bluuebunny/crossref_metadata_2025 huggingface dataset:
549 A Nationwide Pilot Study Testing a Remotely-Delivered Prolonged Nightly Fasting Intervention in Stressed Midlife Adults Living with Obesity and Memory Decline
Authors: James Dara L. , Larkey Linda K. , Maxfield Molly , Ofori Edward , Hawley Nanako A. , Alperin Kate , Osha Peyton , Mun Chung Jung , Sears Dorothy D.
Published: April 2024

OBJECTIVES/GOALS: Cognitive decline is associated with obesity, stress, poor sleep, and circadian rhythm misalignment, which are themselves functionally intertwined. Irregular food intake timing exacerbates these all. Prolonged nightly fasting (PNF) aligns food intake with innate circadian rhythms. METHODS/STUDY POPULATION: A nationwide, remotely-delivered, 2-arm randomized controlled trial was conducted to assess feasibility and 8-week outcomes of cognition, stress, sleep, eating behaviors, and general eating habits, after a PNF intervention (14-hr nightly fast, 6 nights/week, no calories after 8pm) compared to a health education control (HEC) condition. Eligible participants were living with obesity, stress (Perceived stress scale-4 (PSS-4) total score ≥5), and memory “not as good as it used to be.” Data were collected via Zoom meetings with participants and trained staff and entered into REDCap. All participants had weekly staff check-in calls to report fasting times (PNF group only) and feedback. RESULTS/ANTICIPATED RESULTS: Eligible participants were enrolled from 37 of 50 US states; N=58, 86% women, 71% white, 93% non-Latinx, mean (SD) 50.1 (5.1) years of age, BMI 35.6 (3.6) kg/m^2. No group differences existed at baseline. Linear mixed-effects models were used to compare group differences across all outcome changes. Compared to the HEC condition, the PNF intervention was associated with improved sleep quality (Pittsburgh Sleep Quality Index; B = -2.52; SE = 0.90; 95% CI-4.30 to -0.74; p=0.006). Stress, everyday cognition, and emotional eating behavior significantly changed over time (p<0.02), but there were no group differences. Analysis of feasibility outcomes are on-going. DISCUSSION/SIGNIFICANCE: Changing food intake timing 6 days per week, to exclude nighttime eating without mandating food quality/quantity change, may benefit many individuals living with obesity, stress and memory decline to improve their sleep. Improved sleep quality may lead to more health benefits over time.
553 Creating an In-Person Workshop Series Addressing Core Team Science Principles for Early Career Investigators
Authors: Whitehurst Lauren N. , Kelly Thomas H. , King Victoria L. , Elam Carol L.
Published: April 2024

OBJECTIVES/GOALS: A barrier to the proliferation of team science is that academicians are often trained in disciplinary silos where “independent” research contributions are lauded. To tackle some of the most pressing scientific challenges, dismantling silos and increasing team science training efforts that focus on early career investigators is a must. METHODS/STUDY POPULATION: A team science training workshop for early career investigators from varied disciplinary backgrounds was informed by a 20-item needs assessment that addressed essential team science competencies and was completed by early career investigators participating in federally funded professional development programs on our campus. During the workshop, the benefits of cross-disciplinary teaming was discussed. Strategies including team formation, team effectiveness and/or dysfunction, diagnosing team strengths and weaknesses, and teaming in community settings were discussed. Instructional methods included short presentations, video clips, case studies, group discussions, pair and share activities, and panel discussions with expert role models encouraged active learning. RESULTS/ANTICIPATED RESULTS: The impact and value of the workshop series to participant’s professional development and knowledge of team science concepts will be evaluated before and after the workshop. Multiple Likert-scale items focused on team science competencies (e.g., confidence in your ability to carry out responsibilities specific to your role on a team, recognize when the team is not functioning well; engage team science practices in on-going research), and open-ended questions (e.g., importance of engaging community partners in academic research teams, vision of what factors contribute to an effective team science collaboration) will be completed by program participants before and after completing the workshop. DISCUSSION/SIGNIFICANCE: Effective collaboration among scientists with expertise in different disciplines is needed to address and solve complex scientific problems. We believe our interactive approach to team competency training sessions would work in a variety of settings and improve team skills.
555 Design Lab Methodology Supports Innovation in Clinical Trials
Authors: Palm Marisha E , Beninger Paul , Daudelin Denise , Duenas Noe , Hirsch Gigi , Markman Kris , Reed Ellaina , Trinquart Ludovic , Trusheim Mark , Welch Lisa , Selker Harry
Published: April 2024

OBJECTIVES/GOALS: Since 2017, we have used the Design Lab methodology to support investigators taking innovative approaches to clinical effectiveness trial design. To date we have held 12 Design Labs and this year we are creating a handbook that will support dissemination of this approach across the Clinical and Translational Science Award consortium. METHODS/STUDY POPULATION: The Clinical Trial Design Lab brings together a multi-stakeholder group to consider innovative and impactful clinical trial designs. An investigative team is selected from a competitive pool of applicants, after which expert-led consultations support the investigator team to think about evidence generation in the context of the full treatment development pathway. Teams map the stakeholders at each step of this pathway (e.g. clinicians, patients, researchers, funders, industry experts, policy experts, regulatory experts, payers) and consider innovative design solutions. These consultations prepare investigators for an event that involves all stakeholders in a structured and facilitated discussion about trial designs that generate the best evidence and increase potential for health impact. RESULTS/ANTICIPATED RESULTS: The result of our work will be a set of Design Lab principles, a handbook with templates that support stakeholder mapping and structured discussions, and educational resources to accompany the handbook. The work is supported by a literature review that characterizes the multi-component processes included in the Design Lab, situates them within the larger context of team science interventions, and lays groundwork for the development of process metrics and impact evaluation criteria to assess the Design Lab method. In this poster presentation, we will share our multi-component broadly engaged team science approach, provide a brief outline of the principles and educational resources, and include an early version of the evaluation criteria. DISCUSSION/SIGNIFICANCE: Broadly engaged team science supports innovative thinking about study design and is especially important in the development of clinical trials. We have grown the Design Lab program of work over the past seven years and are now able to characterize our team science methodology and support others to use this approach to innovate for health impact.
558 Investigation of the Epidemiological Differences associated with Post Acute Sequelae of Sars-CoV-2 infection
Authors: Ofotokun Igho , Mehta Christina , Dansby Kamaria
Published: April 2024

OBJECTIVES/GOALS: In this work investigating the epidemiological differences associated with Post Acute Sequelae of SARS-CoV-2(PASC) patho genesis we willassess the sex differences inocular viral persistence and the immunologic profile in tear film obtained from COVID-19 patients. METHODS/STUDY POPULATION: Participants will be enrolled from the NIH funded RECOVER Consortium at the 15 adult hubs in the US and will include those with acute COVID-19 (n=250), followed up at baselineto 48 weeks post infection. RT-PCR will be used to detect viral RNA and electro chemiluminescence assays will be used to detect IgG, IgA1 and IgA2 antibodies.Tear film antibody titers will be measured longitudinally in all participants to assess the kinetics of the immune responses in those who developed PASC and those who did not. Tear film antibody titers will be correlated with antibody titers in the blood and compared between those individuals with or without measurable viral RNA in tear film. RESULTS/ANTICIPATED RESULTS: Logistic regression models will be used assess the association of viral persistence with PASC status controlling for relevant covariates. Linear mixed regression models will be used to assess the association of IgA1/IgA2 with PASC status. We expect to observe delayed clearance of viral RNA and elevation in SARS-CoV-2 specific IgA2/IgA1 in the tear film of patients with PASC compared with those without PASC. Given evidence of increased PASC risk in women we expect to observe higher rates of SARS-CoV-2 ocular viral persistence and higher SARS-CoV-2 specific IgA2/IgA1 ratios in women with COVID-19 when compared to men with COVID-19. DISCUSSION/SIGNIFICANCE: There is concern that PASC will pose a major global health challenge given the scale of the Covid-19 pandemicand the patho genesis remains unclear. This work is highly likely to improve our understanding of the mechanisms of PASC and the reasons why women are more vulnerable to this condition.
559 Ideation Jams: Catalyzing Interdisciplinary Teams to Maximize Research Impact
Authors: LaPensee Elizabeth , Salem Barabara , Bugden Jane , Cantrell Mark , March Maureen Brudzinski , Samuels Elias , Somers Emily
Published: April 2024

OBJECTIVES/GOALS: There is broad recognition that interdisciplinary research teams are uniquely suited to address complex research questions. At the Michigan Institute for Clinical & Health Research, we recognized a significant gap in support services at the University of Michigan for coordinating interdisciplinary teams to advance translational research. METHODS/STUDY POPULATION: The initial team science challenge we tackled was how to bring together cross-disciplinary groups, for the first time, to engage meaningfully and collaboratively with a ‘wicked’ problem of interest and create a shared vision. To address this, we developed Ideation Jams, which are facilitated experiences that help new groups build community, identify and prioritize research opportunities, determine how individual interests and other potential partners align with opportunities, and commit to next steps that will advance collaborative efforts. Ideation Jams leverage the methods and mindsets of design thinking, including divergence and convergence; making information visual; amplifying diversity; horizontal distribution of responsibility; and bias towards action. RESULTS/ANTICIPATED RESULTS: We have facilitated 11 Ideation Jams with 255 participants, including faculty, staff, health practitioners, and community members, who brought diverse expertise and insight to the research problems. Participant feedback has been overwhelmingly positive, with Ideation Jams fostering shared vision and innovation, and positively impacting various measures related to team performance. Participants have reported that Ideation Jams catalyzed various outcomes, including submission and award of grants, the introduction of new and specialized clinical offerings, and development of an interdisciplinary research agenda for their field of interest. Most recently, we trained representatives from five Clinical & Translational Science Award hubs to implement Ideation Jams at their universities. DISCUSSION/SIGNIFICANCE: Ideation Jams are ideal for mobilizing new groups around complex research problems, moving them from blue-sky thinking to action planning in three hours. Ideation Jams will be integrated into a suite of facilitated experiences, trainings, and grant development services to provide iterative support as teams advance their research priorities.
560 Associations of human placental lactogen and oxytocin during pregnancy with maternal-fetal attachment, anxiety and depression
Authors: Coté Remington , Stessman Holly , Handelzalts Jonathan , Doerman Pooja , Dilsaver Danielle B. , Walters Ryan W. , Badura-Brack Amy S. , Coté John
Published: April 2024

OBJECTIVES/GOALS: The goals of the present study were to examine levels and potential changes in oxytocin and HPL over the course of pregnancy. We assessed the potential predictive value of oxytocin and HPL on maternal-fetal attachment, anxiety and depression at three timepoints during pregnancy. METHODS/STUDY POPULATION: Pregnant women (n=70) enrolled in a longitudinal, rolling protocol study. Eligibility criteria included 1) singleton pregnancy confirmed at early pregnancy screen (EPS) ultrasonography, 2) mother aged 19 or greater, and 3) fluent in English. Predictors (oxytocin and HPL levels) were measured via blood draws at the same three times (early-stage, mid-stage, and late-stage) that MFA, anxiety and depression questionnaires were completed. RESULTS/ANTICIPATED RESULTS: An increased OT level compared to a mother’s average OT level did not have a statistically significant effect on MFA (within-person estimate = 0.02, 95% CI: -0.03 to 0.05, p = 0.427. An increased HPL level compared to a patient’s average HPL level did not have a statistically significant effect on MFA (within-person estimate = -0.10, 95% CI: -0.67 to 0.47, p = 0.730). The main effect of between-person HPL was significant; such that a one-unit increase in average HPL level was associated with a 0.52 higher anxiety score (between-person 95% CI: 0.08 to 0.96, p = 0.022). The main effect of between-person HPL was significant, such that an increased average HPL level was associated with a 0.45 higher depression score (between-person estimate = 0.45, 95% CI: 0.04 to 0.86, p=0.031). DISCUSSION/SIGNIFICANCE: To our knowledge, our study is the first to measure HPL and MFA over the course of a pregnancy. At this point, perhaps the best we can say is that HPL is a promising new target hormone that may be related to psychological symptoms surrounding pregnancy.
562 AI Translation Advisory Board: Mastering team science to facilitate implementation of AI into clinical practice
Authors: Ohde Joshua W. , Malik Momin M. , Overgaard Shauna M. , Brereton Tracey A. , Zheng Lu , Peterson Kevin J. , Rost Lauren M.
Published: April 2024

OBJECTIVES/GOALS: Healthcare sectors are rushing to develop AI models. Yet, a dearth of coordinated practices leaves many teams struggling to implement models into practice. The Enterprise AI Translation Advisory Board uses across-disciplinary team to facilitate AI translation. METHODS/STUDY POPULATION: The Mayo Clinic Enterprise AI Translation Advisory Board was established to assess AI solutions lever aging cross-disciplinary team science to accelerate AI innovation and translation. The 23-member board reflects expertise in data science, qualitative research, user experience, IT, human factors, informatics, regulatory compliance,ethics, and clinical care, with members spanning thought leadership, decision-making, and clinical practice. Taking an approach of respectful communication, transparency, scientific debate, and open discussion, the Board has consulted onover two dozen projects at various stages of the AI life cycle. RESULTS/ANTICIPATED RESULTS: Common issues identified for projects earlier in the AI life cycle, sometimes fatal but often address able once identified, include a lack of buy-in from potential product users, a lack of planningabout integration into clinical workflow, inadequately labeled data, and attempting to use machine learning when what is desired is really a causal model for intervening. Recommendations for projects later in the AI life cycle include details of a testing plan (silent evaluation, pragmatic clinical trials), advice about clinical integration, both post-hoc and on going auditing for performance disparities, and planning for regulatory clearance. DISCUSSION/SIGNIFICANCE: Advising is more valuable for projects at the ideation phase, when multi disciplinary interrogation can identify weaknesses. But at all phases, projects have gaps related to a lack of specific disciplinary expertise. A multi disciplinary cluster like the AI Translation Advisory Board seeks to address these gaps.
33 Risk and protective factors for persistent depressive symptoms among transgender and non-binary youth: A prospective cohort study
Authors: Conn Bridgid Mariko , Durazo-Arvizu Ramon , Wong Carolyn F. , West Amy E. , Olson-Kennedy Johanna
Published: April 2024

OBJECTIVES/GOALS: While most transgender and non-binary (TNB) youth experience improved mental health post-initiating gender-affirming hormones (GAH), some continue to experience persistent, significant depressive symptoms two years post-GAH. Importantly, few studies have examined this issue given the lack of existing longitudinal studies. METHODS/STUDY POPULATION: We aimed to identify intervenable factors predicting persistent clinical depressive symptoms (PD) among TNB youth two years post-initiation of GAH utilizing the Trans Youth Care U.S. Study, an ongoing, multisite, observational study of TNB youth from four major pediatric hospitals across the U.S. We compared TNB youth (ages 12-20 at baseline) with persisting depression symptoms (PD) two-years post-GAH (i.e., PD; N=59) and those youth without (non-PD; n=215). Logistic regression estimated the association between PD and risk (e.g., negative expectations) and protective factors (e.g., parental acceptance, self-efficacy), measured at baseline and longitudinally. A mixed-effects model compared the rate of change of these factors between PD and non-PD youth. Models controlled for birth sex. RESULTS/ANTICIPATED RESULTS: Participants (Mean age=16) identified as transmasculine, then transfeminine, followed by non-binary. PD youth had higher negative expectations at baseline and internalized transphobia by 2-years, while non-PD youth reported greater parental acceptance over 2-years. The odds of PD compared to non-PD decreased with increasing self-efficacy at baseline (OR=0.7, 95% CI:0.5-0.9), whereas negative expectation for the future was associated with increased odds (OR=1.3, 95% CI:0.9,1.8). Moreover, the odds of PD increased 50% with increased rate of change in negative expectations, and odds decreased 50% with increased rate of change in self-efficacy, after adjusting for baseline negative expectations and self-efficacy, respectively. DISCUSSION/SIGNIFICANCE: We identified key intervenable factors for mental health treatment for TNB youth with PD; specifically, negative expectations increased risk for PD while self-efficacy appeared to buffer against PD risk. These findings also support assessment of youth for negative expectations for the future conferring greater risk for later PD.
35 Total-body symptom assessment in patients with idiopathic orthostatic intolerance to improve symptomatic management
Authors: McGeoch Catherine , Steinberg Rebecca S. , Thadani Siya , Cutchins Alexis C.
Published: April 2024

OBJECTIVES/GOALS: Total-body symptom surveys among patients with idiopathic orthostatic intolerance (OI) at our referral center suggest that non-conventional OI symptoms, such as pelvic pain, impact quality of life. We seek to identify additional common yet unconventional symptoms reported during clinic visits to improve targeted symptom management. METHODS/STUDY POPULATION: Pelvic pain symptom surveys were completed by 178 patients age 18 and over with a chief complaint of OI. Pelvic pain prevalence was assessed using the International Pelvic Pain Society (IPPS) and Pelvic Congestion Syndrome (PCS) surveys. Expanding on this work, surveys will be distributed to a population with the same inclusion criteria but with a broader symptom scope, chosen based on patient reports during clinical encounters—including presence of migraines, cold digits (Raynaud’s phenomenon), anxiety and depression. The Migraine Disability Assessment Test (MIDAS), modified Assessment of Systemic Sclerosis–Associated Raynaud’s Phenomenon (ASRAP), Generalized Anxiety Disorder-7 (GAD-7), and Patient Health Questionnaire-9 (PHQ-9) surveys, respectively, will be used to obtain symptom prevalence. RESULTS/ANTICIPATED RESULTS: Of the pelvic pain survey participants, pelvic pain was endorsed by 144/178 (80.9%) of respondents. Prevalence of the additional surveyed symptoms—migraines, cold digits, anxiety, and depression—will similarly be assessed. Given that in our referral clinic we have observed a trend of patients reporting these additional symptoms, we anticipate that at least some of them will be prevalent in a majority of the patient population formally surveyed, similar to the trend observed with pelvic pain prevalence. In particular, we anticipate many patients will report significant migraines, as migraine pain severity on a scale of 0-10 with 0 being no migraine pain and 10 being the most severe migraine pain imaginable is one of the elements of the IPSS survey, and 106/178 (59.6%) reported migraine pain of 5 or higher. DISCUSSION/SIGNIFICANCE: Novel treatment approaches for OI are needed, as lifestyle management is the current treatment paradigm. Several patients reporting pelvic pain have undergone targeted workup and subsequent symptomatic treatment that has improved their quality of life. Other targeted symptom approaches to prevalent symptoms could have the same effect.
44 Trends in Management of Chronic Kidney Disease among Adults with Diabetes, NHANES 1988-2020
Authors: Venkatraman Siddharth , Shin Jung-Im , Grams Morgan , Chang Alex , Coresh Josef , Selvin Elizabeth , Fang Michael
Published: April 2024

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.
56 Impact of ACTIV-6 treatment on PROMIS-29 at 7, 14, 28, and 90 days
Authors: Whitman Julia , Sulkowski Mark , Rothman Russell , Lindsell Chris , Barrett Jennifer , Stewart Thomas
Published: April 2024

OBJECTIVES/GOALS: As mortality and morbidity from acute COVID-19 decline, the impact of COVID-19 on short- and long-term quality of life (QoL) becomes critical to address. We assessed the impact of re-purposed COVID-19 therapies on QoL as a secondary outcome measure in ACTIV-6, a decentralized platform trial. METHODS/STUDY POPULATION: Adults aged ≥30 with mild-to-moderate COVID-19 enroll in ACTIV-6 online or through a study site. Patients are randomized to a medication of interest or placebo. Medications are mailed and symptoms are tracked using electronic diaries. QoL is measured#_msocom_1 using the PROMIS-29 questionnaire. Adjusted Bayesian logistic regression models are used to measure effects of treatment on the seven PROMIS-29 QoL domains at days 7, 14, 28#_msocom_2 and 90. Covariates are treatment, age, gender, symptom duration and severity, vaccination status, geographic region, call center#_msocom_3#_msocom_4, and calendar time. Treatment effects are described using ORs, 95% credible intervals, and posterior probabilities of efficacy, P(eff). RESULTS/ANTICIPATED RESULTS: There are 5,362 patients included, representing four of the study arms in ACTIV-6. We report results where P(eff)<0.025 and P(eff)>0.975 in the table below. Table 1. Scale Day: OR* (95% credible interval, P(eff)) Therapy Physical Anxiety Depression Fatigue Sleep Social Pain Ivermectin 400 — Ivermectin 600 D7: 0.77 (0.61-0.96, 0.01) D14: 0.65 (0.49-0.85, <0.01) D28: 0.69 (0.52-0.92, 0.01) — D7: 0.79 (0.64-0.97, 0.01) — D14 0.78 (0.60-1.00, 0.02) D28: 0.66 (0.50-0.87, <0.01) Fluticasone - D14: 0.77 (0.60-0.99, 0.02) — D7: 0.76 (0.62-0.93, <0.01) D90: 0.79 (0.64-0.98, 0.01) — D7: 0.74 (0.59-0.93, 0.01) Fluvoxamine D7: 0.66 (0.51-0.84, 0.01) — D28: 1.38 (1.02, 1.85, 0.98) D7: 0.78 (0.63-0.97, 0.01) D7: 0.77 (0.62-0.95, 0.01) — *OR > 1 favors active intervention DISCUSSION/SIGNIFICANCE: Results suggest fluvoxamine may improve depression scores by day 28, while placebo is favored in several other scales across treatments. Differences between treatment and placebo are not seen at most other timepoints. This trial is ongoing and future work will include results from additional ACTIV-6 study arms.
57 Utilizing a Digital Phenotype for Metabolic Syndrome to Elucidate Risk Profiles for Neurocognitive Disease: An Electronic Medical Record Study
Authors: Gosalia Jigar , Brinkerhoff Annabelle , Qiu Juan Jan , Pawelczyk James A. , Proctor David N.
Published: April 2024

OBJECTIVES/GOALS: Metabolic syndrome (MetS), defined as a cluster of cardiometabolic disease risk factors, is seldom coded using the ICD-10 system in electronic medical records (EMR). The goal of this study was to use EMR to construct MetS with a digital phenotype to amplify the pool of patients available to assess risk for neurocognitive disease in this population. METHODS/STUDY POPULATION: A digital phenotype using the EMR platform TriNetX (n=38 million patients between age 50 and 80) was created by clustering codes for the individual components of MetS (insulin resistance, hypertension, dyslipidemia, and central adiposity). The research network database on TriNetX was utilized to elucidate risk ratios for neurocognitive decline, Alzheimer’s disease and related dementias (ADRDs), and cerebrovascular disease between a preclinical sample of older adults with and without MetS. Propensity score matching was used to match cohorts on demographic variables, medication use, and relevant comorbidities. Risk ratios (RR) and confidence intervals (95% CI) were presented for all outcomes. RESULTS/ANTICIPATED RESULTS: The digital phenotype for MetS expanded the sample from 29,830 to 274,703, a 10-fold increase. Sensitivity to the standard MetS ICD-10 code was 95.1%, showing strong agreement between coding schema. Older adults with MetS had higher risk of cognitive decline (RR: 1.30, 95% CI: 1.15–1.48, p <0.001), ADRDs (RR: 1.48, 95% CI: 1.25–1.75, p <0.001), and cerebrovascular issues (RR: 1.62, 95% CI: 1.55–1.70, p <0.001) when controlling for demographics, medication, and comorbidities. MetS individuals with cerebrovascular dysfunction had even greater risks for neurocognitive decline (RR: 1.70, 95% CI: 1.38–2.08, p < 0.001) and ADRDs (RR: 2.09, 95% CI: 1.56–2.80, p < 0.001) than those with only MetS. DISCUSSION/SIGNIFICANCE: Implementing a digital MetS phenotype in EMR effectively increased sample size and power for analyses. Older adults with MetS have higher risk for neurocognitive decline, especially among those with cerebrovascular dysfunction, highlighting a critical intervention window prior to overt cardiometabolic disease.
64 Detecting and monitoring Salmonella infection and chronic carriage in living mice using bioluminescent in vivo imaging
Authors: Bennett Aliyah , Gunn John S.
Published: April 2024

OBJECTIVES/GOALS: SalmonellaTyphi primarily persists in human chronic carriers by forming biofilms on gallstones in the gallbladder (GB). We developed a mouse model of GB chronic carriage, and using this model, aim to detect Salmonella in living mice and track the progression of GB carriage with bioluminescent S.Typhimurium and in vivoimaging. METHODS/STUDY POPULATION: S.Typhimurium 14028 (WT) was transduced with the lux operon from the S. Typhimurium Xen33 strain from Perkin Elmer©, creating 14028lux. 129X1/SvJ mice were fed a lithogenic diet for 6 weeks to induce gallstone formation. After cessation of diet, these mice were infected with 5x103-1x104 colony forming units (CFU) of either the 14028lux isolate, WT (non-luminescent) isolate, or an equal volume of sterile saline. Mice were serially imaged (IVIS SpectrumCT) every 2-3 days for up to 63 days. Images were quantified by measuring average radiance over selected regions of interest. The presence of bioluminescent bacteria in specific organs was confirmed by imaging the abdominal cavity post-mortem. Organs were homogenized and CFUs per mg of tissue were quantified and compared between each group. RESULTS/ANTICIPATED RESULTS: Compared to the controls, mice infected with 14028lux showed luminescence in the abdomen as early as three days post-infection. Within 15 days, the resolution was sufficient to discriminate signal in specific organs, notably the gallbladder, liver, spleen, and cecum. The presence of bacteria was confirmed in these organs via direct imaging and by quantifying CFUs in the tissues. At 63 days post-infection, we identified >103 CFUs and significant luminescence in the GB of a portion of 14028lux-infected mice. For all days post-infection, 14028lux-infected mice that lacked observable luminescence had <100 CFUs/mg tissue. DISCUSSION/SIGNIFICANCE: We have developed a technique using bioluminescent S.Typhimurium and in vivo imaging that, without sacrificing infected mice, enables us to reliably distinguish between mice that have maintained gallbladder chronic carriage >60 days and those that have cleared infection.
65 Testing the effects of rigid encapsulations on bovine primordial follicle quiescence versus growth
Authors: McElhinney Kathryn L , Rowell Erin E , Laronda Monica M
Published: April 2024

OBJECTIVES/GOALS: There is an interest in developing a bioprosthetic ovary for ovarian tissue transplantation. The properties of the ovarian extracellular matrix need to be better understood in order to replicate the human ovary. We tested the effects of an encapsulating hydrogel at different rigidities on bovine primordial follicle activation, growth, and survival. METHODS/STUDY POPULATION: Bovine primordial follicles were isolated from ovarian cortex. A mean of 9.9 follicles (range 3-24) were encapsulated per bead in either 1% or 5 % alginate across 4 experiments. The encapsulated follicles were subsequently crosslinked in a calcium sulfate solution. Follicles were then cultured for 8 days with light microscopy imaging taken every other day along with media exchanges. Follicles were then examined using immunofluorescence. Growth and survival curves were constructed and all statistical analyses were performed using Graph Pad Prism 9. RESULTS/ANTICIPATED RESULTS: A total of 372 follicles were encapsulated across 32 beads (16 in 1% alginate and 16 in 5% alginate). There were no differences in initial follicle size between the two conditions (33.53 µm vs. 32.45 µm, p=0.47). At the end of 8 days, there was no difference between follicle size (59.55 vs. 56.06, p=0.48). Additionally, there was no difference in survival between 1% and 5% alginate encapsulation (57.75% vs. 52.43%. p=0.40). Immunofluorescence is being performed on encapsulated follicles to confirm the presence of DDX4, a molecular marker of oocytes, after 8 days in culture. Additional encapsulated follicles have also been submitted for histologic sectioning and hematoxylin and eosin staining to better characterize the viability and health of these follicles after 8 days in culture. DISCUSSION/SIGNIFICANCE: There was no significant difference in growth or survival between primordial follicles cultured in 1% or 5% alginate gels. Immunofluorescent analysis confirmed the presence of viable follicles at the end of 8 days of culture. Future work needs to further explore how factors in the ovarian extracellular matrix impact follicle maintenance and growth.
68 Visiting endowed chair: a new model to support Hispanics junior investigators
Authors: Ramos Carlamarie Noboa , Soto de Laurido Lourdes E. , Frontera Walter R.
Published: April 2024

OBJECTIVES/GOALS: Analyze how the Endowment HIREC ‘s Mentoring and Career Coach Model A productive mentoring relationship is essential to advance researchers into being independent and bring extramural funds. METHODS/STUDY POPULATION: Provide Hispanic researchers mentoring and career coaching to strengthen their pathway as researcher. The HiREC’s Career Coach and Mentoring Component (CCMC) is an innovated approach to support long-lasting research mentoring relationships in our institution. This approach was developed to advance research to eliminate health disparities, promote multidisciplinary translational research in a Minority Institution and sustain research infrastructure and services, career, and workforce development initiatives. Promising Faculty are target and early and mid-career investigators interested in pursuing a research career. To implement the CCMC with the Visiting Endowed Chair a HiREC Advisory Leadership Group in Mentoring will be established, with researchers from Puerto Rico, and US mainland. RESULTS/ANTICIPATED RESULTS: Three Hispanic mid-career women from the School of Medicine and one from the School of Health Professions from the University of Puerto Rico received a HiREC Advanced Research Award of $50,000. The awardees achieved their goals; completed their research plan, research infrastructure needs, peer-reviewed publications, and submission of a competitive grant. They also provided successful perspectives on mentoring relationships in a Minority institution. Each one showed the mentor’s and mentee’s experiences as fundamental for their research advancements, productivity, leadership, and successful results. HiIREC’s mentoring component with the Visiting Endowed Chairs improves a healthy work environment and expands the research agenda for each awardee sustaining the institutional research culture. DISCUSSION/SIGNIFICANCE: A productive mentoring relationship is essential to advance researchers into being independent and bring extramural funds. Four mentees received formal, long-term guidance and endowment funds for their research infrastructure requirements with successful outcomes. HiREC contributes to building up an institutional mentoring program.
73 Use of Probabilistic Linkage to Create a Novel Database to Study the Care of Bronchiolitis in Pediatric Intensive Care Units (PICU)
Authors: Flaherty Brian F , Smith McKenna , Srivastava Rajendu , Cook Lawrence J , Keenan Heather T
Published: April 2024

OBJECTIVES/GOALS: Bronchiolitis is a major cause of PICU admission, yet identifying best practices is limited by the lack of existing databases containing the needed demographic and clinical variables. We used probabilistic linkage to join the Virtual Pediatric System (VPS) and Pediatric Health Information Systems (PHIS) databases to overcome this data barrier. METHODS/STUDY POPULATION: We performed a single site study joining VPS and PHIS data. These national databases contain clinical (VPS) and billing and resource use (PHIS) data. Limits on the use of patient identifiers (PI) for multi-center research, makes direct linkage techniques impossible. To demonstrate that probabilistic linkage can accurately link VPS and PHIS records, we obtained our single site VPS and PHIS records and linked them using probabilistic linkage without PI and compared this to a gold standard linkage created with PI. We also compared demographic features of linked and unlinked records to assess the ability of probabilistic linkage to create a representative sample. RESULTS/ANTICIPATED RESULTS: We obtained 920 VPS records of patients with bronchiolitis and linked 91% (839/920) to a PHIS record with 4 (0.5%) false-positive matches. Characteristics of linked and unlinked records are compared in Table 1. Comparison of probabilistically linked and unlinked records showed no difference in median age in years (0.7 [Interquartile range (IQR) 0.3-1.5] v 0.7 [IQR 0.2-1.5], p = 0.76), median number of complex chronic conditions (0 [IQR 0-1] v 0 [IQR 0-1], p = 0.16), median Pediatric Index of Mortality 3 severity of illness scores (-4.6 [IQR -4.7 – 4.4] v -4.6 [IQR -4.7 – 4.4], p = 0.44), median days of PICU stay (4 [IQR 3-6] v 4 [IQR 2-6], p = 0.36), proportion female ( 44% v 46%, p = 0.82), or proportion of patients intubated (28% v 24%, p = 0.41). DISCUSSION/SIGNIFICANCE: Probabilistic linkage creates an accurate combined VPS-PHIS database. Extending our methodology to join data from all 38 hospitals contributing to VPS and PHIS will allow creation of a large database containing the demographic, treatment, and outcome data needed to enable Comparative Effectiveness Research of bronchiolitis care.
74 Trial-CARE: Centralized Support Services for Investigator-Initiated Multi-Site Clinical Trials
Authors: Keenoy Katie , Vedantham Suresh , Lake Emily
Published: April 2024

OBJECTIVES/GOALS: To describe the impact of Trial-CARE (Coordination, Acceleration, and Recruitment Enhancement), a centralized service core at Washington University (WU), aimed at enhancing the capability of investigator-initiated multi-site clinical trials at WU and partner CTSA institutions. METHODS/STUDY POPULATION: Through review of our marketing materials and service tracking system we defined the following Trial-CARE offerings: Infrastructure: Trial-CARE is a centralized service core at WU. Whereby, a team member is sourced to an investigator-initiated multi-site clinical trial (II-MCT) to ensure the achievement of study milestones across any phase of the clinical trial life cycle. Team: Our team consists of research professionals with expertise in II-MCT project management, data management, and administrative/regulatory management. Services: * One free 60-minute case consultation * Tiers of Service * Academic Research Organization (ARO) support * Clinical Coordinating Center * Data Coordinating Center * II-MCT project management support * Time-limited targeted support RESULTS/ANTICIPATED RESULTS: Trial-CARE has completed 94 consultations in support of WU and partner CTSA institutions enabling the streamlining of study start-up; guidance for study recruitment, implementation, and operations; and offering resources to foster career development. Consultations can be completed at any phase in the clinical trial lifecycle, with Trial-CARE completing: * 12% in the idea phase * 45% in the grant development and submission stage * 28% after funding has been awarded Top reasons researchers connect with Trial-CARE about II-MCTs: * regulatory guidance (40%) * general information about Trial-CARE Services and II-MCTs (35%) * protocol development (21%) * data management (20%) * study budgeting (20%) DISCUSSION/SIGNIFICANCE: In response to a WU wide survey, Trial-CARE plans to generate informational webinars and is creating a clinical trial tracking dashboard, to pro-actively offer support services to researchers prior to grant funding. The goal is also to increase the percentage of consultations completed in the idea phase and the grant development and submission stage.
76 Lessons learned during implementation of OMOP common data model across multiple health systems
Authors: Garneau William , Martin Benjamin , Gebo Kelly , Nagy Paul , Hopkins Johns , Boyce Danielle , Cook Michael , Robinson Matthew
Published: April 2024

OBJECTIVES/GOALS: Adoption of the Observational Medical Outcomes Partnership (OMOP) common data model promises to transform large-scale observational health research. However, there are diverse challenges for operationalizing OMOP in terms of interoperability and technical skills among coordinating centers throughout the US. METHODS/STUDY POPULATION: A team from the Critical Path Institute (C-Path) collaborated with the informatics team members at Johns Hopkins to provide technical support to participating sites as part of the Extract, Transform, and Load (ETL) process linking existing concepts to OMOP concepts. Health systems met regularly via teleconference to review challenges and progress in ETL process. Sites were responsible for performing the local ETL process with assistance and securely provisioning de-identified data as part of the CURE ID program. RESULTS/ANTICIPATED RESULTS: More than twenty health systems participated in the CURE ID effort.Laboratory measures, basic demographics, disease diagnoses and problem list were more easily mapped to OMOP concepts by CURE ID partner institutions. Outcomes, social determinants of health, medical devices, and specific treatments were less easily characterized as part of the project. Concepts within the medical record presented very different technical challenges in terms of representation. There is a lack of standardization in OMOP implementation even among centers using the same electronic medical health record. Readiness to adopt OMOP varied across the institutions who participated. Health systems achieved variable level of coverage using OMOP medical concepts as part of the initiative. DISCUSSION/SIGNIFICANCE: Adoption of OMOP involves local stakeholder knowledge and implementation. Variable complexity of health concepts contributed to variable coverage. Documentation and support require extensive time and effort. Open-source software can be technically challenging. Interoperability of secure data systems presents unique problems.
80 Venous thromboembolism diagnosis definition in claims data: implications for research
Authors: Schootman Mario , Fuccello Ashlynn , Corbin Seana , Martin Bradley , Mavros Michail
Published: April 2024

OBJECTIVES/GOALS: Venous thromboembolism (VTE) is a major cause of morbidity and mortality. Due to its relatively low incidence, prospective studies are limited. This makes administrative claims a promising data source to study VTE. We sought to examine the reproducibility of results using different VTE definitions from the published literature. METHODS/STUDY POPULATION: We conducted a retrospective analysis of a random 10% sample of the 2010-2022 IQVIA LifeLink PharMetrics Plus™ database, an administrative claims database representative of the commercially insured population of the United States. We selected cancer patients undergoing major gastrointestinal surgery, who have a higher risk for postoperative VTE (deep venous thrombosis [DVT] and/or pulmonary embolism [PE]). VTE was defined using ICD-9-CM and ICD-10-CM codes using definitions from 4 individual published studies. We compared the 4 definitions with respect to the incidence of VTE and factors associated with post-discharge VTE using standard univariate and multivariable logistic regression models. The same logistic regression models were used for each of the 4 definitions. RESULTS/ANTICIPATED RESULTS: There were substantial differences in VTE coding among the 4 definitions (range 107 to 225 ICD-9/10 codes for DVT and 12 to 24 codes for PE). The eligible population comprised 2,360 patients (49% female) with a median age of 49 years (interquartile range 47-52 years). During the index surgery hospitalization, a total of 58, 62, 63, and 83 patients developed VTE using the 4 definitions. In the 2,126 patients eligible for VTE prophylaxis, a total of 108, 68, 73, and 107 patients developed post-discharge VTE (range for DVT 35 to 81, range for PE 39 to 76). On multivariable analysis, factors independently associated with VTE included age using 1 of 4 definitions, esophageal surgery type using 3 of 4 definitions, and liver surgery type and Elixhauser score using all 4 definitions. DISCUSSION/SIGNIFICANCE: The incidence of VTE is directly affected by differences in ICD-9/10 codes used. Definitions for important clinical outcomes should be standardized when using administrative claims data in order to improve reproducibility of findings.
83 Automated PDMS Engraving and Assembly of a Prototype Microfluidic Artificial Lung
Authors: Zhang Andrew , Zhang Andrew , Wang Jennifer , Seilo Gabriele , Tharwani Kartik , Potkay Joseph A
Published: April 2024

OBJECTIVES/GOALS: We report an automated manufacturing system, and a series of cylindrical multi-layer microfluidic artificial lungs manufactured with the system and tested for fluidic fidelity and function. METHODS/STUDY POPULATION: A Roll-to-Roll (R2R) system to engrave multiple-layer devices was assembled. A 100 um-thick silicone sheet passes through an embedded CO2 laser engraver, which creates patterns of any geometry on the surface. The sheet is plasma-activated to create an irreversible bond, and rerolled into a processed device. Unlike typical applications of R2R, this process is synchronized to achieve consistent radial positioning. This allows the fluidics in the device to be accessed without being unwrapped. The result is a cylindrical core surrounded by many layers of microfluidic channels that can be accessed through the side of the device or through fluidic vias. This core is cut to expose the microfluidic layers, and then installed into a housing which routes the fluids into their respective microfluidic flow paths. RESULTS/ANTICIPATED RESULTS: To demonstrate the capabilities of the R2R manufacturing system, this method was used to manufacture multi-layer microfluidic artificial lungs (µALs). Gas and blood flow channels are engraved in alternating layers and routed orthogonally. The close proximity of gas and blood separated by gas-permeable PDMS permits CO2 and O2 exchange. Three µALs were successfully manufactured. Their flow paths were visualized using dyed water and checked for leaks. Then they were evaluated using water for pressure drop and CO2 gas-exchange. The top performing device had 15 alternating blood and gas layers. Test with whole blood demonstrated oxygenation from venous (70%) saturation levels to arterial (95%) saturation levels at a flow rate of 3 ml/min. DISCUSSION/SIGNIFICANCE: The ability to cost-effectively produce high surface area microfluidic devices would bring many small-scale technologies from the realm of research to clinical and commercial applications. In particular, most microfluidic artificial lungs only have small rated flows due to a lack of manufacturing processes able to create high surface area devices.