitative survey, along with the Knowledge to Action framework and Theory of Planned Behavior, guided development of the interview protocol. Convenience and snowball sampling recruited CHCPs in the Division of Cardiology at Columbia University Irving Medical Center (CUIMC). Descriptive statistical analysis was performed on survey data. Qualitative interviews were conducted with survey respondents who volunteered to participate. Interviews were audio recorded, transcribed, and analyzed thematically. A descriptive review of the educational materials offered by the Division of Cardiology was conducted to identify FH knowledge domains presented. RESULTS/ANTICIPATED RESULTS: CHCPs with MDs, at CUIMC for 6-10 years, in clinical practice for 1-5 years, and in Inpatient Services had the highest average total FH knowledge scores. CHCPs with RNs, at CUIMC for less than 1 year, in clinical practice for 6-10 years, and in Cath Lab had the lowest average FH knowledge scores. Twenty interviews were completed, and four themes emerged- variability in FH care; issues related to addressing FH at institutional, practice setting and individual levels; importance of identifying FH early; and intervention approaches to overcome barriers to caring for FH patients in cardiology. CHCPs with MDs or with experiential FH knowledge were the only CHCPs to describe FH care beyond the point of screening. The document review revealed that only MDs were provided four lectures over the course of 4 years pertaining to FH. DISCUSSION/SIGNIFICANCE: CHCPs with didactic or experiential FH knowledge provided care beyond screening. Future interventions should increase didactic and experiential FH knowledge by incorporating institutional, local, and national FH resources. Improving the FH care CHCPs provide, can reduce FH-related morbidity and mortality as well as improve FH health outcomes.
272 Differential expression of two Plasmodium falciparum variant surface antigen families in Malian children with cerebral malaria compared to mild malaria
Authors: Lawton Jonathan G. , Zhou Albert E. , Coulibaly Drissa , Stucke Emily M. , Dara Antoine , Laurens Matthew B. , Silva Joana C. , Thera Mahamadou A. , Travassos Mark A.
Published: April 2023

OBJECTIVES/GOALS: Recent in vitro evidence suggests that diverse parasite protein families called RIFINs and STEVORs are displayed on the surface of infected red blood cells and may have a role in severe malaria, but they remain sparsely studied in natural infections. We measured the RNA expression of these antigens in Malian children with severe or mild malaria illness. METHODS/STUDY POPULATION: We collected blood samples from Malian children aged six months to five years, including 14 with cerebral malaria, 10 with severe malarial anemia, and demographic-matched controls with mild, uncomplicated malaria. We extracted total RNA from each patient and used a custom capture array to selectively enrich Plasmodium falciparum parasite RNA. We then performed Illumina next-generation RNA sequencing and reconstructed parasite transcriptomes using reference-free de novo assembly. We identified RNA encoding RIFINs and STEVORs using an in-house classifier, then measured the diversity and abundance of gene expression for each infection. Expression diversity was defined as the number of unique variants transcribed. Expression abundance was calculated as transcripts per million (TPM). RESULTS/ANTICIPATED RESULTS: Cerebral malaria cases, but not severe malarial anemia cases, had higher diversity and abundance of RIFIN expression compared to mild infections. Type A RIFINs predominated over Type B RIFINs, and the same two RIFINs were predominantly expressed in all disease phenotypes. We anticipate that predominantly expressed RIFINs share high sequence homology with variants previously shown to bind blood antigens or immune inhibitory receptors. STEVOR expression was also higher in cerebral malaria compared to mild malaria, but STEVOR transcripts were sparse overall. DISCUSSION/SIGNIFICANCE: Elevated RIFIN expression in cerebral malaria over mild malaria supports a role for these antigens in pathogenesis. Severe malarial anemia may progress through a different pathogenic mechanism. Predominantly expressed RIFIN variants may be promising targets for vaccines and therapeutics to protect children against cerebral malaria.
280 Estimating Latent Attitudinal and Behavioral Risk Profiles and Associations with Food Allergy-Related Quality of Life
Authors: Catlin Perry A. , Hecke Amy Van , Warren Christopher , Gupta Ruchi S.
Published: April 2023

OBJECTIVES/GOALS: Childhood food allergy (FA) is a chronic condition that can profoundly impact patient and caregiver quality of life (QoL). Risk factors for impaired FA-related QoL remain largely unknown. This study aims to estimate latent profiles of caregiver attitudes and behaviors, and examine if group membership correlates with established QoL outcomes. METHODS/STUDY POPULATION: This project is subsumed under the FORWARD study (5R01AI130348-04), a multisite longitudinal cohort study conducted at four major pediatric medical centers. Eligible participants include caregivers of children ages 12 years and under who identify as Black or White and have at least one physician-diagnosed FA. Participants complete intake surveys, annual clinical visits, and quarterly surveys administered via REDCap. As of November 2022, 413 Non-Hispanic Black and 486 Non-Hispanic White participants were enrolled. RESULTS/ANTICIPATED RESULTS: We anticipate that specific latent profiles will emerge based on caregiver-reported attitudes and behaviors. We predict these profiles will demonstrate configural, metric, and scalar invariance across key sociodemographic strata (e.g., child race/ethnicity, household income, caregiver educational attainment, and child sex). Relatedly, we anticipate that sociodemographic factors, such as race, sex, ethnicity, parental education, and income, will significantly predict group membership. Finally, we predict that latent profile membership will be associated with different levels of quality of life, as assessed by the parental food allergy-related quality of life questionnaire (FAQLQ-PF-10) and other validated measures of FA-related psychosocial burden. DISCUSSION/SIGNIFICANCE: Given the psychosocial burden associated with FA, and limited mental health resources for patients and families, it is essential to improve understanding of how caregiver attitudes influence behavior and disease management outcomes. In so doing, we will inform the development and implementation of tailored interventions for those at highest risk.
285 Genetic Variation in the SLC22A1-3 Genes Influence the Risk of Congenital Anomalies
Authors: Brokamp Elly , Shuey Megan , Miller-Flemming Tyne , Cox Nancy J.
Published: April 2023

OBJECTIVES/GOALS: Congenital anomalies (CA) are common, but the cause is often unknown. The interplay between known environmental teratogens, such as medication use in pregnancy, and genetic predisposition impacts CA risk, but such interactions are poorly understood. We test the hypothesis that pharmacogenomic (PGx) variation impacts CA risk. METHODS/STUDY POPULATION: We performed a drug absorption, distribution, metabolism, and excretion (ADME) gene-wide association study (GWAS), which tests for a possible association between ADME gene single nucleotide polymorphisms and individuals with CAs. This analysis was performed in BioVU and utilized billing codes to identify 5,845 cases, individuals with at least one CA, and 50,059 controls of genetically European ancestry. Using Plink software we analyzed 5,398 SNPs in 292 ADME genes across cases and controls. Results from this analysis drove us to further investigate the association between CA risk and SLC22A1-3. Next, we performed PrediXcan analyses to estimate the association between genetically predicted gene expression (GPGE) of SLC22A1-3 genes across all available tissues in the GTEx resource and CA risk. RESULTS/ANTICIPATED RESULTS: The ADME GWAS identified multiple variants on chromosome 6 in the region of SCL22A1-3 that were associated with the risk for CAs. The most significant variants were rs2048327, rs2292334, rs3088442, rs1810126, rs376563, and rs7758229, p DISCUSSION/SIGNIFICANCE: The combination of the known crucial pharmacological roles of OCT1-3 and the results of our ADME GWAS / PrediXcan analyses demonstrates that PGx burden, specifically variation in the SLC22A1-3 genes, influences the risk of developing CAs. This new understanding has the potential to personalize care for pregnant individuals to reduce the risk of CAs.
288 Harnessing the potential of transcriptional adaptation as a mechanism for Amyotrophic lateral sclerosis
Authors: Gomez Adriana Morales , Staff Nathan , Ekker Stephen C.
Published: April 2023

OBJECTIVES/GOALS: Understanding the mechanism of transcriptional adaptation may contribute to an explanation for variation in clinical manifestations of Amyotrophic lateral sclerosis patient phenotypes. METHODS/STUDY POPULATION: To examine transcriptional adaptation, we utilized gene editing tools in HT1080 cells and patient samples with known CHCHD10 mutations causative for Amyotrophic lateral sclerosis. Frameshift mutations were performed via CRISPR-Cas9. Ribonucleoprotein electroporation was used to transfect cells and DNA sequencing was conducted to validate gene editing. To validate transcriptional adaption, changes in levels of protein and gene expression will be measured via immunoblot and quantification of CHCHD10 and CHCHCD2 from whole cells lysates of the edited cells. RESULTS/ANTICIPATED RESULTS: We anticipate that CHCHD2 transcriptional adaptation can functionally compensate for the locus loss of function of CHCHD10. This mechanism of transcriptional adaptation may contribute to an explanation for variation in clinical manifestations of patient phenotypes. DISCUSSION/SIGNIFICANCE: Our approach would advance discovery science towards by exploring CHCHD10/2 transcriptional adaptation mechanism that can lead to novel therapies for rare Amyotrophic lateral sclerosis, such as CHCHD10-R15L.
295 Identification of Proteomic Biomarkers in Puerto Ricans with Pancreatic Cancer
Authors: Santiago-Gonzalez Juan C. , Miranda Eric , Hernandez Pedro , Serrano Horacio , Hallman Deana
Published: April 2023

OBJECTIVES/GOALS: Our objective is to establish a proteomic protein labeling method from tumor tissue and blood samples obtained from patients undergoing surgery for pancreatic cancer in Puerto Rico. Our goal is to discover potential biomarkers in the patient tumor/blood samples that are not expressed in normal control samples obtained from potential organ donors. METHODS/STUDY POPULATION: A pilot study with ten patients undergoing surgery for pancreatic cancer will obtain tumor tissue and blood samples. Protein extracts isolated from tissue/cells will be reduced, alkylated, and digested overnight. Samples will be labeled with TMT reagents and mixed before fractionation and cleanup. Labeled samples will be analyzed with a high-resolution Orbitrap LC-MS/MS before data analysis to identify peptides and quantify the reporter ions. The altered proteins will be analyzed by ELISA to confirm their presence. The protein arrangements will be compared with results from proteomic profile banks to assess their prevalence. As controls, parallel protein analyses will be performed on normal tissue/blood samples from organ donors, facilitated by our local organ procurement organization. RESULTS/ANTICIPATED RESULTS: We anticipate finding proteogenomic material defining PC and new proteomic subtypes not previously described in this population. In addition, studying protein overexpression and underexpression can identify relevant genes and potential biomarkers. We hypothesize that PC in the Hispanic population will show slight variations in tumor protein expression than in other populations, which could lead to the discovery of a new Hispanic-specific biomarker. DISCUSSION/SIGNIFICANCE: We expect to provide essential information that will influence the next steps in developing future screening tests. Identifying specific proteins with the potential to become a preventive test should eventually lead to a reduction in morbidity and mortality of PC. The results of this work should lay the foundation that can guide future research.
315 Non-invasive and quantitative surgical outcome evaluation of patients with sagittal craniosynostosis undergoing sagittal craniectomy
Authors: Elkhill Connor , Liu Jiawei , Linguraru Marius George , LeBeau Scott , Khechoyan David , French Brooke , Porras Antonio R.
Published: April 2023

OBJECTIVES/GOALS: Craniosynostosis is the premature fusion of one or more cranial sutures that produces brain growth constraints and typically requires surgical treatment. We present an age- and sex-specific method to evaluate surgical outcomes using non-invasive 3D photogrammetry that brings objectivity to the current approach for clinical assessment. METHODS/STUDY POPULATION: First, we created standardized head anatomy representations for 2,020 patients (1,081 males, 939 females, age 3.14 ± 3.05 years) without cranial pathology from their computed tomography (CT) images based on our previous methods. We used principal component regression stratified by sex to establish age-specific normative ranges of anatomical variability and we designed a new metric called cranial shape abnormality (CSA) index that calculates the number of standard deviations from normality of a given patient’s head anatomy. We calculated our CSA index in a group of 56 patients (44 male, 12 female) with sagittal craniosynostosis who underwent sagittal craniectomy from their pre- (22 ± 30 days before surgery) and post-surgical (267 ± 63 days after surgery) 3D photograms to evaluate surgical outcomes. RESULTS/ANTICIPATED RESULTS: We observed a reduction in the CSA index from 1.28 ± 0.26 before surgery to 0.87 ± 0.22 after surgery (p < 0.001 with a paired Wilcoxon test). The CSA index decreased in 53 of 56 patients (94.6%), who consistently showed head shape improvements after corrective surgery during clinical evaluation. Linear temporal regression indicates a CSA index decrease of 0.43 ± 0.05 during the first year after surgery. We found no significant correlation between a patient’s age at surgery and the patient’s CSA index after surgery (Pearson’s correlation coefficient 0.17, p = 0.20) or the patient’s change in CSA index before and after surgery (Pearson’s correlation coefficient 0.22, p = 0.11), suggesting that sagittal craniectomy is equally effective for all patients who are between 85 and 331 days old at the time of surgery. DISCUSSION/SIGNIFICANCE: Our new CSA index is a sex- and age-specific metric of head shape anomalies built upon the observed statistical distributions in the normative pediatric population. Our metric can objectively evaluate pre- and post-surgical head shapes and will allow the investigation of the reported variability in surgical outcomes among patients and procedures.
318 Optimizing the Identification and Prediction of Statin Intolerance to Improve Statin Adherence Using Natural Language Processing and Machine Learning
Authors: Sun Boguang , Zhang Rui , Chi Chih-Lin , Straka Robert
Published: April 2023

OBJECTIVES/GOALS: Aim1: To develop a natural language processing (NLP) algorithm to effectively identify statin associated muscle symptoms (SAMS) in patients’electronic health records (EHRs). Aim2: To develop a machine learning model based on clinical features within EHRs that predict the likelihood of SAMS occurrences. METHODS/STUDY POPULATION: A retrospective cohort of adult patients initiated on statins within the Minnesota Fairview Healthcare System EHRs from 2010 to 2020 will be analyzed. NLP-PIER (Patient Information Extraction for Research) platform will be used to search and identify patients who developed SAMS after statin initiation. Manual annotation of clinical notes will be completed to validate the accuracy of identified SAMS cases. Then, a selection of clinical features within the EHRs will be input as predictors for machine learning algorithms development. Select machine learning classifiers will be deployed to generate models for the prediction of SAMS and the best-performing model will be selected based on model performance. RESULTS/ANTICIPATED RESULTS: The expected outcomes include generation of a fine-tuned NLP algorithm that can rigorously identify SAMS occurrences within EHRs. Further, we anticipate having a practical risk model that accurately predicts patients’risks of developing SAMS when taking statins. DISCUSSION/SIGNIFICANCE: The positive and translational impact of our research will be to equip healthcare providers with such informatics tools to improve statin adherence, ultimately promoting patient optimal health and outcomes by maximizing the tolerance and thus realizing the therapeutic benefits of statins.
331 Reusing EHR Phenotyping Algorithms in Practice: Developing the Colorado Diabetes EHR Research Repository (CODER)
Authors: Wilson Melissa P. , Mayer David A. , Rasmussen Luke V. , Khanal Pramod , Nuriyeva Maryam , McRae Michael , Raghavan Sridharan , Wiley Laura K.
Published: April 2023

OBJECTIVES/GOALS: The rates of computational phenotyping algorithm reuse across health systems are low, leading to a proliferation of algorithms for the same trait. We propose a framework for reusing computational phenotyping algorithms and describe the real-world deployment of this framework for the development of the Colorado Diabetes EHR Research Repository. METHODS/STUDY POPULATION: The novel phenotype reuse framework consists of 4 steps: select algorithms that are appropriate for reuse by assessing whether they are fit for purpose; extend the algorithm to account for changes in data and care practice standards; localize the algorithm to use local database standards and terminologies; optimize the algorithm by applying a data driven approach to achieve the desired local performance. To identify individuals with type 1 diabetes (T1D) or type 2 diabetes (T2D), we selected and implemented T2D algorithms in a cohort of adults with any diabetes or pre-diabetes related diagnosis code, medication, or abnormal glucose-related laboratory test in the clinical data warehouse for UCHealth and the University of Colorado. RESULTS/ANTICIPATED RESULTS: We included a total of 926,290 patients who were identified by initial filters. Patients were more likely to be female (53%), identify as non-Hispanic white (69%) and had a median age of 58 years (IQR: 41, 70). Implementation, extension, localization, & optimization through iterative chart review prioritized high sensitivity for all-cause diabetes and high specificity for T1D and T2D. Of the original cohort, 252,946 (27%) were identified by the all-cause diabetes algorithm. Of these 11,688 were identified as T1D and 135,588 as T2D. After optimization the all-cause diabetes algorithm had 88% sensitivity, 90% specificity, 74% positive predictive value (PPV), and 96% negative predictive value (NPV). Our algorithms for T1D and T2D had high specificity (100% and 99%, respectively) and PPV (100 and 96% respectively). DISCUSSION/SIGNIFICANCE: Developing computational phenotyping algorithms is expensive and time consuming, yet algorithm reuse is low due to a lack of practical approaches for reusing algorithms. We demonstrate application of a novel framework for algorithm reuse, yielding good alignment of algorithm performance with study goals for identifying individuals with diabetes.
348 Translating a precision dosing approach for opioid use disorder in Puerto Rico: Pilot testing of the clinical utility and patient/provider acceptability
Authors: Santiago Darlene , Duconge Jorge , Venkataramanan Raman , Gonzalez Francisco
Published: April 2023

OBJECTIVES/GOALS: The purpose of this pilot study is to evaluate the clinical utility and patient/provider acceptability of a buprenorphine (bup) precision dosing approach for opioid use disorder (OUD) in Puerto Rico (PR) to in estimate the most adequate bup dosing regimen based on the unique pharmacological and clinical characteristics of these patients. METHODS/STUDY POPULATION: The goal of this pilot study is to evaluate the extent to which people delivering (providers) or receiving (patients) opioid use disorder care in PR consider our 'bup precision dosing approach' to be appropriate, based on anticipated or experienced cognitive and emotional responses. We will use the Theoretical Framework of Acceptability (TFA) to conduct this evaluation. We expect to generate a baseline understanding of the acceptability of our bup precision dosing approach in terms of clinical utility and attitudes by OUD patients and providers in clinics in PR, We will conduct focus groups and surveys to document patients and providers perceptions, beliefs, attitudes and reception of our bup evidence-based dosing approach. RESULTS/ANTICIPATED RESULTS: We seek to answer the following questions: How do OUD providers and patients in PR view, and how will they engage with our buprenorphine precision dosing approach? Will our intervention based in science be accepted be these individuals? What are their attitudes towards this? How they perceive the efficacy of this intervention to be? What are the barriers and facilitators of this evidence based intervention? This knowledge is crucial before clinical implementation is pursued, we expect to comprehend the unique attitudes and perceptions of these population that supports the successful implementation in the nearby future and enhance the innovation uptake of our bup dosing model for OUD in PR. DISCUSSION/SIGNIFICANCE: It is important that adequate assessments that assess acceptability and feasibility prior to implementation and while still in developmental phases are conducted to plan ahead for the implementation of interventions since innovation uptake depends largely on contextual factors, not just innovation effectiveness.
358 Using autism symptom profiles at intervention baseline to predict social cognitive outcomes
Authors: Dillon Emily F.
Published: April 2023

OBJECTIVES/GOALS: 1) Investigate the utility of pragmatic communication profiles in a sample of children with autism at baseline to predict response to treatment in a randomized clinical trial (RCT) of oxytocin augmentation and social cognitive skills training at week 12. 2) Determine if levels of anxiety or hyperactivity moderate child outcome performance. METHODS/STUDY POPULATION: 40 children (37M, 3F), aged 8-11(M=9.25, SD=1.10), with confirmed autism spectrum disorder (ASD), enrolled in an RCT(NCT02918864) were evaluated at baseline on: an assessment of ASD (Autism Diagnosis Observation Schedule, ADOS-2), a task of perspective taking, Theory of Mind ToM, (Reading the Mind from the Eyes Task), pragmatic communication (Pragmatic Rating Scale-School Aged; PRS-SA), IQ (WAIS_I, WISC-V) and anxiety and hyperactivity (Behavior Assessment Scales for Children-3; BASC-3). A Tobii T60 XL was used for eye-tracking visual patterns and attention during the RMET. The PRS-SA was coded by trained, reliable clinicians. Parent ratings indicated over half of the participants’ had At Risk levels or higher on anxiety and hyperactivity on the BASC-3. Week 12 measures included all but the PRS-SA and ADOS-2. RESULTS/ANTICIPATED RESULTS: Baseline preliminary analysis indicated the participants spent more time looking at words (.41ms) than eye images on the RMET(.15ms, p DISCUSSION/SIGNIFICANCE: Findings at baseline suggest pragmatic communication skills are more related to ToM than gaze and attention on the RMET. This relationship will be further investigated over the time of the trial. Mental health indicators need to be considered further in this population. Child profiles at baseline may inform appropriate triage and treatment targets.
388 Early Neurorehabilitation of Disorders of Consciousness after Acute Hemorrhagic Stroke
Authors: Woodward Matthew , Arnold Shannon , Wells Chris L. , Salasky Vanessa , Overholt Brandon , Morris Nicholas , Badjatia Neeraj , Podell Jamie , Motta Melissa , Braun Robynne , Dorman Farra , Parikh Gunjan
Published: April 2023

OBJECTIVES/GOALS: Accurate classification of disorders of consciousness (DoC) is key in developing rehabilitation plans following brain injury. The Coma Recovery Scale-Revised (CRS-R) is a sensitive measure of consciousness. We explore feasibility, safety and impact of CRS-R guided rehab in hemorrhagic stroke patients with DoC and evaluate predictors of recovery. METHODS/STUDY POPULATION: Consecutive patients with non-traumatic hemorrhagic stroke, defined as subarachnoid hemorrhage (SAH) or intracerebral hemorrhage (ICH), receiving serial CRS-R assessments during their ICU stay at University of Maryland Medical Center from 2017-2021 were retrospectively identified. Outcomes of interest included the association with CRS-R and discharge disposition, therapy-based function and mobility and occurrence of safety events during CRS assessment. We also examined the association between CRS-R and physiological and anatomical injury pattern on electroencephalography (EEG) and magnetic resonance imaging (MRI), respectively. CRS-R RESULTS/ANTICIPATED RESULTS: 76 patients with≥2 CRS-R assessments were identified (22 SAH, 54 ICH, median age = 59, 50% female). Median CRS-R completed was 3 with no SAEs identified during sessions. We identified 4 patterns: persistent VS/UWS (49%), persistent MCS or better (13%), emergence from VS/UWS to MCS or better (27%) and regression from MCS or better to VS/UWS (11%). Persistent low CRS-R correlated with older age in SAH (p=0.01), female gender in ICH (p=0.04), and history of diabetes (p=0.01). 2% of patients with final CRS-R DISCUSSION/SIGNIFICANCE: Early neurorehabilitation guided by CRS-R appears to be feasible and safe acutely following hemorrhagic stroke complicated by prolonged DoC and may enhance access to inpatient rehabilitation with a lasting benefit on recovery. Further characterization of DoC patterns and their correlation to clinical markers, including EEG and MRI is needed.
395 Hindering Generic Antiretroviral Treatment Competition for Human Immunodeficiency Virus: Anti-Competitive Agreements and HIV Disease Management Concerns
Authors: Crovetto Arianna
Published: April 2023

OBJECTIVES/GOALS: To understand the implications of minimal HIV generic drug availability on long-term HIV disease management, including anti-competitive agreements and patent strategies that hinder (ART) competition and ART medication safety and efficacy improvement. METHODS/STUDY POPULATION: Individuals living with Human Immunodeficiency Virus (HIV) require sustained ART treatment. Despite excessive ART costs, the treatments use active ingredients known to be toxic, causing bone and renal impairments. A review of pharmaceutical legal cases examined the role of strategic patenting–product hopping–and anti-competitive agreements, which prevent generic competition and contribute to minimal ART improvement. A literature review explored the long-term safety effects of ART medications on HIV patients and disease management. A cost analysis of HIV disease management assessed the implications of using treatments with known toxins and their contribution to comorbidities and their effect on the cost of overall HIV disease management. RESULTS/ANTICIPATED RESULTS: Ongoing lawsuits of major ART medication manufacturers demonstrate the intentional agreements made to hinder generic competition, which is an inherently anti-competitive strategy. Thus, prices for ART medications remained high, causing treatment costs to be a significant barrier to treatment access. Further, the entry of a new ART, Tenofovir Alafenamide Fumarate (TAF), was delayed despite knowing the key active ingredient in Tenofovir Disoproxil Fumarate (TDF) was toxic to patients long-term. As a result, patients were more likely to experience comorbidities, significantly increasing the cost of HIV care. The average cost of HIV care without comorbidities is $30,312. However, HIV care is $46,000 for two comorbidities and about $219,000 for people with 11 or more. DISCUSSION/SIGNIFICANCE: Abuse of patent rights prevents more effective HIV medication and generic option development. Thus, HIV disease management is inhibited. The only method of HIV disease management is patient adherence to ARTs. Patients taking less effective medications increase the development of comorbidities from toxic treatments, magnifying the cost of HIV care.
398 Researcher Perceived Barriers in Translational Research
Authors: Mukherjee Sunaina , Gonzalez Anthony , Anwar Farah , Parzecki Isabel
Published: April 2023

OBJECTIVES/GOALS: To identify, categorize, and streamline the wide range of commonly encountered barriers in translational research that prevent studies from progressing along the translational research spectrum through a comprehensive needs assessment survey. Results will be utilized to institute potential solutions to overcome these identified barriers. METHODS/STUDY POPULATION: The comprehensive survey consisted of three sections, Demographics and Background, Self-Reporting of Barriers, and Comments and Feedback. An extensive literature review was conducted to develop and compile questions and barrier categories for the survey. The survey content was derived from primary literature sources and supplemented with the NCATS Translational Science course material. The target population for the survey included all researchers engaged in translational research at the NJ ACTS CTSA hub. The hub includes Rutgers, Princeton, and NJIT and all of their affiliated institutions and partnered healthcare systems, such as Robert Wood Johnson Barnabas Health and University Hospital. Results will be analyzed according to the type of research conducted and stage of translation research (T0-T4). RESULTS/ANTICIPATED RESULTS: Examples of the survey barrier categories being analyzed include Regulatory/IRB, Funding, Collaborations and Networking, and Training. Initial analysis (N=106) consisted of these top barriers in the NJ ACTS CTSA hub: obtaining timely IRB approval, inadequate staffing for the research team, and lack of holistic institutional support. After completion of data collection, the survey results will be further analyzed to determine common barriers and patterns in barrier type across the different institutions, schools, positions/roles in research, and translational research stages. Given that the Comments and Feedback section of the survey entailed ranking the top three barriers across the entire survey as a whole, the results will also indicate the relative prevalence of specific barriers and categories. DISCUSSION/SIGNIFICANCE: The impact of the survey and its results is to develop feasible institutional solutions to overcome the prevalent barriers and improve efficiency in all parts of the research process. Possible solutions encompass accessible resources for researchers, longitudinal training programs, consultative services, and workshops for investigators.