OBJECTIVES/SPECIFIC AIMS: Our goals were to understand the pattern, location, and extent of cardiac replacement fibrosis seen as late gadolinium enhancement on cardiovascular magnetic resonance imaging in a large cohort of cancer patients treated with anthracyclines and/or trastuzumab. METHODS/STUDY POPULATION: We performed a retrospective cohort study of consecutive adult cancer patients treated with anthracyclines and/or trastuzumab from 2004 through 2017. CMRs were analyzed for the presence, location, and pattern of LGE. RESULTS/ANTICIPATED RESULTS: Of 238 patients, 220/(92.4%) had no LGE. Among the 18/(7.6%) patients with LGE, 13/(72.2%) were ischemic in pattern (myocardial infarctions); 10 of these had known coronary artery disease (CAD). Of 5/(27.8%) patients with non-ischemic LGE, the etiologies were known for 4 – myocarditis, cardiac sarcoidosis, eosinophilic myocarditis, and acute myocardial calcification. Only 4/(1.7%) patients had unexpected LGE, of which 3 were unrecognized myocardial infarctions. DISCUSSION/SIGNIFICANCE OF IMPACT: The assessment of fibrosis helps to diagnose the cause of LVSD in cancer patients treated with potentially cardiotoxic medications. This is necessary because currently, the cause of LVSD in cancer patients cannot be established conclusively even though the cause is closely linked to patient outcomes. Our results demonstrate that cancer treatment-related LVSD is not associated with fibrosis. A minority of cancer patients with LVSD have fibrosis related to other reasons, most commonly CAD. Identification of the correct cause of LVSD in cancer patients treated with cardiotoxic medications allows for appropriate treatment. This, in turn, could improve patient outcomes.

OBJECTIVES/GOALS: Development of interventions that improve social functioning (SF) in first episode psychosis (FEP) is hindered by a poor understanding of the neural mechanisms underlying SF deficits. This research aims to identify neural correlates of social functioning in FEP, and to evaluate whether this substrate is malleable in response to cognitive training. METHODS/STUDY POPULATION: This is a secondary data-analysis of participants in an ongoing randomized clinical trial investigating whether 12 weeks of targeted cognitive training is neuroprotective in FEP, versus treatment as usual. Baseline and post-training assessments include a brain MRI, three measures of SF, and a neurocognitive battery. Healthy controls complete MRI only. Differences in cortical thickness (CTh) and gray matter volume (GMV) in regions of interest between FEP and controls will be determined with ANCOVA. Multiple linear regression will be used to determine the relationship between neural substrate and SF in FEP. Linear mixed models will be used to examine the relationship between change in CTh and GMV and change in SF. Data collection is ongoing for this study. RESULTS/ANTICIPATED RESULTS: In preliminary data including 12 FEP and 9 healthy controls, FEP demonstrated cortical loss in the right superior frontal cortex and the right isthmus-posterior cingulate. Greater cortical thickness in the posterior cingulate cortex was associated with better social functioning across multiple measures when controlling for global cognition. Gray matter volume in the parahippocampal gyrus was also associated with better social functioning. Preliminary results evaluating whether targeted cognitive training is neuroprotective in these regions of interest in a manner that is associated with improved social functioning will also be presented. DISCUSSION/SIGNIFICANCE OF IMPACT: Preliminary results link the posterior cingulate and parahippocampal gyrus to SF in FEP. Further research will investigate the contribution of changes in these brain regions to improved SF. The identification of biological treatment targets for SF may lead to development and optimization of novel interventions to alleviate SF deficits in FEP.

OBJECTIVES/GOALS: In vitro models that mimic the human respiratory system are needed to assess the toxicity of inhaled contaminants. Therefore, our goal is to establish a Dosimetric Aerosol in-Vitro Inhalation Device (DAVID) that delivers aerosols in different patterns to human lung cells cultured at an air-liquid interface (ALI). METHODS/STUDY POPULATION: The collection unit of DAVID was modified in this study to accommodate different deposition patterns (spots, annular ring, rectangle & circle). CuO aerosols of varying concentrations were generated using a 6-jet Collison nebulizer for varying time periods to achieve different doses. To quantify the doses that were delivered to cells, the samples were digested with nitric acid & analyzed by Inductively Coupled Plasma-Optical Emission Spectrometry. Following the exposure of A549 cells to CuO aerosols, cytotoxicity and mRNA expression (i.e., HMOX1 & IL-8) will be assessed via LDH and RT-qPCR to determine the effect of regional (mass deposited/area of the pattern) and global (mass deposited/area of the cell culture insert) doses in cells. RESULTS/ANTICIPATED RESULTS: The deposition areas covered by rectangular, spot, annular ring, and circular patterns are estimated to be 6, 17, 27 and 85% of the insert’s surface area, onto which cells are cultured. Results for the patterns tested (spots and annular ring) show that both the regional and global doses were greater for spots than annular ring. Also, the regional doses were higher than global doses. Irrespective of the patterns, the global doses were the same for nebulizer suspensions of 0.1-1 mg/mL. Statistical analysis by ANOVA revealed there was no significant difference in doses between replicate inserts used in the same trial. We anticipate that regional doses with aerosol deposition to a larger surface area of the cell culture insert will correspond with higher cytotoxicity and mRNA expression of HMOX1 and IL-8 in cells. DISCUSSION/SIGNIFICANCE: There are limited in vitro exposure systems that can efficiently deliver aerosols to lung cells, while also mimicking inhalation by humans. In addition to addressing this knowledge gap, we will show the role of regional & global doses in studying cellular response & the ability of DAVID to deliver aerosols in different deposition patterns.

OBJECTIVES/SPECIFIC AIMS: Cocaine use is a significant health problem in the United States and associated with increased risk of adverse cardiovascular outcomes. Our goal was to evaluate the effects of rapid cocaine infusions on cardiovascular hemodynamics among patients with cocaine abuse disorder. METHODS/STUDY POPULATION: Patients with a history of cocaine abuse but no overt cardiovascular disease received 4 consecutive intravenous infusions of cocaine (0, 10, 20, 40 mg) given in randomized, double-blinded order. The infusion procedure was repeated on 2 consecutive days (4 infusions each day). Following each dose, patients underwent continuous monitoring via fingertip plethysmography for 30 minutes, followed by an additional 30 minutes washout procedure. Patients were surveyed throughout this timeline to record symptoms of cocaine response. Finger tracings were then used to calculate arterial pressure curves and parameters of heart rate, blood pressure, cardiac output, stroke volume, and systemic vascular resistance according to device-specific algorithms. Mean values were calculated over the entire 30 minutes follow-up and peak values were defined as the maximum value sustained over any 60-second interval during the follow-up period. RESULTS/ANTICIPATED RESULTS: Seven patients were enrolled and received cocaine infusions of 2 consecutive days. Cocaine dose was positively associated with mean cardiac output (R=0.489, p<0.001), peak diastolic blood pressure (R=0.435, p=0.001), mean heart rate (R=0.401, p=0.003), peak systolic blood pressure (R=0.399, p=0.003), peak mean arterial pressure (R=0.362, p=0.008), mean systolic blood pressure (R=0.399, p=0.003), +dP/dt (R=0.346, p=0.012), and peak heart rate (R=0.334, p=0.015). Hemodynamic parameters were also predictive of patient-reported symptoms of cocaine response. DISCUSSION/SIGNIFICANCE OF IMPACT: These data confirm the known pharmacologic effect of cocaine to prevent reuptake of neurotransmitters and demonstrate the feasibility of conducting a noninvasive assessment of cardiovascular hemodynamics as a measure of responsiveness to cocaine infusions. This procedure also provides a benchmark to evaluate the potential impact of pharmacologic treatments on cocaine-induced hemodynamic changes and patient perceptions of cocaine response.

OBJECTIVES/GOALS: Patients who require a hematopoietic cell transplant (HCT) and dont have an HLA-matched related or unrelated donor may rely on a haploidentical donor. The optimal haploidentical donor and guidance for selection is limited. We aim to determine how donor characteristics affect outcomes following haploidentical-HCT for pediatric patients. METHODS/STUDY POPULATION: This is a retrospective cohort study evaluating the effect of donor age and relationship on post-HCT outcomes in children (0-18y) from 2008-2018. Multivariable logistic regression analysis will identify if donor age or donor relationship affect the development of graft-versus-host-disease (GVHD), while adjusting for other patient, donor, and transplant related variables. Two-year overall survival & event-free survival will be determined using Kaplan-Meier curves, stratified by donor age group and donor relationship, and compared by log-rank testing. Sub-analyses will be performed for myeloablative transplants and reduced intensity conditioning, as well as for malignant and non-malignant diseases. RESULTS/ANTICIPATED RESULTS: Our primary aim to is determine the effect of donor age and the effect of donor relationship to patient on the development of GVHD. We hypothesize that utilization of a younger donor will decrease the incidence of GVHD. Further, we hypothesize that utilizing a sibling haploidentical donor will result in less GVHD than a parental donor. Secondary aims include evaluating the effect of donor age and donor relationship on overall survival, event-free survival, non-relapse mortality, relapse, graft failure and time to engraftment. The results of this study will help us to develop criteria for optimal haploidentical donor selection. If donor selection is optimized, this could result in improved outcomes following haploidentical transplants. DISCUSSION/SIGNIFICANCE: Haploidentical donors are increasingly used as many patients, especially ethnic minorities, do not have an HLA-matched donor. This will be the largest study of haploidentical HCT in children. The data gathered will allow us to identify important donor characteristics to help guide physician decision-making when choosing a haploidentical donor.

OBJECTIVES/SPECIFIC AIMS: The primary objective of this study is to determine the prevalence of maternal GBS colonization and demographic risk factors associated with maternal GBS colonization in Latin America. Secondary objectives include: To determine if there is an association between maternal colonization with GBS and stillbirth or preterm birth in Latin America. To determine the effect of cesarean section (CS) on the incidence of neonatal sepsis with GBS in mothers colonized with GBS. METHODS/STUDY POPULATION: Study Population: Pregnant women who received prenatal care at sites that utilize the Perinatal Information System (SIP) from 1989 through 2015, and were screened for GBS between 35 and 37 weeks of gestation. Maternal exclusion criteria included spontaneous abortion, stillbirth before 35 weeks, and lack of screening for GBS. Methods: Estimated prevalence (and 95% confidence interval) of maternal GBS colonization for the entire data set, by region, and by country. The prevalence data for each country further stratified by maternal age, ethnicity, education, civil status and habitation. Descriptive statistics calculated for each clinical prenatal and clinical perinatal health indicator as well as for each clinical history variable for GBS colonized and non-GBS colonized women. Odds ratios will be calculated for each demographic and clinical risk factor. Fisher’s exact tests will be used to test hypotheses about the relationship between maternal GBS colonization and specific perinatal outcomes such as stillbirth or preterm birth. We will use multiple logistic regression models to test the hypotheses about the relationships between demographic variables, maternal GBS colonization and perinatal outcomes. RESULTS/ANTICIPATED RESULTS: Preliminary results: 712,061 records included in database. 98,852 records with data for GBS screening. o90.6% White, 7.4% Mixed, 0.6% Black, 0.3% Native Indian, 0.1% Other. GBS prevalence among screened women, 17.5% There was a significant association between maternal GBS colonization and ethnicity (X2 (4, N=97006)=569.901, p<0.01) o Prevalence rates by ethnicity: 20.5% Black, 18.4% White, 15.2% Native Indian, 8.8% Mixed, 3.3% Other. There was a significant association between maternal GBS colonization and age (X2 (4, N=98655)=119.901, p<0.01) o Prevalence rates by age group:. Age ≤ 20 - 15.2%. Age 21-34 – 17.8%. Age ≥ 35 – 19.6% Anticipated results:. GBS positive mothers will have an increased burden of stillbirth and preterm birth compared to GBS negative mothers. Neonates born to GBS colonized mothers who deliver via cesarean section will have a decreased incidence of sepsis compared to neonates born to GBS colonized mothers who deliver vaginally DISCUSSION/SIGNIFICANCE OF IMPACT: There have been no comprehensive studies to date that use the CLAP data to characterize the epidemiology of maternal GBS colonization and GBS disease and the burden of neonatal GBS disease in Latin America. Taking advantage of this unique database, this is the first region-wide study using systematically collected data. Our preliminary analysis indicates that GBS colonization status among pregnant women in Latin America is 17.5%, which is greater than previously reported. While there is evidence that maternal carriage of GBS is associated with stillbirth, this will be the first study to quantify the burden of GBS-associated stillbirth in Latin America. Additionally, previous work has been inconclusive in regards to maternal colonization with GBS and its association with preterm birth. This will be the largest study to evaluate the association of maternal GBS carriage with preterm birth. Findings from this study have the potential to inform public health policy and interventions by identifying the prevalence and risk factors.

OBJECTIVES/GOALS: Scholarly activity is a key component of most residency programs. To establish fundamental research skills and fill gaps within training curricula, we developed an online, asynchronous set of modules to introduce trainees to various topics that are germane to the conduct of research and evaluated its effectiveness in resident research education. METHODS/STUDY POPULATION: Research 101 was utilized by residents at the Brookdale Hospital Medical Center in Brooklyn, NY. Resident knowledge, confidence, and satisfaction were assessed using pre- and post-module surveys with 5-point Likert scaled questions, open-ended text responses, and a final quiz. RESULTS/ANTICIPATED RESULTS: Pre-module survey results indicated that residents were most confident with the Aligning expectations, Introduction to research, and Study design and data analysis basics modules and least confident with the Submitting an Institutional Review Board (IRB) protocol at UC and Presenting your summer research modules. Post-module survey responses increased significantly compared to pre-module results for all modules and learning objectives (p<0.0001). “This module met my needs” was endorsed 91.4% of the time. A final quiz of 25 multiple choice questions resulted in a median score of 23. Content analysis of open-ended post-module survey responses identified multiple strengths and opportunities for improvement in course content and instructional methods. DISCUSSION/SIGNIFICANCE: These data demonstratethat residents can benefit from completion of Research 101, as post-module survey scores were significantly higher than pre-module survey scores for all modules and questions, and final quiz scores were high and highlighted opportunities for additional resident learning.

OBJECTIVES/SPECIFIC AIMS: Missing data is a common problem in research studies that may lead to inconclusive or inaccurate results. It may even lead to harm secondary to wrong research conclusions. The purpose of this ancillary study is to measure the differences in missing data following implementation of a variety of mechanisms to improve data quality and documentation in a global quality improvement study. Many of the sites involved in the study were in low-income or middle-income countries with minimal research infrastructure. Missing data is defined as “values that are not available that would be meaningful for analysis if they were observed” (The prevention and treatment of missing data, New Engl J Med 367; 14, nejm.org, October 4, 2012). METHODS/STUDY POPULATION: All study sites used REDCap software to enter various data points including hospital and ICU admission and discharge dates as well as whether items on a Checklist relevant to processes of care in the ICU were reviewed. After initial general data collection phase, we categorized data as “must have” and “good to have.” “Must have” variables were defined as data variables that were essential for the study outcomes. “Good to have” variables would not affect the main outcomes of the study if missing. We measured completeness of data using the in-built REDCap data quality check feature. We used several strategies to encourage reduction of missing data. We initially did random data checks but noted that the amount of missing data was substantial and could not be adequately addressed this way. Second, we created excel sheets highlighting missing data for each site and notified sites. This proved onerous to create and made it burdensome for sites to identify easily where data was missing. Third, we built a custom report form in REDCap specifically able to identify which “must have” data points were missing. This could be easily accessed by the principal investigator at each site and made completing the data forms more straightforward. We encouraged all sites to complete their data collection by sending weekly data reports to each site highlighting the patients with missing data. An instructional YouTube tutorial was also created and the link was shared with all sites to demonstrate how to use the custom built report form in REDCap and how to appropriately fill in the missing data. Since this was a global study, we communicated with sites using a variety of locally favored mechanisms including Zoom, FaceTime, WeChat, WhatsApp as well as email. By harnessing the buy-in of local champions our approach was successful. RESULTS/ANTICIPATED RESULTS: The total number of patients recruited for the CERTAIN study is 4843. The rate of all missing variables improved with the efforts described above. Hospital admission dates were missing in 8.4% pre efforts and 4.2% post efforts (p<0.01). ICU admission dates were missing in 5.5% pre and 2.0% post (p<0.01). Documentation of completion of processes of care (including central line review, urinary catheter review, consideration for blood transfusion) improved significantly from pre to post (p<0.01). DISCUSSION/SIGNIFICANCE OF IMPACT: Missing data can be a problem in all types of research studies. This study provides some preliminary evidence for effective approaches that can reduce the problem of missing data when conducting a global study at sites with limited research infrastructure in place. By addressing the concern about missing data, we can be more confident that our results can be accurately analyzed and interpreted, improving the quality of the research.

ABSTRACT IMPACT: This work will impact participants of clinical trials by better informing them of their trial’s results and their important role within the clinical research process. OBJECTIVES/GOALS: This project aims to equip researchers with an online tool for the development, dissemination, and collection of participant feedback for plain language clinical trial (CT) result summaries (PLCTRS). PLCTRS ensure that participants fully understand their trial’s results and their role in the CT process. METHODS/STUDY POPULATION: This online development platform is a web application made with CSS, HTML, and JavaScript. First, general trial identification information including study aims and eligibility will be input by researchers. Then, they will be prompted with tips and suggestions for composing in plain language and to ensure inclusion of all essential trial information. Next, the platform will disseminate this writing electronically to participants. Participants then provide meaningful feedback on the platform about their comprehension for the researcher, which the platform will aggregate and summarize for revisions. This process of drafting and feedback is repeated until a satisfactory PLCTRS is finalized. RESULTS/ANTICIPATED RESULTS: The anticipated results of this project are overall improved comprehension of clinical trial results by participants. This comprehension will be measured by participants ability to answer certain questions not only regarding trial outcomes, but also about the trial in general. For instance, before and after interacting with the PLCTRS, trial participants will be asked if they can identify which investigational drug was being studied and its possible side effects. This project could anticipate identification of trial elements and results deemed difficult to comprehend by participants; thus they would be better informed after interacting with the platform. DISCUSSION/SIGNIFICANCE OF FINDINGS: This project will ensure that participants better comprehend the trials they participated in beyond the required informed consent process - which only covers their comprehension prospectively. This project seeks to address the gap of ensuring participant comprehension retrospectively.

Mini-sabbaticals are formal short-term training and educational experiences away from an investigator’s home research unit. These may include rotations with other research units and externships at government research or regulatory agencies, industry and non-profit programs, and training and/or intensive educational programs. The National Institutes of Health have been encouraging training institutions to consider offering mini-sabbaticals, but given the newness of the concept, limited data are available to guide the implementation of mini-sabbatical programs. In this paper, we review the history of sabbaticals and mini-sabbaticals, report the results of surveys we performed to ascertain the use of mini-sabbaticals at Clinical and Translational Science Award hubs, and consider best practice recommendations for institutions seeking to establish formal mini-sabbatical programs.

Well-designed, accessible short-term research training programs are needed to recruit and retain underrepresented persons into clinical and translational research training programs and diversify the workforce. The Michigan Institute for Clinical and Health Research developed a summer research program, training over 270 students in 15 years. In response to the 2020 COVID-19 pandemic, we pivoted swiftly from an in-person format to a fully remote format. We describe this process, focusing on factors of diversity, equity, and inclusion including enabling student participation in remote research activities. We collected data about students’ learning experiences since the program’s inception; therefore, we could evaluate the impact of remote vs. in-person formats. We examined data from five cohorts: three in-person (2017–2019; n = 57) and two remote (2020–2021; n = 45). While there was some concern about the value of participating in a remote format, overall students in both formats viewed the program favorably, with students in the remote cohorts rating some aspects of the program significantly more favorably. In addition, more students who identified as Black or African American participated in the remote format than in the in-person format. We describe lessons learned from this unprecedented challenge and future program directions.

Clinical translational neuroscience (CTN) is positioned to generate novel discoveries for advancing treatments for mental health disorders, but it is held back today by the siloing of bioethical considerations from critical consciousness. In this article, we suggest that bioethical and critical consciousness can be paired to intersect with structures of power within which science and clinical practice are conducted. We examine barriers to the adoption of neuroscience findings in mental health from this perspective, especially in the context of current collective attention to widespread disparities in the access to and outcomes of mental health services, lack of representation of marginalized populations in the relevant sectors of the workforce, and the importance of knowledge that draws upon multicultural perspectives. We provide 10 actionable solutions to confront these barriers in CTN research, as informed by existing frameworks such as structural competency, adaptive calibration models, and community-based participatory research. By integrating critical consciousness with bioethical considerations, we believe that practitioners will be better positioned to benefit from cutting-edge research in the biological and social sciences than in the past, alert to biases and equipped to mitigate them, and poised to shepherd in a robust generation of future translational therapies and practitioners.

OBJECTIVES/GOALS: Nearly half of mothers who report electronic (e)-cigarette use during pregnancy believe e-cigarettes are less harmful than traditional cigarettes. We aim to determine the association of quitting e-cigarette use in pregnancy with the risk of preterm birth and low birth weight. METHODS/STUDY POPULATION: We conducted a cross-sectional study of women participating in the Pregnancy Risk Assessment Monitoring System and with live singleton birth during 2016-2019. Women were classified based on their e-cigarette use: before pregnancy only (quitters), last three months of pregnancy only (initiators), at both times (sustained users), and neither time (non-users). We used a modified Poisson regression to determine the association between quitting e-cigarette use and preterm birth (<37 weeks) and low birth weight (<2,500 grams) adjusting for demographic, social-economic, and behavior-related risk factors. Analyses were weighted to account for the survey design and non-response. RESULTS/ANTICIPATED RESULTS: Based on 150,950 women who responded to the survey, there were estimated 2.9% quitters, 0.2% initiators, 1.0% sustained users, and 95.9% non-users in the U.S. Compared to sustained e-cigarette users, quitters had a similar risk in preterm birth (adjusted risk ratio [ARR]: 0.84, 95% confidence interval [CI]: 0.65, 1.08) and a significantly reduced risk in low birth weight (ARR: 0.77, 95%CI: 0.61, 0.97) adjusting for traditional cigarette use, age, race/ethnicity, education, marital status, family income, prior preterm birth, prior live births, BMI prior to pregnancy, pregnancy weight gain, kotelchuck index, multivitamin use, drinking prior to pregnancy, year of birth, and residential state. DISCUSSION/SIGNIFICANCE: As FDA authorizes the sales of certain e-cigarettes, women smokers may switch to e-cigarettes, believing they are reducing harm. Our study shows that quitting e-cigarette use is associated with a reduction of low birth weight. Clear messaging is needed to help women cease e-cigarette use in pregnancy.

OBJECTIVES/SPECIFIC AIMS: The iobio project enables anyone (eg, diagnosticians, MDs, genetic counselors, citizen scientists) to perform useful analysis of genomic data, without a need to rely on bioinformaticians. iobio uses a novel real-time analysis framework, coupled with powerful visualizations delivered in a standard web browser. The project successfully supports free academic/nonprofit users, but occasions exist where it is more applicable for the project to be delivered commercially. Frameshift Genomics is developing commercial applications and functionality, which will exist alongside and in coordination with the academic project. These products will be marketed to large institutions including genome institutes, hospitals, diagnostic labs etc., but also to individual users who do not have access to large compute resources, or bioinformatic analysts, and everything in between. METHODS/STUDY POPULATION: The commercial iobio project under Frameshift Genomics aims to develop applications and features that cannot be successfully supported by an academic model. For example, when analyses are scaled up to processing of extremely large data sets, a commercial product with access to compute resources makes more sense than an academic tool. Bam.iobio is an application that samples data from sequencing alignment files, taking seconds to generate and visualize statistics representative of the entire file. This app is offered for free academically. When analysis involves thousands of such files, however, the commercial application, multibam.iobio, is more suitable. Other examples, including support for licensed third-party software and permitting extensive computation via cloud platforms, can also only be reasonably be supported via commercial software. Finally, development of commercial applications is driving adoption of more rigorous testing platforms, delivering more robust products. A particular strength of the iobio platform is allowing non-bioinformaticians to understand their data, for example providing quality control functionality providing confidence in data sets and the conclusions drawn from them. Such analyses are critical to all users of genomic data, and the iobio platform is ideally suited to provide an intuitive, integrated framework for performing them. RESULTS/ANTICIPATED RESULTS: The iobio project has been readily adopted by many in the community and shows significant promise for democratizing genomic analysis. Work is ongoing, supported by NIH small business grants, to develop commercial applications that will be marketed to analysts and medical professionals from large genome institutes and universities, to individual project users and citizen scientists. DISCUSSION/SIGNIFICANCE OF IMPACT: There are currently a number of iobio tools available academically, and they have been embraced by many in the genomics community. In fact, a number of popular platforms (eg, Galaxy, the International Cancer Genome Consortium (ICGC) data portal, mygene2 at the University of Washington) have incorporated iobio tools into their own platforms. To date, the gene.iobio variant interrogation tool has been used in a number of diagnostic projects, aiding identification of putative causative variants, and the pre-release version of the commercial multibam.iobio tool has been critical in unearthing data quality problems in project level data.

ABSTRACT IMPACT: The importance of this study is to evaluate the responses following the exposure of opioid drugs in young adults to address the current opioid epidemics OBJECTIVES/GOALS: To compare the proportion of patients between 18 and 25 years of age, who develop an opioid abuse disorder following dental surgery, to those following other surgical procedures, when an opioid drug is used for acute postoperative pain control. METHODS/STUDY POPULATION: We fashioned an IRB-sponsored retrospective cohort study of patients, ages 18 to 25 years old, who presented for dental surgery or other medical surgical procedures, at Strong Memorial Hospital Medical Center, at the University of Rochester and received opioid drug treatments, for acute surgical pain management. Patients with the diagnosis of acute surgical pain were included in the study. However, those with chronic pain or other related abnormalities were excluded, even if a diagnosis of acute surgical pain was present in the electronic chart. The clinical data were retrieved from electronic medical records and NYS-iStop records. All statistics were significant at the level of <0.1 RESULTS/ANTICIPATED RESULTS: We identified 167 subjects, of whom, only 150 subjects met inclusion criteria (n=100) in dentistry and (n=50) in other medical specialties. Patients were followed up in a 7-year period. Most of the subjects were females (n=91), Caucasian (n=80), and lived in a suburban location (n=78). The most frequently prescribed opioid included hydrocodone (n=119). A significantly higher proportion (8.7%) of patients developed opioid abuse disorders in the control group, compared to 1% of subjects in the experimental group (p 0.02). Those in the control group received marginally significant higher doses of MMEs 447.2 +/-644.8 mg vs 306.2 +/-354.7mg in the experimental group (p 0.086). Those in the control group had significantly longer periods of opioid treatment 10 (+/-12) compared to 6(+/-6) days in the experimental group DISCUSSION/SIGNIFICANCE OF FINDINGS: It is paramount to evaluate the morphine milligram equivalents, and duration of opioid treatment given to the young population with acute surgical pain, to prevent opioid abuse disorders in this vulnerable cohort.

Objectives/Goals: Intra-amniotic inflammation (IAI) is one of the leading causes of maternal/fetal morbidity globally, yet it is undiagnosed in 90–95% of cases. The purpose of this study was to assess precision and accuracy of a novel microsampling device for measuring cytokines in amniotic fluid (AF) to enable noninvasive evaluation of localized inflammation. Methods/Study Population: AF was obtained from discarded amniocentesis samples from 3 deidentified patients without known inflammation. Samples were spiked to 5 concentrations of interleukin-6 (IL-6) and tumor necrosis factor-a (TNF-a), then sampled using the Neoteryx Mitra volumetric microsampling device (20 µL). Dried/reconstituted samples were analyzed using the Luminex R&D Mag XL multiplex (IL-6, TNF-α) and compared to free-flowing AF. Inter-and intra-assay performances were evaluated across 5-runs in 3 standard cytokine concentrations. Recovery/linearity was assessed by a recovery curve and parameter estimates. Precision was assessed between-run and within-run using coefficients of variance (%CV). Accuracy was evaluated as agreement between microsampled and free-flowing AF using Bland–Altman plots. Results/Anticipated Results: TNF-α results were linear for all 3 patients across 5 concentrations. However, accuracy and recovery consistently failed (mean±SD percent recovery 176±21%). TNF-α results had acceptable precision with %CV within-run of 6.8–12.1% and across-runs of 14.0–15.9%. Microsampled TNF-α agreed with free-flowing sample: 16 of 18 (89%) were within 1SD of the mean difference (-24±36 pg/ml). IL-6 results were linear for 1/3 patients and had unacceptable accuracy and recovery for 13/15 samples (mean±SD percent recovery 764±469%). IL-6 results had acceptable precision (%CV within-run 6.2%, 7.5% and 11.2%; across-run .9–15.2%). Microsampled IL-6 agreed with free-flowing sample; 17 of 18 (94%) were within 1SD of the mean difference (-148±180pg/ml). Free-flowing vs. microsampling methods agreed best at low concentration. Discussion/Significance of Impact: This study provides preliminary support for noninvasive measurement of cytokines leveraging small amounts of leaking AF providing a promising alternative to amniocentesis and potential for assessing inflammation intrapartum. Clinical application requires development of reference ranges and association between cytokine levels and outcomes.

Objectives/Goals: Triple-negative breast cancer (TNBC) is a highly aggressive and prevalent breast cancer subtype that lacks targeted therapies. This study aims to investigate whether the niclosamide derivative HJC0152 can modulate tumor-derived PD-L1 expression and enhance the effectiveness of anti-PD-1 immunotherapy in treating TNBC. Methods/Study Population: Niclosamide derivative HJC0152 was developed as a novel cancer therapeutic and immunomodulating agent. Human TNBC cell line (MDA-MB-231) was treated with HJC0152, and activation of the STAT3 signaling pathway was evaluated using Western blotting. RNA-Seq was employed to analyze the expression of protein-coding genes, particularly those related to immune response. To study therapeutic potential in vivo, TNBC mouse models will be treated with single agent treatments as well as a combination therapy of HJC0152 and anti-PD-1. Tumor volume and mass will be measured over time to determine growth inhibition. Results/Anticipated Results: Preliminary studies indicate that HJC0152 exhibits enhanced solubility compared to Niclosamide, along with high anticancer potency both in vitro and in vivo. HJC0152 was found to effectively inhibit the activation of phosphorylated STAT3 (p-STAT3) in MDA-MB-231 cells, a key signaling pathway associated with cancer progression and immune evasion. RNA-Seq analysis of HJC0152-treated MDA-MB-231 cells revealed a decrease in PD-L1 expression, an essential immune checkpoint protein involved in tumor immune suppression. These findings suggest that HJC0152 is a promising immune modulator that may enhance the efficacy of immune checkpoint blockade therapy for TNBC. Discussion/Significance of Impact: This study explores an innovative immunotherapy for TNBC using the Niclosamide derivative HJC0152, which inhibits STAT3 signaling and downregulates PD-L1. Results from this study will provide a foundation for HJC0152’s inclusion in clinical trials and potentially offer a new and promising therapeutic option for TNBC treatment.