OBJECTIVES/GOALS: ICD-10 coding inconsistencies hinder timely recognition and treatment of metabolic syndrome (MetS), posing a significant risk for cardiometabolic disease progression. This study employed a digital phenotype for MetS and compared odds for medication and lifestyle intervention compared to those coded for MetS. METHODS/STUDY POPULATION: MetS is a cluster of cardiometabolic risk factors that increase risk for numerous adverse clinical outcomes. Patients with MetS were identified through electronic medical records on TriNetX LLC using the standard ICD-10 code or through a digital phenotype, involving grouping codes for the individual components. Percentage of patients with MetS not captured with the standard code was identified. In addition, disparities in blood pressure, glucose, lipid-lowering medication, and lifestyle intervention between the coding schemas were assessed, shedding light on healthcare inequities and informing targeted interventions. Odds ratios (RR) were presented for all outcomes. RESULTS/ANTICIPATED RESULTS: Patient demographics and lab values were similar between the standard code and digital phenotype cohorts. Of the 4.3 million individuals aged 50 to 80 identified as having MetS using the digital phenotype in the TriNetX research network, only 1.78% of participants shared the standard code. Individuals with the digital phenotype for MetS were at lower odds in receiving glucose lowering medication (OR: 2.11, 95% CI: 1.98–2.13, p <0.001) and exercise or nutrition-based intervention advice (OR: 1.76, 95% CI: 1.55–1.96, p <0.001) after controlling for demographics and lab values for each MetS component. DISCUSSION/SIGNIFICANCE: This project utilized TriNetX to create a digital phenotype for MetS, and suggests most patients are not coded for it using the standard ICD-10 system. This is troublesome given those with the standard code are less likely to receive certain interventions.

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: The goal of this study is to leverage a national database to see if autologous reconstruction rates differ in patient and clinical characteristics, readmission rates, and overall survival (OS) compared to other forms of reconstruction. Autologous reconstruction has not been looked at in this way before. METHODS/STUDY POPULATION: • Aim 1: Use the National Cancer Data Base to construct three patient cohorts for women under 70 and above 18 treated surgically for breast cancer with A) mastectomy only, B) implant-based reconstruction, and C) autologous breast reconstruction. • Aim 2: Examine receipt rates of surgical intervention in Cohorts A vs. B vs. C based on clinical and patient demographic/socioeconomic characteristics. • Aim 3: Compare readmission and overall survival (OS) rates for Cohorts A vs. B vs. C while controlling for age and other key variables. RESULTS/ANTICIPATED RESULTS: Based on the literature, we expect rates of autologous reconstruction (Cohort C) to be lower for patients of minority backgrounds compared to white individuals. In addition, we do not expect overall survival to differ between implant-based (Cohort B) and Cohort C reconstruction. Still, we expect mastectomy-only (Cohort A) survival to vary from the two cohorts even when adjusting for different clinical factors, as similar but smaller studies have shown. Finally, we expect readmission rates to be higher for Cohort C, compared to Cohorts A & B, as it is a more complicated procedure typically done in academic institutions with skilled surgeons. DISCUSSION/SIGNIFICANCE: Autologous reconstruction is now considered the gold standard due to its ability to restore the breast shape with higher patient satisfaction and superior long-term outcomes. Multiple studies have documented ongoing racial disparities in post-mastectomy breast reconstruction and autologous reconstruction, with lower rates and referrals.

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: 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: Dietary fiber has been used in other clinical populations to improve mineral disorders, but there is limited data in chronic kidney disease, despite the high prevalence of mineral and bone disorder (known as CKD-MBD). Our objective was to evaluate the effect of dietary fiber based on viscosity and fermentability on CKD-MBD outcomes. METHODS/STUDY POPULATION: 22-week-old male CKD rats (mild-to-moderate CKD) were randomly assigned to receive one of four fiber treatments (10% w/w each) based on fermentability and viscosity: 1) Cellulose (-fermentability, -viscosity), 2) Inulin (+fermentability, -viscosity), 3) Psyllium husk (-fermentability, +viscosity), or 4) Pectin (+ fermentability, +viscosity). Treatments lasted 10 weeks, and rats were euthanized at 32 weeks of age (kidney failure). Rats were placed in metabolic cages for 3 consecutive days the last week before euthanasia for mineral balance. At euthanasia, blood, tibia, heart, and aorta were collected for CKD-MBD assessment. Additional tissues collected included kidneys and all intestinal segments. RESULTS/ANTICIPATED RESULTS: Our preliminary data indicates that weight trajectories and survival were similar between treatment groups. At 33 weeks of age, kidney weight index (an indirect measurement of kidney function as this animal model develops polycystic kidneys) was lower in the psyllium-treated rats compared to all of the other treatments. Plasma phosphorus was lower with Psyllium and Pectin compared to Cellulose-treated rats. Left ventricular mass index was lower in the Inulin, Psyllium, and Pectin-treated rats compared to the Cellulose-treated rats. Ongoing tissue analyses include biochemical markers of mineral and bone metabolism (parathyroid hormone, fibroblast growth factor-23, and phosphorus balance), bone parameters (dynamic histomorphometry and microCT), and cardiovascular calcification. DISCUSSION/SIGNIFICANCE: Our preliminary data indicate that dietary fiber based on fermentability and viscosity impacts CKD-MBD outcomes and may be an innovative, low-cost intervention that can be trialed in people with CKD for the prevention and treatment of CKD-MBD.

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: Our aims are to 1) describe changes in thumb Carpometacarpal (CMC1) joint stability following an 8-week clinic-based dynamic stability exercise program using computerized tomography (CAT) and 2) to evaluate the agreement between ultrasound and CAT (reference standard) when quantifying thumb CMC stability. METHODS/STUDY POPULATION: Aim 1: We have enrolled 13/49 participants in a prospective pre-post interventional study of an 8-week clinic-based occupational therapy dynamic stability program. The primary outcome will be change in stability (thumb metacarpal subluxation in mm) when forcefully loading the thumb as per CAT from pre-treatment to post-treatment at 9 weeks. Aim 2: Same 49 participants are undergoing a one-time ultrasound during baseline assessment. Agreement of ultrasound and CAT measurements (thumb metacarpal subluxation in mm) will be assessed by the Bland-Altman method. RESULTS/ANTICIPATED RESULTS: Exercise is a first-line treatment of CMC1 OA yet there is insufficient evidence to support this. Progression of CMC1 OA is characterized by altered joint mechanics. Joint replacement surgery may reduce pain but often worsens thumb mechanics and overall hand function. This study is the first to test the sustained biomechanical effects of non-invasive thumb exercises. Should these benefits exist, this will further support exercise as a first-tier intervention. Should ultrasound be a suitable proxy for CAT, therapists/physicians could monitor thumb CMC mechanics in response to treatment without risk of radiation exposure. We anticipate 1) a statistically significant reduction in thumb CMC subluxation at 9 weeks follow up and 2) high agreement between sonographic and CAT measures of thumb stability. DISCUSSION/SIGNIFICANCE: This study will lay the foundation for future work and may offer critical support for the use of a non-pharmacological and non-surgical approach as first-line treatment of a highly disabling disease. Future study should include controlled trials where hand function, activity limitation, disease progression, and costs are the outcomes in interest.

OBJECTIVES/GOALS: The CTSI Research Infrastructure Network (RIN) expands CTSI’s reach into the regional health systems to provide our services to a broad and diverse translational science community. We create and support research collaborations that span multiple geographies and patient populations and serve as a bridge between the affiliate sites and CTSI programs. METHODS/STUDY POPULATION: We conducted needs assessments at each site (n=6) via in-depth, semi-structured interviews with key stakeholders. Informants (n=40) included investigators, study personnel, and research administrators. Investigators were selected across a variety of departments and career stages. Interview transcripts and notes were analyzed using matrix-based qualitative methods to identify both the common and unique research infrastructure needs of each site. Individualized support plans were shared with each site and a comprehensive summary report was presented to CTSI leadership. RIN met with UCSF’s Comprehensive Cancer Center, which conducts clinical trials at 2 sites, to coordinator our effort and services. When possible, RIN addressed service requests in real time that arose during interviews. RESULTS/ANTICIPATED RESULTS: We identified heterogeneous needs across multiple sites. However, among the community health systems with non-academic clinicians, there were common needs for research training, consultations in biostatistics/study design, and finding academic collaborators. The needs of sites with UCSF academic faculty differed from those of community sites and mainly included improved awareness and access to CTSI programs, ease of use of data extraction services, training programs, and assistance with regulatory approvals. Site needs are best addressed with individual plans created with CTSI Program leaders. A developing governance structure will include representation on a CTSI advisory committee and an annual conference to facilitate the sharing of best practices and foster collaboration across member sites. DISCUSSION/SIGNIFICANCE: Providing an individualized, site-specific approach to expanding CTSI services to regional health systems, will increase research collaborations across Northern California through building relationships, addressing unique infrastructure needs and sharing best practices throughout the network.

OBJECTIVES/GOALS: We prioritize Chlamydia’s public health impact, aim to develop rVCG-MECA for practical use, study robust immunity for effective strategies, and assess animal models for human vaccination adaptation. Our work highlights rVCG-MECA’s translational significance in public health. METHODS/STUDY POPULATION: Female Mice C57BL/6J mice (N=8) were immunized intramuscularly(IM) and intranasally(IN) and boosted twice, two weeks apart, with rVCG-MECA, once with live Chlamydia (C. trachomatis serovar D elementary bodies) and PBS. Specific mucosal and systemic immune responses were characterized. Vaccine efficacy was determined from chlamydia shedding following the transcervical challenge. Additionally, Chlamydia-specific cytokine (IFN-γ and IL-4) production by splenic and ILN T cells was assessed after 16 weeks RESULTS/ANTICIPATED RESULTS: Immunization with rVCG-MECA via intramuscular and intranasal routes triggered notable humoral responses in systemic and mucosal tissues. Intramuscular vaccination produced higher IgG2c levels in both tissues, while intranasal vaccination led to elevated IgA levels in mucosal tissues. rVCG-MECA-immunized mice exhibited significantly higher IFN-γ (Th1) secretion compared to IL-4 (Th2), with intramuscular immunization showing the highest IFN-γ levels. These findings anticipate robust immune responses, promising protection against Chlamydia, particularly through the intra muscular route. Overall, our results support rVCG-MECA as a promising Chlamydia vaccine, aligned with public health goals. DISCUSSION/SIGNIFICANCE: This study suggests that IM and IN immunization with rVCG-MECA induces immune effectors such as IFN-gamma and IgG2c that mediate chlamydial clearance in the genetical tract.

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: Social isolation/loneliness is a public health crisis and one that is unlikely to be solved through pharmacology. Nonpharmacological approaches, such as dance, are needed. The objective of this study is to investigate the physiological correlates of dance-induced improvements in social connection. METHODS/STUDY POPULATION: Participants were randomly assigned to participate for 4 weeks (2 times per week, 90-minute sessions) in either 1) improvisational dance training (experimental group; n=7); or a 2) dance movie watching experience (control group; n=7). Before and after the intervention, using mobile brain-body imaging techniques, participants and their instructor had their brain (via electroencephalography) and body physiology (via photoplethysmography) recorded during a series of verbal and nonverbal interactive experiences. Participants were also video recorded via 4 surrounding cameras for later motion capture analysis. Neuropsychological assessments were also conducted before and after the intervention. RESULTS/ANTICIPATED RESULTS: We found that dance significantly increased social skills including empathy, interpersonal skills, emotional regulation, mindfulness, and attention. Additionally, we found that dance significantly increased interbrain synchrony during nonverbal experiences including theta (4-8 Hz), beta (12-35 Hz), and gamma (35-45 Hz) frequencies in the occipital lobe. Increases in interbrain synchrony were also positively correlated with increases in empathy. Additionally, intercardiac synchrony between the participant and instructor showed a significant correlation at post-intervention only. Future investigations will focus on the relationship between interbrain, intercardiac, and movement synchrony. DISCUSSION/SIGNIFICANCE: Our findings support the idea that dance increases interpersonal synchrony at the level of the brain, heart, and behavior. Understanding the neural and somatic mechanisms of social behaviors will help promote understanding and development of interventions for the critical problem of social isolation and loneliness.

OBJECTIVES/GOALS: Ebolavirus disease survivors report persistent, debilitating health concerns dubbed Post-Ebola Syndrome (PES). Attention to PES in young survivors is lacking, we describe PES in pediatric EVD survivors in Eastern Sierra Leone. Additionally, we introduce our proposal investigating differential presentations of PES in pediatric survivors. METHODS/STUDY POPULATION: EVD survivors were enrolled a median of 2.5 years after resolution of disease. Survivors were eligible if listed in a national register maintained by the Sierra Leone Association of Ebola Survivors. Household contacts (HCs) were identified by survivors. Participants were assigned into three comparison groups: pediatric (7-11), adolescent (12-17) and young adult (18-25). A self-reported symptom questionnaire, and a physical exam were conducted. Variables were clustered within organ system and compared across groups. RESULTS/ANTICIPATED RESULTS: Pediatric survivors had lower levels of long-term sequelae compared to adolescents and young adults. Symptoms and abnormal physical exam signs increase with age. Musculoskeletal, psychiatric, ophthalmologic, and GI signs and symptoms were significantly different between groups. Pediatric survivors had significantly more persistent sequelae than age-matched HCs with no history of EVD; particularly within the cardiac/GI (p=.006) and psychiatric/neurological (p=.025) clusters. PES is heterogeneous with respect to age, calling for a deeper understanding of age-based differences. Even the youngest group of survivors experienced significantly more sequelae than HCs, highlighting the elevated symptom burden in these children over their peers. DISCUSSION/SIGNIFICANCE: Understanding mechanistic drivers will ultimately improve targeted treatments for PES. We will characterize symptom groups defining PES in children, determine the relationship between accelerated aging and PES in this population, and test how immune profiles associated with accelerated aging relate to the development of PES in children.

OBJECTIVES/GOALS: Neonatal hypoglycemia is seen in 65% of maternally diabetic pregnancies, and can lead to severe neurological damage. Neonatal glycemia may also be an indicator of placental function in these pregnancies. The purpose of this study is to identify patterns of neonatal glycemia, and associated endothelial dysfunction, by maternal diabetes subtype. METHODS/STUDY POPULATION: Pregnancies with maternal Type 1 (T1DM), Type 2 (T2DM), and gestational diabetes mellitus (GDM) are being enrolled. Maternal hemoglobin A1c (HbA1c) and umbilical cord insulin/glucose are being collected from 20 pregnancies in each group, 10 of which also undergo placental/umbilical cord tissue collection. Following delivery, neonatal blood glucose levels are also collected every 3-4 hours (4+ measurements) to determine rate of glycemic change. Linear regression modeling will be used to determine associations with placental and umbilical endothelial RNA expression, umbilical cord insulin levels, and maternal HbA1c within each diabetic subtype and between normoglycemic and hypoglycemic neonates. Endothelial gene expression will be compared using paired t-tests with Benjamini-Hochberg correction. RESULTS/ANTICIPATED RESULTS: Thus far, 5 T1DM, 10 T2DM, and 13 GDM samples have been collected. Gestational age at delivery and birth weight were similar between groups (38.1 ± 1.05 weeks; 3.6 ± 0.59 kilograms) and delivery method is evenly distributed (Cesarean section or vaginal delivery). Currently, with limited cohort size, no association is evident between maternal HbA1c and umbilical cord glucose/insulin (p=0.114) or neonatal hypoglycemia diagnosis (p=0.674) when controlled for gestational age and infant birthweight. We hypothesize that, with pending analyses, maternal HbA1c and umbilical cord insulin levels will correlate negatively with the rate of neonatal glycemic change, and positively with the level of inflammatory and angiogenic transcription identified in placental and umbilical endothelium. DISCUSSION/SIGNIFICANCE: Characterization of postnatal glucose control is key to prognosis and risk stratification of infants of diabetic mothers. Understanding placental response to glucose, as well as sequela in the fetal endothelium, is also critical to understanding the pathogenesis of neonatal hypoglycemia and other adverse outcomes of diabetic pregnancy.

OBJECTIVES/GOALS: The objective is to describe the process for developing two measurement tools to measure confidence (self-efficacy) of the anti-racist advocate in an academic setting. METHODS/STUDY POPULATION: We proposed five spheres encountered by the academic trainees: Academic/Research, Clinical, Policy, Interpersonal, and Intrapersonal. We evaluated a book, by Shereen Daniels, used in anti-racism literature: The Anti-Racist Organization - Dismantling Systemic Racism in the Workplace. Using the proposed metric of RACE framework, Recognize the problem, Analyze the impact, Commit to action, Empower for change, we sought to establish readiness on the spectrum of anti-racism advocacy. We developed a list of anti-racism and anti-bias advocacy skills based on: 1) Informational interviews with anti-racism and anti-bias experts, 2) Scoping literature review and 3) Academic trainees’ and faculty lived experience. RESULTS/ANTICIPATED RESULTS: The first assessment, “5-Spheres”, consists of 10 items that perform, 1) Analysis of readiness on the spectrum of anti-racism advocacy using RACE framework (Figure 1 [https://drive.google.com/file/d/1A3nMArEn7ZSxZSuSgDkYl_row-VOhOXf/view?usp=drive_link]), 2) Assessment of workplace environment. The second assessment, “Skills”, consists of 25 items (Figure 2 [https://drive.google.com/file/d/1GTdfSgn0-mPu-flSUVSN-vIKTxBCkFW3/view?usp=drive_link]) that perform assessment of confidence of specific skills within each of the five spheres using the following scale: 1 – Not confident at all, 2 – Lacking some confidence, 3 – Somewhat confident, 4 – Completely confident DISCUSSION/SIGNIFICANCE: This proposed measurement tool can extend to anti-bias as well as anti-racism. Potential uses of the self-assessment includes: 1) Measurement and 2) Gap-spotting.

OBJECTIVES/GOALS: 48,000,000 people in the U.S. have hearing loss, negatively impacting quality of life and work. Unveiling axon guidance for auditory type II spiral ganglia neurons (SGNs) will aid development of new therapies. I study the role of Eph/Ephrin and planar cell polarity (PCP) signaling during type II SGN turning and outer hair cell (OHC) innervation. METHODS/STUDY POPULATION: This quantitative study was conducted on Efna3 and Vangl2 null mice possessing Neurog1CreERT2 and R26RtdTomato mutations. Spontaneous Cre activity within the Neurogenin1CreERT2 line causes recombination and expression of fluorescent Rosa26 Reporter (R26R)tdTomatoin a restricted number of SGNs, including type IIs. Together, these lines permit SGN sparse labeling. Immunostaining and confocal imaging were used to analyze dsRed in Efna3 and Vangl2 mice and quantify type II SGN turning. In combination, Imaris 3D renderings were used to quantify type II SGN turning, branching, navigation features and temporal effects of EPHRIN-A3-Fc on type IIs via cochlear cultures (a gain-of-function manipulation). For both sexes, 5-6 cochleae per genotype were analyzed and compared by t-test to wildtype (WT) controls. RESULTS/ANTICIPATED RESULTS: Efna3 nulls showed a small rise in type II SGNs incorrectly turning toward the apex at an error rate of 16.0% compared to WTs (n=6; p=0.05). P0 Efna3 nulls had reduced branch number compared to WTs, 4.1 and 7.2, respectively (n=129; p=<0.0001), suggesting EPHRIN-A3 acts as a positive growth cue. In cochlear cultures, EPHRIN-A3-Fc led to type II SGN collapse at E15.5, indicating a repulsive function. However, at P0, EPHRIN-A3-Fc treatment led to type II SGNs with elevated branch numbers compared to Control-Fc treatment: 18.1 and 11.4, respectively (n=116; p=<0.0001). This indicates a positive growth function. At E16.5, EPHRIN-A3 protein immunoreactivity on Deiters’ and pillar cells appears reduced in Vangl2 nulls compared to WT cochleae, suggesting that EPHRIN-A3 acts downstream of PCP signaling. DISCUSSION/SIGNIFICANCE: Results suggest that Eph/Ephrin signaling acts downstream of PCP signaling to mediate type II SGN guidance and EPHRIN-A3 switches its mode of activation. The clinical implications of these findings are that therapeutics targeting EPHRIN-A3 and/or VANGL2 in their given pathways could stimulate new OHC innervation following auditory damage.

OBJECTIVES/GOALS: A Mayo Clinic in Florida committee completes 100+ Scientific Reviews annually through manual e-mail and Excel tracking, placing a manual burden on reviewers and coordinators. REDCap, an electronic data capture system, was leveraged to reduce the administrative burden.#_ftn1 #_ftnref2 METHODS/STUDY POPULATION: Historically, emails were sent by a coordinator to physicians, requesting their initial review and following up with reminders. This process was tracked using Excel, presenting a need to make this process more efficient, so a workgroup was created. To ensure all perspectives were accounted for, the workgroup included the review coordinator, a physician reviewer, and study team members who submit development requests for studies. The process was mapped using the existing Excel spreadsheet, and email templates. Critical data elements were identified, ensuring the database would identify bottlenecks. Two REDCap instruments were then created: one to outline the coordinator workflow and a survey for physician reviewers to complete the scientific reviews. #_ftn2#_ftnref1 RESULTS/ANTICIPATED RESULTS: The workflow is live in REDCap and has effectively processed over 100 scientific reviews in <1 year. The system captures the review status and guides the coordinator through the workflow, capturing dates when tasks are completed. When review criteria are met, the database sends an email to the assigned reviewer. The email includes a link to a REDCap survey, containing all pertinent documents. The reviewer uploads their completed review form within the survey, if this is not completed within a given period, the database sends email reminders. Once the review is complete, a notification is sent to the review coordinator. The review workflow is accessible to the study team who requested scientific review, making them aware of their request status ad giving them access to the review the moment it is completed. DISCUSSION/SIGNIFICANCE: Leveraging REDCap has increased visibility, reduced overall manual processes, and simplified the reviewer burden by providing all the information needed in a single notification. REDCap is a cost-effective, impactful solution to simplifying administrative burden in managing committee reviews.

OBJECTIVES/GOALS: Contingency management (CM) procedures yield measurable reductions in cocaine use. This poster describes a trial aimed at using CM as a vehicle to show the biopsychosocial health benefits of reduced use, rather than total abstinence, the currently accepted metric for treatment efficacy. METHODS/STUDY POPULATION: In this 12-week, randomized controlled trial, CM was used to reduce cocaine use and evaluate associated improvements in cardiovascular, immune, and psychosocial well-being. Adults aged 18 and older who sought treatment for cocaine use (N=127) were randomized into three groups in a 1:1:1 ratio: High Value ($55) or Low Value ($13) CM incentives for cocaine-negative urine samples or a non-contingent control group. They completed outpatient sessions three days per week across the 12-week intervention period, totaling 36 clinic visits and four post-treatment follow-up visits. During each visit, participants provided observed urine samples and completed several assays of biopsychosocial health. RESULTS/ANTICIPATED RESULTS: Preliminary findings from generalized linear mixed effect modeling demonstrate the feasibility of the CM platform. Abstinence rates from cocaine use were significantly greater in the High Value group (47% negative; OR = 2.80; p = 0.01) relative to the Low Value (23% negative) and Control groups (24% negative;). In the planned primary analysis, the level of cocaine use reduction based on cocaine-negative urine samples will serve as the primary predictor of cardiovascular (e.g., endothelin-1 levels), immune (e.g., IL-10 levels) and psychosocial (e.g., Addiction Severity Index) outcomes using results from the fitted models. DISCUSSION/SIGNIFICANCE: This research will advance the field by prospectively and comprehensively demonstrating the beneficial effects of reduced cocaine use. These outcomes can, in turn, support the adoption of reduced cocaine use as a viable alternative endpoint in cocaine treatment trials.

OBJECTIVES/GOALS: The objective of this study is to assess the feasibility and preliminary impact of a physiotherapy protocol for developing an individualized home-based physical activity program to increase physical activity (PA) levels in sedentary older adults with Type II Diabetes Mellitus (T2DM) living in Puerto Rico (PR). METHODS/STUDY POPULATION: This will be a pilot study with two phases. In phase 1, we will design a novel patient-centered home-based PA program protocol for adults ≥65 years with T2DM based on the Information-Motivation-Behavioral Skills model. Its content validity will be assessed through focus groups with 10 experts and 10 older adults and analyzed using a directed content analysis. Phase 2 we will be program implementation using a one-group, repeated measures design with 12 adults ≥65 years with T2DM. PA levels will be assessed by recording active minutes with a Fitbit. Risk of falls, balance, strength, and physical function will be assessed through standardized tests validated for this population. Statistical analysis will include descriptive statistics, comparisons via chi-square/Fisher’s exact test, and non-parametric tests. RESULTS/ANTICIPATED RESULTS: We expect to recruit a minimum of 12 participants and to administer the program for 12 weeks at a frequency of two visits per week. We anticipate that implementing and supervising the home-based PA protocol will be feasible as determined by recruitment and retention rates, patients’ satisfaction, and compliance with the program. We also expect that this protocol will increase physical activity levels, improve general strength, balance, physical function, and reduce the risk of falls in sedentary older adults with T2DM. DISCUSSION/SIGNIFICANCE: As the third cause of death in PR, T2DM represents a public health challenge. An effective home-based PA program may decrease morbidity and mortality rates in older adults by increasing PA and functional health. This study will provide data for planning a randomized controlled trial to assess its effectiveness in the outcomes of interest.

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.