bluuebunny/crossref_metadata_2025 huggingface dataset:
Special educators' Lived Experiences Supporting Black Middle and High School Students with Disabilities
Authors:   , Banks Belinda Melissa , Blakely Bridget , Hill Deanna
Published: January 2024

Black students are disproportionately represented in special education, especially in categories that are subjectively determined by educators. Also, Black students with disabilities experience disproportionate rates of exclusionary discipline in schools and have disproportionately higher dropout rates and lower graduation rates. Research has identified various factors that contribute to these issues, including the lack of teacher training required by special education law, implicit bias of educators who identify and serve Black students with disabilities, and the lack of training in cultural responsiveness. However, there is limited research on the lived experiences of the teachers who work with Black students with disabilities and who are responsible for utilizing system-wide supports. The purpose of this qualitative, phenomenological study was to explore the lived experiences of special educators in supporting Black students with disabilities in middle and high schools. The following research questions guided the study: 1. How do special educators describe how district-level policies and practices affect their ability to support Black students with disabilities? 2. How do special educators describe how school-level policies and practices affect their ability to support Black students with disabilities? 3. How do special educators describe how their own classroom-level practices affect their ability to support Black students with disabilities? The researcher distributed a demographic questionnaire and conducted interviews and focus groups with 12 middle and high school special educators. A researcher's journal served as an additional data source to bracket researcher biases and capture field notes. Analysis revealed both themes and subthemes, including the prevalence of alternative teacher training, the prevalence of teachers teaching special education despite other career intentions, multiple perspectives on the causes of disproportionality of Black students in special education, lack of funding, overwhelming paperwork, lack of RtI and PBIS knowledge and support, limitations of professional development specific to special education, varied leadership support, shortages in special education teachers, parents as advocates for student needs, differentiation as key, and conflicting perspectives on culturally responsive teaching. Based on the findings, recommendations are offered for practice and future research. Keywords: Special education, Black students, students with disabilities, disproportionality
Progress in Stroke Prevention and the North Carolina Stroke System of Care
Authors: Brown Anna Bess
Published: January 2024

The Stroke Advisory Council and its partners created the NC Stroke System of Care, an online repository of strategies and resources, in efforts to prevent rising rates of stroke in our state and to steer our work. A stroke registry was developed to gain a more comprehensive view of stroke in the state and identify gaps in care and health inequities.
The role of risk factors, partner compatibility, organizational creativity and co-creation value on firm performance: evidence from SMEs in Vietnam
Authors:   International University, Vietnam National University, Ho Chi Minh City, Vietnam, Van Trang Tran Thi , Khuong Mai Ngoc ,   International University, Vietnam National University, Ho Chi Minh City, Vietnam
Published: January 2024

This research aims to analyze how risk and compatibility between partners affect organizational creativity, co-creation value, and firm performance in a developing economy. The PLS-SEM method was utilized to process and evaluate a dataset of 454 valid cases from property owners, chief executives, vice presidents, broad assistants, and department managers of SMEs in Vietnam. The results validated the connections between risk variables, partner compatibility, organizational creativity, co-creation value, and firm performance. This study further enhances the current knowledge base in the realm of partner selection and provides valuable insights that can be applied in managerial contexts. Companies must consider external factors like risk and partner compatibility to improve organizational creativity, co-creation value, and firm performance. While risk factors, partner compatibility, organizational creativity, co-creation value, and business performance have garnered significant attention in academic circles globally, there is a shortage of studies exploring the interrelationships among these five phenomena together. This research is one of the initial studies that presents a complete model elucidating the interconnections between different categories.
Abortion in The United States – The Impact of Changing Legislation on Prescription Patterns in Pediatric and Maternal Populations
Authors: Zuch Camryn , Kirkpatrick Lindsey , Zhang Pengyue , Quinney Sara K.
Published: January 2024

Background and Hypothesis: Changes in healthcare legislation may have unintended consequences for patient care at the individual level. Following the Supreme Court case Dobbs vs Jackson Women’s Health Organization in 2022 resulting in the reversal of Roe V. Wade, many states enacted new abortion legislation. Currently, there are many restrictions and barriers to abortion and reproductive care that may limit access across the country. Given the volatile political environment surrounding abortion legislation, there may be some confusion among clinicians about the legality of abortion and miscarriage care. Abortion legislation and restriction may have an impact on other areas of healthcare, including prescription patterns of Category X medications in women of childbearing age. Based on the current legislation, we hypothesize that prescription rates of Category X medications will decrease while prescription rates of birth control methods will increase.
Project Methods: Real world data on prescribing patterns will be obtained from IUH Cerner database and the Cerner Learning Health Network. Demographic information including age, race and insurance status will be obtained. Data will be analyzed to assess trends in prescription patterns for women of childbearing age that correlate with dates of changing abortion legislation.
Potential Impact: The findings from this study will help direct future research on medication prescription and administration in people of childbearing age. Results may also inform future policy changes surrounding women’s healthcare.
Factors Predictive of Surgical Success in Medial Rectus Resection/Advancement for Consecutive Exotropia
Authors: Lockwood Tate , Knight Tyler
Published: January 2024

Background and Objective: Consecutive exotropia after unilateral or bilateral medial rectus recession is a common clinical problem. One surgical intervention to address the misalignment involves isolating and reattaching healthy muscle to the globe. The purpose of this study was determining factors indicative of surgical success in medial rectus resection and advancement with non-adjustable sutures for consecutive exotropia.
Methods: Through retrospective chart review, 118 patients were identified to have consecutive exotropia using billing codes from June 2016 to October 2020 at Indiana University Health. 60 of these patients who maintained adequate follow-up either underwent the above intervention (n = 49) or underwent resection only (n = 11). Exclusion criteria included lack of medial rectus procedure or poor postoperative documentation. Patient demographics and data were gathered, including preoperative and intraoperative measurements, final postoperative deviation, and whether additional surgeries were necessary. Chi-squared and two-sample t-tests were performed to analyze the effect of each parameter on surgical success, defined as distance deviation ≤ 10 prism diopters of esotropia or exotropia at final postoperative visit.
Results: Smaller total intraoperative adjustment–resection plus advancement–was significantly associated with surgical success (p = 0.044). Additionally, smaller preoperative deviations were significantly associated with patients who underwent unilateral surgery (p = 0.0093 near and 0.0021 distance).
Conclusion: Patients with smaller preoperative deviations tended to have better outcomes, and those patients tended to have unilateral surgery. It is unclear whether a smaller deviation might have led surgeons to select unilateral medial rectus surgery or if the smaller deviation itself is a predictor of success. Relatively limited time of follow-up is a limitation in this study, as there is well-documented postoperative drift of increasing exotropia over time. A larger cohort or randomized controlled trial may provide additional insight that could increase the percentage of successful outcomes with a single surgery.
Impact of Comorbidities as Predictors on Hospital Length of Stay (LOS) and Mortality in Hip Fracture (HF) Patients in a Rural Community
Authors: Lutz Gabrielle , Zhu Thein
Published: January 2024

Purpose: Studies on HF at a rural health system area are rare. The research question is “Which demographic, preoperative variables would be independent predictors of outcomes on mortality and hospital LOS?”
Methods: The design is a community-based cross-sectional study with risk factor analyses. We ascertained HF cases from hospital trauma center registry and Epic software. We employed both descriptive and analytic approaches including multivariable regression analyses of predictors on outcomes.
Results: Of 201 HF patients, 85.6% occurred in 65 and above years (seniors). Among seniors, females consisted of 64.0% with mean age ± SD: 83.72 ± 7.56 years; extracapsular HF, 55.2%; specified falls, 51.7%; obesity, 15.2%; complication, 3.5%; surgery interventions, 80.8%; mortality within 1, 9.3%; 3, 11.6%; 6, 15.1%; and 12 months, 22.1% after hospital admission. Holding all other variables constant, no surgical intervention increased mortality risk within 1-month (OR=28.87, 95% CI: 4.43; 188.16), 3-months (OR=33.47; 95% CI: 5.24; 213.88), 6-months (OR=21.78; 95% CI: 3.67; 129.48), and 12-months (OR=4.17; 95% CI: 1.33;13.04) compared to surgical intervention; obesity increased 1-month mortality risk (OR=6.00; 95% CI: 1.06; 34.09) compared to no obesity; and patients transferred from community hospital compared to those who were not had an increased 1-month (OR= 8.54; 95% CI: 1.25; 58.13), 3-month (OR=15.31; 95% CI: 2.21; 106.16), 6-month (OR=21.19; 95% CI: 3.34; 134.43), and 12-month (OR=5.14; 95% CI: 1.85; 14.28) mortality risk. Hospital LOS was 3.06 days higher in obese patients than non-obese patients and 2.11 days higher in surgery greater than 48 hours when compared to surgery within 48 hours, holding all other variables constant.
Conclusions and Potential Impact: We believe that surgical intervention decreases, and obesity increases HF mortality. Obesity and delayed surgical intervention increase hospital LOS. The results of this study have the potential benefit for improving community health of rural, elderly populations in northeast Indiana.
One Hundred Percent Tumor Necrosis is Associated with Survival in Ewing Sarcoma
Authors: Marley Matthew , Collier Christopher
Published: January 2024

Background and Objectives:Ewing sarcoma is a primary malignancy affecting both bone and soft tissue. Following preoperative chemotherapy and surgical resection, histologic response (tumor necrosis) is correlated with patient survival. The most prognostic cutoff for tumor necrosis continues to be debated. The objective of this study was to explore several cutoffs and determine their prognostic value in a contemporary cohort of Ewing sarcoma patients.
Methods:The National Cancer Database was used to identify 564 patients with osseous and soft tissue tumors in the Ewing sarcoma family from 2010 to 2015. All patients had documented preoperative chemotherapy, surgical resection, and vital status. Survival was stratified by tumor necrosis using Kaplan Meier analysis. 356 patients with osseous tumors were included in multivariate logistic and cox regression analyses to identify predictors of histologic response and survival, respectively.
Results:In a combined soft tissue and osseous tumor cohort, there was a significant difference (p = 0.01, log-rank test) in overall survival between patients with 100% necrosis and patients with less than 100% necrosis. This was observed over the 5-year study period. Other cutoffs were not statistically different. In patients with osseous tumors, less than 100% necrosis was negatively associated with survival (HR 3.48 [95% CI 1.19-10.13]; p< 0.05), with only skip metastasis having a stronger negative association (HR 4.31 [95% CI 1.22-15.29]; p< 0.05). Male sex (OR 0.50 [95% CI 0.28-0.90]; p<0.05), tumors located in the axial skeleton (OR 0.30 [95% CI 0.12- 0.77]; p<0.05), and positive surgical margins (OR 0.28 [95% CI 0.08-0.95]; p<0.05) were negatively associated with 100% necrosis.
Conclusion and Implications:A cutoff of 100% tumor necrosis was associated with improved survival in Ewing sarcoma. This association was strong relative to other commonly used prognostic factors in osseous cases and is a valuable tool to counsel patients and guide future clinical trials.
Clinical Markers for Small Vessel Pathology in Alzheimer’s Disease
Authors: McBride Quinn , Nho Kwangsik , Risacher Shannon L. , Saykin Andrew J.
Published: January 2024

Background:White matter hyperintensities (WMH) and cerebral microhemorrhages (MH) are common small vessel pathologies that often co-occur with hallmarks of Alzheimer’s Disease (AD) including amyloid-β and tau deposition, neurodegeneration, and decreased cognition. We investigated the relationship among these pathologies to better understand their roles in AD pathogenesis.
Methods:A sample from the AD Neuroimaging Initiative (ADNI) with baseline WMH volume WMHV), MH counts, and serum lipids measurements using the Nightingale Health metabolomics platform included cognitively normal, mild cognitive impairment, and AD participants. Spearman rank correlations coefficient and rank regression models were generated to assess the relationship between vascular pathology and mean arterial pressure (MAP), history of hypertension, and serum biomarkers. Models were covaried for age, sex, APOE status, BMI, and years of education. Further analysis was conducted by dividing participants based on APOE status. False discovery rate was controlled by the Benjamini-Hochberg method.
Results:WMHV and MH were weakly positively associated (ρ=0.197, p<1*10-10). MH and MAP were positively correlated (p<.05), but MH was not related to history of hypertension, or serum lipids. WMHV was negatively associated with serum VLDL cholesterol (p<1*10-12), LDL cholesterol (p<.0001), and remnant cholesterol (p<1*10-11). In APOE4 carriers only, WMHV was negatively associated with triglycerides (p<.001) and total fatty acids (p<.001), and positively associated with HDL cholesterol (p<.002). WMHV was not related to MAP or history of hypertension.
Conclusion:Vascular imaging markers have distinct risk factors with lipid profiles most associated with WMH burden, whereas MAP was predictive of MH. Counterintuitively, lipids associated with higher risk of systemic vascular pathology appeared protective against WMH in the ADNI sample. This phenomenon was particularly notable in APOE4 carriers. Further investigation should be conducted to better understand the relationship between serum lipids and small vessel pathology, and how these contribute to AD pathogenesis.
Analysis of Nutritional Composition and Glycemic Control in Patients with Gestational Diabetes Mellitus
Authors: McGuire Evelyn , Smith Brenda , Scifres Christina
Published: January 2024

Background:The association between meal content and glycemic control is not well-understood in pregnancy, limits our ability to counsel patients regarding the optimal diet. We therefore sought to evaluate the relationship between maternal dietary content and glycemic control.
Methods:This is a secondary analysis of the GDM-MOMS study, which was a randomized controlled pilot trial that compared glycemic targets in 60 pregnant individuals with GDM and either overweight or obesity. During the pilot trial, participants wore a blinded continuous glucose monitor (CGM) for two five-day periods, with the first data collection between 12-32 weeks and the second data collection between 32-36 weeks. During the time that participants wore their CGM, they also collected 3-day food diaries with detailed information regarding intake and cooking technique. These food diaries are being entered into the Nutrition Data System for Research (NDSR) software, which analyzes nutritional composition for each meal. Glycemic control as assessed by CGM will then be assessed based on maternal nutritional intake.
Results:The American Diabetes Association recommends a 2,000-calorie daily diet with a minimum of 175g of carbohydrates (with 35% of the total calories coming from carbohydrates), 71g of protein, and 28g of fat. Preliminary data extracted from NDSR includes nutritional analysis of 38 daily food diaries from 14 patients. 12/38 (31.6%) food logs show consumption of less than 35% of their total calories from carbohydrates, with the other 26 consuming 36-62%. Glycemic load can be used to assess how a patient’s diet affects their glycemic levels. 25/38 (65.8%) of food logs demonstrate a daily glycemic load (GL) of 100, with the other 13 showing daily GLs rangingfrom 108-252.
Conclusions and Further Directions:Further analyses will assess post-meal glycemic response using both patient-monitored glucose values and reports from their CGM to determine which types of diets allow for optimal glycemic control.
Affinity Purification of Anti-Parkin Antibodies from Rabbit Serum for their Application in Immunohistochemistry
Authors: McMurtry Noah , Zhao Bo
Published: January 2024

Background:Parkin is a mitochondrial autophagy protein that is associated with Parkinson’s Disease (PD), as well as auditory function. Parkin dysfunction in the context of PD allows accumulation of protein aggregates, leading to dopaminergic neurotoxicity. Previous work has demonstrated that Parkin plays an essential role in normal auditory function, as Prkn-/- mice exhibit significantly reduced hearing sensitivity. However, Prkn-/- mice also experience a protective effect from cochlear hair cell death and hearing loss caused by aminoglycosides, which are commonly used antibiotics that can cause permanent hearing loss. Multiple antibodies marketed as suitable for immunohistochemistry (IHC) have been validated using Prkn-/- tissues; however, they exhibit non-specific activity. This project aims to generate a highly specific antibody for accurate and reliable detection of Parkin expression.
Project Methods:Rabbits were immunized using two Parkin peptides, notated P1 and P2, and the resulting serum was collected. A two-step purification process was utilized in this project, first isolating the IgGs from serum via protein A/G columns, and secondly using affinity purification to obtain specific antibodies against antigens P1 and P2. Additionally, two different protocols for affinity purification were tested and compared. Purity of serum, IgG, and specific antibodies was assessed by Western blot and immunofluorescence.
Results:Utilizing the first purification protocol, IHC antibodies were applied in Western blot, and all demonstrated a prominent ~50kD band specific to Parkin, with some degree of nonspecific binding. Immunostaining confirmed functionality of the IHC antibodies and revealed those against P2 exhibited higher binding specificity. The second purification protocol generated IHC antibodies of similar, if not slightly superior specific interaction.
Conclusion/Implications:Further investigation of Parkin expression would facilitate a better understanding of how it may be associated with the development of PD, as well as auditory function, with the potential of utilizing Parkin as a therapeutic target in PD treatment and preventing aminoglycoside ototoxicity.
Changes in Address and the Child Opportunity Index after Delivery in a Cohort of First-time Mothers
Authors: Modrall Katherine , Yusman Alexander , Guise David , Abraham Olivia , Jampa Alekhya , Quinney Sara , Haas David
Published: January 2024

Background: The Child Opportunity Index (COI) characterizes social determinants of health across the United States including education, health and environment, and social and economic factors. The objective of the study was to determine if the nulliparous pregnant persons changed addresses between the time of delivery and at the time of follow-up 9-11 years after delivery and to evaluate the trajectory of the COI over time.
Methods: We analyzed data from nulliparous pregnant people participating in the nuMoM2b Heart Health follow-up Study (HHS). Residential addresses at delivery and at follow-up (~9 years) were compared to determine if the participant changed addresses and to evaluate the COI trajectory. Descriptive characteristics (age, race, income, pregnancy outcomes) and the COI trajectory were compared for those who did and did not move using chi-square and t-tests.
Results: 410 participants were analyzed. 304 (74%) of the participants changed addresses resulting in changes in census tracts. Moving was associated with a lower mean maternal age (24.3 vs. 27.2 yrs, p≤0.001) and a lower average income (62.3% vs 41.1% <200% FPL,p≤0.001) compared to the participants who did not move. 40.5% moved to a neighborhood with a higher COI quintile, 56 (18.4%) participants moved down a COI quintile, and 125 (41.1%) participants did not have a change in COI category. White participants who moved addresses were significantly more likely to increase their COI category (55%) compared to non-White participants who moved addresses (22.2%, p≤0.001). There were no differences in how COI changed between White and non-White participants who did not move.
Conclusion: The majority of the participants moved in the years after delivering their first child. Moving was typically associated with an improvement in COI categories, with disparities seen as White participants were more likely to increase their COI if they moved compared to non-White groups.
Delayed Prescribing of Non-Vitamin K Antagonist Oral Anticoagulants (NOACs) in Patients with Low Socioeconomic Status
Authors: Coffey Gillian , Unni Puja , Butler James
Published: January 2024

Background/Objective: Atrial fibrillation (AF) and venous thromboembolism (VTE) are conditions with significant morbidity and mortality when left untreated. American Heart Association guidelines changed in 2019 to make non-vitamin K antagonist oral anticoagulants (NOACs) the preferred method for preventing stroke and systemic embolism in patients with AF or history of VTE. NOACs were first introduced to the United States in 2010 and now include dabigatran, apixaban, rivaroxaban, and edoxaban. There is a dearth of research concerning the speed with which new treatments are prescribed to those in different socioeconomic status (SES) groups. We hypothesized that patients with lower SES were prescribed NOACs later than higher SES counterparts following the introduction of NOACs in 2010.
Methods: The IU Cardiovascular Research Consortium/Sidus Dataset was mined for AF and VTE patients prescribed a NOAC between 2010 and 2022. The SES groups were determined using 2020 U.S. Census income data that correlated to patients’ zip codes. The yearly number ofpatients in each SES group were compared to assess for proportional uptake of NOAC prescribing. The primary outcome was the proportion of low SES to high SES prescribing over each year between 2010 and 2022.
Results: Low SES patients (n=101,945) were prescribed NOACs at an average of 0.65 times the rate of high SES patients (n= 89,130) from 2010 to 2012, the first three years of NOAC market availability. Prescribing rates equilibrated in 2013 and low SES prescribing has outpaced high SES prescribing since 2021.
Conclusion/Impact: Low SES patients experienced a three year delay in receiving NOAC prescriptions at the same rate as their high SES counterparts. Systemic changes, like more frequent prescribing guideline updates and improved evidence-based education amongst providers in low-income areas, could prevent a similar delay when introducing similarly transformative treatments in the future.
Deciphering the Immune Microenvironment of NF1-associated Peripheral Nerve Sheath Tumors: Identifying Early Biomarkers of Disease Progression and Malignant Transformation
Authors: Mukherji Janak , Mitchell Dana , White Emily , Burgess Breanne , Smith Abbi , Albright Eric , Khan Jaffar , Horvai Andrew , Clapp D. Wade , Angus Steve , Rhodes Steven
Published: January 2024

Background/Objective:Neurofibromatosis type 1 (NF1) is a multisystem disorder that affects ~1/3000 newborns. Plexiform neurofibromas (PN) are present in about half of cases and can transform (lifetime risk of 8-13%) into malignant peripheral nerve sheath tumor (MPNST), a highly aggressive and metastatic sarcoma with poor survival. Unfortunately, there are currently no reliable biomarkers to identify PN at risk of undergoing malignant transformation. Our research has revealed that a subset of benign-appearing and atypical PN exhibit deregulated immune surveillance and T-cell infiltration that precede malignant transformation. In this study, we are analyzing tumor microenvironment and immune landscape in NF1-related tissue specimens to identify biomarkers of disease progression. To power these studies, this project focused on constructing a dataset of NF1-related samples to be analyzed.
Methods:701 patients were identified via Cerner billing codes and pathology archives. De-identified clinical data, including presenting symptoms, relevant clinical history, pathology diagnoses, disease features, prior chemotherapeutics/radiation, prior gene profiling, and imaging features were collected.
Results: We selected 86 patients with a total of 175 samples. 81% of patients had a clinical diagnosis of NF1, and 6% had a history of MPNST. Out of the 175 samples, 54 were in the head and neck, 42 in the thorax, 28 in the lower extremity, 27 in the upper extremity, 26 in the pelvis/abdomen, and 15 in the paraspinal region. The leading causes of procedures were pain (41%), growth (40%), and concern for malignancy (27%). The most common tissue diagnoses were neurofibroma (51.4%), PN (20%), and undefined-grade MPNST (11%). Out of the 46 MPNSTs, 30 were primary tumors, 4 metastases, and 12 local recurrences.
Conclusion and Potential Impact:The results of this study will provide valuable insights to inform preclinical models of NF1-tumorigenesis to validate these findings and identify novel treatment approaches for individuals affected by these rare but devastating tumors.
The Role of Heterozygous PAI-1 Deficiency in Pathological Aging in the Human Cardiovascular System
Authors: Nelson Allison , Vaughan Douglas
Published: January 2024

Background and Objective: Plasminogen activator inhibitor (PAI-1) is a member of the fibrinolytic system and a marker and a mediator of cellular senescence. Experimental evidence in humans suggests that higher levels of PAI-1 are associated with increased pathological aging in several major organ systems of the human body. To better understand the role of PAI-1 in humans, specifically in the cardiovascular system, we studied the effects of a loss-of-function mutation in SERPINE1, the gene encoding PAI-1, in an Old Order Amish community in Berne, Indiana. Overall, carriers of the null SERPINE1 variant had greater leukocyte telomere lengths, lower fasting insulin levels, and less prevalent diabetes mellitus. To further the conclusions previously published, our goal is to continue to analyze data collected alongside demographic data to determine if there is a link between PAI-1 deficiency and protection against aging-related changes in the human cardiovascular system. We hypothesized that the differences between the cardiovascular endpoints between carriers and non-carriers will be most significant in older groups.
Methods: Participants included 177 members of the community, 43 of which were carriers for the SERPINE1 mutation. To test our hypothesis, we divided participants into tertiles and compared the results of selected cardiovascular parameters of those with and without the mutation in each tertile.
Results: Our analysis revealed a statistically significant difference in brachial pulse pressures between carriers of the null mutation and normal individuals in the third tertile, corresponding to individuals ages 55 to 82. Those heterozygous for the mutation in this age group had a lower brachial pulse pressure, suggesting there are protective effects of PAI-1 haploinsufficiency against endothelial senescence as people age.
Potential Impact: By identifying the age group with the most pronounced effects of PAI-1 deficiency, we can further investigate the means by which these results manifest in humans and better understand where in the aging process they are most significant.
Novel Method for Development of Nanobubbles with Consistent Size Distribution
Authors: Ravichandran Karthik , Solorio Luis , Du Jinyang
Published: January 2024

Background/Objective:Ultrasound is a versatile non-invasive clinical tool that can be used for monitoring, diagnosis, and management of disease. Contrast-Enhanced Ultrasound (CEUS) takes advantage of microbubbles which are small gas filled bubbles made of lipids to image and evaluate functioning of organs such as the heart, liver, and kidneys. CEUS is better for assessing vascularization of tissues compared to US. However, ultrasound contrast agents have been limited by their size and cannot extravasate blood vessels easily. Current methods also have high polydispersity. We hypothesize that a microfluidic device could deliver nanobubbles with improved size distribution by mixing through micro sized pores.
Methods:The microfluidic device was fabricated using 3D printing for a proof of concept and photolithography for functional use and was done in a class 1-10-100-1000 cleanroom. SU-8 photoresist was spun onto a 4” silicon wafer at 3000 rpm for 30 seconds. The silicon wafer was then baked and exposed under UV with a photomask designed on AutoCAD. The wafer was then developed, hard baked, and was cross linked with Polydimethylsiloxane (PDMS).
Results:Dynamic light scattering data of a shaken formulation shows a monodisperse distribution. Further work will have to be done to determine if this can be delivered by microfluidic device and the parameters that affect size and polydispersity.
Conclusion and Potential Impact:This study will determine the parameters needed for the microfluidic device to efficiently create microbubbles for contrast enhanced ultrasound.
Interferon Beta Modulation of Brain Endothelial Cell Activation in Ischemic Stroke
Authors: Rodefeld August , Kuo Ping-Chang , Scofield Barbara , Yen Jimmy
Published: January 2024

Background and Hypothesis:Every year, more than 690,000 people in the United States suffer an ischemic stroke. Many survivors are left with long-term disability. While the initial insult to the brain is caused by hypoxia resulting from cerebral artery occlusion, a secondary insult is caused by peripheral immune cell infiltration across the blood brain barrier (BBB) and subsequent cytotoxic insult. Previous studies have demonstrated that interferon beta (IFNβ) limits peripheral immune cell infiltration across the BBB and reduces brain infarction volume. We hypothesize that during ischemic stroke IFNβ suppresses brain endothelial cells (bECs) activation to reduce their expression of adhesion molecules as one of the mechanisms by which it decreases peripheral immune cell infiltration across the BBB.
Experimental Design:In this project, bEnd.3 cells, a cell line of bECs, were activated by TNF-α, a pro-inflammatory cytokine. Tissue plasminogen activator (tPA), an FDA-approved thrombolytic for ischemic stroke, was included in the study. bEnd.3 cells were treated with IFNβ at 1.5 hours prior TNF-α or TNF-α + tPA stimulation to evaluate its modulation of adhesion cell expression. The adhesion molecule expression was determined by flow cytometry. Results were further confirmed by in vivo studies in which stroke animals were subjected to tPA treatment in the presence or absence of IFNβ.
Results:Our results showed that TNF-α induced ICAM-1, VCAM-1, E-selectin, and P-selectin expression. Importantly, we found IFNβ suppressed the expression of aforementioned adhesion molecules in bEnd.3 cells treated with TNF-α or TNF-α+tPA. Our in vivo results demonstrated that IFNβ treatment reduced ICAM-1 and E-selectin, but not VCAM-1 or P-selectin expression in the ischemic brain.
Conclusion and Potential Impact:Our study demonstrates that IFNβ modulates bEC expression of adhesion molecules in vitro and in vivo of ischemic stroke, suggesting IFNβ, an FDA-approved drug for Multiple Sclerosis, shows potential to improve ischemic stroke outcomes.
In-Theatre Simulation as a Training Tool for Laparoscopic Salpingectomy in Eldoret, Kenya
Authors: Roop Lauren , Iliwa Samson , Yang Jenny , Wu Wan-Ju
Published: January 2024

Background/Objective: Minimally invasive surgery (MIS) offers many advantages over open procedures including decreased patient safety risks and reduced burden on healthcare infrastructure. As low- and middle-income countries (LMICs) are disproportionately affected by these aspects of surgery, there is motivation to increase MIS. A multimodal training program in laparoscopic salpingectomies was piloted with a small cohort of OB-GYN registrars and consultants at Moi Teaching and Referral Hospital (MTRH) in Eldoret, Kenya. This project assesses the in-theatre simulation’s (1) effectiveness in improving laparoscopic knowledge and skill confidence, and (2) feasibility for long-term implementation at MTRH and in similar settings.
Methods: Participants completed a half-day in-theatre simulation of a laparoscopic salpingectomy. The simulation required participants to demonstrate knowledge of laparoscopic setup, proper patient positioning, procedure completion, equipment troubleshooting, and peri-and intra-operative complication management. Participants completed a multiple-choice laparoscopic knowledge quiz and Likert scale skill confidence survey immediately prior to and following the simulation. Pre- and post-simulation responses were compared to assess knowledge and confidence acquisition overall and across content topics.
Results: There was a significant increase in the average knowledge quiz score from pre- to posttest (p=0.028). A significant difference between pre- and posttest confidence was noted in four of the six skills assessed. By topic, equipment troubleshooting (p<0.001), and complication management (p<0.01) saw the most improvement. Barriers to long-term sustainability include unpredictable theatre and laparoscopic tower access and availability of supplies for uterine modeling. A modified model using nitrile gloves as fallopian tubes will be piloted in future simulations as a more accessible alternative for long-term implementation.
Conclusion: Despite limitations, in-theatre simulation has the potential to be an effective and sustainable teaching tool within a long-term MIS training program at Moi Teaching and Referral Hospital. The low-cost model and methods outlined may also be replicable in similar low-resource settings.
Indiana Contraceptive Use Metrics through PATH4YOU Program: Initial Review
Authors: Ruggles Molly , Wendholt Kathleen , Bernard Caitlin
Published: January 2024

Objective—PATH4YOU is Indiana’s first state-wide contraceptive access project and provides contraceptive access via in-person and telehealth visits using a reproductive justice framework. Our objective was to evaluate outcomes of the PATH4YOU program to determine the distribution of contraceptive access among people in Indiana.
Study Design—We analyzed programmatic data of reproductive-age people who received care in the PATH4YOU program from September 2021 to June 2023. All participants received pregnancy intention screening, comprehensive contraceptive counseling and decision support, and no-cost contraceptive method access, including long-acting reversible contraception (LARC). We evaluated age, location (county), primary method of contraception received, partner site visited, and in-person vs telehealth visit type using descriptive statistics. Geographical mapping analysis was used to determine areas of Indiana most impacted by the PATH4YOU program.
Results—Between September 2021 and June 2023, 1,024 people received care at 1,231 visits through the PATH4YOU program. The average age of participants was 27.6 years old. A significant (49.3%) proportion of the participants live in Marion County. The most common primary methods of contraception were the implant (25.8%), contraceptive pills (20.5%), and intrauterine devices (16.0%). The most visited partner sites included People’s Health Center in Indianapolis (24.8%) and via telehealth (22.5%). Most people received contraceptive access in one in-person (66.0%) or telehealth (17.9%) visit.
Conclusion—The PATH4YOU state-wide contraceptive access project provided a range of contraceptive methods via both in-person and telehealth visits to a wide reach of people across multiple counties in Indiana.
Implications—The unique PATH4YOU model of care using both in-person and telehealth visits is a novel way to increase contraceptive access throughout a state with highly variable access to traditional in-person contraceptive care. Further research is necessary to evaluate direct impacts of the program on minoritized and traditionally excluded populations to evaluate long-term outcomes like maternal mortality.
Immune Infiltrate Profiling of Cutaneous Melanoma with Spatial Transcriptomics
Authors: Sankar Meghana , Zhou Hong-Ming , Wang Qun , Liu Yunglong , Xuei Xiaoling , Gao Hongyu , Alomari Ahmed , Warren Simon , Turner Matthew
Published: January 2024

Background and Objective:In 2023, an estimated 97,610 melanomas will be diagnosed in the U.S. Immunotherapy has revolutionized care for melanoma patients and highlighted the prognostic value of characterizing immune infiltrates in melanoma tissue. This project used spatial transcriptomics (ST) to analyze immune infiltrates in cutaneous melanoma specimens.
Methods:Visium Spatial Gene Expression platform generated datasets from formalin fixed paraffin embedded cutaneous melanoma specimens were analyzed using Loupe Browser software v6.5.0 (10x Genomics Inc.). Unsupervised clustering and manual region selection identified areas enriched in immune cell specific differentially expressed genes (DEGs). The transcript for Collagen alpha-1(XIX) chain  (COL19A1) was identified as a DEG co-expressed with B cell marker DEGs. Fluorescence activated cell sorting was used to isolate primary B and T cells from mouse secondary lymphoid organs and human peripheral blood mononuclear cells to measure COL19A1 with quantitative PCR (qPCR).
Results:Transcripts for CD19 (B cell marker) were concentrated in an immune DEG- rich region adjacent to a melanoma micrometastasis in one specimen. There was overlap between the tertiary lymphoid structure [TLS] markers SELL, CXCR5, CCR7, and CXCL13 with CD19 and/or COL19A1. Though qPCR revealed minimal Col19a1 in mouse B and T cells, COL19A1 was abundant and specific for human B cells.
Conclusions & Potential Impact:This study demonstrates the feasibility and potential of using ST to characterize immune cell infiltrates in melanoma. Though COL19A1 expression is typically understood to be enriched in muscle and neuronal cells, the studies presented here suggest this transcript could be a novel human (but not mouse) B cell marker. Future studies are needed to determine if collagen XIX (protein) is expressed in B cells and if it is, what the biological functions of this protein are in B cells under physiologic and pathologic (e.g. melanoma) conditions.
Sex differences in region-specific hippocampal areas in Alzheimer’s Disease: an animal-based approach
Authors: Sawyer Jackson , Shahid Syed Salman , Wu Yu-Chien
Published: January 2024

Background: Atrophy in the hippocampus is responsible for memory and cognitive decline in Alzheimer’s Disease (AD). Progression and presentation of AD in men and women are different, and the hippocampus and its subregions could be affected differently. By identifying what areas of the hippocampus are affected by sex, diagnostic tools can be better used to clinically identify and treat AD.
Aims: The goals of the proposed research are: (1) use in vivo MRI techniques to isolate the hippocampus in a mouse model, (2) use data analysis to compare the volume of the hippocampus and its subregions in 5xFAD mice, and (3) see if sex plays a role in differing hippocampal volume, and (4) assess the translational utility of using structural MRI to measure hippocampal integrity for future in vivo human brain studies/clinical practice.
Methods: We used the imaging software FSLeyes to examine MRI images and isolate hippocampal subregion masks. MRI images were taken at the 2-month age period when amyloid-B deposition begins in the forebrain. Upon isolation of the hippocampal mask of each MRI, group classification was identified, and quantitative analysis was performed to compare groups.
Results: We found significant lower spatial volume in Stratum Granulosum (SG) of the hippocampus in female mice compared to male mice. The SG contains dentate granule cells, responsible for spatial memory. Apart from this, the data that we obtained was nonsignificant but did show that female mice contained mainly smaller hippocampus subregions and total volumes despite TICV being larger in females.
Conclusion and Impact: More data is needed to observe the degeneration of SG over a lifetime and assess if it is the reason why males retain spatial memory in AD as opposed to females. Otherwise, analyzing hippocampal volume in the early stages of AD doesn’t appear to be sufficient in explaining outstanding sex differences in AD presentation and progression.
Energizing the Lung Vasculature in the Premature Infant to Promote Alveolar Formation
Authors: Schaff Mackenzie , Kim Andrew , Arsenault Evan , Musselman Mary , Ranasinghe Dushani , Schwarz Margaret
Published: January 2024

Background/Objective: Chronic lung disease of prematurity, bronchopulmonary dysplasia (BPD) occurs when infants born with underdeveloped immature lungs are forced to navigate the expansion of future air spaces, with irregular vascular formation proceeding development of BPD. Lung development has distinct and dynamic metabolic requirements. We recently identified by mass spectrometry that nicotinamide adenine dinucleotide (NAD+), generated from vitamin B3 ‘Nicotinamide’ (NAM), was significantly reduced in a hyperoxia murine model of BPD. As NAM/NAD+ are dynamic regulators of tissue regenerating neovascularization in otherdisease processes, we hypothesized that NAM/NAD+ metabolic deficiencies contribute to compromised angiogenesis formation and alveolar formation.
Methods: Impact of NAM supplementation on circulating human neonatal endothelial colonyforming cells (ECFCs) were assessed for differential capillary formation properties of angiogenesis (Matrigel), migration (wound healing), proliferation (WST1 and crystal violetstaining), and mitochondrial function in normoxia and hyperoxia (85% oxygen) conditions.
Results: Hyperoxia suppresses ECFC angiogenesis, while NAM supplementation in hyperoxia significantly rescued vascular networks, branched nodes, and branch points (p<0.001). Wound healing assays suggest that NAM promotes cell migration in normoxia and hyperoxia (p<0.0001). Although NAM increased WST1 activity in hyperoxia, crystal violet analysis determined that NAM had no impact on ECFC proliferation. Lastly, NAM significantly reduced hyperoxia induced mitochondrial oxidative stress in a dose dependent manner (p<0.05).
Conclusion and Clinical Implications: Lung development has specific metabolic needs during different stages of development that are disrupted by premature birth. Replenishment of NAM promotes angiogenesis and migration in hyperoxia while reducing mitochondrial activity. Future studies are necessary to explore the role of NAM/NAD+ axis in the developing lung.
Exploring Relationships Between Fear of Cancer Recurrence, Psychological Distress, and Mental Health Service Use in Breast Cancer Survivors
Authors: Danner Ana , Hays Matthew , Li Yang , Johns Shelly
Published: January 2024

Background: Breast cancer survivors (BCS) have an increased risk of psychological distress compared with healthy controls. Fear of cancer recurrence (FCR) is one of the most reported forms of distress, with approximately 50% of BCS reporting clinically significant FCR. Designed to give alternatives to avoidant coping, acceptance and commitment therapy (ACT) has shown promise in reducing distress and FCR in BCS. The primary objective of this study was to explore relationships between psychological distress and mental health service use in BCS with FCR.
Methods: Baseline data from 384 early-stage, post-treatment BCS with clinically significant FCR at screening enrolled in an RCT comparing 3 FCR interventions were analyzed. Prevalence of clinically significant FCR and symptoms of anxiety, depression, and posttraumatic stress was measured. Associations between each distress measure and mental health service use were assessed, in addition to the association between FCR and avoidant coping.
Results: Clinically significant levels of at least one form of psychological distress besides FCR were reported in 226 (58.85%) BCS. Of 298 (77.60%) BCS with at least one significant distress score including FCR at baseline, only 61 (20.47%) reported using any mental health service within the 3 months before baseline. Clinically significant anxiety (p = 0.0027), depression (p = 0.0015), and post-traumatic stress symptoms (p = 0.0227) were significantly associated with mental health service use. FCR was significantly associated with fewer visits to certain mental health services. FCR was strongly correlated with increased avoidant coping (ρ = .6313, p < .0001).
Conclusion: Anxiety, depression, and post-traumatic stress symptoms may be better predictors of mental health service use than FCR given the tendency for patients with fear to cope with avoidance. ACT interventions emphasizing alternatives to avoidant coping may benefit BCS with FCR. Further research is needed to identify barriers to mental health service use in BCS.