OBJECTIVES/GOALS: With a growing intеrеst in tailoring disеasе diagnosis to еach individual as opposеd to a “onе-sizе-fits-all” approach, our aim is to еnhancе thе robustnеss of thе Itеrativе Clustеring for Subtypе Discovеry (iKCAT) algorithm in charactеrizing lung cancеr subtypеs for individualizеd trеatmеnt. METHODS/STUDY POPULATION: Our mеthod еxplorеs thе robustnеss of thе prеviously dеvеlopеd iKCAT algorithm. This itеrativе clustеring mеthod finds robust—homogеnеous and diffеrеntiablе—subtypеs of lung nodulеs through itеrativе K-mеans clustеring that hеlps classify thеm and lеavеs somе data unclustеrеd. This sеt of unclustеrеd or “hard” data rеprеsеnts imagеs that cannot confidеntly bе assignеd to any subtypеs and may rеquirе morе rеsourcеs (е.g., timе or radiologists) to diagnosе. Wе еxplorе thе robustnеss of iKCAT across multiplе fеaturе spacеs, including dеsignеd imagе fеaturеs (which arе еnginееrеd to capturе somе propеrtiеs such as lеvеl of еlongation, еccеntricity and circularity), rеducеd dеsignеd imagе fеaturеs using Principal Componеnt Analysis (PCA) and Uniform Manifold Approximation and Projеction (UMAP). RESULTS/ANTICIPATED RESULTS: Whеn running our еxpеrimеnt on thе 64 imagе fеaturеs, our rеsults consistеntly carvеd out a singlе purе, homogеnеous clustеr ovеr thе coursе of 30 iKCAT runs. From an initial datasеt of 1490 data points, 1430 points wеrе lеft unclustеrеd in this fеaturе spacе. Whеn conducting thе 30 iKCAT runs on thе PCA fеaturе spacе with 10 componеnts, wе found it did not producе any distinct clustеr abovе thе dеfinеd homogеnеity thrеshold. Thе 2D UMAP fеaturе spacе consistеntly gеnеratеd 8 clustеrs with an avеragе homogеnеity of 87. 22% ovеr 30 runs, and only lеft 9 points unclustеrеd. Ovеr 30 iKCAT runs, wе idеntifiеd 8 pеrsistеnt clustеrs or subtypеs, 3 mostly malignant and 5 mostly bеnign clustеrs. DISCUSSION/SIGNIFICANCE: Through our еxpеrimеnt using thе iKCAT algorithm, wе found that iKCAT’s clustеring functionality producеd thе most pеrsistеnt rеsults on thе 2D UMAP fеaturе spacе duе to its high avеragе homogеnеity scorеs and consistеncy in idеntifying clustеrs/subtypеs, hеlping improvе tailorеd disеasе diagnosis.

OBJECTIVES/GOALS: Women are twice as susceptible to ailments like anxiety, PTSD, and Alzheimer’s disease compared to men. The locus coeruleus (LC), the primary source of noradrenaline for the brain is implicated in these disorders, however physiological sex differences have never been assessed in the LC. METHODS/STUDY POPULATION: To address this gap, In vivo electrophysiology under anesthesia was used to measure single unit activity of noradrenergic LC firing patterns in 4-month-old wild-type Fischer male and female rats. Recordings measured neuronal activity under basal conditions and in response to a footshock stimulation which elicits burst firing in LC neurons. Single unit activity is sorted via automatic valley seeking scan PCA, additional manual sorting is done via line and template method. Analysis is done extracting interspike interval (ISI) and firing rate of single units, additional analysis is done to quantify properties of bursting patterns (burst duration, spikes per burst, interburst interval, etc…). RESULTS/ANTICIPATED RESULTS: This data shows that during LC burst firing, females have longer interspike intervals compared to males, supporting the inhibitory effect of E2 on LC firing. Additionally, females have significantly different waveform patterns than males, indicating possible differences in intrinsic properties, but further supporting sexually distinct physiology of the LC . Because female rats have been estrous cycle tracked via vaginal lavage, stratification into estrus groups and further analysis may uncover differences within females. These data suggest that estrogen acts as a potent neuromodulator of noradrenergic LC neurons, providing valuable insights into the physiology of this brain region. DISCUSSION/SIGNIFICANCE: This study is the first exploration of LC physiological sex differences. This work offers insights into a critical brain region implicated in many diseases, and may pave the way for future therapeutic approaches, particularly for women, who are at a higher risk of neurological disease developing.

OBJECTIVES/GOALS: Building community-engaged research capacity is imperative to improve translation, but not everyone exhibits capacity to conduct research, especially community. We modified the research institute planning and implementation process between 2022 and 2023 to increase community appeal and engagement. METHODS/STUDY POPULATION: The 2022 and 2023 Community-Engaged Research Institutes (CERI) varied in their formats. For 2022, we hosted a one-hour planning session with community-academic dyads from our Community Advisory Board facilitated by the CEO director and co-director. The 2022 CERI consisted of five sessions totaling 12 hours. The first session was hybrid, followed by four virtual sessions. For 2023, we hosted two, facilitated one-hour planning sessions with community partners who attended the 2022 CERI, based on feedback and attendance from 2022. The 2023 CERI was consolidated to a seven-hour, one-day hybrid session. RESULTS/ANTICIPATED RESULTS: In 2022, two community partners participated as CERI panelists. There were 95 unique attendees spanning five days. Of the 95 attendees, 67% (n=64) were researchers and 33% (n=31) were community members. In 2023, eight community partners participated as CERI panelists and presenters. There were 57 unique attendees, of which 61% (n=34) were researchers and 39% (n=23) were community members. When comparing attendance for 2022 (29%, n=28) and 2023 (86%, n=49), in-person attendance was increased by 57%. DISCUSSION/SIGNIFICANCE: In 2023, we focused on research capacity building for community partners to align with community engagement principles and increasing research impact across the translational spectrum. Partnering with community elevated appeal for community participation and an increase in-person attendance.

OBJECTIVES/GOALS: Limited access to medication and poor medication adherence exacerbate chronic diseases following disasters. Experts recommend individuals in disaster-prone areas be prepared to manage their chronic diseases in the event of resource disruption. This study’s goal is to identify factors underlying personal medical preparedness. METHODS/STUDY POPULATION: A cross-sectional survey of 120 insured adults age ≥50 in Southeast Louisiana with hypertension and ≥1 daily medication during the 2023 Atlantic Hurricane Season is underway. The survey includes the Household Emergency Preparedness Index Access and Functional Needs Section (HEPI AFN), a validated measure of medical preparedness that accounts for special circumstances including refrigerated medication and electricity-dependent medical equipment. The mean score of the 9-item tool ranges from 0 to 1, with higher scores indicating more preparedness. The survey also includes 3 open-ended questions where participants can explain difficulties with medication adherence during hurricanes in their own voice. Data collection is ongoing. This interim analysis provides descriptive statistics. RESULTS/ANTICIPATED RESULTS: An interim analysis of the first 50 respondents included 46% women, 52% Black, mean age 61.2 (SD=7.3) years, and mean 52.5 (SD=16.2) years living in a hurricane-impacted area. Participants had a median of 1 comorbid condition; 72% reported taking >5 daily medications. Most respondents (94%) stated their household was at least “somewhat prepared” to handle a disaster and reported medical preparedness on an average of 82% of HEPI-AFN items (mean score = 0.82, SD=0.18); 90% reported that they had never had a healthcare worker talk to them about personal medical preparedness. On open response questions, participants cited insurance restrictions as the primary barrier to having extra medication on hand. In the final sample, regression models will be used to examine factors associated with increased preparedness. DISCUSSION/SIGNIFICANCE: While most participants in this insured, disaster-experienced preliminary sample are medically prepared, few have discussed preparedness with a healthcare provider. Identifying socio-demographic factors associated with preparedness will help to strengthen mitigation strategies addressing widening of health disparities during disasters.

OBJECTIVES/GOALS: There is a scarcity of research examining the views of Black and Latine HIV care consumers on healthcare experiences that influence medical mistrust. The present qualitative study aims to bridge the existing gaps in the literature pertaining to the experiences of Black and Latine HIV care consumers. METHODS/STUDY POPULATION: We conducted 21 semi-structured interviews with Black and Latine HIV care consumers from November to December 2021 to explore perceptions of provider behaviors that increase or decrease HIV care consumers’ trust and mistrust, experiences of stigma, and behaviors and responses when experiencing medical mistrust. Conventional content analysis was conducted to derive meaning from the narratives shared by participants. RESULTS/ANTICIPATED RESULTS: Provider behaviors that increase HIV care consumers’ mistrust include lack of person-centered care, lack of partnership in health decision making, perceived provider incompetence, lack of adequate follow-up to care, and lack of trustworthiness of providers and organizations. Perceived experiences of intersectional stigma in healthcare included feeling judged and discriminated against by healthcare providers regarding HIV status and observing differential care outcomes and delayed care delivery by race and ethnicity. DISCUSSION/SIGNIFICANCE: Findings can inform the development of provider-level interventions to address medical mistrust.

OBJECTIVES/GOALS: This study examined youth tobacco use, disaggregated by sexual and gender minority (SGM) identity and race, in Massachusetts before and after the state implemented a flavored tobacco restriction. We assessed if the policy differentially impacted groups that have had higher rates of flavored tobacco use (i.e., SGM and African Americans [AAs]). METHODS/STUDY POPULATION: Data for this analysis came from the 2019 and 2021 Massachusetts Youth Risk Behavior Survey (YRBS), a biennial, national survey conducted among high school students, provided by the Massachusetts Department of Elementary and Secondary Education. Changes in current use of cigarettes and e-cigarettes between 2019 and 2021 were examined for the entire sample and by SGM identity and race/ethnicity. Current cigarette use and current e-cigarette use were defined as reporting any use of the product in the past 30 days. We received confirmation from the IRB that because the data are de-identified and available to the public, this research is considered Not Human Subjects Research. RESULTS/ANTICIPATED RESULTS: Between 2019 and 2021, current cigarette use and current e-cigarette use decreased for the entire sample (3.78% to 2.79% and 27.69% to 15.74%, respectively). Decreases were also observed after disaggregating results, but smaller changes were observed among minoritized groups (i.e., SGM and AAs), particularly for e-cigarettes. Current e-cigarette use decreased 25.56% among individuals identifying as SGM (28.14% to 20.95%) compared to a 49.33% decrease among non-SGM individuals (27.63% to 14.0%). Among all races, AAs had the lowest prevalence of current e-cigarette use in 2019 (15.10%), but also saw the lowest percentage decrease (17.68%). Among whites, current e-cigarette use decreased 45.75% from 32.33% in 2019 to 17.54% in 2021. DISCUSSION/SIGNIFICANCE: After implementation of Massachusetts’ flavored tobacco restriction, current cigarette and e-cigarette use declined among Massachusetts youth overall and among groups that have been most affected by flavored tobacco. However, minoritized groups (i.e., SGMs, AAs) had lower percentage decreases compared to non-minoritized groups.

OBJECTIVES/GOALS: Our project aims to assess the composition or characteristics of research papers that score high on alternative metrics. These alternative metrics including the number of newspaper mentions, social media mentions, and the attention score as catalogued on Altmetric, a tool used to document community attention for a given research paper. METHODS/STUDY POPULATION: Our study intends to 1) Utilize topic modeling to identify prevalent themes on Altmetric, and 2) Apply network analysis to elucidate the interconnectedness among universities, funding sources, journals, and publishers associated with high-attention papers. 3) Examine how these patterns vary when attention metrics shift, such as social media mentions, newspaper mentions, or the Altmetric score. We'll first perform this analysis on all types of papers and then limit the networks to Biomedical and Clinical Sciences, and Public and Allied Health Sciences to help inform what health topics garner attention. RESULTS/ANTICIPATED RESULTS: Our initial Altmetric topic models revealed sustained attention for COVID-19 and vaccination-related publications well beyond the pandemic (specifically, papers from January 2023). Health topics like cancer, dementia, and obesity also garnered high attention. Additionally, political papers (elections, democracy), climate change, and battery research had notable attention values. Further analysis needs to be done to explain why these topics gain attention and the type of attention they garner. We will construct networks to see the relationship between attention and entities like universities, funding sources, journals, and publishers. This will identify whether certain clusters of these entities produce papers with high attention or if attention is distributed evenly amoung them. DISCUSSION/SIGNIFICANCE: To gauge the broader impact of scholarly research alternative metrics beyond citations are needed. Altmetric is used widely by CTSA’s to measure the community interest in research. Understanding the types of research that gain traction on Altmetric can help researchers understand how to garner interest from the community.

OBJECTIVES/GOALS: Disparities persist among minority and marginalized populations in immunizations and research. The Clinical Research Vehicle Team aimed to bring research to our community’s doorstep, building generalizability of research outcomes. Our mission adapted due to the pandemic to include increasing COVID-19 vaccinations and health education. METHODS/STUDY POPULATION: Community Engagement Events are planned when event organizers submit a request, then the proposal is discussed by the Clinical Research Vehicle (CRV) Team and UF HealthStreet. We go to underserved communities throughout Florida, food distributions, churches, community centers, rural areas, etc. At these events we offer services at no cost, including: COVID-19 and flu vaccines, as well as health screenings. We provide health education to individuals and refer them to UF HealthStreet for community resources, as appropriate. Research events are planned when researchers submit a request for the CRV, then the request is discussed by the CRV Team. The studies covered topics from COVID-19 research to the development of a diverse health database. Our fleet consists of two Community Health Vehicles and the CRV. RESULTS/ANTICIPATED RESULTS: As Community Engagement Events are ongoing, the presented numbers are reflective of the data available at the time of submission. Our impact includes administering 1,606+ COVID vaccines, conducting 1,081+ health screenings, collecting data from 944 screenings, providing 265 Flu vaccines, supporting 267+ community health events, and serving 25+ communities. The Clinical Research Vehicle facilitated 6 IRB-approved studies, administration of monoclonal antibody infusions, extended the capabilities of the Clinical Research Center, and enabled clinical trials aimed for novel treatments for COVID-19 positive participants. DISCUSSION/SIGNIFICANCE: Championing this initiative has shown an impact on vaccination rates and health education in communities. Experience and knowledge gained by our team throughout the pandemic while engaging with community members provided a platform from which to build generalizability of research outcomes and support translational science.

OBJECTIVES/GOALS: Congenital cytomegalovirus (cCMV) remains to be the leading infectious cause of fetal anomalies. The role of fetal natural killer (NK) cells during cCMV remains largely unknown. The objective of this study is to define the transcriptomes of fetal NK cells exposed to human cytomegalovirus (HCMV) infection during gestation. METHODS/STUDY POPULATION: Four sets of umbilical cord blood and matching umbilical cord tissues were collected from two HCMV seropositive (HCMV+) and two HCMV seronegative (HCMV-) fetuses that did not experience any complications during gestation. These samples were provided by the Medical College of Wisconsin Tissue Bank and were processed within 24 hours following live birth. CD7+ CD3e-CD14-CD19-CD20- fetal NK cells were isolated, using the BD FACSAria sorter. Following cell sorting, single-cell RNA sequencing (scRNA-seq) was performed, and cDNA libraries were constructed and sequenced via NextSeq 550. Cell Ranger was then used to algin the cDNA reads and the Seurat R package was used to analyze the transcriptional data. Cells were filtered and clustered based on the number of uniquely expressed genes. RESULTS/ANTICIPATED RESULTS: Four sets of umbilical cord blood and matching umbilical cord tissues were collected from two HCMV+ and two HCMV- fetuses. We were able to successfully sort and capture fetal NK cells and perform scRNA-seq on these samples. Following unbiased clustering, we observed and characterized five distinct fetal NK cell subsets in the umbilical cord blood and four fetal NK cell subsets in the corresponding umbilical cord tissue. Our findings revealed that HCMV+ fetal NK cells primarily consisted of mature NK cell subsets, while HCMV- fetal NK cells constituted the majority of the immature subsets. Importantly, we identified a unique subset of NKG2CHi fetal NK cells that were significantly elevated in the HCMV+ fetuses. Finally, we defined a group of transcription factors involved in the formation of antiviral fetal NK. DISCUSSION/SIGNIFICANCE: Here, we demonstrate that HCMV infection can induce the formation of distinct NK cell subsets and drive their unique transcriptional profiles. These findings have the potential to guide the development of an innovative NK cell immunotherapy that could help prevent fetuses from developing symptomatic cCMV.

OBJECTIVES/GOALS: This project presents the Post-doctoral Master of Science in Clinical and Translational Research (MSc) program’s outcomes in 20 years of its implementation. This program is a joint offering between the Schools of Health Professions and School of Medicine of the University of Puerto Rico. METHODS/STUDY POPULATION: This study consists of secondary data analysis of academic and administrative documents. It also includes data from the Annual Evaluation retreats reports and an Alumni Follow-up Survey using an electronic questionnaire. All 121 Scholars admitted to the program from academic years 2003 to 2023 were included in the sample. Data analysis included descriptive statistical analysis of quantitative data and qualitative content analysis regarding recruitment/admissions, faculty composition, curriculum design, Scholars’ outcomes, and program’s financial support sources. Quantitative data were analyzed using the statistical software SPSS. RESULTS/ANTICIPATED RESULTS: Scholars of the program had been recruited from the UPR-MSC and several partner institutions with diverse backgrounds, disciplines, and research areas. Faculty and committee members have representation from the six MSC-Schools and partner institutions. The academic Program structure has changed over the years, and currently, more than 65% of the courses are offered online. Several financial sources have been identified to support the scholars. The Scholars’ portfolios of grant submission and publication productivity evidence the program’s success. Graduates have also been successful in advancing to positions that foster research impacting Hispanics. DISCUSSION/SIGNIFICANCE: The Post-doctoral Master’s in Clinical and Translational Research program (MSc) has contributed to the formation of committed Hispanic clinical and translational researchers impacting minorities and contributing to diversity in the research workforce.

OBJECTIVES/GOALS: The objectives of the Academy of Community Reviewers (ACR) serve to: (1) provide comprehensive education and training to community members about clinical research and the community review process for clinical research grants; and (2) collaborate with the community in the development of the training to ensure benefice and meaningful engagement. METHODS/STUDY POPULATION: This training targets community members who will serve as future grant reviewers for The Ohio State University Center for Clinical Translational Science (CCTS) pilot grant submissions, other grant submissions and as expert consultants on other projects needing community perspectives. In 2019 and 2020, this training was offered as a live session. Thirty-eight community reviewers were trained and have served as grant reviewers and consultants on over 70 projects. Based on feedback of former graduates, time demands, logistics, and technology advances warranted transitioning the course to an online learning platform. ACR graduates were consulted in course redesign and updates. Course revisions include material on DEIA, implicit bias and health equity in clinical research with narrated lectures. RESULTS/ANTICIPATED RESULTS: Each of the 7 modules (including a total of 15 submodules) will have a brief summary knowledge check. The module “How to incorporate diversity, equity, inclusion and accessibility in health research” will invite trainees to independently explore their own social identity and biases through a guided exercise. The last (7th) module will have interactive opportunities for submitting grant reviews and participation in an online grant review session, geared to The Ohio State University CCTS. ACR graduates have been invited to consult on educational material and pilot the new course. Demographic, knowledge assessments and module evaluations will be collected. An overall course evaluation and focus group interviews with graduates will also be analyzed for quality improvement and contributions in grant reviews. DISCUSSION/SIGNIFICANCE: The increased accessibility of the ACR course will foster more inclusive community engagement and support the development of clinical and translational research that is innovative, efficient, equitable, and relevant to its beneficiaries. This in depth community reviewer training has been designed to be used and customized to other CTSA Hubs.

OBJECTIVES/GOALS: Non-operative management is preferred for pediatric solid organ injury (SOI). Despite this children treated at adult trauma centers (ATC) are more likely to be treated surgically and have worse outcomes than those treated at pediatric trauma centers (PTC). We hypothesize there are disparities by sex and race in management of pediatric SOI at ATC vs PTC. METHODS/STUDY POPULATION: Retrospective review of the National Trauma Data Bank (NTDB) from 2010-2018 was conducted. Inclusion criteria were age£18 and injury to spleen, liver or kidney. Outcomes at American College of Surgeons accredited ATC, PTC, and combined ATC/PTC trauma centers were evaluated. The primary outcome was operative management. Secondary outcomes include length of stay, and in-hospital complications. Multivariate logistical regression adjusting for race, sex, and insurance type will be performed. RESULTS/ANTICIPATED RESULTS: 40,111 children were treated for SOI from 2010-2018. 39.3% were treated at an ATC and 26.4% at a PTC. Of children treated at an ATC, 62% were White, 17% were Black, and 1% were Asian. Children treated at the PTC were 60% White, 20% Black, and 0.9% Asian. Primary insurance type was Medicaid for 33% of patients at an ATC and 39% at PTC. Median length of stay at ATC and PTC was 4 days (2-7) and 3 days (2-6) respectively. 3.85% of patients at ATC underwent splenectomy compared to 0.8% at PTC. It is anticipated that further analysis will demonstrate that ICU admission, transfusion, embolectomy, and other operative interventions will be more prevalent at ATC than MTC. Moreover, we anticipate that multivariate logistical regression will show the odds of receiving operative management at each center differ by race, sex and insurance type. DISCUSSION/SIGNIFICANCE: Initial analysis of the NTDB from 2010-2018 shows that children treated for SOI at ATC receive operative interventions more often than those treated at PTC. Elucidating disparities in SOI care is an important step towards minimizing the impact of these disparities and better allocating resources such that they may be eliminated.

OBJECTIVES/GOALS: Chronic kidney disease (CKD) affects nearly 40% of adults with diabetes. Our objective is to assess trends in risk factor control and use of 2022 ADA and KDIGO guideline-recommended medications. METHODS/STUDY POPULATION: Using data from 1988 to 2020 from the National Health and Nutrition Examination Survey, we will examine trends in sociodemographic risk factors and glycemic, blood pressure, and lipid control among adults with CKD and diabetes. Glycemic control will be defined as a hemoglobin A1c (HbA1c)<7%, blood pressure control will be examined at cutoffs of 130/80 and 120/80 mmHg, and lipid control will be defined as a fasting triglyceride level ≥150 mg/dL, a low-density lipoprotein (LDL) <100 mg/dL without atherosclerotic cardiovascular disease (ASCVD), or LDL<70 mg/dL if they have ASCVD. We will assess changes in the use of commonly used antidiabetic, antihypertensive, and lipid-lowering medications. RESULTS/ANTICIPATED RESULTS: We hypothesize that from 1988-2020, blood pressure control has improved while glycemic and lipid control has not improved among adults with diabetes and CKD. We expect decreases in sulfonylurea use and increases in DPP-4 inhibitor, metformin, ACE inhibitor, angiotensin receptor blocker, statin, and insulin use over time among those with diabetes and CKD. In addition, there is likely a significant gap between those who are eligible to use newer medications like SGLT2 inhibitors or GLP-1 receptor agonists and who are currently using them within this subpopulation. DISCUSSION/SIGNIFICANCE: This study will examine adherence to guideline-recommended management and identify gaps in care for adults with CKD and diabetes, which may inform how best to optimize medication use for cardiorenal protection in this high-risk patient population.

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.

OBJECTIVES/GOALS: This project aims to improve the design of medical technology for global health by addressing gaps in engineering education. Our primary goal is to develop open educational resource’curriculum boosters’ that can be added to existing BME curricula to build skills in transdisciplinary collaboration, practical ethics, and failure resilience. METHODS/STUDY POPULATION: A phasic mixed-method research strategy has been employed. The Needs Analysis includes a systematic review and meta-analysis of existing knowledge regarding the three conceptual pillars of Transdisciplinary Collaboration, Practical Ethics, and Integrated Resilience. The Behavioral Study includes surveys, interviews, observations, and biometric data collection from working engineers, engineering students, global health stakeholders, and clinicians. The Validation Study will be conducted via small group workshops, a semester-long engineering design course, and a summer study-abroad course. Data collected will be analyzed and used to refine the proposed educational strategies. RESULTS/ANTICIPATED RESULTS: The final educational strategies will be structured into 'curriculum boosters' and published as open educational resource materials. The boosters and their supporting data will be made available to other engineering education programs with the goal of promoting widespread adoption and integration of these methods. DISCUSSION/SIGNIFICANCE: The long-term outcome of this ongoing work is to train a new generation of engineers prepared to participate adeptly in the co-design of technological solutions for complex global healthcare challenges by working ‘with, not for,’ clinicians, communities, and other stakeholders in peripheral healthcare settings.

OBJECTIVES/GOALS: Super refractory status epilepticus (SRSE) is associated with high mortality, often due to withdrawal of life sustaining therapy (WLST) based on perceived poor neurological prognosis. Factors influencing decision making are underreported and poorly understood. We surveyed clinicians who treat SRSE to identify factors that influence WLST. METHODS/STUDY POPULATION: Health care providers (HCP), including physicians, pharmacists, and advanced practice providers, who treat SRSE answered a 51-question survey on respondent demographics, institutional characteristics and SRSE management that was distributed though professional societies. Respondents described approaches to prognostication and rated the importance of clinical factors in the management of two hypothetical clinical cases followed by their prediction of recovery potential for the same two cases. Neurointensivists and other HCP responses were compared using descriptive statistics to differentiate group characteristics; a p-value <0.05 was considered significant. Logistical regression models were employed to identify associations between clinician specific factors and prognostication. RESULTS/ANTICIPATED RESULTS: One-hundred and sixty-four respondents were included in the analysis. Compared to other HCPs (neurologists, epileptologists, neurosurgeons, other intensivists; n=122, 74%), neurointensivists (n=42, 26%) [Odds ratio (OR) 0.3, 95% confidence interval (CI) 0.14-0.68), p=.004)] were less likely to use prognostic severity scores and were less likely to prognosticate likelihood of good functional recovery (OR: 0.28 (95% CI: 0.13-0.62), p=.002) compared to non-neurointensivist HCPs, controlling for potential confounders including professional degree, years of experience, country of practice, and annual volume of SRSE cases. There was, however, significant overlap in factors deemed necessary for determining futility in care escalation. DISCUSSION/SIGNIFICANCE: Neurointensivists value similar clinical factors to other HCPs when evaluating medical futility in SRSE but are less likely to predict definitive outcomes. Pending final survey results, future studies aimed at understanding why neurointensivists may be less likely to decisively prognosticate (i.e. avoiding nihilism) in SRSE may be warranted.

OBJECTIVES/GOALS: We will reduce the number of research staff by 50% within 6 months that are non-compliant with completing the Good Clinical Practice (GCP) course without increasing costs as measured by salary and benefits for staff involved in the tracking and assignment process. We will also introduce a GCP policy to define the education requirements for GCP training METHODS/STUDY POPULATION: We touted focus groups to stakeholders for input on workflows with graphs, surveys, and meetings in the onset and throughout the project. This input prompted us to develop a staff guide outlining the modification process of removing a staff name from an IRB trial if they are no longer active in the trial. A workflow and root cause analysis were done resulting in the implementation of one gatekeeper for assigning and tracking completions, instead of three staff. Successfully reconciling the non-compliant report, which extracted data from three databases, allowed us to eliminate 174 names from the report, which originally comprised 792 names. IRB modifications were entered into the IRB system for these 174 names. We also put into effect a GCP policy for the institution, where none had previously existed. RESULTS/ANTICIPATED RESULTS: * In 3.5 months, we decreased the GCP non-compliance rate by 50% from 792 to 399. * We removed 22% of names from the 792 from the report due to their status of being non-employees, or Emeritus, or not in research anymore. * We discovered a data type issue in the non-compliance report that shuffled the MAX calculation, therefore not requiring some staff to complete the training. * We developed a new process for assigning training, resulting in faster compliance rates for the institution. It included sending emails to users two months before their training expired before we assigned the course to them. * We reconciled the non-compliance report, and it decreased the effort with staff involved in GCP for grant renewals and audits in numerous other departments. * Developed an escalation procedure for non-compliant staff. DISCUSSION/SIGNIFICANCE: Failure to address our GCP non-compliance rates could have put our institution at risk for potential penalties. With 4400+ research personnel listed on active trials the interventions we implemented accelerated our compliance rate by assigning the refresher course monthly and this also resulted in no disruption to staff completing the training.

OBJECTIVES/GOALS: Using the NIH’s expanded definition of underrepresented populations in the biomedical, clinical, behavioral and social science research enterprise, we examined the impediments for conducting translational research experienced by those from underrepresented groups. [https://acts.slayte.com/calls/detail/740a13de-316c-11ee-90f4-0e0ce905385c/draft/389221c1-434e-11ee-90f4-0e0ce905385c#_ftn1] #_ftn1 METHODS/STUDY POPULATION: One hundred and ninety-nine people completed a survey distributed to 750 persons who had interacted with our Center’s service cores as users, awardees, mentors, committee members, seminar attendees, and/or participated Center sponsored programming (response rate = 26.5%). The survey addressed barriers to conducting clinical and translational research at the respondent’s institution, awareness of and interest in using specific Advance RI-CTR services, and satisfaction with their institution’s efforts to support clinical and translational research. RESULTS/ANTICIPATED RESULTS: Women reported access to collaboration across institutions as a barrier to clinical and translational research that existed to a great extent (28%) significantly more than men (10%). More than half (53%) of the other underrepresented researchers surveyed identified insufficient grant administration supportas a barrier that occurs to a great extent, compared with 35% of researchers who were not from an underrepresented group. Other barriers reported more frequently among underrepresented researchers included lack of pilot project funding, inadequate space for conducting research, lower access to collaborators across institutions, and difficulty obtaining advice on regulatory issues and commercial development. DISCUSSION/SIGNIFICANCE: Efforts to address the barriers identified by underrepresented groups will include, but not be limited to, improving collaborations across institutions, support for grant administration, and a discussion of plans for the Center to augment and advocate at the partner institutions on behalf of these underrepresented individuals.

OBJECTIVES/GOALS: Investigators are looking to integrate DE&I into trials, increasing study population diversity. In response, the Community and Recruitment programs of the Oregon Clinical and Translational Research Institute (OCTRI), built a collaborative, community-focused system for investigators interested in community engagement and recruitment. METHODS/STUDY POPULATION: Historically, the OCTRI Community and Recruitment programs operated independently. To build a community-focused support system for investigators, we began with the programs learning about each other’s goals, values, and operations over a six-month period. Over the next two years, we then began integrating into each other’s team meetings and processes. Each team has their own process for providing services to investigators, consisting of intake and consultations. To these, we added tags for the other’s program topics. This allowed efficient identification of opportunities for referrals and joint consultations. Program leads meet regularly to discuss referrals and partnerships allowing for more effective and consistent collaboration. RESULTS/ANTICIPATED RESULTS: Over the last two years, OCTRI Community and Recruitment built a collaborative process that allows investigators to work with both programs, receiving comprehensive, supportive assistance and education on how to design their study, engage with community, and recruit participants in a community-based setting. During this time, the programs have: provided consultations that discussed the other’s program (N=21); made direct referrals to the other program (N=4); and, provided joint consultations (N=2). Studies that are investigator-initiated, in planning phase, and population focused were found to benefit most from the collaborative efforts. Additionally, we have improved the collaborative process during this time, resulting in more streamlined, efficient support services for investigators. DISCUSSION/SIGNIFICANCE: Diverse study populations and DE&I are essential to research. This collaborative, community-engaged recruitment approach by our programs allows investigators to leverage both programs’ resources and expertise. We continue to identify best practices and study types that benefit from this collaborative approach to improve our services.

OBJECTIVES/GOALS: The peer-reviewed journal Progress in Community Health Partnerships (PCHP) promotes health research partnerships to improve community health. PCHP’s Writing, Dissemination and Reviewer Learning Community Pilot aims to increase stakeholders writing and reviewing for greater relevance and diversity. METHODS/STUDY POPULATION: Led by PCHP’s Editorial Team, Morehouse SOM, Community-Campus Partnerships for Health (CCPH) and a community-academic Workgroup, the LC will guide stakeholders on scholarly writing and publish collaborative research. It builds on the 2017 Writing/Dissemination Learning Institute held by Morehouse, CCPH, and Community Based Organization Partners with the APHA Public Health Caucus. The LC begins with a Workshop [https://sites.google.com/view/pchp2023/pchpcommunity2023] alongside the 2023 APHA Annual Meeting. Wrap arounds include a PCHP Special Issue (participants work), Webinars, PCHP Reflections/Community Perspectives Article Guidelines [https://www.press.jhu.edu/journals/progress-community-health-partnerships-research-education-and-action], “Beyond the Manuscript [https://open.spotify.com/show/2LiBanXAyHyOqNSeGnBPHs]” Podcast, Toolkit/Resources; and coaching. The evaluation will inform PCHP practices. RESULTS/ANTICIPATED RESULTS: Key outcomes include successful implementation of all LI activities. The cohort (approximately 40 stakeholders representing partnerships) will increase exposure to scholarly writing and peer review, ideally publish 12+ manuscripts (e.g., PCHP special issue), increase diversity in scholarly writing, and strengthen recognition/significance of stakeholder authorship in the research community. The year 1 pilot evaluation (e.g., tracking participant authorship, documenting outcomes/lessons learned) will provide evidence to encourage sustainability, model responsiveness among other peer reviewed journals, inform PCHP, and increase diversity in scholarly writing on health disparities research. DISCUSSION/SIGNIFICANCE: The pilot will build a sustainable model and how PCHPaddresses health disparities to increase diversity, equity, and inclusion. The LC aims to diversify framing community health research, supporting/publishing stakeholders work, and increasing diversity among reviewers, all impacting the field.