bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of 18F-FDG PET/CT in primary cutaneous lymphoma: an educational review
Authors: McDonald Elysia O. , Amanullah Amir A. , Park Peter Sang Uk , Song William , Werner Thomas J. , Alavi Abass , Revheim Mona-Elisabeth
Published: April 2023

Introduction

Primary cutaneous lymphoma (PCL) is a cutaneous non-Hodgkin’s lymphoma that originates in the skin and lacks extracutaneous spread upon initial diagnosis. The clinical management of secondary cutaneous lymphomas is different from that of PCLs, and earlier detection is associated with better prognosis. Accurate staging is necessary to determine the extent of disease and to choose the appropriate treatment. The aim of this review is to investigate the current and potential roles of 18F- fluorodeoxyglucose positron emission tomography–computed tomography (18F-FDG PET/CT) in the diagnosis, staging, and monitoring of PCLs.

Methods

A focused review of the scientific literature was performed using inclusion criteria to filter results pertaining to human clinical studies performed between 2015 and 2021 that analyzed cutaneous PCL lesions on 18F PET/CT imaging.

Results & Conclusion

A review of 9 clinical studies published after 2015 concluded that 18F-FDG PET/CT is highly sensitive and specific for aggressive PCLs and proved valuable for identifying extracutaneous disease. These studies found 18F-FDG PET/CT highly useful for guiding lymph node biopsy and that imaging results influenced therapeutic decision in many cases. These studies also predominantly concluded that 18F-FDG PET/CT is more sensitive than computed tomography (CT) alone for detection of subcutaneous PCL lesions. Routine revision of nonattenuation-corrected (NAC) PET images may improve the sensitivity of 18F-FDG PET/CT for detection of indolent cutaneous lesions and may expand the potential uses of 18F-FDG PET/CT in the clinic. Furthermore, calculating a global disease score from 18F-FDG PET/CT at every follow-up visit may simplify assessment of disease progression in the early clinical stages, as well as predict the prognosis of disease in patients with PCL.
Dissecting Psychiatric Heterogeneity and Comorbidity with Core Region-Based Machine Learning
Authors: Lv Qian , Zeljic Kristina , Zhao Shaoling , Zhang Jiangtao , Zhang Jianmin , Wang Zheng
Published: April 2023

Machine learning approaches are increasingly being applied to neuroimaging data from patients with psychiatric disorders to extract brain-based features for diagnosis and prognosis. The goal of this review is to discuss recent practices for evaluating machine learning applications to obsessive-compulsive and related disorders and to advance a novel strategy of building machine learning models based on a set of core brain regions for better performance, interpretability, and generalizability. Specifically, we argue that a core set of co-altered brain regions (namely ‘core regions’) comprising areas central to the underlying psychopathology enables the efficient construction of a predictive model to identify distinct symptom dimensions/clusters in individual patients. Hypothesis-driven and data-driven approaches are further introduced showing how core regions are identified from the entire brain. We demonstrate a broadly applicable roadmap for leveraging this core set-based strategy to accelerate the pursuit of neuroimaging-based markers for diagnosis and prognosis in a variety of psychiatric disorders.
Optimization of Chelating Process of Amino Acids of Leather Waste and Glycine with Different Minerals and Its Relationship with Arthrospira platensis Biological Activities
Authors: Jacob Rania H. , Afify Adel S. , Shanab Sanaa M. M. , Shalaby Emad A. , Hafez Rehab M.
Published: April 2023

There are several factors were taken in consideration such as time, ratio, temperature and pH to improve the chelation process between the amino acids and inorganic ions. The current study aims to optimize the physical factors controlling the synthesis of chelated amino acids with different minerals and to enhance antioxidant and biodiesel production from Arthrospira platensis cultivated in culture enriched with different chelated minerals. In this study; various physical factors such as (ratio of amino acids and minerals; temperature, time and pH) were used for optimization of chelation formation. The blue -green alga Arthrospira platensis was cultivated under different synthesized chelated minerals (T1-T13), the growth rate, antioxidant, antiradical and biodiesel production were determined in all treated alga. The obtained results showed that the optimum conditions for production of chelated amino acid were ratio (2:1 M), temperature at 60 °C, the duration between 4:5 days and the suitable or stability of chelation at pH = 4, Also, the growth rate of A. platensis with Cu-glycinate higher than Cu-leather waste and Zarrouk media. The antioxidant activity results of different extracts of Arthrospira platensis showed that the water extract gave high antioxidant activity against DPPH radical assay than acetone extract in all treatments when compared with untreated culture (Zarrouk’s medium). Arthrospira platensis cultivated on Zarrouk medium supplemented with chelated amino acids with metals was showed an increase in algal pigments and lipids with Mn-LW, Zn-LW and Mg-LW treatments. Also, the results showed that the produced biodiesel was observed with M-LW treatments, which was more than that of glycinate treatments, untreated culture (Zarrouk) and LW biodiesel. Therefore, the highest biodiesel percentages were founded with Zn, Mn and Mg-LW (5.37, 5.25 and 4.86% respectively). The recorded results and material balance data concluded that possibility for use the chelated minerals (glycine and leather wastes) as plant fertilizer in future because its high yield and low fees for production.

Graphical Abstract
Uncertainty from the Aharonov–Vaidman identity
Authors: Leifer Matthew S.
Published: April 2023

In this article, I show how the Aharonov–Vaidman identity $$A\left| \psi \right\rangle = \left\langle A \right\rangle \left| \psi \right\rangle + \Delta A \left| \psi ^{\perp }_A \right\rangle $$

A

ψ

=

A

ψ

+
Δ
A

ψ
A
⊥

can be used to prove relations between the standard deviations of observables in quantum mechanics. In particular, I review how it leads to a more direct and less abstract proof of the Robertson uncertainty relation $$\Delta A \Delta B \ge \frac{1}{2} \left| \left\langle [A,B] \right\rangle \right| $$

Δ
A
Δ
B
≥

1
2

[
A
,
B
]

than the textbook proof. I discuss the relationship between these two proofs and show how the Cauchy–Schwarz inequality can be derived from the Aharonov–Vaidman identity. I give Aharonov–Vaidman based proofs of the Maccone–Pati uncertainty relations and show how the Aharonov–Vaidman identity can be used to handle propagation of uncertainty in quantum mechanics. Finally, I show how the Aharonov–Vaidman identity can be extended to mixed states and discuss how to generalize the results to the mixed case.
The labour market perspective on the role identities of vocational teacher educators: a case study in Malta
Authors: Said Alison
Published: April 2023

The overall purpose of this qualitative study is to gain a deeper understanding of how employers, who represent the Maltese labour market, view the role identities of Vocational Teacher Educators (VTEs). Data were collected through semi-structured interviews, adopting thematic analysis. Findings from this research, where it gives a voice to a group that has too often been neglected in policy and research, may help policymakers in small states to be wary of taking on board concepts related to the roles of VTEs originating from much larger countries and from the mainstream education contexts. Implications on how the relationship between the labour market and VTEs are discussed.
Characterising sediment thickness beneath a Greenlandic outlet glacier using distributed acoustic sensing: preliminary observations and progress towards an efficient machine learning approach
Authors: Booth Adam D. , Christoffersen Poul , Pretorius Andrew , Chapman Joseph , Hubbard Bryn , Smith Emma C. , de Ridder Sjoerd , Nowacki Andy , Lipovsky Bradley Paul , Denolle Marine
Published: April 2023

Distributed Acoustic Sensing (DAS) is increasingly recognised as a valuable tool for glaciological seismic applications, although analysing the large data volumes generated in acquisitions poses computational challenges. We show the potential of active-source DAS to image and characterise subglacial sediment beneath a fast-flowing Greenlandic outlet glacier, estimating the thickness of sediment layers to be 20–30 m. However, the lack of subglacial velocity constraint limits the accuracy of this estimate. Constraint could be provided by analysing cryoseismic events in a counterpart 3-day record of passive seismicity through, for example, seismic tomography, but locating them within the 9 TB data volume is computationally inefficient. We describe experiments with data compression using the frequency-wavenumber (f-k) transform ahead of training a convolutional neural network, that provides a ~300-fold improvement in efficiency. In combining active and passive-source and our machine learning framework, the potential of large DAS datasets could be unlocked for a range of future applications.
Bridging the gap between pricing and reserving with an occurrence and development model for non-life insurance claims
Authors: Crevecoeur Jonas , Antonio Katrien , Desmedt Stijn , Masquelein Alexandre
Published: April 2023

Due to the presence of reporting and settlement delay, claim data sets collected by non-life insurance companies are typically incomplete, facing right censored claim count and claim severity observations. Current practice in non-life insurance pricing tackles these right censored data via a two-step procedure. First, best estimates are computed for the number of claims that occurred in past exposure periods and the ultimate claim severities, using the incomplete, historical claim data. Second, pricing actuaries build predictive models to estimate technical, pure premiums for new contracts by treating these best estimates as actual observed outcomes, hereby neglecting their inherent uncertainty. We propose an alternative approach that brings valuable insights for both non-life pricing and reserving. As such, we effectively bridge these two key actuarial tasks that have traditionally been discussed in silos. Hereto, we develop a granular occurrence and development model for non-life claims that tackles reserving and at the same time resolves the inconsistency in traditional pricing techniques between actual observations and imputed best estimates. We illustrate our proposed model on an insurance as well as a reinsurance portfolio. The advantages of our proposed strategy are most compelling in the reinsurance illustration where large uncertainties in the best estimates originate from long reporting and settlement delays, low claim frequencies and heavy (even extreme) claim sizes.
Shortcuts for the construction of sub-annual life tables
Authors: Pavía Jose M. , Lledó Josep
Published: April 2023

Fuelled by the big data explosion, a new methodology to estimate sub-annual death probabilities has recently been proposed, opening new insurance business opportunities. This new approach exploits all the detailed information available from millions of microdata records to develop seasonal-ageing indexes (SAIs) from which sub-annual (quarterly) life tables can be derived from annual tables. In this paper, we explore whether a shortcut could be taken in the estimation of SAIs and (life insurance) sub-annual death rates. We propose three different approximations, in which estimates are attained by using just a small bunch of thousands of data records and assess their impact on several competitive markets defined from an actual portfolio of life insurance policies. Our analyses clearly point to the shortcuts as good practical alternatives that can be used in real-life insurance markets. Noticeably, we see that embracing the new quarterly based approach, even using only an approximation (shortcut), is economically preferable to using the associated annual table, offering a significant competitive advantage to the company adopting this innovation.
3 Addressing Recovery Support, Social determinants of Health and Treatment Retention in Postpartum and Parenting women with Opioid Use Disorder
Authors: Titus-Glover Doris , Shaya Fadia , Welsh Chris , Unick George , Doran Kelly
Published: April 2023

OBJECTIVES/GOALS: The purpose of this study is to determine critical recovery support factors (SDOH, postpartum and post-discharge continuity of care), to optimize continuity of recovery and to determine the best intervention among postpartum and parenting women for treatment retention. METHODS/STUDY POPULATION: Through a mixed methods approach, we will review retrospective hospital discharge data to identify hospital-based gaps in treatment. We will conduct key informant interviews with postpartum women, treatment providers and stakeholders to broaden understanding of critical recovery factors from lived experiences and test a parent-centered evidence-based intervention for a comprehensive and targeted approach to recovery. RESULTS/ANTICIPATED RESULTS: This research will lead to new understanding of critical maternal recovery support factors for sustaining treatment retention for 6-12 months after childbirth and to improve long term maternal health outcomes. DISCUSSION/SIGNIFICANCE: The recovery journey and postpartum period are challenging and lack specific recovery support evidence. Recovery support and continuity of care protocols are unclear after childbirth. Maternal opioid-related overdose deaths occur 6-12 months after childbirth. Therefore, this study will impact and inform recovery retention strategies.
10 Chronic cadmium exposure is associated with Alzheimer’s Disease-related mortality in adults over age 60 in a representative US sample
Authors: Jenson Tara E. , Kalkbrenner Milwaukee Amy E. , Bakulski Milwaukee Kelly M. , Dookeran Keith , Driscoll Milwaukee Ira
Published: April 2023

OBJECTIVES/GOALS: Cadmium is a widespread neurotoxic metal pollutant; however prior study results of Cd and later-life cognition are mixed. We investigated association of urinary cadmium on Alzheimer’s Disease (AD) mortality risk, accounting for key co-pollutants smoking and lead, in the presence of competing risks. METHODS/STUDY POPULATION: We included 5692 persons, 60 years old from the 1998-2018 National Health and Nutrition Examination Survey. Underlying cause of death was determined via linked 1999-2019 National Death Index data. Urinary cadmium (UCD) reflects prolonged exposure and was adjusted for creatinine. We used multiple imputation (5 iterations) to recapture substantial model observation drop-out (N=782). We used three Cox proportional hazard models to estimate hazard ratios (HR) and 95% confidence interval (CI) per unit increase in UCD and time to AD mortality: a competing risks model, a survey-weighted model, and a baseline model including neither, all adjusted for demographic characteristics, lead, and smoking. RESULTS/ANTICIPATED RESULTS: Follow-up ranged from 0 to 20.8 years (mean 8.2 years), with a total of 1,987 individuals deceased (14,232 person-years at-risk), including 88 individuals dying from AD. Mean UCD was 0.50 μg/g creatinine (standard error=0.01). In baseline and survey-weighted models fully adjusted for NHANES cycle, poverty income ratio, age, race/ethnicity, sex, marital status, education, smoking status, and blood lead levels, a per unit increase in UCD was associated with approximately twice the rate of AD mortality (baseline model HR: 1.92, 95% CI: 1.28, 2.89; survey-weighted model HR: 2.08, 95% CI: 1.42, 3.06). In the competing risks model, this association was attenuated (HR: 1.58, 95% CI 1.06 2.36). DISCUSSION/SIGNIFICANCE: Our study finds chronic cadmium exposure associated with AD mortality even after accounting for competing risks of AD mortality and confounding effects of cigarette smoking and lead exposure, strengthening the evidence that long-term cadmium exposure adversely affects later-life cognitive health.
11 Clinical Manifestations of Neuroaxonal Injury
Authors: Keleman Audrey A. , Wisch Julie K. , Bollinger Rebecca M. , Schindler Suzanne E. , Morris John C. , Ances Beau M. , Stark Susan L.
Published: April 2023

OBJECTIVES/GOALS: The preclinical stage of Alzheimer disease (AD) is a clinically silent period that can be detected through neuroimaging and biofluid biomarkers. The goal of this study was to determine whether performance of complex daily tasks is associated with plasma biomarkers of brain amyloidosis or neuroaxonal injury in cognitively normal (CN) older adults. METHODS/STUDY POPULATION: This is a cross-sectional analysis of an ongoing longitudinal cohort study. CN older adults performed three complex daily tasks (shopping, checkbook balancing, medication management) from the Performance Assessment of Self-Care Skills in their home. Tasks were scored for independence, with more assistance required indicating worse performance. Participants had a plasma sample obtained within two years of completing the tasks. Plasma amyloid (Aβ42 and Aβ40) were evaluated by high precision immunoprecipitation mass spectrometry assays and neurofilament light (NfL) was measured with single molecule array (Simoa) assays. Nonparametric partial correlations were used to quantify the associations between task performance and plasma AD biomarkers, controlling for age and gender. RESULTS/ANTICIPATED RESULTS: 105 CN participants (mean age 74.7 years, 55% female, 88% white) were included. After controlling for age and gender, worse performance of complex daily tasks (more assistance required) was associated with increased plasma NfL (Spearman’s: 0.23, p=0.04) but not plasma Aβ42/Aβ40. DISCUSSION/SIGNIFICANCE: This study suggests that worse performance of complex daily tasks in CN older adults may be associated with increased plasma NfL a marker of neuroaxonal injury, but not with plasma amyloid. These findings could lead to a better understanding of clinical changes that may occur prior to the onset of noticeable memory symptoms in AD or related dementias.
22 Flavored tobacco sales restrictions and youth e-cigarette use by tobacco retailer density
Authors: Dove Melanie , Gee Davis Kevin , Tong Davis Elisa
Published: April 2023

OBJECTIVES/GOALS: Flavored tobacco sales restrictions (FTSR) may reduce youth tobacco use, but may not be as effective in areas with greater tobacco retailer density (TRD), which is associated with greater tobacco access and more common in low-income areas. We examined the association between FTSRs and e-cigarette use for youth in high and low TRD cities. METHODS/STUDY POPULATION: We analyzed data from the California Healthy Kids Survey using a difference-in-differences (DID) strategy. We compared pre- and post-policy changes in ease of access to e-cigarettes, current use, and ever use one year after implementation among students (9th and 11th graders) attending school in a city with a FTSR (n=20,832) versus without (n=66,126). Separate analyses were conducted for students in cities with low and high TRD, with a median cutoff of 3.3 tobacco retailers per square mile. RESULTS/ANTICIPATED RESULTS: Students attending schools in cities with high TRD (compared with low TRD) had a higher percentage of parents with a high school education or less, and were more likely to identify as Hispanic or Non-Hispanic Asian/Pacific Islander. Among students with low TRD, FTSRs were associated with reduced ease of access to e-cigarettes (DID=0.76, 95% CI: 0.58, 0.99). However, among students with high TRD, FTSRs were associated with increased ease of access (DID: 1.25, 95% CI: 1.02, 1.56) and current use (DID=1.57, 95% CI: 1.31, 1.87). DISCUSSION/SIGNIFICANCE: FTSRs were associated with lower youth e-cigarette access in low, but not high TRD areas. Stronger policies or enforcement may be needed in high TRD areas.
35 Novel statistical methods to unlock the clinical potential of liquid biopsy sampling
Authors: McDeed Arthur Patrick , Jain Sidarth , Barefoot Megan , Ahn Jaeil , Wellstein Anton
Published: April 2023

OBJECTIVES/GOALS: Decoding the origins of cell-free DNA (cfDNA) released from dying cells in a liquid biopsy sample (e.g. blood) can provide insight into the dynamic, organism-wide changes reflective of health and disease state. Making cfDNA an ideal target for genomic monitoring of disease-related changes. METHODS/STUDY POPULATION: Methylome-wide sequencing (WGBS) data present unique statistical challenges. To this end, we developed a novel statistical method using an Expectation-Maximization algorithm to decode the cellular origins of cfDNA fragments in liquid biopsies. Our flexible, probabilistic method leverages the co-regulation of neighboring CpG sites on the individual sequencing read to facilitate tissue of origin analysis, as opposed to prior methods that focus on the methylation rate of a single CpG site. We assess the performance of our model in various simulated settings and apply our model to an important clinical example in which we are able to detect early off-target tissue damage from radiation therapy via minimally invasive blood draws. RESULTS/ANTICIPATED RESULTS: We found our model more effective at capturing the range of biologically plausible methylation patterns on cfDNA read fragments compared to prior models that use single CpG sites. We also show our model is robust to high levels of noise inherent with WGBS data. We demonstrate the accuracy of cell-type proportion estimation on in-silico mixed cfDNA samples from real WGBS data. Finally, we use our model in a clinical application. We detect significant (p < 0.05) increases in cellular contributions from lung and cardiac tissue in breast cancer patients (n=15) undergoing radiation therapy compared to baseline. We also detect novel signals of radiation induced toxicity to the liver in right-sided breast cancer patients (n=8) receiving radiation treatment compared to matched left-sided breast cancer patients (n=7). DISCUSSION/SIGNIFICANCE: Here we address an unmet need in developing novel statistical methodologies that can handle the unique complexities of methylated cfDNA obtained from liquid biopsy samples. We also demonstrate the far-ranging clinical utility of serial liquid biopsy sampling to complement and advance standards of clinical care in oncology and other pathologies.
41 Prevalence of Diabetes Among Veterans by Sexual Orientation
Authors: Duncan Meredith , Streed Carl G. , Beach Lauren B. , O’Leary John R. , Skanderson Melissa , Goulet Joseph L.
Published: April 2023

OBJECTIVES/GOALS: There is evidence that lesbian, gay, and bisexual (LGB) adults have poorer cardiovascular health than their heterosexual peers, but studies of the association between sexual orientation (SO) and diabetes mellitus (DM) have been few with mixed findings. To further investigate this association, large cohorts with objective data capture are needed. METHODS/STUDY POPULATION: We used data from the Veterans Healthcare Administration Lesbian, Gay, Bisexual, Transgender EHR cohort which includes veterans with at least 2 encounters October 1, 2009-September 30, 2019. The first clinic visit in this window was the index date with the baseline date one year later; the intervening year served as a baseline period for observation of prevalent disease and comorbidities. We did not include transgender veterans in this analysis in order to focus on SO rather than on the intersection of SO with gender identity. The SO of 1,108,990 veterans was identified using a natural language processing tool; 185,788 veterans were classified as LGB. We first examined sample characteristics by sex and SO and then used logistic regression to assess the association between SO and prevalent DM. RESULTS/ANTICIPATED RESULTS: DM was present among 193,330 veterans (32,986 LGB). Mean age was similar across SO in women (41) and men (53). Distribution of race was similar across groups, but LGB veterans were more likely to be Hispanic (11%, both sexes) than non-LGB men (6%) and women (8%). Current smoking was more prevalent among LGB (44% men, 39% women) than non-LGB veterans (40% men, 30% women). Adjusting for age, sex, race, Hispanic ethnicity, BMI, smoking status, health insurance, marital status, and enrollment priority, LGB veterans had 1.12 [1.10, 1.13] times the odds of DM vs. non-LGB veterans. Bisexual (0.87 [0.74, 1.01]) or lesbian (1.03 [0.97, 1.10]) women did not have significantly different DM odds than non-LGB women. Bisexual men had lower DM odds (0.86 [0.80, 0.93]) while gay men had higher odds (1.04 [1.01, 1.06]) than non-LGB men. DISCUSSION/SIGNIFICANCE: This is one of the first studies to report DM in a veteran cohort stratified by SO. Our findings highlight the importance of examining SO groups separately and jointly, as to further elucidate the association between SO, cardiovascular risk factors, and general cardiovascular health. Future work will examine the intersection of SO and gender identity.
52 Temporal association of new onset alcohol use disorder following SARS-CoV-2 infection from 2020-2022
Authors: Olaker Veronica , Terebuh Pauline , Kaelber David , Xu Rong , Davis Pamela
Published: April 2023

OBJECTIVES/GOALS: During the pandemic, alcohol related deaths increased by 25%. To help understand how we might mitigate this negative outcome, we sought to examine the association of new diagnosis of alcohol use disorder (AUD) with SARS-CoV2 through two years of the pandemic. METHODS/STUDY POPULATION: Using a non-date-shifted TriNetX database, we conducted a retrospective cohort analysis of electronic health records of patients age ≥12 years who had been diagnosed either with COVID-19 (n=1,359,817) or other respiratory infections with no record of COVID-19 (n=2,013,031). Patients were then matched for propensity score risk for AUD, and results were analyzed by three-month intervals from January 2020 through January 2022, in blocks numbered 1-8. Results were expressed as hazard ratios (HR) and 95% confidence intervals (CI) for diagnosis of AUD from two weeks to six months following COVID-19 diagnosis. RESULTS/ANTICIPATED RESULTS: There was significant excess risk compared to control cohorts of AUD following COVID-19 diagnoses made during the first three months of the pandemic (HR (CI)): block 1: 2.41(1.89,3.08); no excess risk was seen for the remainder of 2020 (blocks 2-4) (HR1.01-1.14, NS). The excess risk increased again in 2021 as the delta and omicron variants emerged (HR and 95% CI): block 5 were: 1.26(1.11, 1.43)); block 6: 1.88(1.62-2.18)); block 7: 1.24(1.10,1.41); block 8: 1.12(1.0-1.25). COVID-19 diagnosis was associated with clinically-evident AUD under some pandemic circumstances. DISCUSSION/SIGNIFICANCE: COVID-19 early in the pandemic (block 1) was associated with substantial excess risk for new diagnosis of AUD, with smaller excess risk after COVID-19 during 2021 (blocks 5-7), and no excess risk otherwise. Diagnosis of COVID-19 and pandemic contextual factors are associated with increased risk for AUD.
53 The development of a multi-institutional prospective registry for patients with metastatic invasive lobular carcinoma: identifying new markers of disease progression
Authors: Rothschild Harriet T , Chien A Jo , Jankowitz Rachel C , Magbanua Mark JM , Mouabbi Jason A , Shatsky Rebecca A , Levine Julia , Mukhtar Rita A
Published: April 2023

OBJECTIVES/GOALS: We are launching a multi-center prospective registry for patients with metastatic invasive lobular carcinoma (ILC), the second most common type of breast cancer, to better understand patterns of progression, imaging features of metastatic sites, and if serial cell free DNA measurements can serve as a surrogate marker of disease progression. METHODS/STUDY POPULATION: Patients with biopsy proven metastatic ILC of any receptor subtype will be included in the registry. We will exclude patients with ductal histology only or those with multiple primary malignancies. Patients will be enrolled at four large academic medical centers across the country. Cell free DNA measurements using a tumor informed assay will be obtained every 3 months concurrent with regular clinical imaging. Disease status will be determined by the patient’s medical oncologist by taking into account imaging, tumor markers, symptoms, and cell free DNA measurement. At each time point, patients will be surveyed on their quality of life and their medical oncologists will be asked to rate the clinical utility of the cell free DNA value. Patients will be followed indefinitely. RESULTS/ANTICIPATED RESULTS: We will explore whether the use of serial cell free DNA or a combination of blood-based biomarkers and clinical endpoints can reliably identify treatment response and disease progression in patients with metastatic ILC. Many patients with metastatic ILC have unmeasurable disease on imaging and are thereby excluded from clinical trials. The end goal of this registry is to determine if blood-based biomarkers can be used as a proxy for measurable disease in ILC patients and therefore increase clinical trial enrollment for this subgroup of patients. DISCUSSION/SIGNIFICANCE: The creation of this prospective registry will open the door for future studies of blood-based markers that reflect disease stability and progression, which is an unmet need specifically in ILC. Identification of such markers could lead to a novel treatment response endpoint, changing the way patients are enrolled in trials and managed clinically.
54 The Association of Patient Characteristics on Provider Referrals to a Health-system Based Diabetes Prevention Program in the Bronx, NY.
Authors: Stephenson-Hunter Cara , Pachecho Giovanni , Chambers Earle
Published: April 2023

OBJECTIVES/GOALS: The Diabetes Prevention Program (DPP) has been shown to reduce diabetes risk by 58%. Men, particularly men of color, are underrepresented in DPP, while they experience higher diabetes-related morbidity. We examine whether race, ethnicity, and gender disparities in engagement are associated with the risk of referral to DPP in primary care METHODS/STUDY POPULATION: Using electronic health record (EHR) from a large urban health system in the Bronx, NY, with an in-house DPP, we examined patient, visit, referral data for DPP-eligible, adult patients with a primary care visit between July 2015 and December 2017. Eligibility included: hemoglobin A1c between 5.7-6.4%; a body mass index (BMI)≥24 kg/m2 (≥22 if Asian); and having no prior diagnosis of diabetes. A total of 26987 patients were included in this study. We examined patient race, ethnicity, preferred language, visit and prescription history, and health payer, among other characteristics. SPSS was used for univariate and bivariate analyses to examine associations between patient characteristics and referral followed by a logistic regression to examine the multivariate association between predictors and referrals. RESULTS/ANTICIPATED RESULTS: Of all DPP-eligible patients, 49% were Hispanic/Latino, and 39% were non-Hispanic Black. Around one-third (34%) of all eligible patients were men. Among all eligible patients in the sample, only 10% were referred to DPP. There were significant differences in the proportion of eligible patients who were referred versus those who were not referred. Women were referred at more than twice the prevalence of men (8.26% to 2.41%), with Hispanic women being referred most frequently (3.59%), and non-Hispanic white men being referred least frequently (.07%) Ethnicity, race, sex, age, number of provider visits, and number of chronic conditions all impacted healthcare provider referral rates to DPP. The health system’s unique free-of-charge DPP likely influenced the lack of significance of patient health insurance. DISCUSSION/SIGNIFICANCE: Given the implementation of DPP at-scale there is an urgent need to understand the patient and systems-level factors that are associated with referring individuals in the DPP. By detecting characteristics of health systems and patients that warrant special attention, we can improve equitable access to evidence-based diabetes prevention.
57 Utility of Digital Phenotyping in Big Data to Answer Clinical Questions: Puberty as a Transdisciplinary Science Case Example
Authors: Schnabel David J. , Dorn Lorah D.
Published: April 2023

OBJECTIVES/GOALS: A disease-agnostic translational science framework for data mining is proposed for use across disciplines to: Answer clinical questions, justify future clinical research recruitment, and explore under-represented populations. As a case example, male puberty demonstrates utility of the framework. METHODS/STUDY POPULATION: As a case example using the generalizable framework, the following interdisciplinary question was asked: Does early pubertal timing increase the risk of developing type II diabetes (T2d) in boys? A digital phenotype of males < 18 years old was created in the TriNetX Diamond Network utilizing Boolean operator data queries. TriNetX contains patient electronic health record information (ICD-10 diagnoses, anthropometric measures). A case control analysis leveraging patient counts from various digital phenotypes allowed for outcome (T2d) comparison of boys diagnosed with precocious puberty (E30.1, ICD code for early pubertal timing) to those without, while controlling for body mass index (BMI). RESULTS/ANTICIPATED RESULTS: Subjects (N=12,996,132) displayed the following digital phenotype: Male, < 18 years old, without ever having a BMI documented >85th percentile. Boys diagnosed with precocious puberty (E30.1) were 6.89 times more likely to develop T2d when aged 14-18 years old than those without (OR 6.89, 95%CI: 5.17-9.19, p. DISCUSSION/SIGNIFICANCE: Boys are under-represented in the early pubertal timing literature, justifying future human subjects research on male puberty. This case example demonstrates a broader disease-agnostic framework which can be adapted across disciplines. Opportunities may include public health digital phenotyping.
59 Where are the viral loads? Searching for additional HIV laboratory results in South Africa’s National Health Laboratory Services Database
Authors: Geiger Keri , Farley Jason E.
Published: April 2023

OBJECTIVES/GOALS: Guidelines suggest people with HIV (PWH) receive routine HIV viral load (VL) testing at least yearly and upon diagnosis with multidrug-resistant tuberculosis (MDR-TB). Many PWH and MDR-TB in South Africa seem to be missing VL results. This study’s goal was to find results which may be available from the National Health Laboratory Service (NHLS). METHODS/STUDY POPULATION: We abstracted HIV laboratory results, specifically baseline VL and CD4 count and VL at MDR-TB cure, from PWH enrolled in a cluster-randomized clinical trial of nurse case management for PWH and MDR-TB in South Africa who were cured of MDR-TB. For any participant missing one or more of these results, we thoroughly searched the electronic NHLS database using multiple separate searches varying terms including patient name, surname, date of birth, medical record number where available, and South African identification number. Returned results were compared to results abstracted from the parent study and any additional results were entered into the parent study data. RESULTS/ANTICIPATED RESULTS: Of 929 PWH cured of MDR-TB, 879 (94.6%) were missing at least one expected VL or CD4 result in the parent study database. Though our search strategy was successful in identifying participants and returning CD4 and VL results, we rarely found additional results that were not already in the parent study database. Following the search and entry of the few additional results retrieved, 116 (12.4%) participants were missing a baseline CD4, 309 (33.3%) missing baseline VL, and 385 (41.4%) missing VL at MDR-TB cure, representing 572 individuals or 61.6% of participants with at least one unavailable result. This high level of unavailability of key laboratory results used to guide MDR-TB and HIV treatment suggests that these tests were either not ordered, not collected, or not completed due to electronic gatekeeping at NHLS. DISCUSSION/SIGNIFICANCE: Unknown CD4 count or VL leaves PWH open to including MDR-TB treatment failure and death. Our search strategy found additional results but was time-consuming and cumbersome. Limitations included lack of information on why laboratory results were missing, which limits our ability to make recommendations for better collection and reporting.
60 Derivation and Validation of a Novel Hospital Capability Score for Sepsis
Authors: Ofoma Uchenna , Deych Elena , Wan Fei , Kollef Marin , Joynt Maddox Karen
Published: April 2023

OBJECTIVES/GOALS: Regionalized sepsis care could improve sepsis outcomes. There are no measures of sepsis capability to guide the identification of hospitals that can best serve sepsis patients. We derived Capability-Based (CB) scores from specific hospital characteristics and evaluated their performance as system predictors of mortality among adults with sepsis. METHODS/STUDY POPULATION: We used the 2018 State Inpatient Databases to identify 90051 adult sepsis encounters at 157 non-federal NY hospitals (derivation cohort), and 130,249 sepsis encounters at 220 hospitals in FL and MA (validation cohort). We used Principal Component Analysis to analyze to reduce 14 hospital-level resource use characteristics to 3 interpretable, linear data combinations (principal components (PC). We calculated CB scores for each hospital as a sum of standardized values for each component multiplied by the respective PC loading. We evaluated the correlation of sepsis volume and each CB score with hospital mortality and with outward sepsis transfer proportions. We fitted linear, nested, predictive models to compare the system predictive abilities of CB scores and sepsis volume in relation to hospital mortality. RESULTS/ANTICIPATED RESULTS: In the derivation cohort, 83963 (93.2%) patients were non-transferred, of which 20230 (24.1%) died. The mean (range) score was 0 (-3 - +5) with higher scores denoting more capable hospitals. Higher scores were weakly and inversely correlated (spearman’s [r]: - 0.28) with outward sepsis transfer proportions. Higher scores had weak but better positive correlation with hospital mortality (r: 0.33), than sepsis volume (r: 0.24). CB scores explained more variation in sepsis mortality (R2 = 0.24, P DISCUSSION/SIGNIFICANCE: Capability-based hospital scores account for three times more variation in sepsis mortality than sepsis volume and outperform sepsis volume as a system predictor of mortality. With further refinement and validation, these scores may find utility for improving system-based approaches to sepsis care.
61 Detecting Parkinson’s Disease Using Computer Vision
Authors: Simmering Jacob , Gerritsen Robert , Narayanan Nandakumar
Published: April 2023

OBJECTIVES/GOALS: Can we detect Parkinson’s-disease-related motor impairments using computer vision and machine learning? METHODS/STUDY POPULATION: A sample of 29 people with Parkinson’s disease (PD) and 29 non-Parkinson’s disease (non-PD) controls were recruited from the University of Iowa Movement Disorders Clinic. Videos of 3 motor assessment tasks performed using the hands were recorded and hand location information was abstracted using the computer vision program MediaPipe. Measures from the raw data series and FFT were used as features to train a model using boosted trees to classify each video as PD or non-PD. Model performance was evaluated using leave-one-out cross-validation. Additionally, we used recursive feature elimination to reduce model complexity. RESULTS/ANTICIPATED RESULTS: A model using two features identified by recursive feature elimination yielded a model with an overall accuracy of 81% in cross-validation. In our sample, the model had 86.2% sensitivity, 75.9% specificity, and an AUC of 0.839. Additional improvement may be possible with more data processing, especially in the time-domain. DISCUSSION/SIGNIFICANCE: We built a classifier that was able to reliably and accurately discriminate between videos of motor assessments in people with Parkinson’s and people without. This may provide a low cost screening tool in rural areas or primary care clinics with limited access to neurologist expertise.
63 Echinococcosis in US patients: retrospective analysis of a neglected zoonosis with regional animal spillover risks
Authors: Mayer Treana , VanDeWoude Susan , Henao-Martanez Andras F.
Published: April 2023

OBJECTIVES/GOALS: Our objective is to address the gaps in our epidemiologic understanding of Echinococcosis, a neglected and emergent zoonotic parasite in the US. Comparing regional differences in human cases with known Echinococcus genotypes in canine reservoirs will reveal landscape-level transmission risks. METHODS/STUDY POPULATION: Retrospective analysis of de-identified diagnosis codes for human echinococcosis in the US from 2002-2022 in a federal multi-healthcare network database (TriNetX). Analyses included Kaplan-Meier survival and specific parasite species cohort comparisons with descriptive summaries of demography and co-morbidities, and odds ratios for interventions (surgery, antiparasitics, cyst aspiration) and complications (anaphylaxis, sepsis, etc.) Mitochondrial genomes of Echinococcus spp. from next-generation sequencing ova-positive archival animal scat (National Park Service), along with sequences from published sources in the US, will be used to compare regional genotypic and reservoir host differences. RESULTS/ANTICIPATED RESULTS: Over 36,000 US patients were diagnosed with Echinococcosis in the past twenty years. Most cases had an unspecified parasite species, primarily affecting pediatrics (average age 16y +/- 10y) in the South/Southeast US, with very few interventions or medical complications reported. Patients with specific parasite species diagnoses (E. granulosus or E. multilocularis, N=500) had higher rates of mortality (11.7% at 10y), surgical (8.8%) and medical (18.2%) interventions, and complications (2%-17.2%), with demographic differences noted. Sequencing data and analysis pending for 47 Echinococcus positive wolf samples, with 78 additional sequences available for two types of Echinococcus spp. in wildlife, and lacking data for domestic dog-adapted strains in the US. DISCUSSION/SIGNIFICANCE: This study revealed a higher-than-expected burden of Echinococcosis in the US, confirming it is an under-recognized neglected and emergent disease. Future studies will address gaps regarding the origin of unspecified infections, with targeted surveillance of domestic dogs in high-risk areas.
64 Finite Element Analysis of a Porous Dual Component 3D-Printed Bone Graft for Alveolar Ridge Augmentation
Authors: Benito Alston Claudia , Villareal Cameron , Moldovan Nicanor , Roudebush Richard L. , Barco Clark , Roudebush Richard L. , Chan Deva , Solorio Luis
Published: April 2023

OBJECTIVES/GOALS: Our goal was to assess the ability of a 3D-Printed dual cover-core design alveolar ridge bone graft, to withstand the average maximum masticatory force of a healthy person. To this end, we characterized the materials, ran a finite element analysis (FEA) model, and validated it using a resin 3D-printed version tested under compression with strain gauges. METHODS/STUDY POPULATION: A tricalcium-phosphate/hydroxyapatite paste and mixed methacrylated alginate-gelatin were used for the core, and polycaprolactone for the cover. These were characterized using ASTM standards D695 and D638 for compression, tensile, and rheological testing. Then we converted cone CT-scan images of a mandibular alveolar ridge defect to an .stl file, and designed the cover and core in Meshmixer. The model was then imported into ANSYS 11.0, and a downward compression force of 500 N, the maximum masticatory force of a healthy adult, was applied on the graft and mandible’s top ridge. The different models included solid and porous covers and cores, as well as comparing screws on one or both sides of the cover, then validated by compressing a resin 3D-printed versions. RESULTS/ANTICIPATED RESULTS: The FEA model provided maximum displacements, Von Mises stress (VMS), and stress/strain values for each model. The highest maximum displacement was found on the solid covers with a combination of both buccal and lingual screws, at 0.162 mm. The lowest maximum displacement was found in the porous cover at 0.085 mm. All VMS values were below the tensile yield strength, meaning that the materials would not yield. The highest maximum stress was found on the porous cover at 13.52 MPa, the lowest was 1.06 MPa on the cover with no screws. The highest strain was found on the porous model at 0.010, which was 5.6x higher than the solid cover. The porous cover also showed less stress shielding, thus allowing a beneficial mechanical stimulation of the bone, and the lowest maximum displacement, possibly due to flexion through the pores. DISCUSSION/SIGNIFICANCE: Preliminary FEA models demonstrated that for the considered materials, a cover-core design of the mandibular implant would sustain the desired 500 N of force without yielding. The porous cover provides the most benefits, causing the least stress shielding and allowing diffusion of biological factors to support the osteoinductive role of the core.
67 Lipid metabolism and synthesis pathway analysis of Sigma-2 Receptor/TMEM97 in breast cancer cells
Authors: Riad Aladdin , Mankof David , Mach Robert H.
Published: April 2023

OBJECTIVES/GOALS: Breast cancer has an increased requirement for lipids. The sigma-2 receptor plays a critical role in the effective uptake of lipoproteins by forming a complex with the LDL Receptor. We investigate the role of the sigma02 receptor in modulating lipid uptake pathways in breast cancers, and how this can be leveraged as a viable therapeutic strategy. METHODS/STUDY POPULATION: CRISPR/Cas9 will be used to ablate TMEM97 in the MDAMB231 and MCF7 cell lines. This study seeks to identify pathways that are dysregulated upon TMEM97 knockout (KO) by characterizing RNASeq data to identify differentially expressed genes and perform pathway analysis. RESULTS/ANTICIPATED RESULTS: Knockout of TMEM97 in breast cancer cells is is expected to decrease lipid uptake. Treatment with statins in these knockout cells is expected to result in decreased cell viability and result in a quiescent cell population. DISCUSSION/SIGNIFICANCE: This is an important mechanistic study to understand the importance of lipid homeostasis in cancer cell proliferation and how it can be targeted to improve therapeutic anti-tumor strategies. Understanding the pathways that TMEM97 modulates is vital for therapeutic strategies to curb the proliferation of breast cancer cells.