Journal of Clinical and Translational Science最新文献

{"title":"251 The Appalachian Translational Research Network (ATRN) Newsletter: Supporting Communication and Collaboration among Academic and Community Partners to Improve Health in Appalachia","authors":"Ashley Gail Hall, Beverly Stringer, Jeff Grever, Ian Moore, Emma Jones, Rebekah Crawford, Keena Moore, Kristin Miller, Gia Mudd-Martin","doi":"10.1017/cts.2024.230","DOIUrl":"https://doi.org/10.1017/cts.2024.230","url":null,"abstract":"OBJECTIVES/GOALS: The Appalachian Translational Research Network (ATRN) Newsletter provides a unique platform that facilitates communication among Appalachian-serving CTSAs/CTSIs and partnering academic and community organizations that strengthens research efforts and advances translational science across the region. METHODS/STUDY POPULATION: Published biannually, each ATRN Newsletter features content submitted by ATRN member universities and organizations. Members of the Communications Committee, who represent both CTSA- or non-CTSA- affiliated ATRN member institutions, provide as well as review and edit content for the Newsletter. Regular features include researcher and community member spotlights; funding opportunity announcements; information on upcoming seminars, trainings, and special events; and opportunities for collaborations among partnering ATRN institutions. Complementing regularly scheduled Newsletters, special editions are released as warranted, such as a special COVID-19 focused edition published in 2020. RESULTS/ANTICIPATED RESULTS: First published in 2012, the ATRN Newsletter initially represented founding ATRN institutions, the University of Kentucky and the Ohio State University CTSAs, and a readership of 50. Reflecting ATRN growth that now represents 9 academic centers including NCATS- and IDeA-funded hubs, affiliated universities and partnering organizations, readership has grown to include 500 subscribers from across the U.S. and 3 other countries. With the establishment of the official ATRN website in 2019, the ATRN Newsletter became a prominent addition, providing ATRN members’ access to both new and archived editions, thereby expanding reach and further strengthening critical communication across the Network. DISCUSSION/SIGNIFICANCE: Providing a vehicle for communication that supports ATRN collaborations and networking, the Newsletter is foundational to the success of the ATRN mission to improve health outcomes across Appalachia by fostering collaborative inter-institutional and community-academic research partnerships.","PeriodicalId":15529,"journal":{"name":"Journal of Clinical and Translational Science","volume":"51 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140581202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"363 A CRISPR/dCas9 Epigenetic Therapuetic Approach for CASK-Related MICPCH","authors":"Casiana Gonzalez, Julian Halmai, Kyle Fink","doi":"10.1017/cts.2024.322","DOIUrl":"https://doi.org/10.1017/cts.2024.322","url":null,"abstract":"<p>OBJECTIVES/GOALS: CASK-related microcephaly with pontine and cerebellar hypoplasia (MICPCH) is a rare X-linked neurodevelopmental disorder caused by mutations in calcium/calmodulin-dependent serine protein kinase (CASK). We aim to rescue CASK expression via an CRISPR/dCas9 epigenetic therapeutic and create iPSC-based CASK relevant in vitro model systems. METHODS/STUDY POPULATION: As females have two X-chromosomes, disease causing mutations present with a 50/50 expression of mutant and wildtype, due to the mosaicism caused by random X-chromosome inactivation (XCI). This project will adapt an established CRISPR/dCas9 epigenetic approach to rescue expression from the silenced, wild-type CASK allele. We aim to accomplish this through testing different dCas9 orthologues and a guide RNA screen targeting the CASK promoter. Constructs will be tested for optimal targeting efficacy in vitro and assessed via RT-qPCR. Additionally, epigenetic modifications from our approach will be analyzed through bisulfite sequencing. We also aim to apply this epigenetic rescue technology in disease relevant cell lines and eventually in engineered patient mutation iPSC-derived neurons. RESULTS/ANTICIPATED RESULTS: Our results show the ability to target CASK and assess gene expression changes with CRISPR/dCas9 paired with an epigenetic modifier and transcriptional activator. Additionally, our fibroblast model with nonpathogenic single nucleotide polymorphisms within CASKallow for allele specific analysis of our targeted reactivation. We anticipate that following an increase of CASK expression, there would be a decrease in region specific promoter methylation. Further, with the identification of clinically described disease-causing point mutations that result in a loss of function of CASK protein, induction of the mutant sequence onto a healthy cell background will result in a similar reduction of CASK protein in our cell model. DISCUSSION/SIGNIFICANCE: This project will demonstrate the first therapeutic avenue for CASK-related MICPCH, and the potential to utilize targeted X-reactivation as a platform approach for X-linked disorders. Further, investigation of smaller dCas9 orthologues prepares our approach for future translational applications such as packaging into AAV for delivery.</p>","PeriodicalId":15529,"journal":{"name":"Journal of Clinical and Translational Science","volume":"11 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140581604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"473 Application of human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) for modeling of Ankyrin-2 p.R990Q variant-induced ventricular arrhythmia and personalized medicine","authors":"Jyotsna Joshi, Neill Schwieterman, Nate Smole, Shuliang Guo, Xiaoping Wan, Angelina Ramirez-Navarro, Cemantha Lane, Isabelle Deschenes, Thomas Hund, Loren Wold, Sakima Smith","doi":"10.1017/cts.2024.401","DOIUrl":"https://doi.org/10.1017/cts.2024.401","url":null,"abstract":"OBJECTIVES/GOALS: The cytoskeletal protein α²II spectrin interacts with actin and ankyrin-2 in cardiomyocytes which is essential to orchestrate ion channels and membrane proteins in the cardiac dyad. Our goal is to understand molecular mechanism causing severe ventricular arrhythmias due to spectrin dysfunction and explore novel therapies to treat such conditions. METHODS/STUDY POPULATION: We previously published a case of a 36-year-old woman with an ankyrin-2 p.R990Q (ANK2) variant, presented with severe ventricular arrhythmias and sudden cardiac arrest, caused by a novel mutation in the ankyrin-B gene (c.2969G&gt;A) that disrupts the interaction of ankyrin-B/βII spectrin. To model the condition, we will use human induced pluripotent stem cell (DF 19-9-7T, WiCell)-derived ventricular cardiomyocytes (iPSC-CMs) having ANK2 variant, engineered using CRISPR/Cas9 method (Synthego Corp.). We will validate the differentiation of iPSCs into ventricular lineage and characterize the ANK2 ventricular phenotype. Next, we will express light-gated cation channel Channelrhodopsin (ChR2) in the ANK2 iPSC-CMs and investigate the potential role of optogenetics in treating such severe arrhythmias. RESULTS/ANTICIPATED RESULTS: Immunostaining shows 87.339% of iPSC-CMs, treated with All-trans retinoic acid (RA) (1 uM) on days 7 and 12 [RA 7,12], and 23.84% of those, treated on days 3 and 5 [RA 3,5], expressed MLC-2V (p&lt;0.001). Calcium reuptake (τ) is 0.5914 s in RA 7, 12 while 0.2247s in RA 3, 5 (p&lt;0.001). APD90 and APD50 of RA 7, 12 are 2- and 5-fold higher than RA 3, 5, showing distinct ventricular and atrial phenotypes. Protein expression of βII-spectrin and ankyrin-2 and their co-localizations were reduced in the ANK2 phenotype compared to the healthy phenotype. We found prolongation of Ca2+ waves and τ with blue light on iPSC-CMs, expressing ChR2. We anticipate that such prolongation of calcium transients would prevent aberrant calcium spikes, rescue Ca2+/calpain-induced βII-spectrin loss and provide electrical stability. DISCUSSION/SIGNIFICANCE: Animal models cannot accurately recapitulate human cardiac electrophysiology. The proposed human iPSC-CM-based ANK2 model would provide better mechanistic insights of severe ventricular arrhythmias. Also, the proposed optogenetic cardioversion has the potential to provide safe, targeted and painless cardioversion to manage arrhythmias.","PeriodicalId":15529,"journal":{"name":"Journal of Clinical and Translational Science","volume":"42 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140581291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"81 A rapid-cycle application of the Consolidated Framework for Implementation Research allows timely identification of barriers and facilitators to implementing the World Health Organization’s Emergency Care Toolkit in Zambia","authors":"Taylor Burkholder, Julia Dixon, Morgan Broccoli, Natasha Chenga, Patricia Chibesakunda, Winnie Kunda, Kephas E Mwanza, James Nonde, Mwiche Chiluba","doi":"10.1017/cts.2024.82","DOIUrl":"https://doi.org/10.1017/cts.2024.82","url":null,"abstract":"OBJECTIVES/GOALS: Implementation science evaluations are often too time-intensive to provide actionable feedback during implementation, suggesting the need for more agile methods. We present an evaluation of the World Health Organization’s Emergency Care Toolkit implementation in Zambia using rapid qualitative methods to provide timely feedback. METHODS/STUDY POPULATION: We evaluated the implementation of the Emergency Care Toolkit in eight general and referral hospitals in Zambia in 2023 using a rapid-cycle, qualitative template analysis approach grounded in the Consolidated Framework for Implementation Research (CFIR). We gathered qualitative data from operational field notes, focus groups, and key informant interviews of administrators, clinicians, nurses, and support staff in all eight hospitals in Zambia. We parsimoniously applied CFIR constructs and tool-specific codes, focused on barriers and facilitators, to allow for rapid but comprehensive cross-case analysis. The results were used to generate a matrix of stakeholder-relevant, plain-language barriers and facilitators for each tool. RESULTS/ANTICIPATED RESULTS: We completed eight site visits with focus groups and interviews following initial implementation in September 2023 to gather firsthand knowledge related to implementation of the Toolkit. The CFIR-focused coding accelerated analysis by centering on barriers and facilitators for each tool while maintaining a comprehensive evaluation framework. Summary tables of barriers and facilitators were easily interpreted by lay stakeholders. Visualization in tables allowed for identification of common themes across tools and hospitals, making comprehensive recommendations to the implementation and dissemination process quickly possible. We anticipate the study findings will empower implementing partners to make timely, actionable improvements. DISCUSSION/SIGNIFICANCE: Rapid-cycle qualitative implementation evaluations allow for rigorous yet timely feedback on the implementation process compared to traditional methods. This efficient strategy is particularly important in resource-constrained environments where inefficient implementation wastes limited resources and create delays that cost lives.","PeriodicalId":15529,"journal":{"name":"Journal of Clinical and Translational Science","volume":"61 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140581298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"51 School Shootings and Mental Health in the United States","authors":"Camerin Rencken, Alice Ellyson, Isaac Rhew, Carol A. Davis, Ali Rowhani-Rahbar","doi":"10.1017/cts.2024.62","DOIUrl":"https://doi.org/10.1017/cts.2024.62","url":null,"abstract":"OBJECTIVES/GOALS: It is estimated that 357,000 children have experienced a school shooting since 1999, yet due to limitations in the firearm violence field broadly, the sequalae are not well understood. The objective of this work is to examine the mental health impacts of school shootings, providing insight into the lasting effects of firearm violence on our communities. METHODS/STUDY POPULATION: We will first conduct a quasi-experimental study using controlled interrupted time series with repeated cross-sectional data to assess school shootings’ impact on US mental health. School shooting data is from the K-12 School Shooting Database, and mental health data will be collected via the Behavioral Risk Factor Surveillance System. Second, we will conduct focus groups with community organizations, school administrators, and the public. Interview guides will be developed to explore the mental health impacts of school shootings, to guide the quantitative results interpretation, and assess educational materials’ usefulness. Qualitative analysis will occur in NVivo software with codebook refinement through thematic analysis. Results will be triangulated through convergence coding. RESULTS/ANTICIPATED RESULTS: This research is situated within the context of the pervasive mental health challenges in the US, where mental illness poses significant health, social, and economic burdens. Thus, we anticipate finding an association between school shootings and decreased self-reported mental well-being among US adults. Literature suggests that there may be a stronger association among specific subgroups, such as parents with school-aged children or individuals living in close proximity to such incidents. We expect to find heterogeneity in the effect estimate based on school shooting attributes, such as the number of casualties. Through focus groups, we anticipate furthering our comprehension of the broad-ranging effects of school shootings on less quantifiable outcomes and the unique trajectories of recovery. DISCUSSION/SIGNIFICANCE: This project will contribute needed information on the impact of school shootings and mental health and assist in reducing the frequency and impact of school shootings. Furthermore, we aim to extend our findings beyond the scientific community, translating them into educational resources advocating for policy and public health interventions.","PeriodicalId":15529,"journal":{"name":"Journal of Clinical and Translational Science","volume":"51 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140581299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"91 Using the Health Stigma Discrimination Framework for Understanding Stigma in the Context of Sexual Assault","authors":"Erin Vernetti, Marie Flannery, Natalie LeBlanc","doi":"10.1017/cts.2024.89","DOIUrl":"https://doi.org/10.1017/cts.2024.89","url":null,"abstract":"OBJECTIVES/GOALS: This theory analysis aims to evaluate a middle-range framework, the HSDF1, in the context of sexual assault stigma incorporating the myriad levels within within culture and society through which stigma can occur and be reinforced. METHODS/STUDY POPULATION: Databases: PubMed, CINAHL, EMBASE, Google Scholar, Organization websites, Citation searchesn = 32Mark Risjord’s “Middle-Range Theories as Models: New Criterion for Analysis and Evaluation” (2019) RESULTS/ANTICIPATED RESULTS: The innovative approach of the HSDF guides understanding of sexual assault stigma in a holistic way, incorporating individual and institutional stratum of the phenomenon. Understanding through integration of this theoretical framework alongside current knowledge may more succinctly inform trauma-informed care for survivors, policy, and cultural awareness for nurses, healthcare providers, police, social workers, and myriad others with whom survivors interact. DISCUSSION/SIGNIFICANCE: Applying the HSDF framework to sexual assault stigma could help break down barriers and raise survivors out of stigmatization, affecting population health through reduced negative health sequelae experienced by survivors.","PeriodicalId":15529,"journal":{"name":"Journal of Clinical and Translational Science","volume":"281 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140581336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"454 The Role of bHLHe40 in Systemic Sclerosis-associated Pulmonary Fibrosis","authors":"Adegboyega \"Tim\" Adewale, Carol Feghali-Bostwick","doi":"10.1017/cts.2024.388","DOIUrl":"https://doi.org/10.1017/cts.2024.388","url":null,"abstract":"OBJECTIVES/GOALS: The dominant complication of Systemic Sclerosis (SSc) is clinically severe and commonly fatal pulmonary fibrosis (PF). We sought to determine the downstream regulatory role of the basic Helix-Loop-Helix protein 40 (bHLHe40), in response to Insulin-like Growth Factor II (IGF-II) on Pro-Lysyl Oxidase cleavage products. METHODS/STUDY POPULATION: We examined the response of primary pulmonary fibroblasts cultured from the lungs of control donors and SSc lung explants to IGF-II as well as human recombinant Lysyl Oxidase Propeptide (LOX-PP). In addition, we utilized an experimentally-induced model of lung fibrosis with intratracheal bleomycin administration. We used qPCR and immunoblotting to quantify mRNA and protein levels, respectively. We used sequence-specific small-interfering RNA to silence targeted genes. Immunoblots were quantified in ImageJ (NIH) and statistical analyses were performed in GraphPad Prism. RESULTS/ANTICIPATED RESULTS: IGF-II regulates levels of Pro-LOX, active LOX, and LOX-PP, as well as isoforms of proteases Bone Morphogenetic Protein 1 (BMP1) and Tolloid-like 1 (TLL1). The transcription factorbHLHe40 localizes to the nucleus in response to IGF-II. bHLHe40 silencing downregulated TLL1, abrogating the enzymatic cleavage of Pro-LOX. SSc lungs have higher baseline levels of the total (N-glycosylated/unglycosylated) LOX-PP than normal lung tissues, and baseline levels of LOX-PP correlated with TLL1 Isoform 2 in SSc lungs. LOX-PP contributes to the development and progression of SSc-PF by mediating changes consistent with the extracellular matrix deregulation implicated in SSc-PF: elevated levels of Collagen 3A1 (COL3A1), Fibronectin-1 (FN1), and Plasminogen Activator Inhibitor-1 (PAI1). DISCUSSION/SIGNIFICANCE: Our findings indicate that bHLHe40, TLL1, and LOX-PP may serve as targets of therapeutic intervention to stop the progression of SSc-PF. Since activation of common fibrotic pathways are involved in different diseases characterized by lung fibrosis such as IPF, our findings may have wider implications for lung fibrosis associated with other diseases.","PeriodicalId":15529,"journal":{"name":"Journal of Clinical and Translational Science","volume":"114 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140581364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"206 Cervical Cancer Disparities: Knowledge, Screening and Willingness to adopt testing modalities among Hispanic/Latinx Women in Lake County, Indiana","authors":"Layla Claure, Lara Balian, Natalia Rodriguez","doi":"10.1017/cts.2024.197","DOIUrl":"https://doi.org/10.1017/cts.2024.197","url":null,"abstract":"OBJECTIVES/GOALS: There are notable disparities in cervical cancer screening. Theobjective of this study was to examine knowledge, screening practices, attitudes towards cervical cancer screening, and willingness to adopt screening innovations such as self-sampling and HPV rapid testing for cervical cancer among Hispanic women in Lake County, Indiana. METHODS/STUDY POPULATION: This mixed-methods study encompassed an online cross-sectional survey (n=231) and in-depth interviews (n=9) of individuals with a cervix aged 21-65 residing in Lake County, Indiana. Outcome variables focused on cervical cancer knowledge, willingness to adopt self-sampling, and willingness to adopt HPV rapid testing. Descriptive statistics included frequencies and percentages. A cervical cancer knowledge score was computed from 7 questions. Scores below the mean 3.62 were labeled ‘low’ while higher scores were ‘high’. We also examined associations between demographic and outcome variables. Quantitative analysis was conducted using SPSS software. Qualitative analysis was conducted using NVIVO software to thematically analyze interviews using deductive and inductive coding techniques. RESULTS/ANTICIPATED RESULTS: Majority of participants identified as Hispanic (58%), aged 31 or older (58%). While 80.5% reported being screened for cervical cancer, only 44.6% demonstrated ‘high' cervical cancer knowledge. 89.6% felt screening is important as emphasized in qualitative findings for its preventive value. Over half were willing to take their vaginal swab in clinic (55.8%) and at home (51.9%). However, among the Hispanic/Latinx groups reluctance to adopt self-sampling was notable (56.7% in clinic and 62.7% at home). Qualitative analysis revealed concerns about test accuracy. Willingness to use a hypothetical HPV rapid had higher acceptance (69.7%), with 52.2% in the Hispanic/Latinx group. Qualitative findings highlight benefits like increased screening access, comfort, and convenience offered by an HPV rapid test. DISCUSSION/SIGNIFICANCE: Hispanic/Latinx women in the sample were less willing to adopt cervical cancer screening methods such as self-sampling and rapid testing compared to non-Hispanic whites. Despite being considered beneficial for testing among vulnerable populations, our study found limited acceptance from these populations for various reasons.","PeriodicalId":15529,"journal":{"name":"Journal of Clinical and Translational Science","volume":"35 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140581515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"30 Characteristics of Infant Emergency Department Utilization","authors":"Mary Beth Howard, Leticia M. Ryan, Oluwakemi Badaki-Makun","doi":"10.1017/cts.2024.47","DOIUrl":"https://doi.org/10.1017/cts.2024.47","url":null,"abstract":"OBJECTIVES/GOALS: Frequent utilizers of emergency departments (ED) make up a substantial share of overall ED use. Within pediatric emergency departments (PED), infants represent an age group that make up a disproportionate share of PED visits. The objective was to compare patterns of PED use for children less than 1 year of age by visit frequency and resource utilization. METHODS/STUDY POPULATION: Retrospective cohort study of infants less than 1 year presenting to 5 EDs in one health system over a 5-year period, with a 365-day follow-up after each index visit. Patient characteristics (age, sex, race/ethnicity, presence of chronic condition) and visit characteristics (arrival day/time, acuity level, disposition, testing (labs and radiographs, medications) were assessed. The relationship between patient and visit characteristics with utilization and repeat visits was assessed using multivariable regression. RESULTS/ANTICIPATED RESULTS: A total of 20,620 patients with 33,127 ED visits during study timeframe. Thirty three percent (n=6842) had more than one visit in a year; 3964 (19.2%) had two visits, 1542 (7.5%) had three visits, and 1336 (6.5%) had 4 or more visits. Across all visits, over half (52%) were low acuity. The most common diagnoses were respiratory diseases (27%), systemic states (including fever, viral illness, 23%), and gastrointestinal diseases (15%). These diagnoses remained the most common for those with 1, 2, 3, and ≥ 4 ED visits during follow up. As ED visit frequency increased, there was an increase in percentage of children who were older, non-Hispanic Black, and triaged as low acuity. Infants with ≥ 4 ED visits were more likely to be without a chronic condition, have no medications or testing ordered, and be discharged. DISCUSSION/SIGNIFICANCE: There was high ED utilization for those without chronic conditions who were least likely to need medications, testing, and hospital admission. With increasing attention paid to high-utilization in healthcare, it is important to assess why infants use the ED at high rates and develop systems to improve high value care while decreasing resource burden.","PeriodicalId":15529,"journal":{"name":"Journal of Clinical and Translational Science","volume":"47 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140581680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"423 Innovation in MS Patient Care: Linking Cognitive Health and Myelin Integrity","authors":"Ashley Pike, GA James, ML Calvert, CD Kilts, RL Archer, T Wolfe","doi":"10.1017/cts.2024.365","DOIUrl":"https://doi.org/10.1017/cts.2024.365","url":null,"abstract":"OBJECTIVES/GOALS: Our objective is to develop a patient-friendly application addressing the progression of cognitive impairments in multiple sclerosis (MS) patients. This initiative aims to augment individualized care and precision management of a major MS comorbidity by generating a cognitive health brain map for each patient. METHODS/STUDY POPULATION: Using the UAMS COMS Database, featuring high-resolution multi-contrast MRIs, and a comprehensive clinical, behavioral, and demographic dataset, we are developing a hierarchical learning-based software tool to compute maps correlating brain structure-function and individual cognitive function. Our MRI analysis employs a three-compartment model (NNLS&gt;0.96). Functional scores are defined by individualized accuracy during the modified information processing speed task (e.g., m-SDMT). We utilize a Bayesian classifier with explicit Pearson’s correlation for tissue classification (BF10&gt;100) to compute an index of the likelihood of correlation with cognitive impairment throughout brain tissue. RESULTS/ANTICIPATED RESULTS: This approach allows us to reveal subtle cognitive changes and their potential links to myelin integrity, offering vital insights into disease progression and management. The m-SDMT strongly correlates with the standard SDMT (r=0.79, p&lt;0.001), confirming reliability as a cognitive assessment tool in clinical and research contexts. Analysis of the COMS dataset emphasized insights into the role of fine myelin structure in MS patients' cognitive functionality. Our findings heightened the pivotal significance of myelin integrity in preserving cognitive abilities and identify disruptions in myelin synthesis and homeostasis as primary contributors to cognitive decline. This discovery stresses the critical role that specialized brain pathways, influenced by myelin integrity, play in the pathology of MS. DISCUSSION/SIGNIFICANCE: This development bridges advanced neuroimaging techniques with practical clinical applications, emphasizing the nuanced role of myelin integrity in MS-related cognitive deficits. Our findings advocate for a multidisciplinary approach to MS management, demanding collaborative workforce development and education in translational science.","PeriodicalId":15529,"journal":{"name":"Journal of Clinical and Translational Science","volume":"34 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140581195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}