The Indiana Medical Student Program for Research and Scholarship (IMPRS) facilitates IU School of Medicine medical student participation in various medical research and experiential opportunities including laboratory, clinical, and health research outcomes and community health education. The program strives to make a wide variety of research and clinical opportunities accessible to all students, enhance intellectual inquisitiveness, and support excellence in the development of physicians, physician-scientists, and educators.
Indiana Medical Student Program for Research and Scholarship
Development of a Novel CAR T-Cell Therapy Targeting Thymic Carcinoma
Background Thymic carcinomas are rare anterior mediastinal malignancies with limited treatment options and modest responses to platinum-based chemotherapy. Immune checkpoint inhibitors have shown activity but often cause severe immune-related toxicities. Although CAR T-cell therapy has revolutionized hematologic cancer treatment, its application in thymic carcinoma is limited due to disease rarity, lack of tumor-specific surface antigens, and risks of on-target off-tumor toxicity, especially given the thymus’s role in immune tolerance. Recent studies have identified overexpression of TROP-2, c-KIT, and CD70 in thymic carcinoma, presenting novel therapeutic targets. Objectives Profile TROP-2, c-KIT, and CD70 surface expression on thymic carcinoma–relevant cell lines. Engineer CAR constructs targeting each antigen and validate CAR expression on T- cells. Evaluate antigen-specific cytotoxicity of CAR T-Cells in vitro to guide development of multi-antigen CAR T strategies. Methods Candidate cell lines were screened for surface expression of TROP-2, c-KIT, and CD70 using quantitative flow cytometry. CAR T-cells were generated from healthy donor PBMCs via lentiviral transduction and expanded ex vivo. Antigen-specific cytotoxicity was evaluated through in vitro coculture assays using selected patient-derived cell lines. Cytotoxic effects were quantified by 7-AAD via flow cytometry. Results Flow cytometry confirmed high surface expression of TROP-2 (83%), c-KIT (88%), and CD70 (99%) in T1889, Kasumi, and U266 cell lines, respectively. Lentiviral transduction produced Fab⁺ CAR-T populations of 48.2% (TROP-2), 24.7% (c-KIT), and 47.5% (CD70). All three CAR-T constructs showed antigen-specific cytotoxicity significantly greater than GFP⁺ CD3⁺ controls. Conclusions This study provides early in vitro evidence supporting CAR T-cell therapy targeting TROP-2, c- KIT, and CD70 for thymic carcinoma. Results confirm strong CAR expression and potent, selective killing of antigen-positive targets.
Copyright (c) 2026 Layla Ahmadi, Malak Khalifeh, Dimitar Donovski, DuyKhanh Pham Ceppa, Patrick Loehrer, Rohan Maniar, Huda Salman http://creativecommons.org/licenses/by/4.0
Taste Perception and Gastrointestinal Responses Following Salt and Ketone Supplementation in Healthy Adults
Background and Hypothesis: Rodent studies indicate that dietary ketones can prevent some of the adverse health effects of high dietary salt. As a result, our laboratory is currently conducting a clinical trial to determine whether this effect can be replicated in humans (NCT:05545501). Both salt loading and ketone supplementation can be unpleasant in terms of taste perception and elicit mild gastrointestinal distress. However, our study needs to mask participants to which conditions they receive from each arm of the study. Therefore, we sought to determine whether we are effectively masking participants. Experimental Design: Young adults aged 19-35 who were free from cardiovascular disease were randomly assigned and masked to the order of three conditions. The three conditions included a) placebo capsules and placebo drink, b) salt capsules and placebo drink, and c) salt capsules and ketone drink. Taste perception and gastrointestinal surveys were taken after each condition. Taste perception was rated from 1-5 (great to terrible). Gastrointestinal distress was rated as 0-3 (none to severe). Participants were also asked to guess the condition they were in for each arm of the study. Results: After survey collection and data analysis, there were no differences across the three conditions regarding taste perceptions (ps ≥ 0.134) or gastrointestinal distress (ps ≥ 0.224), and there was minimal gastrointestinal distress (average scores of 0 to 1 for nausea, vomiting, bloating, cramping, etc). We found that participants were able to guess the capsule condition correctly 45% of the time and were able to guess the drink condition correctly 39% of the time across the study. Conclusion and Potential Impact: The data from this study is important because it tells us that the participants couldn’t correctly guess the arm of the study that they were in. This means that participants were properly masked to the three conditions and that bias will be minimized in our clinical trial.
Copyright (c) 2026 Abigail Aldridge, Soolim Jeong, Kallie E. Dawkins, Braxton A. Linder, Austin T. Robinson http://creativecommons.org/licenses/by/4.0
Emergency Department Identification of and Communication About Hypertensive Disorders in Pregnant Patients: A Retrospective Chart Review
Background: Hypertensive disorders in pregnancy (e.g., chronic hypertension, preeclampsia, HELLP syndrome) are leading causes of maternal and fetal morbidity and mortality. Emergency departments (EDs) serve as a critical access point for pregnant patients, yet gaps remain in early recognition and management of these conditions. This study aims to evaluate how hypertensive disorders in pregnancy are identified and communicated about in the ED setting. Methods: A retrospective chart review was conducted of pregnant patients (aged ≥18 years, including postpartum and pregnancy loss patients) presenting to IU Health emergency departments (January 2021–December 2023) with at least one elevated blood pressure reading (SBP >140 or DBP >90). Data collected from electronic medical records included demographics, visit details, medical history, vital signs, symptoms, comorbidities, medications, diagnostics, procedures, discharge instructions, pregnancy-related follow-up and outcomes. Descriptive statistics were used for analysis. Results: Compared with state averages for pregnancy complications (6-8%), our cohort of hypertensive pregnant patients showed a higher overall complication rate (11.5%, n=80/690). Documentation gaps were most evident in first-trimester patients, with elevated blood pressure recorded for just 8.1% (30/370) of patients despite its clinical significance. This pattern improved in later trimesters, although inconsistencies remained throughout. Among hypertensive pregnant patients that were discharged from the ED (74%, 511/690), elevated blood pressure was addressed in only 2.4% of discharge instructions. Conclusions: The ED presents a key opportunity to improve early identification and management of hypertensive disorders in pregnancy. These findings support evaluating targeted interventions - including standardized documentation and enhanced follow-up protocols - to address gaps in care for this high-risk population.
Copyright (c) 2026 Sana Alfrhan, Andreia Alexander http://creativecommons.org/licenses/by/4.0
Optimization of a Biomolecule-Based Therapy to Induce Motor Endplate Formation for Treatment of Vocal Fold Paralysis
Background and Hypothesis: Vocal fold paralysis (VFP), often caused by recurrent laryngeal nerve (RLN) damage from surgery, scarring, or malignancy, can impair speech, swallowing, and breathing. Current treatments—surgery, injections, and voice therapy—offer symptom relief but do not restore function. Previous work in our lab showed that muscle progenitor cells (MPCs) can be induced into motor endplate-expressing cells (MEEs) using a biomolecule cocktail of agrin, neuregulin (NRG1), and acetylcholine (ACh). The formation of motor endplates triggers the release of neurotrophic and angiogenic factors like endothelial nitric oxide synthase (eNOS). Injecting MEEs into porcine larynges improved neuromuscular junction (NMJ) function, and direct injection of the biomolecule cocktail showed similar effects in mice. However, the optimal concentrations for therapeutic effects remain unknown. We hypothesized that specific combinations or doses of these biomolecules would significantly increase motor endplate formation as demonstrated by upregulated nicotinic cholinergic receptor subunit alpha 1 (CHRNA1) RNA and protein expression, with resultant upregulation of eNOS RNA. Methods: Using two human skeletal muscle cell lines, we tested 51 biomolecule treatment variations. CHRNA1 and eNOS levels were quantified using Dot blots and qPCR. Results: Three biomolecule combinations notably increased expression of CHRNA1 and eNOS, suggesting enhanced potential for NMJ restoration and muscle regeneration. Conclusion and Impact: Select biomolecule cocktails significantly upregulate key markers for muscle repair and angiogenesis. These findings support their potential as therapeutic agents for VFP and related neuromuscular disorders.
Copyright (c) 2026 Alexandra Alva, Ananya Tadikonda, Sunjay Anekal, Patrick Finnegan, Stacey Halum http://creativecommons.org/licenses/by/4.0
Understanding Chronic Pain in Pediatric Sickle Cell Disease: Insights from a Retrospective Chart Review
Background: Sickle cell disease (SCD) is an inherited blood condition characterized by abnormally shaped red blood cells that can obstruct blood flow, often leading to painful vaso-occlusive crises. While the current standard of care utilizes opioid-based strategies to manage acute pain, the development and diagnosis of chronic pain remains poorly understood, particularly in pediatric populations. This study aims to understand the prevalence of chronic pain in pediatric patients with SCD at a single institution. Methods: A retrospective chart review was conducted of children with a confirmed diagnosis of SCD who received care at Riley Children’s Hospital Sickle Cell Clinic between January 1 and December 31, 2024. Data were extracted from the electronic medical record. This study was approved by Indiana University's Institutional Review Board. Results: A total of 441 unique patient charts were reviewed. Twenty-nine were excluded due to being less than 1 year old or not being seen during the study period. Most patients had the Hb SS-genotype (58%) and nearly half (48%) were female. Of the 412 unique patients reviewed, only 16 had an established diagnosis of chronic pain, with an average age of 17 years (SD +/- 2.4). Fifteen of the 412 patients had 3 or more hospitalizations in a year, 12 of whom did not have a diagnosis of chronic pain. Five had 6 or more opioid prescriptions in 12 months. Similar to the larger cohort, most had Hb SS and about half were female. However, the average age of this cohort was younger (13 years +/- 4.6 years). Conclusion: These findings reveal a notable discrepancy between clinical indicators of high pain burden and formal recognition of chronic pain in pediatric patients with SCD, suggesting under-recognition of chronic pain in younger individuals leading to delay in appropriate treatment.
Copyright (c) 2026 Elizabeth A. Andersen, Seethal A. Jacob http://creativecommons.org/licenses/by/4.0
Beyond Joint Hypermobility: Investigating Bladder Dysfunction in Hypermobile Ehlers-Danlos Syndrome
Background and Objective: Hypermobile Ehlers-Danlos Syndrome (hEDS) is the most common subtype of Ehlers-Danlos Syndromes, a group of heritable connective tissue disorders caused by collagen abnormalities. While musculoskeletal features of hEDS are well documented, its impact on visceral organs, including the bladder, remains underexplored. Despite frequent patient reports of urinary symptoms, a definitive link between hEDS and bladder pathology has not been established. This study aims to characterize lower urinary tract symptoms (LUTS) and urodynamic (UDS) findings in patients with hEDS to better understand potential mechanisms underlying bladder dysfunction in this population. Methods: A retrospective chart review was conducted on patients with hEDS who underwent video UDS at a single tertiary-care center between 2022-2025. Inclusion criteria included age >18 years, confirmed hEDS diagnosis (2017 criteria), and completed UDS. Data were analyzed using Welch’s t-test and Fisher’s Exact Test. Results: Among 27 patients, the mean age at hEDS diagnosis was 30.9 years (range 18-49), 92.6% (n=25) were female, and 92.6% (n=25) were white. Common LUTS seen in these patients included urinary frequency in 74.1% (n=20), urinary incontinence in 14.8% (n=4), frequent urinary tract infections in 25.9% (n=7), bladder pain in 33.3%(n=9), nocturia in 48.1%(n=13), and weak urinary stream in 51.8% (n=14) of patients. UDS findings revealed no evidence of detrusor overactivity, stress urinary incontinence, abnormalities in bladder compliance, or incomplete bladder emptying. Pelvic floor dysfunction was seen in 18.5% (n=5) with active EMG noted during emptying. Pelvic floor physical therapy was the most common intervention recommended, followed by beta-3 agonists for overactive bladder symptoms. Conclusion: Our study shows that LUTS are prevalent in patients with hEDS, with findings suggesting pelvic floor and muscular dysfunction as primary contributors rather than classic bladder pathology. These results support a pelvic floor-focused approach to evaluation and management in hEDS patients.
Copyright (c) 2026 Marium Ansari, Mallory Pine, Viktoriya Sapkalova, Emily Brodowsky, Charles R. Powell, Ramzy T. Burns http://creativecommons.org/licenses/by/4.0
New-Onset Atrial Fibrillation and Related Comorbidities in Cardiac Valve Replacement Patients
Background and Objective: Heart valve replacement is a mainstay in managing valvular disease but poses risk of thrombosis, bleeding, infection, and valve failure. New-onset atrial fibrillation (NOAF) is the most prevalent arrhythmia after cardiac surgery. This study analyzes NOAF in mechanical and bioprosthetic valve patients without prior arrhythmias and its association with age-related comorbidities: hypertension, hyperlipidemia, atherosclerosis, valve disease, and heart failure. Methods: Data collected from the IU School of Medicine-Evansville RWEdatalab (CRC/Sidus Insights Real-World Cardiology database). This 20+ year longitudinal dataset comprises over 3 million patients from 37,000 providers across all 50 U.S. states. Odds ratios were calculated for individual comorbidities in 20,000+ patients aged ≥49 who underwent heart valve replacement. Results: Odds ratios greater than 1 for NOAF were found for systolic heart failure (HFrEF) (2.010, 95% CI 1.83-2.20), diastolic heart failure (HFpEF) (1.768, 95% CI 1.63-1.92), mitral valve disease (1.645, 95% CI 1.54-1.75), and tricuspid valve disease (1.573, 95% CI 1.42-1.74). In contrast, hypertension (0.989, 95% CI 0.93-1.05), atherosclerosis (0.969, 95% CI 0.91-1.03), hyperlipidemia (0.823, 95% CI 0.77-0.88), and aortic valve disease (0.668, 95% CI 0.63-0.71) showed neutral or negative odds ratio. Conclusion: Prosthetic valve replacement in patients with mitral or tricuspid valve disease, or HFpEF/HFrEF, may be associated with NOAF development. This association of NOAF with concurrent atrial-involving valvular disease aligns with current literature linking atrial stretch as a predisposition for atrial fibrillation. Clinical Impact and Implications: Limitations include the use of an outpatient database and lack of detail regarding valve replacement type. The current literature indicates that thromboembolic risk peaks within 3–6 months post-surgery. The study results suggest that comorbidities, especially heart failure and valve disease are positively associated with NOAF, emphasizing the need for continued vigilance beyond the early postoperative period. Future research should examine how overlapping comorbidities and valve type influence NOAF.
Copyright (c) 2026 Tatiana Aviles, Nikolai Jones, Vyom Patel, Andrei Feldiorean, Lawrence Judy, Dale Saxon http://creativecommons.org/licenses/by/4.0
HOTFOOT: Acute Effects of Combined Foot Heating and Pneumatic Compression in Type 2 Diabetes: a Preliminary Report
Background and Hypothesis: Despite over 1.2 million annual U.S. Type 2 Diabetic (T2D) diagnoses, effective therapies for diabetic foot complications remain limited. We hypothesized that a device combining pneumatic compression and localized heating could increase leg blood flow and foot oxygenation in individuals with T2D. Design and Methods: Six healthy individuals (age: 67±3 years, A1c: 5.7 ± 0.38%) and five with T2D (age: 68±5 years, A1c: 7.06 ± 0.57%) were fitted with dorsal and plantar surface thermocouples and near-infrared spectroscopy sensors (OxiplexTS, ISS) over the metatarsal heads to assess foot temperature and oxygenation. Both legs were fitted with boot-like garments with a water-circulating pad and inflatable bladders (Aquilo Sports). After 30 minutes supine, heat (40°C) and intermittent compression (20 mmHg) were applied to one leg for 60 minutes, while the opposite leg served as control. Popliteal artery velocity and diameter were measured via Doppler ultrasound (GE Medical Systems) at baseline and after 60 minutes. A two-tailed paired t-test assessed differences between legs. Results: Foot temperature increased by 6.5 ± 1.2°C in healthy controls and by 6.6 ± 1.8°C in participants with T2D (p<0.01). NIRS-derived tissue oxygen saturation (StO₂) increased in the treated foot by 5.3 ± 4.6% in healthy participants (p = 0.01) and by 4.9 ± 10.3% in T2D participants (p = 0.325). Popliteal blood flow increased by 23.0 ± 15.8 mL/min in the treated leg vs. 3.6 ± 18.6 mL/min in the control leg (p = 0.167) in healthy participants. In T2D participants, blood flow increased by 75.8 ± 112.9 mL/min in the treated leg and 8.0 ± 10.7 mL/min in the control leg (p = 0.153). Conclusion and Potential Impact: Combined foot heating and compression increases foot oxygenation and leg blood flow in older adults with/without T2D. This accessible therapy may aid in managing diabetic foot complications.
Copyright (c) 2026 Carolyn Bakx, Bruno Tesini Roseguini http://creativecommons.org/licenses/by/4.0
Targeting Ref-1 in Cancer: Progression of Advanced Generation Ref-1 Inhibitors Through the Drug Discovery Pipeline
APE1/Ref-1 (Apurinic endonuclease1 / Redox factor-1, referred to as Ref-1) is a multifunctional protein with both DNA repair and redox activities. The redox activity of Ref-1 activates transcription factors such as HIF1a, STAT3, and NFkB that are involved in cancer cell survival and proliferation. Targeting Ref-1 with specific inhibitors represents a promising therapeutic strategy across multiple cancer types. This study focuses on screening and characterizing advanced-generation Ref-1 inhibitors to identify potential candidates for further preclinical development. As part of this drug discovery pipeline, we evaluated four advanced generation compounds and compared them to second-generation compound, APX2009. We selected malignant peripheral nerve sheath tumor (MPNST) cells for evaluation because these tumors often exhibit elevated oxidative stress and redox signaling, making them more dependent on Ref-1 activity. Using MPNST cells, I measured inhibition of downstream Ref-1 target, NFκB and cytotoxicity after treatment. NFκB activity was measured via a luciferase-based reporter assay and two viability assays were compared: Alamar Blue and Methylene Blue. Luciferase assays further confirmed on target inhibition of Ref-1–regulated NFκB activity. Both cell viability assays demonstrated dose-dependent reduction in cellular viability, confirming compound efficacy. Among the compounds tested, WGK2105 exhibited high potency with an IC₅₀ of ~2 μM. WGK2110 and WGK2111 demonstrated similar potency and Ref-1 inhibition when compared to APX2009, while WGK2092 required significantly higher concentrations and will not be prioritized for further development. These findings support the potential for discovery of more potent Ref-1 inhibitors and identify multiple promising candidates for preclinical advancement. Future efforts will assess metabolic stability in mouse and human liver microsomes to determine in vivo suitability. In vivo efficacy studies and full pharmacokinetic profiling (ADME) will follow for top candidates. Comparative analysis of active versus inactive compounds will inform structure-activity relationship (SAR) development, guiding next-generation inhibitor design. These efforts are key steps toward Investigational New Drug (IND) applications and clinical trial readiness.
Copyright (c) 2026 Ball Anthony, Silpa Gampala, Tim Griese, Jim Wikel, Mark R. Kelley, Melissa L. Fishel http://creativecommons.org/licenses/by/4.0
Comparison of Patient-Reported Outcomes in Hinged and Non-Hinged Revision Total Knee Arthroplasty: A Matched Cohort Analysis
Background: Hinged prostheses in revision total knee arthroplasty (rTKA) are typically reserved for cases of severe bone loss and/or ligamentous insufficiency. The increased constraint of the hinge (i.e., fewer degrees of freedom) is critical for providing sufficient stabilization in these complex cases, but also results in higher forces throughout the construct, which may increase the risk of re-revision due to aseptic loosening. This study compared patient-reported outcome measures (PROMs) in case-control matched cohorts of hinged versus non-hinged rTKAs. Methods: A retrospective review of 1,477 rTKAs was performed. After exclusions, 62 hinged and 730 non-hinged implants were available for matching. A total of 55 aseptic hinged rTKAs were case-control matched to 55 aseptic non-hinged rTKAs based on demographics of age, sex, BMI, and ASA-PS classification. The primary outcomes of the study were PROMs and reoperation rates. A P-value of 0.05 was considered statistically significant. Results: The two matched groups did not differ by demographics or comorbidities (P≥0.225); except for an increased prevalence of lumbar spine disease in the non-hinged group (26% versus 11%, P=0.048), which did not affect PROMs (P≥0.100). In addition, no differences in PROMs were observed between groups at any time interval (P≥0.105). Furthermore, there was a slightly higher incidence of all-cause reoperation due to patella/extensor mechanism (11% versus 5%) and all-cause septic reoperation (9% versus 2%) in the hinged group, but these differences did not reach statistical significance (P≥0.190). Potential Impact: This study demonstrated that PROMs were not significantly different for patients who received a hinged rTKA compared to a non-hinged rTKA, suggesting that patients may benefit from the increased stability provided by the hinge. The association with extensor mechanism complications in the hinged rTKA group likely reflects the selection bias inherent in this study design, as more complex cases were more likely to receive hinged devices.
Copyright (c) 2026 Ameya V. Belamkar, Leonard T. Buller, Evan R. Deckard, R. Michael Meneghini http://creativecommons.org/licenses/by/4.0
Identifying 8-11B as a Novel Anti-Inflammatory Compound on Attenuating Neuroinflammation and Disease Severity in MS
Background and Hypothesis: Multiple sclerosis (MS) arises due to impairments in immune cell regulation, leading to neuroinflammation via alterations in microglial activation and pathogenic T cell differentiation. One novel compound developed from IUSM Fort Wayne and Manchester University, 8-11B, was recently associated with an in vitro reduction of inflammatory cytokine IL-6. 8-11B was thus analyzed in modulating pro-inflammatory cytokine and chemokine expression in microglia, attenuating pathogenic T cell differentiation, and ameliorating disease in MS animal models. Experimental Design and Methods: The first phase of the experiment incorporated a quantitative polymerase chain reaction (qPCR) to determine if 8-11B would reduce IL-27p28, CCL2, and CCL3 expression in primary microglia in vitro. The second phase of the experiment was performed by flow cytometry to analyze 8-11B in suppressing Th1 and Th17 differentiation via reducing IFN-γ, GM-CSF, and IL-17 production in CD4+ splenocytes in vitro. Finally, MS animal models were employed to assess the therapeutic effect of 8-11B in vivo. Results: We found 8-11B enabled a dose-dependent reduction in IL-27p28, CCL2, and CCL3 RNA expression in microglia in vitro. Furthermore, 8-11B inhibited pathogenic T cell activation and differentiation by suppressing the production of IFN-γ and GM-CSF from Th1 cells and IL- 17 from Th17 cells in a dose-dependent manner in vitro. Finally, our in vivo results showed 8- 11B administration delayed disease onset and reduced disease severity in MS animal models. Conclusion and Potential Impact: Our study demonstrated that 8-11B attenuates neuroinflammation through modulating microglial activation and pathogenic T cell differentiation. Most importantly, the in vivo analysis showed the ability of 8-11B to ameliorate disease severity in MS animal models. Thus, it suggests that 8-11B can be developed as a novel therapeutic agent for MS treatment.
Copyright (c) 2026 Noah Bergsma, Jimmy Yen http://creativecommons.org/licenses/by/4.0
Clinician Perspectives on Eye-Related Content in Medical Curricula
Background and Hypothesis: Though medical students are presented with an incredible amount of information, it is impossible to cover everything from every specialty in medical school. The primary goal of this study was to determine the state and breadth of ophthalmology related content in medical school and what practicing providers believe can be done to improve it. Project Methods: This study was completed by interviewing six providers (two ophthalmologists, three optometrists, and one ENT physician) with a semi-structured set of questions. The interviews were recorded, transcribed, and thematic analysis was conducted. Results: The thematic analysis revealed several themes. The primary themes were what the providers believe the schools are currently teaching, how they can improve, and they should be teaching each medical student. The main things the providers think are being taught are the top emergencies associated with the eye and how the eye is impacted by other systems at a very surface level. Ways the providers suggested medical schools can improve were to increase class time talking about the eyes and its pathologies, requiring a short rotation through ophthalmology, and enforcing more dedicated skills training for the ophthalmic exam. The primary findings for what the providers think every medical student should be taught are the various forms of glaucoma and their treatments, steroid eye drops, and diabetic retinopathy. Limitations and Future Directions: The main limitation for this study is the small sample size and all the providers being from a similar geographic location. Another limitation was the providers’ exposure and experience with medical school curriculum providing response variability. In the future, more providers will be interviewed, and the interview responses will be compared to the Indiana University School of Medicine curriculum to determine the extent that IU covers what the providers believe to be important.
Copyright (c) 2026 Michael Bertram, Polly Husmann http://creativecommons.org/licenses/by/4.0
Intersecting Burdens: Exploring Social Drivers of Food Insecurity in Congestive Heart Failure Patients in Northwest Indiana
Introduction: Congestive heart failure (CHF) affects 6.7 million Americans, costing over $30 billion annually. CHF is targeted by the Hospital Readmissions Reduction Program due to 30-day readmission rates of 20-25%. Food insecurity disproportionately affects those below the poverty line and is associated with increased CHF morbidity and mortality. In Northwest Indiana (NWI), nearly 100,000 individuals experience food insecurity. There is limited research on intersections between food insecurity and other Social Determinants of Health (SDOH) in CHF patients. This study investigated SDOH and clinical factors associated with food insecurity in CHF patients. Methods: This retrospective cross-sectional study analyzed data from CHF patients screened for food insecurity through EPIC-based SDOH screenings at 3 urban hospitals in NWI between January 2021 and March 2025. Descriptive, bivariate (Chi-Square and Mann-Whitney U, p<0.05), and multivariate (logistic regression; p<0.05) analyses were conducted using IBM SPSS V. 31.0. The study was exempted by Indiana University (IRB #14040). Results: The sample consisted of 11,874 CHF patients, with 5.1% experiencing food insecurity. Among patients with food insecurity, 35.4% were Black, 59% had high housing risk, and 71.2% reported stress. Bivariate analysis revealed significant associations (p<0.05) between food insecurity and age, ethnicity, race, language, veteran status, insurance type, family income, financial resource risk, housing risk, intimate partner violence risk, stress, transportation needs, cumulative social risk, hospital, smoking, suicide risk, and BMI. In multivariate analysis, medium (OR= 4.61) and high (OR= 5.05) financial resource risk, high housing risk (OR = 3.24), stress (OR = 6.54), and unmet transportation needs (OR = 3.22) were associated with higher odds of food insecurity. Conclusion: This study highlights the intersection of food insecurity and other SDOH among CHF patients. Findings will inform an ongoing community-health system-academic partnership to explore lived experiences of food insecurity and connect hospitalized CHF patients with medically tailored community food sources.
Copyright (c) 2026 Shivam Bhargava, Jonathan Guerrero, Baraka Muvuka http://creativecommons.org/licenses/by/4.0
Investigating the Roles of miR-148a-3p and miR-126-5p in Mouse and in vitro Models of Diabetic Retinopathy
Purpose: Diabetic retinopathy (DR) is the leading cause of blindness in American adults. Several studies have highlighted the role of microRNAs (miRNAs) in the pathophysiology of DR. Previous studies from our lab showed that long-standing diabetes affects the expression profiles of various miRNAs, including miR-148a-3p and miR-126-5p, in mouse hematopoietic stem cells. However, these miRNAs were not investigated in retinal cells. Therefore, in the present study, we explored the expression profiles of these miRNAs using both animal models and human retinal endothelial cells (HRECs). Methods: For animal studies, retinas were isolated from 6-month-old diabetic db/db mice and age-matched control db/m mice. qRT-PCR was used to analyze the mouse retina miRNA and mRNA targets. For in vitro studies, HRECs were cultured in three conditions: normal glucose [5 mM], high glucose [15 mM + NG], and mannitol osmotic control [15 mM + NG]. After 24-hour treatment, RNA was extracted, and qRT-PCR was performed to determine miRNA expression. miRDB (MicroRNA Target Prediction Database; mirdb.org) was used to identify mRNA targets regulated by these miRNAs. Results: qRT-PCR analysis of db/db mouse retinas showed significant upregulation of miR-148a- 3p compared to db/m control; miR-126-5p was upregulated but not statistically significant. Known targets of miR-148a-3p, ITGA5 and ITGA9, were significantly upregulated in db/db mouse retinas. qRT-PCR analysis of HG-treated HRECs showed an upregulation of miR-148a-3p and miR-126-5p; however, the results were not statistically significant. Conclusions: In the present study, we found that high-glucose conditions alter the expression profiles of miR-148a-3p and miR-126-5p in db/db mice and human retinal endothelial cells. We also found upregulation of integrins ITGA5 and ITGA9 in mouse retinas, potentially implicating the interaction between miR-148a-3p and these extracellular matrix proteins in the pathophysiology of DR. Further experiments to validate these miRNAs and their mRNA targets are required to strengthen the current findings. “This project was funded, in part, with support from the Short-Term Training in Ophthalmology Research for Medical Students funded, in part by T35EY031282 from the National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.”
Copyright (c) 2026 Sarah Boccone, Neha Mahajan, Ashay Bhatwadekar http://creativecommons.org/licenses/by/4.0
Current Landscape and Clinical Progress of Targeted Alpha Radioimmunotherapy
Theranostics is an expanding area of cancer research that describes the use of radiotracers to first diagnose and then treat cancer. By coupling a radioisotope to an agent that selectively targets malignant cells, one can distribute focused radiation to disease sites. There are a variety of different radiopharmaceutical vectors that have been utilized in this way, such as peptides, small molecules and antibodies. Because antibodies bind to highly specific antigens, radioimmunotherapy (RIT) allows radioisotopes to emit energy, inducing DNA breaks and destroying tumor cells, in a specific, systemic manner that other radiation strategies cannot do. Beta (β)-emitting isotopes (e.g., 131I, ⁹⁰Y) have been more commonly coupled in RIT, but the use of alpha (α)-emitters (e.g., 225Ac, 212Pb), for RIT (α-RIT) has rising popularity due to their shorter tissue range and higher linear energy transfer. These characteristics decrease off-target effects in neighboring tissues and increase tumor cell destruction, respectively. There are a variety of α-RIT agents currently in clinical development to treat hematologic malignancies, metastatic castration-resistant prostate cancer, and other difficult-to-treat solid tumors. This literature review highlights these agents and shows there are several challenges to α-RIT. The production of daughter isotopes from α decay makes dosimetric assessments difficult and could cause off target toxicities. Additionally, whole antibodies tend to accumulate in liver tissue and have long biological clearance times, which may cause excess radiation to the blood, marrow and liver. Strategies to widen the therapeutic indices of these agents have been investigated such as pretargeting, use of antibody fragments, chelator optimization and combination therapies. More studies to further evaluate α-RIT are critical to optimize the use of this technology. There are many clinical trials underway, and we eagerly await their results.
Copyright (c) 2026 Owen Booth, Zheng Qi-Huang http://creativecommons.org/licenses/by/4.0
Evaluating Mesh Reinforcements in Abdominal Wall Closure During Autologous Breast Reconstruction with Abdominal Free Flaps
Background/Objective: Breast cancer is the most common cancer among women, and immediate breast reconstruction at the time of mastectomy has become well accepted. Autologous breast reconstruction uses a woman’s own tissue for breast reconstruction, and this technique using abdominal tissue (Deep Inferior Epigastric Artery (DIEP) flap) is increasing in popularity. Abdominal weakness/bulging and hernias are possible complications as a result of dissection of the deep inferior epigastric artery. While rates of abdominal donor site weakness are low, mesh placement in the abdominal wall is becoming more common. The purpose of this study is to compare abdominal wall outcomes in patients who underwent DIEP flaps with and without mesh. Methods: A retrospective chart review was conducted on 227 patients who underwent DIEP flap surgery between 2021 and 2025. Patients were grouped by mesh type Poly-L-lactide, poly-trimethylene carbonate copolymer (TransorbTM) (n = 29), Poly-4-hydroxybutyrate (PhasixTM) (n = 100), and no mesh (n = 98). Demographic data and postoperative complications were collected. Chi-square analysis was used to compare abdominal bulge and hernia incidence between patients with and without mesh placement. Results: There was a lack of postoperative complications associated with mesh use, supporting its safety profile. Mesh placement (transorb and phasix) was linked to a lower rate of abdominal bulge formation compared to no mesh placement (3.10% mesh, 9.18% no mesh, p-value = 0.051). There was no statistically significant effect on hernia occurrence across groups (2.33% mesh, 5.10% no mesh, p-value = 0.261). Conclusion and Clinical Impact: Mesh use in abdominal wall reinforcement is safe with a low complication rate with use. Patients who had mesh abdominal wall reinforcement after DIEP flaps had a lower incidence of abdominal bulge. When considering abdominal wall closure in abdominally based autologous breast reconstruction, surgeons should consider use of mesh to decrease abdominal wall weakness.
Copyright (c) 2026 Kathryn Borders, Parhom Towfighi, Ravi Bamba http://creativecommons.org/licenses/by/4.0
Association Between Anxiety, Depression, and Opioid Use Disorder in Adult Surgical Patients: A Real-World Data Study
Background/Objective: The opioid crisis remains a central issue in public health. Prior research has explored how postoperative opioid prescribing contributes to the development of opioid use disorder (OUD). Pre-existing psychiatric conditions may influence postoperative misuse of opioid medications, but existing research on this association is limited in scope and generalizability. This study aimed to evaluate whether a diagnosis of depression and/or anxiety is associated with increased odds of OUD among adult patients undergoing common opioid-prescribing surgical procedures. Methods: In this retrospective case-control study, we used de-identified Electronic Health Record data from the IU School of Medicine-Evansville RWEdataLab (CRC/Sidus Insights) Psychiatric database. Adult patients aged 18-70 who underwent a common opioid-prescribing surgical procedure were identified using CPT codes. Psychiatric and OUD diagnoses were identified using ICD-10 codes. Patients were grouped based on the presence or absence of an OUD diagnosis. Odds ratios were calculated to assess the association between OUD and prior diagnosis of anxiety, depression, or both. Results: Among 18,440 patients who underwent a qualifying surgery, 653 were diagnosed with OUD. Of these, 288 had depression, 280 had anxiety, and 223 had both diagnoses, indicating substantial overlap between conditions. Patients with depression (OR: 1.91; 95% CI: 1.63-2.23), anxiety (OR: 1.26; 95% CI: 1.08–1.48), and both conditions (OR: 3.84; 95% CI: 3.24–4.54) had significantly higher odds of OUD compared to surgical patients with other psychiatric diagnoses. Conclusion and Clinical Implications: These findings suggest that adult surgical patients with a history of anxiety and/or depression have increased odds of developing OUD. This underscores the clinical importance of individualized pain management and enhanced perioperative support for patients with psychiatric comorbidities. Future research should explore these associations in broader and more diverse populations and evaluate interventions that integrate mental health screening into preoperative planning.
Copyright (c) 2026 Zachary Bowman, Nolan Cook, Tommy Quach, Kevin Jordan, Michael Roscoe http://creativecommons.org/licenses/by/4.0
Assessing Determinants of Prolonged Hospital Stay and Readmissions in Patients with Parkinson’s Disease
Background: Parkinson’s Disease (PD) is the second most common neurodegenerative disease in the U.S. Patients with PD experience more and prolonged hospitalizations compared to age-related peers. There is limited literature on the association between social determinants of health (SDOH), readmissions, and length of stay (LOS) in patients with PD. This study explored the social determinants of readmissions (RA), 30-day readmissions (30RA), and LOS among patients with PD. Methods: This retrospective study analyzed an EPIC-generated dataset from SDOH screenings using the PRAPARE tool for inpatient admissions at three urban Northwest Indiana hospitals between January 2021-March 2025. Patients were identified using ICD-10. Data analysis involved bivariate (Chi-square, Mann Whitney U, Kruskal Wallis) and multivariate analyses (binary logistic and linear regressions) using SPSS 31.0 (p<0.05). This study was IRB exempt by Indiana University (IRB #14040). Results The sample comprised 2,990 patients with PD, predominantly white (73.4%), male (61%), 75 and older (59.2%), and publicly insured (96%). 30RA bivariate analysis revealed race, sexual orientation, insurance type, housing risk, readmissions, LOS, and PD comorbidities as significant factors. Multivariate analysis revealed patients identifying as Black/African American had significantly higher odds (OR 3.96) of 30RA. RA bivariate analysis revealed race, language, social connections risk, hospital, and LOS were significant. Multivariate analysis revealed patients at hospital C had significantly lower odds of RA (OR 0.689). LOS bivariate analysis revealed language, veteran status, insurance type, family income, hospital, ED Disposition, PD comorbidities, and PD type were significant. Multivariate analysis revealed PD with dyskinesia (B=1.561) was associated with longer LOS and both family income (B=-3.940x10-5) and ED disposition-observation (B=-2.010) with shorter LOS. Conclusion: Socio-demographic and health-related factors influenced readmissions and LOS in patients with PD. Since prolonged hospitalization and readmissions can exacerbate motor symptoms in these patients, future research should examine SDOH and health-related factors exacerbating these symptoms.
Copyright (c) 2026 Eleanor Boyle, Jonathan Guerrero, PharmD, BCPS, MSEd, Baraka Muvuka, PhD, MPH, MCHES, Kyle Gosporadek, MD, Joshua Mangum, MS, PhD http://creativecommons.org/licenses/by/4.0
Barriers to Mental Health Care In Indianapolis Latino Youth: A BACE Survey Analysis
Purpose: Latino adolescents in the U.S. experience high rates of depression, anxiety, and suicidal behavior, yet have the lowest treatment rates for mental health conditions like Major Depressive Disorder. Barriers such as stigma, cultural values, and structural limitations contribute to this treatment gap. Past research, particularly on Latinas, has identified self-reliance and fear of family shame as key obstacles. This study focuses on identifying and evaluating these barriers among male and female Latino youth in the Indianapolis area, where current research is minimal. Methods: The Your Life Your Story Latino Youth Summit was a two-week summer camp in Indianapolis for Latino youth ages 12–16 from immigrant backgrounds. Participants (N=8) completed a modified BACEv3 survey assessing perceived barriers to mental health care, rated on a 0–3 scale across 24 relevant items. Small sample size was attributed to unexpected political factors. Responses were averaged overall and then stratified by gender. Results: Top reported barriers were: “Wanting to solve the problem on my own” (1.625) Tie: “Concern about what my family might think, say, do or feel” and “Dislike of talking about my feelings” (1.0) “Thinking the problem would get better by itself” (0.875) When stratified, males emphasized discomfort with emotional discussions and family opinions, while females cited embarrassment and concern over peers’ opinions. Traditional structural barriers like cost and transportation were rated low. Conclusion: Consistent with earlier studies, self-reliance remains a key deterrent to mental health care for Latino youth. Gender differences reveal unique concerns among males and females. These insights can help providers tailor approaches to better engage Latino adolescents and reduce the persistent gap between mental health needs and service use in this population.
Copyright (c) 2026 Sofia Cazares, Silvia Bigatti http://creativecommons.org/licenses/by/4.0
Characterizing Clinical Variants of the Neurodevelopmental Disorder-associated Enzyme KMT5B
Background: Neurodevelopmental disorders (NDDs) are estimated to affect up to 15% of children and adolescents worldwide; however, the underlying pathology of many NDDs is poorly understood. Lysine methyltransferases - the writers of lysine methylation - have been implicated in numerous neurodevelopmental disorders. The lysine methyltransferase KMT5B has a catalytic SET domain that dimethylates lysine 20 of histone H4 as well as non-histone substrates, and KMT5B haploinsufficiency has been implicated in NDDs. Clinical variants of KMT5B have been associated with autism spectrum disorder, intellectual disability, developmental delays, macrocephaly, and Chiari malformations; however, the impact of variants found in patients on KMT5B’s methyltransferase activity is not known. In this work, we aim to 1) characterize the impact of clinical variants of KMT5B on its methyltransferase activity and 2) begin preliminary work on assessing the heterogeneity of cells undergoing single-cell sorting for future experiments to introduce clinical variants of KMT5B into neuronal cells. Methods: Recombinant reference and variant forms of KMT5B were overexpressed and purified from E. coli. Enzymatic activity was assessed using a radiation-based KMT assay with mononucleosome substrate. Neuronal differentiation was monitored by live cell imaging using IncuCyte NeuroTrack software. Results: In vitro assays displayed a varied decrease in enzymatic activity in variants T85I, C200R, L263F, and E302K. Interestingly, the variant S73F showed an increase in KMT activity, despite the patient displaying the phenotype typically associated with haploinsufficiency. Potential Impact: The clinical variants S73F, fsA74PTer10, C200R and L263F will be introduced into a neuronal cell model to assess the impact on differentiation. Characterization of these variants in a differentiation model will help elucidate whether there is a potential role of KMT5B catalytic activity in neuronal development.
Copyright (c) 2026 Morgan Clouse, Malini Iyer, Jocelyne Hanquier, Taylor Evans, Evan Cornett http://creativecommons.org/licenses/by/4.0
Association Between Perioperative Opioid Type and Diagnosis of Opioid Use Disorder Following Total Joint Arthroplasty: An EHR-Based Case Control Study
Background: The opioid epidemic remains a major public health concern in the United States. Total joint arthroplasties (TJA), including total knee, total hip, and total shoulder replacements, are common procedures associated with substantial perioperative opioid use. Prior research suggests that perioperative opioid prescriptions may increase the likelihood of developing opioid use disorder (OUD). This study aims to assess whether the type of opioid prescribed perioperatively influences the odds of developing OUD following TJA. Methods: This study was a retrospective case-control study using the IU School of Medicine-Evansville RWEdatalab (CRC/Sidus Insights), a real-world EHR-based psychiatric database. Patients who underwent a TJA were identified using CPT codes. OUD diagnosis after TJA was identified using ICD-10 codes. Two cohorts were created: patients with an OUD diagnosis after TJA (N = 294) and those without (N = 3,572). Odds ratios were calculated based on the specific opioid each patient was first prescribed in the perioperative period. Results: All opioids analyzed were associated with elevated odds of developing OUD following TJA. Hydrocodone (OR: 3.38; 95% CI: 2.54-4.51), oxycodone (OR: 2.24; 95% CI: 1.64-3.07), and tramadol (OR: 3.75; 95% CI: 2.81-5.00) showed similar associations with no statistically significant differences observed between them. No type of arthroplasty (knee, hip, or shoulder) was associated with a higher likelihood of subsequent OUD. Conclusions: Although differences between opioid types were not significant, the findings show a trend that contrasts from existing literature, which often identifies oxycodone as more commonly associated with misuse and tramadol as less commonly associated. These results highlight the need for further investigation into prescriptive patterns. Limitations include the use of a psychiatric-specific database, which may not fully reflect the general TJA population. Future studies should use broader or orthopedic-specific datasets and control for potential confounders such as dosage, comorbidities, and impact of previous psychiatric diagnoses.
Copyright (c) 2026 Nolan Cook, Tommy Quach, Zachary Bowman, Kevin Jordan, Daniel Roque, Michael Roscoe http://creativecommons.org/licenses/by/4.0
The S.T.A.R. (Support, Tracking, And Referral) Program: A Scalable Wellness Intervention for Improving Collaborative Support for Resident Physicians
Background and Hypothesis: Medical trainees face rising rates of burnout, depression, and psychological distress. Peer support groups have shown promise as an intervention but remain underexplored in the clinical learning environment (CLE). A pilot study among the Emergency Medicine (EM) residency demonstrated that 96% of participants (n=85) reported improved well-being after resident-led peer support sessions, particularly benefiting those experiencing burnout. Building on this success, the S.T.A.R. (Support, Tracking, And Referral) Program was developed and piloted across 10 residency programs, yielding encouraging results. This led to a GME-supported, grant-funded expansion of the program to all residency programs at Indiana University School of Medicine (IUSM), encompassing 1,142 residents. We hypothesize that participation in peer support groups will lead to measurable improvements in resident wellness over a two-year period. Project Methods: This prospective, longitudinal cohort study uses a two-arm waitlist randomized controlled trial design involving 1,146 residents across 42 programs. Participants are randomized into immediate or delayed intervention groups. All residents complete baseline surveys via personalized dashboards before the intervention, which includes a one-hour didactic session followed by monthly peer support meetings. Data collection includes program engagement metrics, pre/post-intervention surveys, and three annual well-being assessments using validated tools measuring anxiety, depression, burnout, and loneliness. Results: All 42 residency programs have enrolled, with 21 scheduled for immediate intervention. Early implementation shows strong engagement: 51% of 351 residents completed baseline surveys during GME orientation. In the first intervention session (n=40 pediatric residents), 67.5% completed pre-session and 25% completed post-session surveys. Conclusion: The S.T.A.R. Program offers a scalable, evidence-based peer support model to address the urgent mental health needs of medical trainees. By equipping residents with the language and skills to support one another, the program fosters a culture of wellness and has the potential to reduce stigma and burnout across medical institutions.
Copyright (c) 2026 Jacob Destrampe, Destiny Folk, Kyra Reed http://creativecommons.org/licenses/by/4.0
Implementation of Patient Reported Outcomes in Head and Neck Squamous Cell Carcinoma: A Prospective Study
Background: Head and neck squamous cell carcinoma (HNSCC) is the seventh most common cancer in the United States and can often lead to high symptom burden, financial strains, and a diminished quality of life after treatment. The use of patient reported outcome (PRO) tools convey an improvement in quality of life, survival, and satisfaction in care for several cancer patient populations, and is understudied in HNSCC phases of surgical treatment. This prospective cohort study seeks to integrate a validated PROs survey into the clinical workflow of a high-volume academic center, with aims to assess implementation for HNSCC patients undergoing advanced-stage surgery at Indiana University. Methods: Participants between ages 18-85 with a new or regionally recurrent HNSCC diagnosis undergoing surgery were recruited. Patients undergoing adjuvant therapy or treatment for any other cancer diagnosis were excluded except local therapy for non-melanoma skin cancer. The validated PRO EORTC-QLQ30 and EORTC-H&N43 surveys were provided using a REDCap questionnaire in-person, via email, or telephone at the initial visit and at 0- to 30-days post-operation. Demographic and oncologic data were collected alongside PROs to aid patient surveillance. Results: From May to July 2025, 27 patients were recruited and filled out baseline surveys, and 2 patients have completed post-operative surveys thus far. At baseline, 77.2% report pain, 77.2% report difficulty swallowing, 52.7% report problems eating, 57.9% report difficulties speaking clearly, and 65% of all patients expressed worry about future health. Conclusions and Potential Impact: HNSCC patients experience a variable range of symptom severity prior to surgery. Pending additional patient recruitment and post-operative PRO completion, this pilot study will continue to improve our understanding of PROs’ impact on survivorship care for the HNSCC patient population and further enable precision survivorship to identify at-risk patients for adverse outcomes.
Copyright (c) 2026 Varuna Dhanabal, Janice L. Farlow http://creativecommons.org/licenses/by/4.0
Barriers to Medication-Assisted Treatment (MAT) and Sustained Recovery for Opioid Use Disorder in Incarcerated Individuals and Community Recovery Centers
Background and Hypothesis Opioid use disorder (OUD) affects millions of Americans and is responsible for thousands of deaths annually in the United States. Although medication-assisted treatment (MAT) is considered first-line treatment for OUD by many, only about 1 in 5 individuals with OUD in the US receive it. Nationwide, approximately 3.7% of people carry an OUD diagnosis, while a disproportionate number of incarcerated individuals, up to 15-20%, carry an OUD diagnosis. The purpose of the present research is to explore the barriers individuals with OUD encounter when accessing MAT and to examine how those barriers differ between incarcerated individuals and those in community-based recovery. Experimental Design or Project Methods Participants enrolled in Indiana’s IRACS program based on peer recovery coaches regularly meeting with inmates in the jail with a handoff to an outside peer recovery team on release were given a cross-sectional survey. They rated six barriers – financial, housing, geographic, stigma, continued care, access, and social support – on a 4-point Likert scale based on how much each barrier made accessing MAT difficult. Results Social support (mean = 2.29 ± 1.07) and stigma (mean = 2.23 ± 1.00) emerged as the most significant barriers, while geographic (mean = 1.67 ± 0.87) and financial (mean = 1.68 ± 0.88) barriers were rated lowest. Age was significantly associated with housing instability, with the 30–49 age group reporting the greatest difficulty (mean = 2.37 ± 1.11, p = 0.006). Conclusions and Future Directions Findings highlight social support and stigma as key barriers to MAT access among incarcerated populations, which varies compared to other studies. The role of the IRACS team is an unknown variable. Future work will involve extending the study to individuals in community recovery centers to compare the relative impact of these barriers across populations and inform targeted intervention strategies.
Copyright (c) 2026 Allison Dittmer, Darian Ghaffari, Lynn Witty http://creativecommons.org/licenses/by/4.0
Surveillance and Treatment Monitoring in Thymic Tumors via Circulating Tumor DNA
Background: Circulating tumor DNA (ctDNA) consists of non-pathologic nucleic acid fragments shed from tumor cells. Thymic epithelial tumors (TETs) are rare malignancies of the anterior mediastinum subdivided into thymomas and thymic carcinomas. The detection of ctDNA in plasma offers a potential marker for minimum residual disease (MRD). This study aims to evaluate the clinical utility of serial ctDNA testing in two patient groups with thymic tumors: (1) those undergoing curative-intent resection monitored for MRD and recurrence, and (2) those with metastatic disease receiving systemic therapy, in whom ctDNA trends may correlate with treatment response. Methods: Retrospective chart review was conducted on a sample of thymic tumor patients (n=36). Charts were assessed for patient demographics, tumor characteristics, ctDNA values, recurrence/progression events, and treatment response. Patient blood samples were tested using bespoke Signatera mPCR-NGS. Testing occurred roughly every 3-6 months, along with corresponding CT examination. Results: In patients who underwent curative-intent resection (n=22), 20% developed radiographic recurrence tested positive for elevated ctDNA postoperatively. No patients with preoperative ctDNA detection experienced recurrence (n=3). Positive ctDNA detection had a potential false positive rate of 11.8%. In patients with advanced disease (n=14), radiographic progression and stable disease were associated with higher mean levels of ctDNA compared to partial/complete response to treatment (10.73, 10.70, and 0.20 mtm/mL, respectively). Disease progression and ctDNA levels had a weak positive correlation (r=0.11) and 55% concordance. Conclusion: ctDNA is not reliable as a standalone surveillance tool or progression marker in thymic tumor patients. Most patients that underwent curative-intent resection and experienced recurrence did not have detectable ctDNA levels postoperatively. The correlation between ctDNA levels and radiographic progression in advanced disease is weak, though consistently low levels were observed in responding patients and may be useful in tracking treatment response.
Copyright (c) 2026 Dimitar Donovski, Layla Ahmadi, DuyKhanh Ceppa, Fatemeh Ardeshir-Larijani, Rohan Maniar, Patrick Loehrer http://creativecommons.org/licenses/by/4.0
Characterizing Non-urgent Ophthalmic Utilization of Emergency Departments in Northwest Indiana
Background: Approximately 25% of ophthalmic-related emergency department (ED) visits are non-urgent, costing an extra $782 and 5.75 hours per patient compared to same-day outpatient care. However, the influences on such inappropriate ophthalmic-related healthcare service utilization remain unclear. This study investigates how demographics, social determinants of health (SDOH), and health characteristics influence non-urgent ophthalmic-related ED utilization. Methods: This retrospective study analyzed data from SDOH screenings in EPIC for ED visits across 3 Northwest Indiana urban hospitals from January 2021-March 2025. Ophthalmic-related ED visits were identified using ICD-10 codes and classified as urgent or non-urgent. Data analysis included descriptive, bivariate (Chi-Square; p<0.05), and multivariate (binary logistic regression; p<0.05) analyses using SPSS 31.0. The study was exempted by Indiana University (IRB #14040). Results: The sample consisted of 6571 ophthalmic patients with similar representations of White/Caucasian (36.9%) and Black/African American patients (40.4%), mostly under 40 (58.0%). Bivariate analysis found a statistically significant (p<0.05) association between ophthalmic visit type and age, ethnicity, race, sex, sexual orientation, insurance type, family income, smoking status, length of stay, ED disposition, hospital, return visits, and number of ED visits. In multivariate analysis, age (OR = 1.005), Black/African American (OR = 1.884), other race (OR = 1.475), public insurance (OR = 1.341), other insurance (OR = 2.290), and hospital B (OR = 2.396) remained significantly (p<0.05) associated with higher odds of non-urgent visits. Female sex (OR = 0.810), admitted ED Disposition (OR = 0.540), other ED disposition (OR = 0.340), and family income (OR = 0.999996) remained significantly (p<0.05) associated with lower odds of non-urgent visits. Conclusion: Lower income, Black/African American, and non-privately insured patients demonstrated higher odds of non-urgent ophthalmic-related ED utilization. Further research should continue examining how socio-structural factors influence healthcare utilization to inform targeted interventions for optimized ophthalmic care delivery.
Copyright (c) 2026 Shaker Erbini, Kyle Gosporadek, MD, Jonathan Guerrero, PharmD, BCPS, MSEd, Joshua Mangum, MS, PhD , Baraka Muvuka, PhD, MPH, MCHES http://creativecommons.org/licenses/by/4.0
Biochemical and Behavioral Analyses Reveal Sex-Dependent Differences in Mice After Mild Blast Traumatic Brain Injury
Background: As military conflicts persist around the world, traumatic brain injury caused by blasts (bTBI) continues to be a health concern in the soldiers and civilians affected. After bTBI, small changes in oxidative stress and neuroinflammation are hypothesized to cause neuropsychiatric disorders, including PTSD and memory deficits. Further, although 15.7% of the U.S. army is female, there is little known about the differences between the two sexes. In this study, a repeated mild bTBI model was used to observe the disease-induced changes in mice of either sex. Methods: Adult male and female C57BL/6 wildtype mice were used. To model bTBI, mice were anesthetized, and a pneumatic shock tube was employed to deliver three sequential blast exposures. Following injury, brains were sectioned into 25μm slices for histological evaluation of acrolein. Behavioral assessments began one week post-injury, with mice undergoing fear conditioning in two distinct contexts over multiple days to evaluate learning and memory of fear-associated cues. All data are expressed as mean ± SEM (n ≥ 6), and statistical significance was determined using unpaired two-tailed t-tests or one-way/two-way ANOVA, with p < 0.05 considered significant. Results: The results showed significant differences in behavior and cellular activity after bTBI between not only the tested and control group, but also the male and female mice. Male mice displayed an extended retention of fear memory, in contrast to the early loss of fear memory observed in female mice. Another key difference was acrolein-lysine adduct elevation between male and female mice, which indicates a correlation between sex and the brain regions vulnerable to bTBI. Conclusion: Collectively, the results demonstrated that while bTBI caused behavioral and functional deficits in all mice, the nature of these impairments varied depending on sex. This study aims to inspire additional research which explores bTBI pathophysiology and sex-specific treatments.
Copyright (c) 2026 Shaheer K. Faruqi, Zaiyang Zhang, Riyi Shi http://creativecommons.org/licenses/by/4.0
Demographic Description of Rectal Cancer Patients Treated at Indiana University between 2019 and 2022
Background: There have been significant recent advances in rectal cancer treatment such that some patients receiving chemotherapy and radiation have no identifiable cancer on posttreatment imaging (complete clinical response, cCR). Historically, these patients would undergo surgery as the next step; however, guideline changes now allow these patients the option to forgo surgery and enter close monitoring for recurrence (watch and wait, WW). This study aimed to examine patients with rectal cancer treated within the Indiana Health system around the time WW started being offered. Methods: We conducted a retrospective chart review of patients with rectal cancer diagnosed between 2019 and 2022 and treated within the Indiana Health system. Demographic, treatment, and recurrence information were abstracted into RedCap. Descriptive statistics were generated in Excel, version 16.98. Results: A total of 100 patients (mean age 58.3 ± 12.70 years, 34% female, 66% male) with rectal cancer were reviewed. Of these patients: 88% were White, 9% were Black, and 3% did not report their race. 94% of these patients were not Hispanic or Latino, 4% were Hispanic or Latino, and 2% did not report their ethnicity. 21% of patients were single, 54% married, 10% divorced, 10% widowed, 3% identified as other (life partners or separated), and 2% did not report. 35% of the group had private insurance, 63% government insurance, and 2% were uninsured. 70.33% are still living, and 29.67% are deceased. Overall, 18.82% of patients had a cCR, with 25.00% entering WW. Of those WW patients, 50.00% had a recurrence. Potential Impact: Our data demonstrated a low number of patients entering WW after achieving a cCR, with 50% ultimately having a recurrence of their rectal cancer, while non-WW patients had 21.18% recurrence. Future studies will examine ongoing trends in rectal cancer treatment and outcomes as WW uptake increases over time.
Copyright (c) 2026 Sophie Forrow, Sanjay Mohanty, Trista Stankowski http://creativecommons.org/licenses/by/4.0
Evaluation of Elastin Composition and Organization in Murine Abdominal Aortic Aneurysms
Background and Hypothesis: The prevalence of aortic aneurysms has increased dramatically over the past 20 years, with over 35 million cases of abdominal aortic aneurysms (AAAs) in 2019 alone. However, AAAs with intraluminal thrombus (ILT) development remain understudied. Elastin is a key component of the aorta that gives it distensibility. Here, we evaluated the organization of aortic elastin with and without ILT. Methods: AAAs were induced in mice by topically applying elastase to the aorta. β-aminopropionitrile was added to drinking water to promote AAA expansion. After 8 weeks aortas were extracted and stained with Movat’s Pentachrome. Images at the largest aortic diameter were collected at 100 μm zoom and separated into 4 quadrants around the lumen. Manual counting was used to determine the number of elastin fibers in the aortic wall. ImageJ’s color segmentation was used to find extracellular matrix component composition of each aortic layer. Results: We found samples without ILT on average had 2.7 more distinct elastin sheets compared to ILT samples. Color segmentation findings showed 7% less elastin in the tunica media in samples with ILT. Further, color segmentation showed there was a statistically significant increase in the amount of proteoglycans in the tunica media in samples with ILT. Conclusion: We found ILT forming aneurysms had fewer intact elastin fibers and greater proteoglycan deposition, indicating more detrimental breakdown of the tunica media compared to samples without ILT. Clinical Implications: Our findings suggest AAA patients with ILT are at higher risk for more severe cases of aortic wall degradation, suggesting special monitoring following identification of ILT. Further Considerations: A larger sample size is needed to identify a statistically significant difference in elastin between groups. Future work should compare changes in aortic wall composition in male and female mice to improve our understanding of pathophysiological differences observed between genders.
Copyright (c) 2026 Annabelle Frazier, Cortland Johns, Abigail Cox, Craig J. Goergen http://creativecommons.org/licenses/by/4.0
Human Liver Organoids as a Model for Metabolic Dysfunction-Associated Steatotic Liver Disease
Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by hepatic triglyceride accumulation without secondary causes such as alcohol consumption or viral hepatitis. Affecting an estimated 24–45% of adults globally, MASLD has emerged as the most common chronic liver condition worldwide, closely associated with obesity, insulin resistance, and metabolic syndrome. Despite its prevalence and potential to progress to metabolic dysfunction-associated steatohepatitis (MASH), cirrhosis, or hepatocellular carcinoma, there remains a lack of physiologically relevant human models for mechanistic studies and therapeutic testing. To address this, we established a three-dimensional liver organoid model of MASLD using induced pluripotent stem cells (iPSC)-derived human hepatocyte progenitor cells, which were differentiated into functional hepatocytes through defined growth factor protocols. These cells self-organized into organoids that recapitulate key features of hepatic architecture and enable more accurate modeling of liver function compared to traditional two-dimensional cultures. We optimized cell seeding density for reproducibility and viability and found that 500 cells per Matrigel drop yielded organoids with robust growth and consistent differentiation. To model steatosis, organoids were treated with increasing concentrations of a 1:1 mixture of oleate and palmitic acids, a standard approach for mimicking lipotoxic conditions observed in MASLD. Lipid accumulation was assessed using Nile Red staining, which selectively labels intracellular lipid droplets, and DAPI counterstaining to quantify nuclear content. Image-based quantitative analysis revealed a dose-dependent increase in the lipid-to-cell area ratio, validating the steatotic phenotype. This organoid-based model recapitulates hallmark features of MASLD and offers a scalable and reproducible platform for studying disease mechanisms. Future directions include integrating liver organoids into a microfluidic organ-on-a-chip platform to support multicellular tri-culture with stellate cells and liver sinusoidal endothelial cells, and real-time monitoring of hepatocellular injury, fibrosis, and inflammation. This approach will enable more comprehensive modeling of MASLD progression and facilitate preclinical drug screening using human cell-based models.
Copyright (c) 2026 Kylee Gall, Jiafei Zhu, Anna Dressman, Sunghee Estelle Park http://creativecommons.org/licenses/by/4.0
Immunotherapy Adherence Patterns in Melanoma Patients: A Retrospective Analysis
Background: Immunotherapy has significantly improved outcomes for patients with melanoma, taking their median survival from 6-9 months to over 5 years. However, this is severely limited by the high discontinuation rate (50-60%). Understanding adherence factors is critical for optimizing treatment success and allows physicians to address potential complications earlier. Methods: In this study, we performed a 5-year chart review in the Indiana University Health system through Cerner’s electronic health records. In order to determine patients with Stage III melanoma, we used ICD-10 codes C43 (malignant melanoma) and C77 (lymph node metastases). Only 28 of 75 patients reviewed satisfied the inclusion criteria. We looked at demographics, clinical features, treatment regimen, patient preferences, and discontinuation outcomes. Descriptive statistics were applied to assess adherence and discontinuation factors. Results: Among those 28 eligible patients, 20 (71.4%) of them discontinued immunotherapy. Those who received ipilimumab-nivolumab therapy had the highest discontinuation rate while patients with nivolumab monotherapy had the lowest. Adverse effects from the treatment itself were the most common cause of discontinuation. Socioeconomic factors like time to treatment centers (mean 29.4, ± 15.9 minutes) and insurance type had no effect on discontinuation. Conclusion: In this retrospective, single-system cohort study, it highlights that immunotherapy discontinuation is still very high in patients with melanoma, likely due to adverse effects. Socioeconomic factors, in contrast, had no effect on the discontinuation rate. Although the sample size is limited, these findings could lead to future studies with larger cohorts that could be used to inform melanoma treatment in real-world patients.
Copyright (c) 2026 Eric Gan, Syril Que http://creativecommons.org/licenses/by/4.0
3D Simulation Model for Training in Minimally Invasive Parafascicular Surgery for Intracerebral Hemorrhage Removal
Background: Advances in minimally invasive neurosurgery demand that residents receive effective, realistic training. Simulation models foster skill development through hands on, low risk practice. Minimally Invasive Parafasicular Surgery (MIPS) is a surgical technique that reduces damage to the brain by using sulci as corridors, brain imaging to avoid white matter tracts, and a tubular retractor to access subcortical regions. Several studies support MIPS for Intracerebral Hemorrhages (ICH) clot evacuation. We developed a 3D model to emulate this procedure to provide residents with the necessary practice in a low acuity environment. Methods: Three-dimensional skull and brain models were digitally designed. The brain model was used to design, and 3D print a mold to create brain gels of phytagel (PHY), polyvinyl alcohol (PVA), cornstarch, agar, and water. Gel texture was compared with soft tofu due to their textural resemblance and strength was tested by inserting a tubular retractor. After initial testing by the researcher, formulations demonstrating optimal texture and strength were selected for resident evaluation. Different clot solutions were then created and inserted into the gels. Results: Brain gels were cooled in the freezer for 15 minutes before inserting the clot solution into the gel. Twenty-seven gels were produced, differing in composition. The five formulations that didn’t break apart and most closely matched tofu texture were selected. Additionally, we designed and 3D printed a larger brain mold to better accommodate the tubular retractor. Future Directions: After finalization of the brain gel, the priority will be modeling the dura as well as 3D printing and testing the skull and replaceable skull cap. We will evaluate sausage casing as an analog for dura in future tests. Chiefly, this simulation platform aims to enhance resident proficiency and confidence in minimally invasive ICH procedures.
Copyright (c) 2026 Futhallah Hamed, Angela Richardson, Noah Burket http://creativecommons.org/licenses/by/4.0
Cancer Screening Communication in a Rural Midwestern County
Background and Hypothesis: Lung cancer is the leading cause of cancer death in the United States, yet screening with low-dose CT (LDCT) remains underutilized. Earlier detection through annual screening could improve outcomes by identifying disease at a more treatable stage. We hypothesized that awareness and discussion of lung cancer screening would be limited in a rural Midwestern population. Methods: A paper survey adapted from the NIH Health Information National Trends Survey (HINTS) was distributed to adults in Putnam County, Indiana, a rural community. Participants received a $10 Walmart gift card for completing the survey. Responses were analyzed using Microsoft Excel and SPSS to assess awareness of cancer screenings and associations with smoking history. Results: Twenty surveys were completed. Overall, 25% of respondents were aware of LDCT screening, compared with 45% for prostate cancer screening, 63% for cervical cancer screening, 82% for breast cancer screening, and 74% for colon cancer screening. Eight participants reported a smoking history of 5–60 pack-years; only one had heard of LDCT, and none had discussed it with a physician or received a recommendation for screening. Conclusions and Potential Impact: Awareness of lung cancer screening was limited in this rural county, particularly among individuals with significant smoking histories. These findings underscore the need for improved provider–patient communication and stronger emphasis on LDCT in primary care. Increasing awareness and recommendations could promote earlier detection and ultimately improve lung cancer outcomes in rural populations.
Copyright (c) 2026 Luke Hargrave, Brea Momah, Joshua VanZant, Peter Gunderman http://creativecommons.org/licenses/by/4.0
Localization of Intracerebral Hemorrhage on Risk of Vascular Dementia: A 10-year Retrospective Study
Background & Hypothesis: Intracerebral hemorrhage (ICH) can be devastating to cognition and constitutes 13% of all stroke cases. Owing to its disproportionate incidence relative to outcome severity, spontaneous ICH accounts for more than two-thirds of all-stroke mortality. Approximately one-third of spontaneous ICH patients develop vascular dementia but the etiological link remains undercharacterized. The aim of this study is to elucidate how ICH locality and volume relate to the disease. Project Methods: A 10-year retrospective chart review was conducted on patients with their first ICH at IU Methodist (01/2014-01/2024). Patient demographics and stroke characteristics were abstracted from IU Health Cerner and charted in REDCap. Using Synapse radiology PACS, hematoma size and location were calculated while referencing neuroradiological reports (ABC/2 estimation). Cognitive characteristics such as duration to develop dementia or MCI, dementia type, and independence metrics were collected. All data were analyzed in RStudio. Results: Of 30 patients meeting inclusion criteria, 5 had a pre-existing dementia (16.7%) and 1 with pre-existing MCI (3.33%), 10 (33.3%) with dementia and 8 (26.7%) with MCI at ICH discharge, and 4 patients had downstream dementia (13.3%) while 2 had MCI (6.67%). Of the 19 dementia patients, the average hematoma volume was significantly higher (21.6 mL) compared to MCI patients (12.2 mL, p<0.05). There were no significant differences between lobar ICH patients (n=13), non-lobar ICH (n=13), or both (n=4) in time-to-diagnosis (p=0.863), however, ICHs in both locations had significantly larger hematomas (p=0.02). Conclusion & Potential Impact: ICH location and volume may not be associated with differential dementia outcomes despite correlatory volumetric differences between dementia groups. This study may guide clinicians in prognosticating and counseling high acuity patients and serve to pilot larger power characterizations of the ICH-dementia relationship.
Copyright (c) 2026 Ryan Harmelink, Aditi Ravikumar, Matthew Tobin, Bradley Bohnstedt http://creativecommons.org/licenses/by/4.0
Aligning Independent Decisions (A.I.D.) for Appearance: Alpha Testing of a Patient Decision Aid for Cleft Revision Procedures
Background and Hypothesis: Cleft lip and/or palate is the most common craniofacial anomaly worldwide, affecting 1 in 700 births. Individuals typically undergo multiple surgeries, with some choosing elective cleft revision later in childhood to improve appearance. To support patients in this process, an online patient decision aid was developed to provide surgical information, outline benefits and risks, and help identify personal values. We hypothesized that during alpha testing, this decision aid will be viewed as acceptable, appealing, and user-friendly by participants. Project Methods: After IRB approval, participants not actively facing a cleft revision decision were recruited by phone for alpha testing: 4 craniofacial surgeons, 7 parents of children with cleft lip, and 2 children with isolated cleft palate. Participants viewed the decision aid using a “think aloud” approach, and sessions were recorded and transcribed. Codes were developed through content analysis, and themes evolved with code review. Participants also completed the Decision Aid Acceptability questionnaire and the System Usability Scale (SUS). Results: Thirteen participants completed alpha testing. Parents rated the decision aid highest for usability (Mean system usability scale score) = 93.2), followed by surgeons (78.8) and children (70.0). Most participants (76%) reported the tool’s length and information were “just right” and perceived its tone as balanced. Nearly all (92%) indicated the decision aid would be helpful for surgical decision-making. Qualitative analysis identified key themes of use of affirming language, supporting realistic expectations, and improving decision aid navigation and usability. Conclusion and Potential Impact: The current decision aid will be adapted based upon both quantitative and qualitative analysis from alpha testing. Improving access and usability may enhance shared decision-making, reduce conflict, and increase confidence in cleft revision decisions. The updated version will undergo beta testing with patients actively considering cleft revision surgery, and the final decision aid will serve to facilitate patient-centered decision-making in a highly preference-sensitive clinical situation.
Copyright (c) 2026 Brody Hendricks, Elizabeth Baker, Khoa Tran, Katelyn Makar http://creativecommons.org/licenses/by/4.0
Examining Sociodemographic and Diagnostic Predictors of Columbia Suicide Severity Rating Scale (C-SSRS) Scores and Suicide Attempts Within Northwest Indiana Emergency Departments
Background: Suicide is a public health crisis, ranked as the 11th leading cause of death in U.S. adults. Indiana suicide rates have surpassed the national average since 2000. Prior research indicates suicide risk factors vary between healthcare systems. This study examined whether analysis of sociodemographic and diagnostic predictors within emergency department (ED) data could provide more information about local suicide risk factors than the Columbia Suicide Severity Risk Scale (C-SSRS) scores alone. Methods: Retrospective analysis of ED data from three urban hospitals in Northwest Indiana from January 2021 to March 2025 was conducted. Suicide attempts were identified via ICD-10. Suicide risk was modeled for sociodemographic factors using ordinal and binary logistic regression, with C-SSRS and suicide attempt as outcomes, respectively. Elastic net penalized logistic regression models were used to examine ICD-10 codes associated with suicide risk. Results: The sample included 322,583 ED visits, with 1,674 (0.52%) visits involving high C-SSRS scores and 454 (0.14%) suicide attempts. Sociodemographic factors with higher suicide risk included age<18 (CSSRS, suicide attempt models: OR=13.2, 11.8; p=0.017, <0.001), age 18-24 (OR=1.96, 3.31; p<0.001,<0.001), mental health diagnosis (OR=24.4, 15.7; p<0.001,<0.001 ), and family income <$15,000 (CSSRS model only, OR=3.37, p=0.045). ICD-10 codes most associated with high C-SSRS were severe major depressive disorder (MDD) with psychosis (OR=130.2); unspecified MDD (OR=73.9); and moderate MDD (OR=71.3). Suicide attempt was most associated with suicidal ideation (OR=71.9), accidental poisoning (OR=16.1), and cannabis dependence (OR=11.4). Notably, negative suicide attempt predictors included schizophrenia, unspecified (OR=0.22), and borderline personality disorder (BPD) (OR=0.23). Conclusions: Consistent screening for social determinants of health may improve suicide risk identification. ED-based models can identify short-term risk factors for attempting suicide. Future research using diverse outpatient settings may provide more information on specific time scales for short- and long-term risk factors using models that can perform time-to-event analysis.
Copyright (c) 2026 Jayden Henneman, Jonathan Guerrero, Joshua Mangum, Baraka Muvuka, Kyle Gospodarek http://creativecommons.org/licenses/by/4.0
Pharmacologic Predictors of Engraftment and Survival in Hematopoietic Stem Cell Transplantation
Background and Hypothesis: For many aggressive hematologic disorders, hematopoietic stem cell (HSC) transplantation is the only curative therapy. This treatment involves collection of stem cells from healthy donors or patients themselves before pre-transplantation chemoablation, and donor cell infusion to reconstitute a healthy blood system. While HSC transplantation can be effective in treating blood diseases with poor prognoses, patient outcomes of HSC transplantation are variable, with overall 5-year survival rates of 40-60%. At early timepoints after transplantation, poor or delayed engraftment can lead to infections, hemorrhage, disease relapse, and increased mortality; however, the complex factors that lead to variable outcomes are yet to be fully understood. A recent study has shed light on a class of anti-hypertension medications that may delay engraftment (PMID: 39786370). Here we aim to more broadly understand common drugs that may impact engraftment rates and overall survival in HSC transplantation patients. Experimental Design or Project Methods: We conducted a retrospective analysis of 500 IU Health allogeneic transplantation patients from 2019-2025. Demographic data, transplant parameters, and blood count recovery from 1 week pre- to 3 months post-transplant were collected. Data was stored securely in REDCap and analyzed using Excel, OpenRefine, and GraphPad Prism. Results: Patients receiving acyclovir, fluconazole, ondansetron, and tacrolimus post-transplant exhibited significantly faster platelet recovery within one month and higher 3-year survival rates compared to patients who were not on these medications. In adult patients, higher CD34+ cell doses modulated medication-dependent platelet recovery and survival. Potential Impact: Our findings suggest that certain medications taken in the peri-transplantation period may enhance platelet recovery and long-term survival, and that early platelet recovery could serve as a surrogate marker for survival. Future work will involve multivariate and machine learning approaches to explore additional variables, including disease type and comorbidities, to better optimize clinical decision making for HSC transplant outcomes.
Copyright (c) 2026 Damon Ho, Aryan Patel, Stephanie N. Hurwitz http://creativecommons.org/licenses/by/4.0
Communication and Learning Improvement Model for Bedside Skills (CLIMBS): An AIBased Feedback Model for the Objective Standardized Clinical Examination
Background: The Objective Standardized Clinical Examination (OSCE) is a tool designed to assess and provide feedback to healthcare students; however, feedback quality is a common point of frustration for students. Common concerns with post-OSCE feedback include that it is generally not timely, comprehensive, and/or individualized. In this retrospective, quasi-experimental pilot study, we created and implemented an artificial intelligence (AI) feedback model and assessed its ability to provide accurate and reliable OSCE feedback. Methods: Using ChatGPT-4o, we developed the Communication and Learning Improvement Model for Bedside Skills (CLIMBS) to reference a 16-metric OSCE rubric and provide feedback on OSCE transcripts derived from a custom workflow. Using a single, full-marks OSCE recording, we assessed CLIMBS by calculating transcription and feedback accuracy and examining feedback reliability against an artificially-generated ‘Poor Performance’ transcript and a manually corrected transcript. Results: The CLIMBS workflow exhibited 92.39% transcript accuracy and good inter-rater reliability (cosine similarity = 0.972 +/- 0.015; ICC2 = 0.744 (95% CI: [0.59, 0.88]). Overall OSCE scores assigned by CLIMBS to the unedited transcript (93.84; 95% CI [91.53, 96.17]) and the manually corrected transcript (87.69, 95% CI [81.37, 94.02]) were statistically different from the ‘Poor Performance’ transcript (78.08; 95% CI [71.59, 84.57]). The metric-based score pattern distribution of the manual transcript was similar to both the unedited and the ‘Poor Performance’ transcripts (cosine similarity = 0.890 and 0.819, respectively), while the unedited and ‘Poor Performance’ transcripts exhibited low overlap with each other (cosine similarity = 0.566). Conclusion: This pilot study demonstrated that an AI model can analyze and provide accurate summative feedback to OSCE recordings – differentiating good from poor performance. The accuracy and reliability of formative feedback require further study. With future testing to improve inter-rater reliability and examine formative feedback, CLIMBS has potential to improve the timeliness, comprehensiveness, and personalization of OSCE feedback.
Copyright (c) 2026 Liam Hobson, Chandler Lutz, David Rodgers http://creativecommons.org/licenses/by/4.0
Primary Care Providers’ Attitudes towards Adolescent Substance Use Disorder as a Predictor of Prevention Advocacy
Of the 2.2 million adolescents in the US that had a substance use disorder (SUD) in 2023, only 0.5% received professional counseling or medication for SUD. Stigma is one of many potential barriers to care. Primary care is an ideal location to integrate SUD care due to frequency of care, access to resources, and provider-patient relationships. Adult primary care providers’ stigmatizing beliefs about SUD is associated with less involvement in SUD care and decreased medication refills and specialist referrals. This study begins to fill the knowledge gap of primary care providers’ attitudes towards adolescent SUD and provider SUD advocacy practices. Data was collected from a cluster-randomized, stepped wedge, hybrid type III effectiveness-implementation randomized clinical trial including 25 clinical sites across 13 counties in a large midwestern hospital system that aimed to implement standardized screening processes and integrated behavioral health services. Survey participants (N=470) included medical assistants, providers (registered nurse, nurse practitioner, and physicians’ assistant), physicians, and clinic staff. Descriptive analyses and inferential statistical testing of two measures for public stigma towards adolescents with a SUD and interprofessional communication (advocacy) about SUD prevention were completed. Univariate logistic regression was conducted to examine the factors of SUD prevention advocacy. A paired samples t-test was performed to evaluate whether there was a difference between the public stigma score between adolescent opioid use and marijuana use. The results showed that the mean stigma towards opioid use (M=2.99, SD=1.00) was significantly lower than the mean stigma towards marijuana use (M=3.17, SD=1.07, t(453)=-6.126, p=<0.001). Providers had significantly higher social disengagement with adolescents with a SUD compared to other measures of stigma, including negative emotions, lack of empathy, and assessment of responsibility. The results of a paired t-test showed that the social disengagement subscore for opioid use (M=6.54, SD=1.88) was significantly higher than the mean opioid use stigma score (M=2.99, SD=1.00, t(453)=45.35, p=<0.001), and the social disengagement subscore for marijuana use (M=6.45, SD=1.97) was significantly higher than the mean marijuana use stigma score (M=3.17, SD=1.07, t(453)=40.31, p=<0.001). Across four substances (nicotine, alcohol, cannabis, and opioids), the percentage of providers with no communication about SUD prevention ranged between 37.0% and 51.2%. Regression findings indicate that male healthcare staff were at reduced odds of advocating for SUD prevention than females (OR=0.21 [95% CI 0.05, 0.61]). Registration staff had greater odds of discussing SUD prevention than providers (OR=6.36 [95% CI 3.51, 11.83]). This study characterizes providers’ stigmatizing beliefs and prevention advocacy towards adolescents with a SUD and identifies demographic differences that can be used to tailor intervention with providers and staff to increase advocacy.
Copyright (c) 2026 Emma Holder, Lauren O’Reilly, Brigid Marriott, Fangqian Ouyang, Patrick Monahan, Emily Owen, Zachary Adams, Leslie Hulvershorn, Matt Aalsma http://creativecommons.org/licenses/by/4.0
Investigating the Role of ANGPTL2 in Glaucomatous Trabecular Meshwork
Background and Hypothesis: Glaucoma is a progressive optic neuropathy and the leading cause of irreversible blindness worldwide, primarily driven by elevated intraocular pressure (IOP). IOP elevation often results from impaired aqueous humor outflow through the trabecular meshwork (TM), where extracellular matrix (ECM) remodeling and cytoskeletal changes increase tissue stiffness and cause dysfunction. Our RNA sequencing study identified angiopoietin-like 2 (ANGPTL2), a TGFβ2-inducible gene, in the TM. Since ANGPTL2 is a secreted protein involved in ECM remodeling in other tissues and TGFβ2 is a well-known glaucomatous insult, we hypothesize that ANGPTL2 contributes to glaucomatous changes in the TM. Experimental Design: GTM3 cells were transfected with either ANGPTL2 siRNA (following dose optimization via western blot) or an ANGPTL2 overexpression plasmid (generated by subcloning ANGPTL2 cDNA into a GFP vector and confirmed by Sanger sequencing). The cells were treated with or without 5ng/ml TGF-β2 to simulate profibrotic conditions. Protein expression of ANGPTL2, fibronectin, and collagen I was assessed by western blotting. Immunocytochemistry with phalloidin and ECM markers was used to evaluate cytoskeletal organization and ECM remodeling. Results: ANGPTL2 knockdown reduced fibronectin and collagen I levels and decreased phalloidin-labeled actin stress fibers, in the presence or absence of TGFβ2. Overexpression of ANGPTL2 increased actin stress fibers. Conclusions and Potential Impact: Our preliminary data indicate that ANGPTL2 likely contributes to TM cytoskeletal remodeling and ECM accumulation in the TM. Further studies are required to validate these findings. Also, ex vivo perfusion culture and in vivo mouse studies are needed to determine the role of ANGPTL2 in IOP regulation.
Copyright (c) 2026 Aileen Huang, Chenna Sugali, Jiannong Dai, Kamesh Dhamodaran, Weiming Mao http://creativecommons.org/licenses/by/4.0
Safety Planning for a Dementia Diagnosis: Understanding the Attitudes of Aging Firearm Owners and Identifying the Physician’s Role in Developing Firearm Retirement Plans
Background/Objective: In the US, 56 million individuals are aged 65 and older with 1 in 10 at risk of developing dementia. Among this population, 1 in 3 report firearm ownership. Dementia poses significant safety risks when coupled with firearm ownership. However, no standardized protocol exists to guide physicians in assisting aging firearm owners with planning for cognitive decline. This study aims to identify the demographic and behavioral factors associated with willingness to engage in firearm retirement planning. Methods: A prospective survey was administered to 106 firearm owners aged 60 or older, including trauma inpatients (n = 58) and vascular clinic outpatients (n = 48). Multivariable logistic regression was used to identify predictors of openness to physician involvement in firearm retirement planning. Results: Among respondents, 51.9% were open to or considering discussing a firearm safety plan with their physician (38.7% open, 13.2% undecided). Black respondents were significantly more likely than white respondents to endorse physician involvement (OR = 3.14, 95% CI 1.06–9.33), as were single respondents compared to married ones (OR = 2.91, 95% CI 1.23–6.89). In contrast, those with above-basic firearm expertise (OR = 2.57, 95% CI 1.12–5.89), prior formal firearm training (OR = 2.21, 95% CI 1.00–4.89), or who stored firearms loaded (OR = 2.90, 95% CI 1.22–6.86) were more likely to oppose physician involvement. Post-survey, single respondents were also more likely to initiate firearm planning discussions with family (OR = 2.66, 95% CI 1.03–6.89). Conclusion: Prior to completing the survey, most respondents had not discussed firearm planning; however, two-thirds intended to do so afterward. Findings suggest that Black individuals, those who are single, and those with less firearm experience may be especially receptive to physician-led firearm retirement conversations. Additional research should be done to understand the perspectives of the less receptive subgroups.
Copyright (c) 2026 Martha Hunter, Linda Schutzman http://creativecommons.org/licenses/by/4.0
Preoperative Hypoglycemia as a Predictor of Postoperative Vitreous Hemorrhage in PDR Patients Undergoing Vitrectomy
Objective This study evaluated the association between preoperative glycemic status—specifically fasting hypoglycemia—and postoperative vitreous hemorrhage (POVH) incidence and visual outcomes in patients with proliferative diabetic retinopathy (PDR) undergoing pars plana vitrectomy (PPV). While much attention has been given to hyperglycemia and its impact on post-op complications, hypoglycemia is an often-underappreciated potential risk factor. Methods Medical records of 144 PDR patients who underwent PPV between 2020-2024 were reviewed. Preoperative fasting blood glucose levels were recorded, and patients were categorized as hypoglycemic (<70 mg/dL), normoglycemic (70–125 mg/dL), or hyperglycemic (>125 mg/dL). Postoperative vitreous hemorrhage was assessed within three months. Visual acuity (VA), measured in LogMAR, was collected preoperatively, specifically at Postoperative Day 1 (POD1), Month 1, and Month 3. Additional demographic, systemic, and ocular variables were collected. Statistical analyses included t-tests, chi-square analysis, and ANOVA to evaluate associations between glycemic status, POVH incidence, and Visual Acuity outcomes. Results Preoperative hypoglycemia was not significantly associated with POVH, though a trend toward increased incidence was noted. Conversely, hyperglycemia was significantly associated with higher POVH rates within three months (P=0.009**). In terms of VA outcomes, hypoglycemic patients demonstrated significant postoperative worsening at Month 1 (P=0.0001***) and Month 3 (P=0.001***). Hyperglycemic patients also experienced significantly worse VA at POD1 (P=0.04*), Month 1 (P=0.01**), and Month 3 (P=0.04*) compared to normoglycemic patients. Normoglycemic patients exhibited the most favorable recovery in visual acuity across all timepoints. Conclusion Both preoperative hyperglycemia and hypoglycemia were associated with worse postoperative outcomes in PDR patients undergoing PPV. While hyperglycemia increased the risk of early POVH, hypoglycemia was linked to poorer visual outcomes. These findings underscore the clinical importance of perioperative glycemic control to potentially improve visual and surgical outcomes in this high-risk population. Future prospective studies are needed to establish evidence-based guidelines for perioperative glycemic management in ophthalmic surgery.
Copyright (c) 2026 Imran Syed Hussain, Frank Bogan, Ali Elobous, Amir Reza Hajrasouliha http://creativecommons.org/licenses/by/4.0
Employment Trajectories and Productivity Outcomes at 1-, 2-, and 5-Years Following Traumatic Brain Injury with Disorder of Consciousness
Background/Objective: Employment status is used both clinically and more broadly as a marker of functionality and independence. Patients who are undergoing rehabilitation for chronic illness or injury often consider return to work as a key milestone in recovery. Within the population of patients diagnosed with a Disorder of Consciousness (DoC), it is poorly understood what factors may contribute or hinder return-to-work. Our study aims to better understand the upstream and downstream determinants of employment status in patients with DoC. Methods: Participants were individuals with traumatic brain injury enrolled into the TBIMS National Database. For the current retrospective, longitudinal study, participants also needed to be eligible for their 5-year follow-up window between June 25, 1998, and December 31, 2024, and have completed follow up interviews at 1-, 2-, and 5- years post-injury with complete employment data. Participants who were retired or age 65 or greater at the time of injury were excluded. Predictive analysis were used to assess what extenuating factors (age, education, injury type, etc.) preclude higher likelihood for return-to-work in patients with DoC. Results: Employment, employability and productive participation gradually increase across years 1, 2, and 5 post-TBI. 15-17% of patients with DoC are employed by year 5 follow-up. Younger age and lower injury severity are associated with better long-term employment outcomes. Conclusion and Impact: This study may contribute to prognostic counseling to patients and their loved ones, allowing for more accurate and better-informed decisions in the context of treatment options, quality of life, planning for the future and trust in the medical system.
Copyright (c) 2026 Harrison Jacobs, Natalie Gilmore, Yelena Bodien, Therese Pirozzi, Brick Johnstone, Joseph Giacino, Matthew Pease, Flora Hammond http://creativecommons.org/licenses/by/4.0
Red Cell Distribution Width as a Prognostic Indicator of Mortality in Extracorporeal Life Support
Background Red cell distribution width (RDW) is a component of routine inpatient blood work that has been indicated as a potential prognostic mortality indicator for various conditions. Extracorporeal membrane oxygenation (ECMO) patients have a high mortality rate, and ECMO does not have easily obtainable prognostic measurements. RDW values may be a potential prognostic factor for ECMO patients and improve clinical decision making. Methods 142 patient charts (70 survivors, 72 non-survivors) placed on ECMO care at Lutheran Hospital met inclusion criteria. RDW values were collected at six specific times during care along with peak RDW value and survivorship outcome. Patients were stratified into high (>14.5%) and low (≤14.5%) RDW groups for each time. Relative risk (RR) and odds ratio (OR) were used to analyze survivorship outcome between the groups. Results Only several RR and OR calculations yielded results that indicated differences in mortality risk and odds and were statistically significant. RDW at 24Hr after ECMO initiation showed a RR of 1.72, 95% CI 1.06-2.76, p<.05 and OR of 2.68, 95% CI 1.24-5.80, p<.05. RDW at ECMO termination and discharge had an OR of 3.88, 95% CI 1.20-12.55, p<.05. Discussion Results showed an association between high RDW value and increased risk and odds of mortality at 24Hr after ECMO initiation. Results also indicated increased odds of mortality at ECMO termination and discharge. These preliminary results are promising for further analysis and encourage the feasibility of potentially using RDW as a prognostic mortality indicator during ECMO treatment. Conclusions Further analysis must be conducted on the samples collected during the study, but these preliminary results demonstrated feasibility of RDW as a prognostic biomarker for clinical decision making with ECMO survivorship outcomes.
Copyright (c) 2026 Jacob Jones, John Morton, Asim Mohammed http://creativecommons.org/licenses/by/4.0
Associations Between Cardiac Comorbidity Burden and Atrial Fibrillation Prevalence: A Real-World-Evidence Based Approach
Background: In the aging US population, atrial fibrillation (AFib) is increasingly prevalent, affecting nearly 5% of individuals. While previous studies have identified independent risk factors such as heart failure (HF), coronary artery disease (CAD), hypertension (HTN), hyperlipidemia (HLD), and type 2 diabetes (T2D), less is known about how these conditions relate to AFib when co-occurring. We aimed to assess how frequently AFib is observed in individuals with one or more of these conditions and to estimate odds ratios associated with both individual and combined disease states. Methods: We performed a retrospective analysis using the IU School of Medicine-Evansville RWEdataLab (CRC/Sidus Insights) cardiac database, which includes electronic health records for 3.5 million de-identified individuals. ICD-9 and ICD-10 codes were used to identify chronic forms of AFib, HF, CAD, HTN, HLD, and T2D. Adults 49+ were included and stratified by sex (total: 3.00M, 1.54M female). Odds ratios (ORs) along with their 95% confidence intervals (CIs) were calculated. Results: AFib was more frequently observed among individuals with cardiac conditions and T2D. Heart failure demonstrated the strongest association with AFib with OR of 7.04 (95% CI: 6.95 – 7.12) in males and 8.12 (95% CI: 8.01 – 8.23) in females. Other conditions, such as CAD, HTN, HLD, and T2D were associated with elevated AFib odds, ranging from an OR of 2.47 with T2D to 6.38 with HTN. 20 ORs were calculated. Clinical Implications and Future Direction: These findings demonstrate that the odds ratio for AFib changes with different combinations of comorbidities, such as HF and HTN, which is consistent with current literature. Future work should involve multivariate models to control for confounders like healthcare utilization and treatment effects. Limitations include inability to determine temporality and causality. Longitudinal studies could help establish temporality and determine whether individuals with certain cardiometabolic profiles might benefit from targeted AFib screening.
Copyright (c) 2026 Nikolai Jones, Tatiana Aviles, Vyom Patel, Andrei Feldiorean, Lawrence Judy, Dale Saxon http://creativecommons.org/licenses/by/4.0
Perioperative Instrumentation and Factors that Impact Intravesical Urothelial Carcinoma Recurrence After Nephroureterectomy
Background: Urothelial carcinoma of the ureter and renal pelvis has a tendency to recur following surgical intervention. A leading theory attributes this pattern to tumor seeding occurring during diagnostic or surgical procedures. Instruments commonly used during diagnostic and surgical intervention, such as ureteral stents, may influence recurrence rates. Methods: Electronic medical records of 201 patients with a history of upper tract urothelial carcinoma and nephroureterectomy were reviewed. Seventy clinical factors were recorded and organized into pre-, peri-, and post-surgical categories. Of these variables pre-procedural ureteroscopy, access sheath use, stent placement, and biopsy were analyzed in connection to recurrence. Perioperative factors analyzed included the presence of a stent during the nephroureterectomy and the surgical approach (open vs. minimally invasive). Odds ratios (OR) and statistical significance (p-value) were used to determine potential correlation. Results: Of the 201 patients, 105 (52.2%) experienced recurrence. Pre-procedural biopsy (OR 0.87, p=0.67), pre-procedural ureteroscopy (OR 0.96, p = 0.90), and surgical approach (OR 1.04, p=0.90) demonstrated no significant impact on recurrence. Use of an access sheath during the diagnostic procedure (OR 1.22, p=0.53) and pre-procedural stent placement (OR 1.26, p=0.45) suggested an increase in recurrence, although not statistically significant. The presence of a stent during nephroureterectomy demonstrated a higher risk of recurrence (OR 1.8) and neared statistical significance (p=0.05). Conclusion: These findings suggest that certain perioperative factors such as the presence of a stent during nephroureterectomy may contribute to increased recurrence rates through mechanisms such as tumor seeding. Our study approaches statistical significance. Analysis of a larger cohort is anticipated to strengthen this association.
Copyright (c) 2026 Joseph Kaefer, Daniel Sidhom, Chandru Sundaram http://creativecommons.org/licenses/by/4.0
The Impact of Manual Correction on Automated Hippocampal Volumetry in a Young Athletic Cohort with Variable Level of Exposure to Head Trauma
[Introduction] An estimated 1.6 to 3.8 million people suffer from sport-related concussion annually, yet the long-term effects of concussion and repetitive head injury exposure are not fully understood. Given the potential risk of future neurodegeneration, the hippocampus has emerged as a key region of interest. While post-mortem studies demonstrated marked hippocampal atrophy in athletes from high-impact sports, more recent in-vivo research reveals more nuanced findings as they rely heavily on imaging and segmentation accuracy. Freesurfer, a widely used tool for automated hippocampal segmentation, has been shown to overestimate the volume, especially in older populations. In this study, we evaluated the accuracy of Freesurfer’s segmentation against manual refinement in a cohort with head impact exposure. [Method] Structural MRI data (T1W and T2W) of the CARE-SALTOS Integrated (CSI) project was used for hippocampal segmentation using FreeSurfer (7.4.1). Twenty participants (age range: 29 to 32) were sex-matched and grouped into high-exposure (n=10, including 5 football players) and low-exposure cohorts (n=10). The hippocampal volumes were compared between initial automatic segmentations and subsequent manually refined delineations by a trained medical professional using paired t-tests. [Results] Our results showed significant differences in the hippocampal volume between automatic segmentation and after manual refinement. By visual inspection, FreeSurfer tends to overestimate hippocampal segmentation volumes as generated masks extend into lateral ventricular spaces and include choroid plexus. In both groups, hippocampal volumes significantly decreased after manual refinement (Left Hippocampus, -788.81±245.30mm3, p=1.15E-11; Right Hippocampus, -649.60±246.83mm3, p=3.59E-10). [Conclusion] Based on our results, we conclude that while automatic segmentation is a feasible and fast method for large datasets, it requires subsequent manual refining to ensure data accuracy by avoiding volumetric overestimation and potential bias from adjacent ventricular areas.
Copyright (c) 2026 Demetrios Kamiotis, Ho-Ching Yang, Yomna Takieldeen, Salman Shahid, Yu-Chien Wu http://creativecommons.org/licenses/by/4.0
PD-1 and VEGF Peptide Vaccine Combination Display Synergistic Anti-Tumor Effect in Cancer Immunotherapy
Cancer immunotherapy with checkpoint inhibitors (PD-1, CTLA-4, etc.) have had promising effects on suppressing tumor growth in numerous cancers. Programmed death-1 (PD-1) is a receptor commonly expressed on T cells where it plays a key role in maintaining self-tolerance and preventing autoimmunity. In a normal functioning immune system, when PD1 ligand (PD-L1) binds PD-1 receptor, T cell activation is suppressed. Meanwhile, vascular endothelial growth factor (VEGF) is a growth factor secreted by tumor cells that promotes angiogenesis, a key requirement by which tumors grow and invade surrounding tissue. In this study, we aim to exploit the immunological roles of PD-1 and VEGF to promote further T cell activation and inhibit angiogenesis in colon tumors, respectively. By administering the combination of B cell epitopes PD-1 and VEGF peptide vaccines in mouse models, we hypothesize the host immune system will elicit a response by generating neutralizing antibodies to the B cell epitopes in a synergistic manner. To test this, BALB/c mice were immunized with the PD-1/VEGF combination three times and subsequently challenged with the CT26 colon cancer cell line. Antigenicity and immunogenicity were monitored by collecting serum and performing enzyme-linked immunosorbent assay (ELISA). Tumor growth was also monitored for 2 weeks. Results indicate increasing immunogenicity upon subsequent immunizations, along with decreased tumor growth compared to controls. These data suggest the combination of PD-1 and VEGF peptide vaccines synergistically enhance survival outcomes by slowing tumor growth and hold a strong potential as an applicable treatment strategy for colon carcinomas. These findings support further investigation of vaccine efficacy in other cancer models.
Copyright (c) 2026 Navjot Kaur, Linlin Guo, Jay Overholser, Pravin T. P. Kaumaya http://creativecommons.org/licenses/by/4.0
Geographic and Socioeconomic Disparities in Mammography Services Across Northwest Indiana and Chicagoland
Background Between 2018-2022, Northwest Indiana (NWI) reported higher breast cancer mortality than the national average, indicating geographic disparities and unmet healthcare needs. Zip codes with greater socioeconomic disadvantage are less likely to have accredited breast imaging facilities. Limited studies have examined the spatial distribution of mammography facilities in NWI. This study examined the spatial distribution and characteristics of mammography services across 7 NWI counties and 4 adjacent Chicagoland counties. Methods Mammography facility data were collected from the Food and Drug Administration’s Mammography Quality Standards Act (FDA MQSA), American College of Radiology (ACR), and National Accreditation Program for Breast Centers (NAPBC). All mammography facilities must meet FDA standards, with ACR providing higher-level accreditation for multiple breast imaging modalities, and NAPBC granting the highest recognition for comprehensive breast cancer care. Facilities were characterized by setting, services, and certification. Facilities were geocoded and mapped using Google Earth Pro 7.3.6, with US Census overlays for Area Deprivation Index (ADI), % publicly insured, % racial minorities, women aged 40-74, and distance. Results Across NWI, 3 out of 7 counties had 1 FDA and/or ACR accredited mammography facility. Communities characterized by higher ADI and public insurance coverage (e.g., Gary, East Chicago, and Hammond) had 1 FDA and/or ACR accredited mammography facility each, with no NAPBC-accredited facility. Contrastingly, lower ADI and % publicly insured communities (e.g., Crown Point, Munster) had higher facility density, including 2 of 4 NWI’s NAPBC-accredited sites. Gary and LaPorte had notable differences in racial/ethnic compositions, but both experienced limited mammography access. Chicagoland followed similar trends. Conclusions The spatial mismatch between facility access and community needs suggests structural inequities in access to breast cancer services, affecting higher ADI and publicly insured communities. Future research will analyze additional barriers, facility capacity, and inform community-engaged strategies to expand access to comprehensive breast cancer care in underserved communities.
Copyright (c) 2026 Ankurpreet Kaur, Joshua Mangum, PhD, Jonathan Guerrero, PharmD, MSEd, BCPS, Baraka Muvuka, PhD, MPH, MCHES http://creativecommons.org/licenses/by/4.0
Exploring the Influence of Social Determinants on Postoperative Coronary Artery Bypass Graft (CABG) Complications in Northwest Indiana
Introduction: Coronary artery bypass grafting (CABG) comprises 70% of all cardiac surgeries in the United States, with approximately 400,000 surgeries performed per year at a cost of $16 billion annually. According to the American Heart Association, women (2.3% versus men 1.6%), and patients identifying as black (2.8% versus white 1.6%) have higher rates of CABG-related mortality. This study examined demographic, clinical, behavioral, and social determinants of post-CABG complications. Methods: This retrospective cross-sectional study analyzed inpatient admissions in patients with a CABG history at three urban hospitals in Northwest Indiana between January 2021 - March 2025. CABG history and complications were identified using ICD-10. SDOH data were generated in EPIC using the Protocol for Responding to and Assessing Patients’ Assets, Risks, and Experiences (PRAPARE). Data analysis consisted of bivariate (Chi-square) and multivariate (Binary Logistic Regression) analyses in SPSS 31.0. The study was exempted by Indiana University Human Research Protection Program (IRB#14040). Results: The sample included 10,941 patients. Bivariate analysis revealed statistically significant (p<0.05) associations between CABG complications and ethnicity, race, veteran status, BMI, Emergency Department (ED) Disposition, 30-day readmissions, and readmissions. Multivariate analysis revealed significantly increased odds of CABG complications among patients identifying as Asian (p=0.019; OR=3.127), underweight (p=0.029; OR=1.919), and veterans (p=0.006; OR=1.399) and decreasing odds with each year increase in age (p=0.001; OR=0.985). Conclusion: Incorporating social determinants of health into CABG risk stratification and management can enhance patient outcomes and quality of life. To optimize CABG outcomes, future research should focus on identifying context-specific determinants and translating findings into evidence-based hospital initiatives guiding the development of programs to meet patients’ needs and promote long-term health improvements.
Copyright (c) 2026 Adam Keeton, Baraka Muvuka, Joshua Mangum, Kyle Gospodarek, Jonathan Guerrero http://creativecommons.org/licenses/by/4.0
Mapping Mitochondrial Interactions with Endoplasmic Reticulum and Plasma Membrane Under DNA Damage in Prostate Cancer Cells
Introduction. Prostate Cancer is the second leading cause of cancer death in men in US. The primary treatment for prostate cancer is androgen deprivation therapy (ADT). If cancer progresses while being treated with ADT, the cancer is classified as metastatic castration-resistant prostate cancer. Poly (ADP-ribose) polymerase inhibitors (PARPi) have demonstrated promising results for castration-resistant (and castration-sensitive) prostate cancer. However, some patients develop resistance to PARPi. The mechanisms of action of these drugs are not fully understood and are vital to overcoming PARPi resistance. Therefore, the aim of this study is to fill our knowledge gap of how PARPi affects organelle crosstalk, specifically mitochondrial interactions with the endoplasmic reticulum and plasma membrane. Methods. LNCaP and MDA PCa 2b, androgen-sensitive cell lines, were treated with 12.5 μM of Olaparib and Rucaparib (FDA-approved PARPi) for 48 hours. A proximity ligation assay (PLA) was used to highlight mitochondrial interactions with the endoplasmic reticulum and with the plasma membrane. Confocal microscopy was used to image these interactions. Kamoshita’s (2023) protocol was modified and implemented to quantify the number of interactions between the organelles in the PLA. A pretrained machine learning model, Cellpose, was used to segment the nuclei and obtain an average number of interactions between organelles per cell. Results. When treated with Olaparib and with Rucaparib, LNCaP cell lines had more mitochondria-endoplasmic reticulum interactions compared to the control (P<0.05). There were no significant changes in the number of mitochondria-plasma membrane interactions in LNCaP cell lines when treated with PARPi. There were no significant changes in the number of mitochondria-endoplasmic reticulum and mitochondria-plasma membrane interactions in MDA PCa 2b cell lines when treated with PARPi. Conclusion. Findings suggest that PARPi affects organelle crosstalk in prostate cancer cells. Further research should investigate how PARPi affects organelle crosstalk in PARPi-resistant cancer cells to improve patient outcomes.
Copyright (c) 2026 Faris Khan, Jennifer Rooks, Asmaa El-Kenawi http://creativecommons.org/licenses/by/4.0
Optimization of a RAG Model Chatbot for Medical Education
Background/Objective: In fast-paced clinical settings like labor and delivery, quick access to accurate, evidence-based guidance is critical. Traditional methods of sharing protocols can be inefficient, especially for trainees managing complex scenarios. Advances in artificial intelligence (AI) and large language models (LLMs) offer the potential to transform how critical clinical decision-making tools are disseminated, making them more accessible, responsive, and integrated into real-time learning. Our objective was to develop our own chatbot to facilitate quick retrieval and enhanced learning. Methods: The AI chatbot was developed by IUSM researchers using Microsoft Copilot Studio and made accessible via Microsoft Teams. The AI chatbot was built on a retrieval-augmented generation (RAG) framework, leveraging a fine-tuned LLM. The base LLM was augmented with domainspecific documents, including IUSM protocols – developed by the Maternal-Fetal Medicine division - which incorporate evidence-based practices and provide a consistent management strategy for OB conditions. The RAG architecture was configured to retrieve contextually relevant documents from the collection of protocols in response to user queries. Results: The chatbot retrieves information from the protocols based on a user’s query and generates a relevant answer with reference to the sources. Upon testing the chatbot, we learned that the chatbot was unable to retrieve information from figures, flowcharts, and diagrams. Therefore, figures were manually annotated and narrated, enabling the model to process and retrieve relevant visual information during inference. With other adjustments, the chatbot is able to read all aspects of the protocols and synthesize accurate answers to clinical questions. Conclusion and Potential Impact: We optimized an RAG model AI chatbot for clinical education, demonstrating that existing educational material can be used to activate a chatbot to serve clinical needs with sufficient oversight to ensure clinical accuracy. Future directions include evaluating its impact on clinical decision making and student perception of the learning environment once the chatbot is more uniformly adopted.
Copyright (c) 2026 Kenzie Knight, Kelsey Pape, Esther Kim, Caroline Rouse, David Hanson, Anthony Shanks http://creativecommons.org/licenses/by/4.0
Diagnosis of metastases to gastrointestinal tract using fine needle aspiration
Context and Hypothesis: Metastases to the gastrointestinal (GI) tract are less prevalent than primary tumors, with the small intestine as an exception. Limited literature exists on using fine needle aspiration (FNA) for diagnosing these tumors. We hypothesize that FNA will have a greater sensitivity for disease detection compared to surgical biopsy. Design: We accessed the pathology database to retrospectively review cytomorphology and radiologic features of 41 metastatic tumors of GI tract diagnosed by FNA. Results were compiled and analyzed in Excel. Results: The cohort included metastases involving stomach (19; 39%), rectum (11; 27%), small intestine (10; 24%) and esophagus (3; 7%) The median age was 66.5 years (range: 26 to 86 years) with female predominance (F/M: 1.92). The median interval between primary diagnosis and metastases was 20 months (range: 0 to 174 months). Metastases were the initial clinical manifestations in 7 patients. Twenty-six patients presented with mass-forming lesions, 13 showed diffuse wall thickening, 1 patient showed wall narrowing, and 1 noted no comment on endoscopic ultrasound. Concurrent core biopsies were obtained in 22 cases (54%), with 14 (64%) yielding falsely negatives due to sampling error. obtained in 20 cases (54%), with 12 (60%) yielding falsely negatives due to sampling error. The most common primary sites were breast (8; 19%), ovary (6; 14%), bladder (5; 12%), pancreatobilliary tract (3; 7%), and colon (3; 7%). Thirty-two patients (84%) had other distant organ metastases. Seventy-eight percent of patients (32) died of disease, with a median follow-up of 11 months (range: 1 to73 months). Among these, nineteen died within a year of GI metastases. Conclusions and Potential Impact: FNA reliably diagnoses secondary GI tract tumors, in contrast to mucosal biopsies, which often yield false negatives. FNA serves as a more reliable way of diagnosing GI metastases tract while also being less invasive.
Copyright (c) 2026 Bain LaFollette, Tieying Hou http://creativecommons.org/licenses/by/4.0
Physician Education and Knowledge, Attitudes, and Practices Surrounding Opioid Education
Background/Objective: Many currently practicing physicians have not received adequate training on opioids, opioid use disorder, and medications for opioid use disorder (MOUDs). The primary goal of this study was to determine physician knowledge, attitudes, and practices regarding these topics. Methods: This was done by interviewing four physicians with a set of predetermined questions and allowing them to elaborate where they saw fit. A thematic analysis was then conducted on their transcripts. Results and Conclusions: The thematic analysis revealed three themes. First, that significant patient and medication complexity leads to physician hesitation to prescribe. Second, that there are inconsistencies in resources offered to patients and providers. Third, for many current providers, continuing medical education (CME) is their only source of opioid and MOUD education. The primary barrier identified in this analysis is finding a balance between providing consistent resources and actions for physicians while tailoring specialty-specific training that best serves patients' needs. Limitations and Future Directions: The major limitation of this study is the sample size and concentration of physicians to one geographic area. Additionally, the physicians practice at different hospitals, leading to both beneficial and detrimental response variability. The interviews conducted for this study will be used to build a larger study considering what changes can be made to increase the efficacy of opioid CME. The objective is to increase physician participation, engagement, and interest in the topic.
Copyright (c) 2026 Victoria Leeder, Polly Husmann http://creativecommons.org/licenses/by/4.0
Neuroregenerative Effects of Human Neuritin 1 on Glaucomatous Human Retinal Ganglion Cells
Purpose: Glaucoma is a group of optic neuropathies characterized by progressive loss of retinal ganglion cells (RGC) and corresponding visual field deficits. Current treatments can only slow the progression of glaucoma, but RGC death is not preventable and irreversible. Thus, neurotrophic factor therapy may be a suitable therapeutic approach. Human Neuritin 1 (NRN1) has demonstrated neurodegenerative and neuroprotective properties, and our group has previously established that NRN1 is downregulated in glaucomatous RGCs. We will investigate the therapeutic potential of NRN1 on human RGCs using a human stem cell-derived RGC model. Methods: Corneal fibroblasts from glaucomatous and non-glaucomatous post-humous donor tissue were reprogrammed into induced pluripotent stem cells (iPSCs) using the CytoTuneTM‐iPSC 2.0 Sendai reprogramming kit. These iPSCs were characterized via PCR (C‐MYC, KLF4, SOX2, NANOG) and immunofluorescence staining (TRA‐1‐60, SOX2) and karyotyped. The iPSCs were differentiated into three-dimensional retinal organoids (ROs) from which RGCs were dissociated. PCR (RBPMS, THY1) and immunofluorescence staining (RBPMS, BRN3A, DAPI) were used to characterize RGCs. The RGC apoptosis and neurite outgrowth were measured with and without NRN1 treatment using markers such as CASP3 and NEFL respectively. Results: NRN1 treatment enhanced neurite outgrowth and reduced RGC apoptosis in NRN1 treated RGCs compared to untreated cells. Conclusions: These findings confirm that NRN1 enhances neurite outgrowth and RGC survival in human glaucomatous cells, further demonstrating its potential as a candidate for glaucoma therapy.
Copyright (c) 2026 Ksenia Lewyckyj, Shahna Hameed, Tasneem Sharma http://creativecommons.org/licenses/by/4.0
Revolutionizing OSCE Preparation Through AI-Driven Synthetic Patients
Background: Objective Structured Clinical Examination (OSCE) preparation is a key component of medical student training. Traditional methods like standardized patient (SP) encounters and peer-to-peer practice provide valuable experience but are limited by inconsistent feedback, access issues, and time constraints. To support OSCE preparation, we developed AI-driven synthetic patients that offer students a flexible, accessible, and consistent practice tool. Using ChatGPT-4o and core clinical competencies expected of first-year students at Indiana University School of Medicine (IUSM), we piloted virtual patients that simulate realistic encounters—enabling conversational interviews with immediate, structured feedback. Methods: Five interactive synthetic patient cases were created to reflect common OSCE scenarios. Each case included a computerized door note, dynamic dialogue, realistic patient responses, and downloadable feedback modeled after IUSM OSCE grading rubrics. We recruited 14 rising second-year medical students at IUSM–Bloomington to interview the synthetic patients. A preinterview survey assessed students' prior OSCE preparation, while a post-interview survey evaluated the tool’s realism, usefulness, and convenience, and gathered qualitative feedback. Results: The pre-interview survey revealed that a majority of students (9 of 14) desired additional tools to support history-taking practice for the OSCE. In the post-interview survey (n=6), students rated the tool an average of 7.5 for usefulness, 7.5 for realism, and 9.5 for convenience on a 10-point Likert scale. Participants appreciated the ability to engage with the tool independently and at their own pace, simulating the structure of a real OSCE. All participants recommended integrating the tool into first-year OSCE preparation and expressed strong interest in expanding its use for second-year OSCE preparation. Conclusion and Future Directions: This pilot demonstrates strong student support for AI-based OSCE preparation. Full implementation is planned for Fall 2025 at IUSM–Bloomington, where we will compare OSCE outcomes between users and non-users.
Copyright (c) 2026 Chandler Lutz, Liam Hobson, David Rodgers http://creativecommons.org/licenses/by/4.0
The Role of Pre-Plus Disease in the Efficacy of Supplemental Oxygen for Stage 2 Retinopathy of Prematurity
Background/Objective: Retinopathy of prematurity (ROP) is a vasoproliferative retinal disorder primarily affecting premature infants and remains a leading cause of preventable childhood blindness. Recent evidence suggests that supplemental oxygen administered to maintain an oxygen saturation of 97-99% may help arrest disease progression from retinal ischemia and hypoxia. The influence of pre-plus disease on treatment response to oxygen supplementation, however, has not been well characterized. We sought to examine whether pre-plus status at oxygen therapy initiation impacts its effectiveness in preventing the need for laser photocoagulation or intravitreal bevacizumab (IVB) in infants with stage 2 ROP. Methods: A retrospective chart review was performed on infants diagnosed with stage 2 ROP at Riley Hospital for Children between 8/2020 and 9/2024. Infants were stratified based on vascular findings at the initiation of oxygen therapy as either “pre-plus” or “normal”. Demographic data and clinical comorbidities known to affect ROP were collected from medical records for both cohorts. The primary endpoint was the requirement for ROP intervention. Results: A total of 152 patients met inclusion criteria, of which 70 had pre-plus disease and 82 had normal vasculature at oxygen therapy initiation. Infants with pre-plus disease had significantly lower birthweights (p = 0.02) and gestational age at birth (p < 0.01), as well as a higher occurrence of sepsis (p = 0.01). The need for treatment was substantially higher in the pre-plus cohort (54%) compared to the normal cohort (22%, p < 0.01). Both cohorts were similar in the type of treatment received, the age of first treatment, and the number of laser spots. Conclusion: The presence of pre-plus disease when supplemental oxygen is initiated correlates with significantly higher rates of subsequent ROP treatment, indicating that oxygen therapy alone may be less effective in this population. Patient stratification based on pre-plus status should be considered when assessing supplemental oxygen use.
Copyright (c) 2026 Nathan Macha, Charline Boente, Kok Lim Kua, Kathryn Haider http://creativecommons.org/licenses/by/4.0
Inpatient Consultation for the Management of Infantile Hemangiomas
Background/Objective: Infantile Hemangiomas (IH) are the most common pediatric benign vascular tumors, affecting approximately 4-5% of infants. To our knowledge, there has not been a dedicated study looking at inpatient dermatology consultation for IH. While the majority of IH do not require treatment, high risk hemangioma may require additional workup and treatment. This study aims to characterize clinical and demographic features, identify associated comorbidities and risk factors, and describe the utilization of pediatric dermatology consult service at Riley Children's Hospital for management of IH. Methods: A REDCap database was used to record demographic and clinical characteristics, treatment details, and Hemangioma Severity Score on 36 patients from 12/19/2022 – 10/17/2024 and 1/20/2025 – 6/20/2025 who consulted dermatology. Excel and REDCap were both utilized for analysis. Results: The majority of consultations consisted of infants born at less than 37 weeks of gestational age (GA). Consultations were evenly split between NICU and general pediatric wards, however, the median GA at the time of consultation was 9.35 weeks for NICU patients and 7.75 weeks for pediatric ward patients. Preterm infants were more likely to present with superficial IH, particularly those with thicker subtype and stepped border. Stepped borders are associated with a higher risk of permanent disfigurement. Notably, 0.25% topical timolol was more frequently recommended over the standard 0.5% formulation recommended by current literature. Conclusion and Potential Impact: This study highlights the importance of dermatological input in the inpatient setting for the management of IH. Characterizing consult patterns provides a foundation for future inpatient IH consultation studies. Future directions may include evaluating off-label timolol use in the inpatient setting and analyzing delays in NICU referral to improve IH outcomes.
Copyright (c) 2026 Madeline Mahoney, Anita Haggstrom, Edita Newton, Jenna Streicher http://creativecommons.org/licenses/by/4.0
Investigating the Impact of NLRP3 inhibitor, Usnoflast, on Interstitial Cystitis/Bladder Pain Syndrome
Background and Hypothesis: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic pelvic pain condition that is highly prevalent in the US population (~5%), particularly in those 50 years of age or older and women. IC/BPS is characterized by symptoms of urinary frequency, dysuria, hematuria, and significant pain. Inflammation is a major contributor to the development and progression of IC/BPS. The NLRP3/caspase1 inflammasome pathway is a major contributor that drives IC/BPS pathophysiology. The purpose of this pre-clinical study was to evaluate the therapeutic effect of an NLRP3 inhibitor, Usnoflast (ZYIL1), in an IC/BPS mouse model. Methods: A vascular endothelial growth factor A (VEGFa) bladder instillation IC/BPS mouse model was used to assess the effect of Usnoflast. Male and female caspase-1 bioluminescence reporter mice were transurethrally instilled with VEGFa 3x once every other day for one week. They are then subjected to in vivo imaging, pain testing to evaluate spontaneous grimace behaviors, and evoked pain Von Frey testing. Their micturition behaviors were assessed via Void Spot Assay. Results: We found that Usnoflast treatment significantly reduced IC/BPS-associated caspase-1 inflammasome activation in vivo and ex vivo tissue of both the brain and bladder. Furthermore, we found Usnoflast significantly improved voiding dysfunction and Von Frey behaviors in female mice compared to males. Finally, we found minimal changes in male grimace pain scores. Conclusion: In conclusion, modulating NLRP3/Caspase 1 activation with Usnoflast significantly attenuates IC/BPS-associated inflammatory response. This reduction in inflammation correlates with a decrease in voiding frequency and pain responses in females, but not much in males. It's interesting to see how IC/BPS, a women-dominant disease, manifests in a mouse model. Potential Impact: Our preliminary study provides the first insights into Usnoflast's effectiveness for IC/BPS, and we aim to advance it to clinical trials as a potential novel therapy.
Copyright (c) 2026 Kyle McClure, Hillarie Arellano, Alexander Li, Michael Fletcher, Tyler Nguyen, Fletcher White http://creativecommons.org/licenses/by/4.0
The Indiana POST Form: Do You Know What You’re Signing?
Background: The Indiana Physician Orders for Scope of Treatment (POST) form is utilized as a baseline to develop Advanced Care Directives (ACDs) for many hoosiers. Designed for those with advanced/terminal disease to plan their end-of-life care, it is often the starting point when developing ACDs in general in Indiana. The form requires a physician signature to be recognized; this is no guarantee that all patients filling it out are provided with the same depth and clarity. With such heavy implications, it should be formatted to be digestible by the general populace. Methods: Patients in the waiting room of a primary care office were recruited through convenience sampling completed three iterations of the POST form in sequence with each having more information than the last. Participants rated how confident they were based on the information they were provided on a seven-point Likert scale to measure the impact of each change throughout the survey. Results: Measuring the impact of each additional change using paired t-tests, we found that compared to the base POST form, both increased participant confidence (p<0.001). Intriguingly, the added risks and considerations for the third time through the form were not significant, likely due to added variables and potential negatives making participants second guess. Addition of these adverse effects could lead to confusion and outline the role of the physician in the discussion. Conclusions and Potential Impact: While the form is streamlined for sake of time, adding only the plain-language summary was enough to significantly increase confidence. With further exploration, the Indiana POST form can be improved to allow for more patient autonomy during the decision-making process. By empowering patients to make end-of-life care decisions more in line with their goals, physicians can foster better relationships with patients and be certain that they are acting in their best interests.
Copyright (c) 2026 Kiernan McCormick, Valerie O’Loughlin, Kathleen Zoppi http://creativecommons.org/licenses/by/4.0
Types of Epidural Analgesia for Labor Pain
Background/Objective: Neuraxial analgesia administered in the epidural space is an effective strategy in controlling labor pain in expecting mothers. Epidural analgesia can also facilitate the transition to surgical anesthesia in patients requiring an emergent cesarean section. However, epidural placement does come with a small risk of accidental dural puncture, or "wet tap,” which can manifest with post-dural puncture headaches. Per recent literature, for patients receiving epidural analgesia for labor pain, the incidence of “wet taps” is 0.5-1.5%. Our study aimed to assess the incidence of “wet taps” in patients undergoing epidural analgesia for labor pain. Methods: We conducted a retrospective chart review of all patients receiving epidural analgesia to control labor pain at Riley Maternity Tower from 1/01/25 to 3/31/25. Our exposures included the different varieties of epidural analgesia used, such as epidural analgesia, combined spinalepidural (CSE) analgesia, and dural puncture epidural (DPE) analgesia. The primary outcome of interest was the occurrence of a “wet tap.” Results: Of the 338 patients who received epidural analgesia for labor pain, the most common type was epidural (88.46%), followed by DPE (8.88%) and CSE (2.66%). Among patients who received an epidural, 274 patients (81%) underwent vaginal delivery while 64 patients (19%) had a cesarean delivery. Overall, the incidence of a “wet tap” during epidural placement was 1%. Conclusions: In this single-site study, the incidence of “wet tap” in patients receiving epidural analgesia for labor pain was 1%, which is consistent with reports from prior studies. 19% of patients who received labor analgesia had cesarean deliveries.
Copyright (c) 2026 Francis Mendoza, Beth Ann Traylor, Erin Dammann, Yar Yeap http://creativecommons.org/licenses/by/4.0
Types of Anesthetics and IV Adjuvants Used for Cesarean Section
Background/Objective: For cesarean sections, urgency, maternal medical history, and patient preferences determine the form of anesthesia administration. Spinal anesthesia is the most common form of anesthesia administration due to its speed, patient safety, and overall reliability. Conversely, general anesthesia is a less common option due to its higher risk of difficult intubation, aspiration, and the mother being deprived of witnessing the baby’s birth. Moreover, intravenous (IV) adjuvant medications, such as ketamine and propofol, are occasionally utilized to further provide analgesic and anesthetic effects. The objective of our study was to describe the different types of anesthesia and IV adjuvants used for cesarean sections. Methods: We conducted a retrospective chart review of all patients undergoing cesarean sections at Riley Maternity Tower from 1/01/25 to 3/31/25. Patients with additional procedures performed were excluded. Our exposures were the different types of anesthesia used, including spinal, epidural, combined spinal-epidural (CSE), dural puncture epidural (DPE), and general anesthesia. Additionally, our outcomes of interest were the type of anesthesia selected, the incidence of intravenous adjuvants, and operative times. Results: Of 278 patients undergoing a cesarean section, 160 patients (58%) received spinal anesthesia, 69 patients (25%) received epidural anesthesia, and 19 patients (7%) received general anesthesia. Additional intravenous adjuvants were required in 55 (20%) patients. Moreover, dexmedetomidine was the most frequently administered adjuvant (22%), followed by fentanyl (11%). Patients who required IV adjuvants had a longer mean operative time (63 min) compared to those who did not receive IV adjuvants (51 min). Conclusions: In this single-site observational study, spinal anesthesia was the most common procedure done in patients undergoing a cesarean section (58%). General anesthesia was used in a smaller proportion of patients (7%). Approximately 1 in 5 patients (55/278) required an intravenous adjuvant. Those requiring IV adjuvants tended to have longer operative times.
Characterizing Predictors of Repeat Emergency Department Visits in Patients with a Cancer Diagnosis
Background: Cancer remains the second-leading cause of death in the United States. The emergency department (ED) plays a vital role in the initial diagnosis of cancer for many patients. There are several studies on cancer identification in the ED and less on ED utilization patterns among patients with cancer. This study characterized patterns and predictors of ED visits in patients with cancer. Methods: This retrospective study analyzed routine EPIC-based social determinants of health screenings for all ED visits involving patients with cancer across three urban hospitals in Northwest Indiana from January 2021-March 2025. Cancer diagnoses were identified using ICD-10. The dependent variable was number of ED visits. Data analysis comprised descriptive, bivariate (Mann-Whitney, Kruskal Wallis) and multivariate analyses (linear regression) using IBM SPSS v.31.0 (p < 0.05). Results: The sample comprised 1026 patients with cancer, with lymphoid/hematopoietic (20.0%), ill-defined/secondary (19.0%), and genitourinary (16.3%) cancers being most represented. Bivariate analysis identified statistically significant associations (p < 0.05) between number of ED visits and age, race, language, family income, and hospital. Multivariate analysis revealed more ED visits in patients identifying as Black/African American (p < 0.05, B = 0.694), Other race (p < 0.001, B = 2.223), and receiving care at Hospital B (p < 0.001, B = 0.841). Age (p < 0.001, B = -0.050), family income (p < 0.005, B = -0.104), and Spanish language (p < 0.05, B = -1.350) were associated with fewer ED visits. Conclusions: This study addresses the gap in identifying predictors of ED utilization among patients with cancer. Future efforts should validate these results in larger samples, focus on ED integration into the cancer care continuum, and support more vulnerable patient populations to minimize cancer disparities.
Copyright (c) 2026 Anastasia Metropulos, Joshua Mangum, Kyle Gospodarek, Jonathan Guerrero, Baraka Muvuka http://creativecommons.org/licenses/by/4.0
Comparison of the Sysmex UF-5000 urine flow cytometer to urine leukocyte esterase and urethral Gram stain in the detection of urethritis in men
Background: Urethritis (urethral inflammation) is a common condition encountered in primary care and sexually transmitted infection (STI) clinics. Urethritis diagnosis requires evidence of inflammation. The Centers for Disease Control (CDC) recommends testing for increased white blood cells (WBCs) by urethral Gram stain smear (GSS) or the presence of leukocyte esterase (LE) by urinalysis. However, the urethral swab procedure is invasive while the LE assay is insensitive. We compared the performance of the Sysmex UF-5000 urinary flow cytometer to LE, urethral GSS, and a clinical diagnosis of urethritis. Methods: Remnant urine specimens collected from males aged 18 and older who presented to the Bell Flower STI Clinic in Indianapolis with STI symptoms, for STI treatment, or screening were analyzed. WBC/µL urine was determined using the UF-5000 and LE was determined by urinalysis. Demographic and clinical metadata were abstracted from the electronic medical record. Welch t-tests were performed to assess statistical significance (p-values < 0.05). Results: Five-hundred fifty (550) specimens were included in this study. Participants’ median age was 32 (range 18-74), 46% were Black, 35% were White, and 79% were non-Hispanic. 64% identified as heterosexual and 26% as men who have sex with men. The UF-5000 mean WBC count was elevated in participants who had a positive LE (676 vs 27 WBCs/µL, p=0.0007), reported urethritis symptoms (162 vs 29 WBCs/µL, p=0.0024), had ≥ 5 WBCs per high-power field by GSS microscopy (507 vs 39 WBCs/µL, p=0.0032), and were diagnosed with urethritis (382 vs 27 WBCs/µL, p=0.0011). Conclusions and Implications: The Sysmex UF-5000 detected increased WBCs in men with confirmed urethritis and could be a rapid, non-invasive point-of care-test for urethritis. Future studies will define the assay performance (ROC curves) to identify optimal WBC cut-offs to diagnose urethritis and predict specific STIs, caused by N. gonorrhoeae or C. trachomatis.
Copyright (c) 2026 Ishaan Modi, Xiaoli Zhang, Evelyn Toh, David Nelson, Stephen Jordan http://creativecommons.org/licenses/by/4.0
Descriptive Study of Nutritional Deficiencies and Core Demographics of Pyoderma Gangrenosum Cases Presenting to Indiana University's Comprehensive Wound Center
Background/Objective: Pyoderma Gangrenosum (PG) is a rare, neutrophilic dermatosis characterized by rapidly progressing skin ulcers. PG has been associated with autoimmune inflammatory conditions. Nutritional deficiencies may impact disease progression and wound healing; however, there are no standardized nutritional assessments for PG. This study aims to characterize the clinical and biochemical profiles of patients with PG at Indiana University. Methods: A retrospective chart review was conducted using Cerner electronic medical records. Patients with an ICD 9/10 diagnosis of PG were included in the initial screening. Charts were reviewed to assess the accuracy of diagnosis. Collected data included demographics, clinical course, autoimmune comorbidities, and biochemical markers. Laboratory values were collected from the period of PG onset through resolution, with the date of diagnosis being prioritized. Data was entered into REDCap and analyzed descriptively in Excel. Results: This 148-patient cohort had a mean age of 49.2 years (SD = 19.41) and BMI of 32.5 kg/m2 (SD = 10.46). Most patients were White (82.19%), non-Hispanic (97.30%), and Female (64.86%). 56.08% of patients had autoimmune comorbidities. Nutritional assessments were performed in 56.76% of patients. Notably, 44.44% were vitamin D deficient, and 51.28% were iron deficient by their iron saturation. Conclusion/Potential Impact: Our cohort is one of the largest single-center studies in the United States. Our findings reveal that PG may occur in patients that are overweight and more likely to have vitamin D deficiency; these associations are nearly as frequent as autoimmune disease associations. Towards our secondary aim of describing associations, PG is frequently associated with autoimmune conditions and metabolic comorbidities, and our study helps narrow down the rate of occurrence. Despite increased recognition of these associations, gaps remain in the standardized evaluation of nutritional deficiencies in PG. Our findings underscore the need for future research to better define the role of nutritional factors in PG onset, progression, and healing.
Copyright (c) 2026 Yatziri Moreno, Sahand Rahnama-Moghadam http://creativecommons.org/licenses/by/4.0
Evaluating the Effectiveness of Fremanezumab on Open Femoral Osteotomy-Induced Pain and Inflammation
Background: People who suffer from fractures frequently have injury-associated pain. The current pain management options are opioids and nonsteroidal anti-inflammatory drugs (NSAIDs), however, these drugs present a challenging recovery process impairing skeletal repair. Recent research efforts found that the neuropeptide calcitonin gene-related peptide-ɑ (CGRP) plays a critical role in both bone repair and pain states post-trauma. CGRP is known to be important to vasodilation, neurogenic inflammation peripherally, mechanical and thermal hyperalgesia centrally, and inflammation-dependent bone repair. This neuropeptide has become a potential therapeutic target for bone fracture pain. Fremanezumab (Ajovy), a monoclonal antibody against CGRP, has been shown to reduce clinical pain states and recently received FDA approval for migraine prophylaxis. This study aims to evaluate the effect of Ajovy as an analgesic therapy following femur fracture. Methods: C57BL/6 female mice were subjected to open femoral osteotomy and then treated with either saline or Ajovy (30mg/kg, intraperitoneally) every day for 7 days following fracture. In vivo bioluminescence imaging (IVIS) was performed to assess caspase-1 mediated inflammation. Grimace Scoring was used to evaluate pain response at various time points before and after treatment. Results: Through IVIS, we found that mice subjected to femur fracture exhibit profound inflammatory response up to 3 weeks post-trauma and this response was attenuated with Ajovy treatment. Furthermore, preliminary behavioral data found a trend of decreased pain behaviors in the Ajovy-treated fractured mice compared to the saline control. Specifically, at 2 weeks postfracture there was a significant reduction in the pain score. Conclusion: The effect of modulating CGRP signaling in bone healing is yet to be determined. However, this preliminary study reveals promising results in reducing inflammation and painful behavior with Ajovy administered near the time of injury. Additional works aiming to increase the cohort number and assess bone healing are currently ongoing.
Copyright (c) 2026 Jackson Moss, Natalie Nguyen, Tyler Nguyen, Alexander Obukhov, Fletcher White http://creativecommons.org/licenses/by/4.0
Fracture Healing in a Late-Onset Alzheimer’s Disease (LOAD2) Mouse Model
Osteoporotic fractures are a major cause of morbidity in the aging population. Alzheimer’s Disease (AD) has been shown to increase fracture risk by ~2-fold (1). Mechanistic studies show that AD-associated neuroinflammation and the late-onset AD (LOAD2) risk alleles APOE4 and TREM2 R34H promote RANKL-mediated osteoclastogenesis, which, along with reduced activity, may lower bone mineral density (2, 3). We also remain uncertain whether fracture itself or the anesthesia required for surgery might modify the trajectory of AD pathology in mice. We hypothesized that APOE4/TREM2-driven neuroinflammation in LOAD2 mice impairs fracture healing. To test this, we used a LOAD2 mouse model carrying humanized APOE4 and TREM2 R34H, which recapitulates AD-like neuroinflammation without extensive amyloid or tau deposition (4). Mice were assigned to four groups: C57BL/6J unfractured, C57BL/6J fractured, LOAD2 unfractured, and LOAD2 fractured. C57BL/6J is henceforth referred to as B6. Femoral fractures were created and stabilized using a surgical osteotomy technique at 1 year of age. Animals that were not in the fracture group were shaved, given Ethica, and received equal isoflurane exposure. Grip strength, Y-maze (distance and % spontaneous alternation), and light/dark testing were performed at baseline, 10 weeks, and 20 weeks post-fracture. Healing was monitored by serial X-rays (biweekly from day 7 to week 5, then weekly from weeks 6-12, and every other week thereafter until sacrifice) and quantified at 40 weeks post-fracture using micro-computed tomography (μCT). Male LOAD2 control femurs showed a smaller cross-sectional area (B.Ar) and a lower bonevolume-fraction (BV/TV) relative to B6. At 40 weeks post-fracture, female LOAD2 fractured femurs displayed a higher BV/TV with unchanged B.Ar. Female LOAD2 control femurs showed greater cortical thickness. Behaviorally, 20-wk post-fracture testing demonstrated no genotype-specific deficits; the only significant difference was a modest reduction in Y-maze distance in fractured B6 males compared to B6 control males. Spontaneous alternation, darkphase locomotor time, and grip strength were unaffected across groups. These findings suggest that LOAD2 produces subtle sex-specific increases in cortical bone density without compromising functional recovery after femoral fracture in mice.
Copyright (c) 2026 Nihal Nagesh, Amy Creecy, Sonali Karnik, Rachel Blosser, Kuldeep Yadav, Sarah Mostardo, Timothy Meyer, Kathyrn Fischer, Adrian Oblak, Melissa Kacena http://creativecommons.org/licenses/by/4.0
Predictive Factors for Hypertensive Disorders of Pregnancy in a Pregnancy Cohort at Risk for Gestational Diabetes
Background/Objective: Hypertensive disorders of pregnancy (HDP) are a leading cause of both maternal and neonatal morbidity and mortality worldwide. Predicting which pregnant patients will develop HDP, however, remains a challenge, as existing models often overlook the value of incorporating both behavioral and genetic factors. The objective of this study was to identify predictive factors for HDP, including behavioral, psychosocial, and genetic characteristics not typically included in other models. Methods: We conducted a secondary analysis of the Hoosier Mom Cohort, a prospective observational study of pregnant individuals preferentially recruited to assess predictors for gestational diabetes. Participants completed detailed surveys on behavioral and psychosocial factors, as well as activity and sleep. Biospecimens including maternal blood, urine, and feces, placental biopsies, infant cord blood, and buccal swabs were collected. Genotyping was performed to calculate ancestry-adjusted polygenic risk scores (PRS) for preeclampsia. After identifying variables associated with HDP, a logistic regression was used to assess for independent HDP associations. Models were evaluated with and without PRS, to evaluate the added value of genetic risk in prediction. Results: Among 399 participants with complete outcome data, 121 developed HDP (30.3%). Significant predictors included higher BMI, non-White race, nulliparity, and elevated snoring scores. Preeclampsia PRS tertiles showed no significant association with HDP and did not improve the performance of the regression model. Conclusion and Potential Impact: In addition to high BMI, nulliparity, and self-reported race, snoring scores were independently associated with developing HDP. However, adding PRS did not improve the model. Multidimensional risk factor evaluation and clinical screening are needed to improve early intervention and care for patients with HDP. Key words: polygenic risk score, pregnancy, hypertensive disorders of pregnancy, preeclampsia
Copyright (c) 2026 Isabel Ortiz, Yuedi Yang, Aric Kotarski, Maha Aamir, Haley Schmidt, Rafael Guerrero, David Haas http://creativecommons.org/licenses/by/4.0
The Role of P-Tau in the Driving of Neurovascular Uncoupling
Background and Hypothesis: Alzheimer’s disease (AD) presently affects more than 50 million people worldwide, with that number projected to rise to more than 150 million by 2050 according to the World Health Organization (WHO). The neuropathologic underpinnings of AD are defined by the accumulation of extracellular amyloid-β (Aβ) plaques and intracellular neurofibrillary tangles (NFT) composed of hyperphosphorylated tau protein (p-tau). Recent evidence suggests p-tau specifically acts as a catalyst for global cognitive degeneration, implicating the protein in neuronal dysfunction at the synaptic level. A robust correlation has been demonstrated between both the reprogramming of cellular metabolism in favor of glycolytic upregulation as well as mitochondrial instability enhancing the oxidative stress response, thus driving the accumulation of cerebral p-tau. These determinants have been empirically linked to the precursors of endovascular debasement and subsequent neurovascular uncoupling in Aβ mouse models. Prior studies support the position of microglial activation as the precipitating source of the comprehensive FDG-PET signal, with diminished glucose uptake corresponding to a more pronounced neurovascular uncoupling. However, the comprehensive implications of increased p-tau in cerebral metabolic dysfunction (CMET), cerebral blood flow (CBF), and neurovascular coupling (NVC) are not presently well defined. In order to further elucidate the relationship, we hypothesize that aggregates of p-tau will drive progressive neurovascular uncoupling, disrupting CMET and CBF in the PS19 mouse model of AD. Experimental Design: To establish clinical significance, we obtained 18F-FDG and 64Cu-PTSM PET/CT images and co-registered these to stereotactic brain coordinates to assess neurometabolic and vascular uncoupling. To assess the co-localization of p-tau on specific cell types involved in metabolic and vascular dysregulation, cryoprotected tissues were stained for co-localization of p-tau in neurons (NeuN), astrocytes (GFAP), microglia (IBA1), vascular endothelia (CD3), and mono-carboxylate transporters (MCT2 and MCT4). Immunopathological assays were conducted to assess cellular communication, neuroinflammation, and oxidative stress. Results: When observing the effects of aging by genotype, B6 control mice exhibited a randomized and dispersed distribution, consistent with the expected physiological variability associated with the normative aging process, while PS19 mice exhibited neuro-metabolic failure, with significant regions including the auditory cortex (dorsal/ventral/medial), caudate putamen (dorsal striatum), cerebellum, dorsal intermediate entorhinal cortex, entorhinal cortex, fornix, frontal association cortex, medial orbital cortex, perirhinal cortex, secondary motor cortex, temporal association cortex, thalamus, and ventral orbital cortex. Conclusion: These findings demonstrate a temporally and regionally progressive pattern of p-tau–driven neurovascular uncoupling, originating in the entorhinal cortex and advancing to higher-order cortical regions. Dysfunction in areas governing executive function, emotional regulation, spatial processing, and memory highlights the behavioral consequences of tau pathology and supports the potential for early diagnostic imaging and therapeutic targeting in AD.
Copyright (c) 2026 Lilly O’Shea, Alyssa Collins, Kierra Eldridge, Rose Diaz, Margaret Bright, Scott Persohn, Paul Territo http://creativecommons.org/licenses/by/4.0
Management and Outcomes of Intra-articular Ballistic Injuries of the Hand
Background and Objective: Intra-articular ballistic injuries of the hand present unique challenges not commonly encountered with other gunshot wounds (GSWs). Due to their rarity, data on demographics, operative trends, and joint preservation outcomes are limited. This study examines management strategies with an emphasis on factors associated with joint salvage. Methods: Patients with hand GSWs treated from 2021–2025 at a metropolitan academic health system—including three Level 1 trauma centers—were identified using CPT and ICD-10 codes. Intra-articular involvement patients were included. Demographics, injury mechanism, procedures, and complications were reviewed. Unpaired t-tests compared patients with salvaged versus unsalvageable joints. Results: Of 83 patients with hand GSWs, 48 were intra-articular. Most were male (89.6%) with a mean age of 30.4 years. Black was the most common racial group (50%) and most patients (75%) had government insurance. Common comorbidities included tobacco use (43.8%) and obesity (16.7%). Assault was the most frequent mechanism (58.3%). Injuries involved the left hand in 73% of cases; the metacarpophalangeal (MCP) joint in 80%; and the third ray in 41.7%. Open reduction and internal fixation (ORIF) was the most common operation (70.8%). Many patients underwent multiple procedures. Frequent complications included ER/hospital returns (27.1%) and infection (6.3%). Eight cases (16.7%) were deemed unsalvageable, resulting in 5 amputations, 2 arthrodeses, and 1 arthroplasty. These patients tended toward being younger (p = 0.2402), having greater bone (p = 0.5195) and soft tissue loss (p = 0.1425), longer hospital stays (p = 0.8459), and more frequent government insurance (p = 0.2654). Conclusions: Intra-articular hand GSWs frequently involve the MCPJ and third ray. Unsalvageable cases often involve younger patients with greater tissue damage. These findings may guide physician-patient discussions on prognosis and treatment planning. Larger studies are needed to identify predictors of joint preservation.
Copyright (c) 2026 C. Max Otterbacher, Melissa Cullom, Joshua Adkinson http://creativecommons.org/licenses/by/4.0
Complications Following Aseptic Knee Revision Based on Tourniquet Use
Background: Tourniquet use in revision TKA (rTKA) is used to enhance visualization and improve cement penetration. However, concerns exist about ischemic muscle injury, increased postoperative pain, wound complications, and venous thromboembolism (VTE). This study compared early clinical outcomes in aseptic rTKA performed with no/minimal tourniquet use versus standard tourniquet use. Methods: In this retrospective matched cohort study, 105 aseptic rTKAs with no/minimal tourniquet use were matched to 105 rTKAs with standard tourniquet use (P≥.210). Average tourniquet times were 12.9±15.8 and 80.1±23.6 minutes, respectively (P <.001). Postoperative complications, outcomes, and pain were compared between groups. Statistical analysis included Chi-square tests, t-tests, and Pearson correlation (α≤0.05). Estimated blood loss (EBL) was calculated using the Hahn-Klimroth et al. formula. Results: Mean EBL (no/minimal 5.9±1.2 vs. standard 5.8±1.1 g/dL, P=.819) and blood products received (no/minimal 2% vs. standard 4.8%, P=.445) showed no significant differences between groups. There were no major inpatient events or significant differences in 90-day VTE, wound complications, or reoperations. Inpatient opioid requests were higher in the standard tourniquet group (no/minimal 95.2% vs. standard 100%, P=.059). Opioid use in the first 24 hours was higher in the standard group (26.2±12.8 vs. 21.9±13.9 MME, P=.023) despite similar pain scores (standard 4.1±1.7 vs. no/minimal 4.3±2.2, P=.492). After 24 hours, opioid use (standard 4.2±10.9 vs. no/minimal 9.7±23.6 MME, P=.035) and pain (standard 0.9±1.9 vs. no/minimal 1.7±2.7, P=.016) were significantly lower in the standard group. Final pain scores were similar (standard 4.1±2.3 vs. no/minimal 3.8±2.8, P=.362). Some null results may be due to low statistical power. Conclusion: In rTKA, the use of tourniquets does not seem to affect blood loss, early complications, or reoperation rates. Differences in postoperative pain and opioid use indicate an association worthy of further exploration. Tourniquet decisions based on individual patient and surgical factors may remain the best approach in rTKA.
Copyright (c) 2026 Will Pater, Leonard Buller, Mary Ziemba-Davis, Kevin Sonn http://creativecommons.org/licenses/by/4.0
Clinical Correlates of Opioid Use Disorder Symptom Scores: Retrospective Analysis of Patient-Reported Treatment History
Background: Opioid Use Disorder (OUD) remains a critical public health issue, particularly in pain management settings where long-term opioid therapy is common. While identifying patients at risk for developing OUD is essential for safe treatment, validated screening tools remain underutilized in clinical practice. This study aimed to validate an OUD symptom checklist and investigate whether distinct opioid prescribing patterns correlate with OUD symptom severity. Methods: We conducted a retrospective, cross-sectional analysis using de-identified data from patients seen in the Indiana University Health Pain Navigation Service during 2023, who completed an 11-point OUD Symptom Checklist measuring symptom severity through REDCap. Participants were categorized into opioid exposure groups (low: 1-2 opioids; medium: 3-4 opioids; high: 5+ opioids). Exploratory analyses investigated opioid exposure grouped by pharmacological mechanism (full agonists vs. partial/mixed agonists). One-Way Analysis of Variance (ANOVA) was performed, with analyses stratified by current opioid prescription status to account for variations in OUD symptom score computation. Results: Our findings revealed no statistically significant overall differences in OUD symptom checklist scores across the defined opioid exposure groups in either the "currently prescribed for pain" or "not currently prescribed for pain" subgroups. Similar results were found for mechanism-based grouping. For participants currently prescribed opioids for pain, median OUD scores were 0 (Low, N=42), 0 (Medium, N=51), and 1 (High, N=63). For those not currently prescribed opioids for pain, median OUD scores were 0 across all groups (Low, N=41; Medium, N=48; High, N=49). Mean OUD scores were consistently low across all groups. Conclusions: Neither the number of distinct prescribed opioids nor broad pharmacological mechanism groupings served as primary predictors of OUD symptom severity. These findings suggest that simple prescribing pattern metrics may be insufficient for OUD risk stratification and highlight the need to explore additional patient characteristics and factors.
Copyright (c) 2026 Saisantosh Ponna, Michael Bushey http://creativecommons.org/licenses/by/4.0
Disparities in Hospitalization Outcomes Among Pediatric Cancer Patients: A Nationwide Healthcare Cost Utilization Project (HCUP) Analysis
Introduction: Pediatric cancer poses major health and economic challenges, with Medicaidinsured and low-income children facing disproportionate hospitalization burdens. One study found that socioeconomic status explained 44% of excess mortality among Black and 31% among Hispanic children with acute lymphoblastic leukemia. Yet, inpatient care patterns remain underexplored. This study examines socio-demographic and institutional predictors of hospitalization outcomes among pediatric cancer patients. Methods: This retrospective cross-sectional study analyzed the 2019 and 2022 HCUP Kids’ Inpatient Database. Pediatric cancer admissions were identified using NEO001–NEO074 codes. Dependent variables included length of stay (LOS), total charges, debilitation, and mortality risk scores. Predictors included insurance, Zip income quartile, race, sex, admission year, hospital and county characteristics. Multivariate analyses using linear and ordinal logistic regressions were conducted in SPSS v31.0 on significant factors in bivariate analyses (p< 0.05). This study received Indiana University IRB exemption (#27940) on 7/2/2025. Results: The sample comprised 46,322 admissions. Longer hospital stays were significantly (p< 0.05) associated with Black race (B=0.318), uninsured (B=0.625), publicly insured (B=0.865), lower-income ZIP codes (B=1.044, 0.633, and 0.350 for quartiles 1,2, and 3 respectively), and admission to government hospitals (B=1.135). Total charges were significantly higher with Hispanic, Asian/Pacific Islander, and other racial groups (B=31,746.43, 30,302.35, and 30,016.68 respectively) uninsured status (B=78,176.82), and 2022 admission year (B=13,687.92), but significantly lower with lower income (B=-26,126.61, -18,725.60, and - 20,683.30 for quartiles 1,2, and 3 respectively) and rural, urban non-teaching or government hospitals (B=-57,581.43, -72,394.08, and -42.574.95 respectively). Higher debilitation was associated with (p< 0.05) public or no insurance (OR=1.146 and 1.207 respectively), and lower debilitation with females (OR=0.773) and rural and urban non-teaching hospitals (OR=0.611 and 0.520 respectively). Mortality risk increased with Black race (OR=1.010) and decreased with Hispanic ethnicity (OR=0.923) and urban non-teaching hospital admission (OR=0.811). LOS and total charges were positively correlated. ZIP income and debilitation were negatively correlated. Conclusion: Public insurance, lower income, and certain racial groups were significant predictors of longer stays, greater debilitation, and disparities in total charges. Government and non-teaching hospitals had lower costs. These patterns reflect structural inequities, warranting policy reforms and equitable resource allocation.
Copyright (c) 2026 Tyler Porter, Baraka Muvuka, Joshua Mangum, Jonathan Guerrero http://creativecommons.org/licenses/by/4.0
Testing Repeatability of DTI-ALPS in Assessing the Brain Glymphatic System of Neonates with Prenatal Opioid Exposure
Background: Prenatal opioid exposure (POE) is a public health concern with risk for neonatal opioid withdrawal syndrome and poor neurodevelopmental outcomes. The glymphatic system is a waste clearance pathway in the brain, and its dysfunction may contribute to adverse outcomes in infants with POE. Diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) has recently been proposed as a method to assess the glymphatic system. This project aims to test the reproducibility of DTI-ALPS in neonates and assess correlations of DTI-ALPS with POE. Methods: This prospective, HIPAA compliant, IRB-approved study included neonates with POE and control neonates not exposed to prenatal opioids. MRI including DTI was performed at< 48 weeks postmenstrual age. Blinded repeat manual ROIs were drawn along the corticospinal projection fibers to measure ALPS values on the DTI-FA maps in subject space (SS) and template space (TS) using DSI Studio software. Intraclass correlation coefficients (ICC) were used to assess repeatability and reproducibility. Linear regression assessed the association of POE and ALPS index with demographic and exposure related covariates. Results: There were 36 subjects – 19 with POE and 17 unexposed controls. There was good to excellent ICC (0.74-0.95) of ALPS indices between the two trials in SS and TS. However, comparing ALPS indices between SS and TS showed poor ICC (0.14-0.37). With linear regression, there was no significant association between POE and brain ALPS indices obtained through SS or TS measurements. Conclusions: Despite good intra-technique repeatability of ALPS measurements in subject space or template space in the neonatal brain, there was high variability with ALPS indices measured between the two techniques. Our results suggest a greater need for standardization of methods for calculating the ALPS index in neonates. Greater reproducibility in metrics will be needed before reliably assessing the clinical correlations of glymphatic system function measured by DTI-ALPS.
Copyright (c) 2026 Anna Puderbaugh, Ramana Vishnubhotla, David Haas, Senthilkumar Sadhasivam, Rupa Radhakrishnan http://creativecommons.org/licenses/by/4.0
Generation of Affinity Reagents for the Study of Photoreceptor Neurons
Background: Photoreceptor cells are highly polarized neurons with distinct compartments essential for visual function. Their outer segments contain specialized ciliary membranes, called disks, that detect photons. Actin contributes to disk morphogenesis, while rhodopsin, a transmembrane photopigment, is a major component of disks involved in phototransduction. Conventional fluorescence microscopy (200-300 nm resolution) is suboptimal for visualizing these subcellular structures (5–100 nm). The goals of this project are to enhance fluorescence microscopy resolution and refine protein labeling strategies to visualize actin and rhodopsin dynamics during disk formation. By generating recombinant affinity reagents (nanobodies and class-switched IgG), we aim to probe actin filaments in photoreceptor outer segments. Methods: The DNA sequences encoding actin nanobody and its derivative were PCR-amplified and incorporated into the PET22B vector. Genetically modified nanobodies were expressed in Bl21 E. Coli for high-yield production, efficient purification, and detection via fluorescent tags or secondary IgG antibodies. In addition, a recombinant monoclonal antibody against rhodopsin was produced by introducing two expression vectors, coding 1D4 IgG heavy and light chains, to ExpiCHO cells. Western blotting was employed to measure the quality and quantity of these nanobodies and antibodies. These affinity reagents were used for immunofluorescence microscopy of mouse retinal sections with the Nikon AX R NSPARC super resolution confocal microscope. Results: We successfully produced a recombinant rabbit monoclonal antibody against rhodopsin (1D4 mAb) in ExpiCHO cells. Based on immunoblotting analysis, we estimate approximately 1 mg of antibody is present in 35 ml of culture. The antibody labeled mouse rod outer segment structures, indicating it is specific to rhodopsin. We are currently attempting to express actin nanobodies in E. coli cells for fluorescence imaging. Expected Impact: The successful staining of actin and rhodopsin in the outer segment of photoreceptors help reveal their spatial relationship during disk morphogenesis, highlighting a potential interplay between cytoskeletal elements and membrane proteins. This discovery offers new insight into how photoreceptor architecture is built and maintained, offering a foundation for understanding mechanisms linked to photoreceptor dysfunction and degeneration in diseases including retinitis pigmentosa and other inherited retinal dystrophies.
Copyright (c) 2026 Amee Punater, Kaitlyn Shook, Sanae Imanishi, Yoshikazu Imanishi http://creativecommons.org/licenses/by/4.0
Association Between Combined Nicotine and Opioid Dependence and Osteoporosis in Women: A Real-World Data Analysis
Background: Osteoporosis is the most common bone disease in the United States, with women exhibiting a higher prevalence compared to men. Chronic cigarette smoking and opioid use are each recognized as independent risk factors for osteoporosis. However, it is unclear whether these substances contribute an additive effect on the development of osteoporosis. Therefore, we hypothesize that women with a combined history of nicotine and opioid dependence have an increased odds of developing osteoporosis compared to those with nicotine dependence alone. Design and Methods: We conducted a retrospective case-control study using a psychiatric dataset from the IU School of Medicine-Evansville RWEdataLab (CRC/Sidus Insights), a U.S. electronic health record (EHR) database. Diagnoses were identified using ICD-10 codes for: nicotine dependence (cigarette-related), opioid dependence, and osteoporosis. Female patients with an osteoporosis diagnosis following documentation of both dependencies were included. Odds Ratios (ORs) were calculated to compare the likelihood of developing osteoporosis in patients with both dependencies compared to patients with nicotine dependence alone. Results: Nicotine dependence was more strongly associated with osteoporosis than opioid dependence alone (OR: 1.88; 95% CI: 1.32-2.68; N=153,539). Women with both nicotine and opioid dependencies had significantly higher odds of osteoporosis compared to those with nicotine dependence alone (OR: 5.99; 95% CI: 3.46-10.37; N=79,247). The order in which the dependencies developed did not significantly differ in association with odds of developing osteoporosis. Conclusion and Impacts: These findings suggests that women with a chronic history of nicotine use are more likely to develop osteoporosis than those with a history of opioid use. Furthermore, women with a cooccurring nicotine and opioid dependence may be more strongly associated with osteoporosis than nicotine dependence alone. Stratification by age was limited by sample size and may be a confounding variable. Future studies should adjust for age and explore these associations.
Copyright (c) 2026 Tommy Quach, Zachary Bowman, Nolan Cook, Kevin Jordan, Daniel Roque, Michael Roscoe http://creativecommons.org/licenses/by/4.0
Exploring Alzheimer’s Disease Progression Through a Graph-based Retrieval System
Background and Objective: The cognitive decline spectrum includes cognitively normal (CN), mild cognitive impairment (MCI), and dementia stages. Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder that predominantly causes dementia. Thus, identifying patients likely to progress to AD is clinically pertinent. The Alzheimer Disease Neuroimaging Initiative (ADNI) dataset features chronological imaging, biomarker levels, and cognitive scores for over 2,500 individuals across the cognitive decline spectrum. A current challenge in AD research is comprehensively utilizing the volume and variety of information in databases like ADNI. Knowledge graphs (KG) simplify information using points (nodes) and connections (edges). Retrieval systems extract information from a source. In this work, we developed a graph-based retrieval system that utilized ADNI data to classify patients progressing from CN to MCI or AD. Methods: The ADNI KG, containing 2,513 patient nodes, 15,497 visit nodes, and 1,135,912 measurement nodes, was processed using NetworkX. Our retrieval system was coded in python and performed Amyloid-Tau-Neurodegeneration (ATN) scoring for each patient in the KG using conventional criteria. Patient progression was determined by comparing diagnoses from the first 25% of visits with the last 25% of visits. The system’s ability to make predictions using cognitive, biomarker, and imaging data was validated on 200 randomly selected patients from the KG. Results: The system processed a KG with 1,153,922 nodes and 1,164,395 edges. For N=200 validation, the system removed 6 outliers, found 19 progressors (10 CN→MCI, 9 CN→AD), and achieved 76.7% accuracy when provided adequate biomarker data. Conclusion and Potential Impact: We present a graph-based retrieval system that can analyze large quantities of patient data, identify potential AD database errors, output patient-specific insights, and predict cognitive decline progression with reasonable accuracy. Future work will integrate this system with graph neural networks (GNN) and large language models (LLMs) to further improve its accuracy and clinical utility.
Copyright (c) 2026 Aryan Rai, Eun Hye Lee, Taeho Jo http://creativecommons.org/licenses/by/4.0
Exploring the Outlook on Genetic Testing Among Black Donors of Healthy Breast Tissue
Background: While direct-to-consumer DNA testing has increased public awareness of genetic testing, historical injustices and persistent barriers—such as cost and limited access to education—continue to influence trust and participation, particularly in marginalized communities. The Komen Tissue Bank (KTB), originally created to collect healthy breast tissue for research, has evolved into a longitudinal study with annual follow-ups. In collaboration with the National Cancer Institute, the KTB now includes genetic testing and is re-consenting participants to assess interest in receiving potentially actionable genetic results. This health communication study applied the Integrated Behavioral Model (IBM) to explore how norms, attitudes, and personal agency influence Black women’s understanding of and engagement with genetic testing following their participation in the KTB. Methods: Thirty-three women who self-identified as Black and previously donated healthy breast tissue to the KTB were recruited via email to complete an online survey administered through Qualtrics. An initial 75 emails were sent, followed by up to 50 additional emails to reach a minimum target sample of 30. Results: Black women expressed clear evidence of the constructs of the legacy norm (altruism, personal sacrifice, care for others, and awareness of the future) when discussing their outlook towards genetic testing and spoke of overcoming mistrust to benefit their families and communities in the future. They also described positive instrumental attitude and evidence of perceived control as drivers of their desire to be educated on their health and empowered to make informed decisions on their healthcare. Conclusions: Findings highlight the influence of culturally rooted values in motivating engagement with genetic testing among Black women. This study is part of a longitudinal project where next steps include analyzing data from Latina and Asian participants to identify their norms and attitudes toward genetic testing and explore cross-group similarities and differences among these minoritized population members.
Copyright (c) 2026 Julia Roehm, Arnima Singh, Katherine Ridley-Merriweather http://creativecommons.org/licenses/by/4.0
Predictors of Residual Obstructive Sleep Apnea in Children following Adenotonsillectomy
Background: Obstructive sleep apnea (OSA) is the most frequently diagnosed pediatric sleep disorder, affecting 3-6% of the 74 million children in the US. Children with moderate to severe sleep apnea, defined by an Apnea-Hypopnea Index (AHI) score of 5.1 or higher, are candidates for adenotonsillectomy. Follow-up sleep studies are frequently ordered following the adenotonsillectomy in these patients due to the absence of a standardized protocol that elucidates when a follow-up sleep study is needed in children with OSA. This retrospective cohort study will investigate predictors of residual OSA in children following adenotonsillectomy. Methods: In this single-center retrospective study, data was collected by reviewing the medical records and PSG REDCap database from 2021-2024. Patients aged 2-18 with two sleep studies, one before and one after adenotonsillectomy, and a baseline AHI of 5.1 or higher were included. Variables related to the severity of OSA such as body mass index (BMI), neck circumference, hypoxic burden, AHI, rapid eye movement (REM) AHI, and Epworth Sleepiness Scale (ESS) were evaluated. Results: 370 patients met the criteria for the study, including 206 males and 164 females ranging in age from 2-17 with a median age of 6. Patient BMIs pre-adenotonsillectomy ranged from 11-62.4 with a median of 18.6. Pre-adenotonsillectomy, 50 patients had moderate OSA, and 320 patients had severe OSA with a median AHI of 17.55. Post-adenotonsillectomy, 189 patients had mild OSA, 80 patients had moderate OSA, and 73 patients had severe OSA with a median AHI of 3.8. Conclusion: Evaluation of variables related to the severity of OSA may be used to help predict the necessity of follow-up sleep studies secondary to adenotonsillectomy. A metric that determines if a follow-up sleep study is warranted in children with OSA who undergo adenotonsillectomy could reduce unnecessary sleep studies and improve accessibility of sleep studies for other patients.
Copyright (c) 2026 James Rooney, Hasnaa Jalou, Anuja Bandyopadhyay, Harish Rao http://creativecommons.org/licenses/by/4.0
Association Between Non-alcoholic Fatty Liver Disease (NAFLD) and Atherosclerotic Cardiovascular Disease (ASCVD)-Associated Myocardial Infarction and Ischemic Stroke Using Real World Data
Background/Objectives: ASCVD-related conditions are the leading cause of death in individuals with NAFLD/nonalcoholic steatohepatitis (NASH). Despite this, the current 10-year ASCVD risk assessment tools do not consider a patient’s NAFLD/NASH history. The aim of this study is to examine the association between NAFLD/NASH and ASCVD-associated myocardial infarction and ischemic stroke, and to reinforce existing evidence showing that NAFLD/NASH patients are at greater risk for ASCVD-associated cardiac events. Methods: We used de-identified patient data from the IU School of Medicine–Evansville RWEdataLab (CRC/Sidus Insights) National Real-World Cardiology database. Patients with diagnoses of NAFLD or NASH who later developed ischemic stroke (IS) or myocardial infarction (MI) were identified using ICD-9&10 codes. Odds ratios were calculated to estimate the likelihood of MI/IS in patients with NAFLD/NASH. Results: Of 3,396,429 patients in the database we identified 674 patients with NAFLD/NASH and MI/IS. In 424 patients, the odds of MI/IS after NAFLD/NASH diagnosis were significantly higher (OR 1.648; 95% CI: 1.489–1.823) compared to patients without NAFLD/NASH, with females at significantly greater odds (OR 1.983; 95% CI: 1.730–2.273) than males (OR 1.366; 95% CI: 1.176−1.587). Patients with type 2 diabetes mellitus (T2DM) and NAFLD/NASH had increased odds of subsequent MI/IS (OR 2.328; 95% CI: 2.015-2.689) compared to those without NAFLD/NASH. Additionally, T2DM females had significantly greater odds of MI/IS (OR 2.861; 95% CI: 2.358-3.470) than T2DM males (OR 1.873; 95% CI: 1.508-2.327) following NAFLD/NASH diagnosis. Conclusions/Impact: Our results support an association between NAFLD/NASH and ASCVD-related MI/IS suggesting NAFLD/NASH may be an important early marker of cardiovascular risk. One limitation of this research includes 4-year binning of patient age. Furthermore, NAFLD/NASH is progressive, and diagnosis underrepresents true incidence in the population analyzed. Nonetheless, these results may support revising current ASCVD risk calculators to include NAFLD status, improving risk stratification and encouraging earlier preventive interventions.
Copyright (c) 2026 Jonathan Rusche, Uday Lomada, Steven Wu, Gattadahalli Seetharam http://creativecommons.org/licenses/by/4.0
Predicting Deep Vein Thrombosis in Glioblastoma: A Competing Risk Regression Analysis
Background: Glioblastoma multiforme (GBM) patients face a high risk of developing venous thromboembolism (VTE), such as deep vein thrombosis (DVT). VTE is linked to worse survival. Typical DVT treatment is anti-coagulation but 25% of GBM patients suffer major intercranial bleeding within 1 year. This study addresses a research gap by assessing both genetic and clinical variables to predict DVT development in GBM patients. Objective: Identify DVT predictors in GBM using clinical and next-generation sequencing (NGS) data Methods: This retrospective cohort study analyzed clinical/NGS data from GBM patients at University of Pittsburgh Medical Center from 2008-2020. NGS data included 32 genes. To account for the competing risk of death, common in GBM patients, Fine-Gray CRR (Competing Risk Regression) models were used. An unadjusted cumulative incidence function (CIF) curve showed lifetime DVT risk. Univariate, multivariate, and backwards stepwise selection CRR analyses were performed to identify significant DVT predictors. Results: Of 578 patients with NGS data, 87 developed DVT, 367 died, and 124 were censored (lack of follow-up). 1-year cumulative incidence of DVT was 14% with median survival of 10 months. Avastin (bevacizumab) use, increased BMI, and a TP53 mutation were significant predictors of increased DVT risk (p1) in the final stepwise selection model. In a 3- predictor model, Avastin and BMI remained significant, with a 2.48- and 1.03-fold increased DVT risk, respectively. Adjusted CIF curves for Avastin and BMI showed a 5.6% and 2.7% increased DVT risk 1-year post-surgery, respectively. Although TP53 had a p-value of 0.053, its significance in the broader stepwise model indicates predictive power among other variables. Impact: Avastin use, increased BMI, and a TP53 mutation predict DVT risk in GBM patients, supporting a clinical-genetic risk tool for DVT prediction. This combined model can guide clinical trials to include DVT treatment for high-risk GBM patients post-surgery, improving survival.
Copyright (c) 2026 Tushar Sardesai, Matthew Pease http://creativecommons.org/licenses/by/4.0
Applying the Integrated Behavioral Model to Better Understand Asian Women’s Decisions to Participate in a Unique Clinical Trial
Background: Breast cancer (BC) has the highest cancer incidence among U.S. women. Although Asian women have lower BC rates than non-Hispanic white and Black women, their incidence has increased by 2.6% annually over the past decade. Cultural and language barriers often limit screening and healthcare access, contributing to disparities. Despite this rising trend, Asian women remain underrepresented in clinical trials and biobanking initiatives. The Komen Tissue Bank (KTB) is a clinical trial and biorepository that provides researchers with healthy breast tissue to advance BC research. This health communication study applies the Integrated Behavior Model to explore the motivations of Asian women who donated healthy breast tissue to the KTB. Methods: Participants (N=20) who self-identified as Asian and had previously donated healthy breast tissue to the KTB were recruited through an email requesting their voluntary participation in an interview conducted over Zoom or Microsoft Teams. Fifty emails were sent weekly until the predetermined goal of a minimum of 20 participants was reached. Results: In this study, participants were highly motivated by a desire to address underrepresentation of Asian women in research and contribute meaningfully to scientific advancement, reflecting positive instrumental attitudes. Many expressed altruistic motivations and wanted to help future generations, demonstrating a strong legacy norm. Having scientific backgrounds, familial support, and lack of external barriers (like cost or transportation) enhanced participants’ perceived control. Participants also felt empowered by contributing to research, which displayed high self-efficacy. Conclusion and Future Work: This study highlights the legacy norm, desire to increase representation, and support for research that drives Asian women to participate in healthy breast tissue donation through the KTB. These findings can inform targeted strategies to increase Asian women’s participation in research. Future work can test these approaches and explore motivational differences across Asian subgroups to guide recruitment efforts.
Copyright (c) 2026 Arnima Singh, Julia Roehm, Katherine Ridley-Merriweather http://creativecommons.org/licenses/by/4.0
Comparative Analysis of AI vs. Human Reasoning in Clinical Trial Interpretation: A Study Using Large Language Models
Introduction: The emergence of advanced LLMs has created new possibilities for medical research interpretation and clinical decision support. While these models have demonstrated impressive capabilities in various medical tasks, their ability to independently reason through clinical trial data and arrive at sound medical recommendations remains understudied. Understanding the alignment between AI and human expert reasoning is crucial for the future integration of AI tools in medical research and practice. Methods: We found 20 landmark clinical trials that were published in the last 30 years in the New England Journal of Medicine. We took those articles and removed all the text from it leaving only the clinical trial data and graphs. We then plugged the data into four different AI platforms (ChatGPT, Gemini, Grok 3, and Claude) with the standardized prompt of : “With the tables and figures provided, interpret the following: evidence, statistics, clinical relevance, limitations, and practical applicability. Do not reference the original paper this was obtained from.” We then had two people compare the AI analysis of the data to the conclusions drawn in the article and rate each of the sections on a scale of 1-5. Results: ChatGPT and Gemini were successful in accurately analyzing the clinical data and drew similar conclusions as the article. Claude and Grok 3 were less accurate in its conclusions and oversimplified much of the data in its interpretation. ChatGPT was generally the most accurate in its conclusion with 97.9% accuracy followed by Gemini with an 88.3% accuracy. Grok3 was 78.2% accurate in its conclusions while Claude was only 64.5% accurate in its conclusions. Conclusion: ChatGPT and Gemini were accurate in analyzing the clinical data and drawing conclusions that were almost identical to the ones in the original article. This opens the door for AI to be used in healthcare to accurately summarize clinical data.
Copyright (c) 2026 Arshjeet Singh, Gordon Mao, Barnabas Obeng-Gyas, Anoop Chinthala, William Snyder, Ethan Brown, Kyle Ortiz http://creativecommons.org/licenses/by/4.0
Inflatable Penile Prosthesis and Mini-Jupette Sling for Treating Climacturia in Men with Erectile Dysfunction
Background: Climacturia and arousal incontinence commonly present substantial challenges to patients' quality of life after pelvic surgeries. When accompanied by erectile dysfunction (ED), the concomitant implantation of an inflatable penile prosthesis (IPP) and Mini-Jupette sling emerged as a promising option to simultaneously address both sexual function and continence. Therefore, our study aimed to assess efficacy and patient satisfaction of combined IPP and Mini-Jupette sling for treating climacturia and concurrent ED in post-pelvic procedure patients. Methods: We retrospectively analyzed charts of men with concomitant ED and climacturia who underwent simultaneous IPP and Mini-Jupette sling placement from December 2022 to May 2025. Key endpoints included climacturia and continence status, residual leakage pattern, and subjective patient satisfaction. Results: Preoperatively, all 29 patients presented with climacturia, 11 reported arousal incontinence, and 24 had stress urinary incontinence. At a mean follow-up of 9 months, 26 patients reported resolved climacturia, and 14 patients had complete continence. The average number of pads used per day reduced from 2.2 to 0.9. Among men with persistent leakage, 53% achieved a clinically meaningful improvement in leakage pattern. Overall, 72% of patients reported satisfaction with their outcomes. Of those not fully satisfied, 37% nonetheless experienced a clinical improvement in leakage pattern. Conclusion: In our cohort, simultaneous IPP and Mini-Jupette sling placement proved to be a safe and streamlined approach, delivering marked improvement in climacturia and high satisfaction rates among men with ED and climacturia after pelvic surgery. While not specifically intended for incontinence, the Mini-Jupette sling also improved continence in select cases.
Copyright (c) 2026 Kate Snook, James Malony, Lucas de Amorim, Jeremiah Dallmer, Thairo Pereira, Helen Bernie http://creativecommons.org/licenses/by/4.0
Somatomotor Network Connectivity as a Neural Correlate of Clinical Status, Symptom Severity, and Cognitive Performance
Background/Objective: Alzheimer's disease pathology begins years before clinical symptoms emerge. Most functional connectivity research has focused on "higher order" networks (default mode, frontoparietal, attention), consistently showing decreased connectivity in patients with dementia or cognitive impairment. However, primary sensory-motor networks remain relatively understudied. This study investigated somatomotor network connectivity across the AD spectrum and its relationships with cognitive and neuropsychiatric measures. Methods: 146 participants (ages 60-92) from the Indiana Memory and Aging Study were stratified into preclinical (cognitively normal + subjective cognitive decline; n=81) and clinical (mild cognitive impairment + Alzheimer's disease; n=65) groups. Resting-state fMRI data were parcellated using the Desikan-Killiany atlas, with mean functional connectivity computed using Yeo's seven-network parcellation. Wilcoxon rank-sum tests and Welch’s t-tests compared FC between groups across all networks. Spearman correlations assessed associations between all networks and NPI-Q composite domains and MoCA-derived cognitive domains, with FDR correction. Results: The somatomotor network was the only network among seven that significantly distinguished clinical from preclinical groups, showing a 37.6% effect size reduction. LASSO regression identified somatomotor connectivity as the sole predictive feature. Somatomotor FC showed specific positive relationships with executive function (ρ = 0.251) and language performance (ρ = 0.268), and negative correlation with vegetative/motor symptoms (ρ = -0.226). These associations remained significant after controlling for demographics. Conclusions/Potential Impact: These results suggest that somatomotor network integrity may be an early biomarker of disease progression, reflecting shared neural substrates between motor control and higher-order functions.
Copyright (c) 2026 Valentino Sorto, Meichen Yu http://creativecommons.org/licenses/by/4.0
Diagnostic Delays and Socio-Demographic Factors Among Patients Referred to an Undiagnosed Rare Disease Clinic
Background: Rare diseases affect 25 million Americans, with average diagnostic delays of 6–7 years, 2–3 misdiagnoses, and approximately $29,000 in added annual costs. Patients with rare, undiagnosed conditions experience diagnostic delays influenced by social and demographic disparities. This study examined relationships between socio-demographic factors and diagnostic delay among patients at the Undiagnosed Rare Disease Clinic (URDC). Methods: This study retrospectively analyzed 149 patients at URDC (Jan 2020–Jun 2025), a rare disease program at Indiana University School of Medicine and clinical site for the NIH-funded Undiagnosed Diseases Network. Diagnostic delay was measured as: 1) time from symptom onset to first genetic testing (TSO-GT), and 2) time to first in-person URDC visit (TSO-UV). Independent variables included demographics and social determinants of health. Analysis included descriptive, bivariate (Mann–Whitney U, Kruskal–Wallis, Spearman’s correlations), and multivariate (Multiple linear regression) analyses in SPSS v31.0 (p< 0.05). This study was approved by Indiana University IRB (#2005902680). Results: Among 149 patients, 52.3% were female, 91.3% white, 57.7% publicly insured, and 57.4% urban. Median time from symptom onset to first genetic testing was 2.4 years (IQR: 6.2) and to URDC visit was 7.6 years (IQR: 9.4). Bivariate analysis revealed significant associations between TSO-GT and race (p=.010), number of Human Phenotype Ontology (HPO) terms (p=.039), and presence of constitutional HPO terms (p=.014). Having more HPO categories was associated with shorter TSO-UV. Following multivariate analysis, only constitutional HPO terms (p=.027) remained significantly associated with TSO-GT. Conclusions: Most factors were not significantly associated with diagnostic delays, reflecting limitations in sample size, diversity, and referral criteria. Findings highlight the importance of expanding rare disease programs and research to engage diverse and underserved urban populations. Findings will guide efforts to raise community and provider awareness, build larger multi-site cohorts, and identify socio-structural barriers to ensure timely, equitable rare disease care.
Copyright (c) 2026 Dylan Kim, Katherine Stanford, Vanessa Vital, Melissa Gillette, Amy Han, Baraka Muvuka http://creativecommons.org/licenses/by/4.0
Combined Treatment with Dietary Inulin and a Calcimimetic Agent Improves Cortical Bone in a Rat Model of Chronic Kidney Disease
Background: Chronic kidney disease (CKD) leads to an increased risk of fractures. The increased skeletal fragility is partly due to secondary hyperparathyroidism commonly seen in CKD patients, which leads to cortical bone deterioration. Pharmacological lowering of parathyroid hormone (PTH) via calcimimetics is a key treatment, but fracture risk is not altered in clinical trials. Previous preclinical work has shown dietary inulin reduces PTH levels potentially through alterations of the gut microbiome to reduce gut-derived uremic toxins, but bone mechanics did not improve. Due to the complex nature of CKD, combination therapy with a PTH lowering pharmacotherapy, like etelcalcetide, and dietary inulin may better mitigate skeletal fragility. Methods: Male Cy/+ rats were treated with either 10% dietary inulin, 3x/week KP injections (a rat analog of etelcalcetide), or combination for 10 weeks. Bone mechanical properties were tested via three-point bending of femora. Microstructural cortical bone parameters of the midshaft femur were assessed via micro-computed tomography. Bones were analyzed via histomorphometry to evaluate bone turnover, and serum PTH and kidney biomarkers were obtained. Results: Both treatments significantly lowered PTH independently and in combination, with the combined treatment demonstrating a 60-fold lower PTH compared to untreated CKD. Bone mechanical properties, including ultimate force, stiffness, total work, and toughness, were significantly improved in combination treatment compared to untreated CKD. Combined treatment had the greatest effect on bone microarchitecture, displaying 10.6% higher cortical bone area than untreated CKD. Additionally, untreated CKD had an average of 7.4% cortical porosity while combined treatment had approximately 0.1% cortical porosity. Combined treatment lowered bone turnover compared to untreated CKD. Conclusions/Implications: These data demonstrate that combined treatment was the most effective at improving bone structure and mechanical properties. This indicates combined treatment with dietary inulin and a calcimimetic could be a promising treatment option for treating the bone complications of CKD.
Copyright (c) 2026 Daniel Stephen, Corinne Metzger, Emily Matter, Shruthi Srinivasan, Kalisha O’Neill, Neal Chen, Sharon Moe, Matthew Allen http://creativecommons.org/licenses/by/4.0
Prevalence of Critical Illness at Moi Teaching and Referral Hospital in Western Kenya
Rationale: Despite the disproportionate burden of critical illness in low- and middle-income countries (LMICs), access to intensive care units (ICUs) remains limited. At Moi Teaching and Referral Hospital (MTRH), a public referral hospital in Western Kenya serving over 24 million people, critically ill patients are often managed in general wards without close monitoring due to insufficient ICU space. While qualitative evidence suggests a significant need for increased ICU capacity, the actual demand is unknown. Methods: This mixed-methods study quantified the prevalence of critical illness, defined as a National Early Warning Score (NEWS) greater than six, among adults presenting and admitted to MTRH between November 2024 and June 2025. Participants were enrolled from the emergency department and all general wards during three separate 24-hour periods. Adults with NEWS > six were followed for outcome, ICU admission, and subsequent NEWS at 7, 14, 21, and 28 days. Key informant interviews with healthcare providers directly involved in the care of critically ill patients explored workflows, perceptions of critical illness, and barriers to ICU expansion. Results: Of 1,274 patients enrolled, 187 (14.7%) had a NEWS > six. Six (3.2%) were admitted to an ICU and 33 (17.6%) died by day 28. Most critically ill patients were identified in the internal medicine wards (50.3%), general surgery wards (15.5%), and emergency department (12.3%). Preliminary qualitative findings among 6 key informants suggest nursing and bed shortages are the primary barriers to ICU transfer. Other factors include reliance on ambulance transport, proximity of the ICU, dialysis, and imaging facilities, and the absence of standardized protocols for critical illness assessment and transfer. Conclusion: This study may help inform resource planning, ICU capacity building, and the development and implementation of protocols to improve recognition, management, and transfer of critically ill patients at MTRH and similar referral hospitals in sub-Saharan Africa.
Copyright (c) 2026 Allison Stogsdill, Betty Sirera, MBChB, MMed, Josephat Kerema, MBChB, MMed, Sarah Fortna, MD, Babar Khan, MD, Neelima Navuluri, MD, MPH, Maria Srour, MD, MPH http://creativecommons.org/licenses/by/4.0
Examining In-Hospital and Post-Discharge Surgical Complications Following Cardiac Interventions in Northwest Indiana
Introduction: Post operative complications contribute to prolonged hospital stay and adverse outcomes. While prior research has primarily focused on in-hospital cardiac intervention outcomes, the impact of Social Determinants of Health (SDOH) on postdischarge surgical complications remains underexplored. This study examined in-hospital and post-discharge surgical complications following cardiac interventions in Northwest Indiana (NWI). Methods: This retrospective cross-sectional study analyzed a limited dataset of patients who underwent a cardiac intervention within three hospitals in NWI during January 2021- March 2025. SDOH data were generated from routine EPIC-based SDOH screenings using the Protocol for Responding to and Assessing Patients’ Assets, Risk, and Experiences (PRAPARE). Cardiac interventions and surgical complications (in-hospital and postdischarge) were identified using ICD-10 codes. Data analysis comprised bivariate (Chi Square) and multivariate analysis (Multinomial Logistic Regression) using SPSS v31.0. This study was exempted by Indiana University Human Research Protection Program (IRB#14040). Results: The sample included 8993 patients who were primarily white (62.1%), female (55.5%), 75 and older (29.7%), English-speaking (96.1%), and publicly insured (78.6%). Bivariate analysis revealed significant associations between both in-hospital and post discharge surgical complications with multiple demographic (e.g., age, ethnicity, race, language, insurance type), social (e.g., family income, housing risk, transportation needs), and health factors (e.g., smoking, BMI, and emergency department (ED) disposition). Multivariate analysis found that surgical complications were significantly associated with public insurance (p=0.045; OR=2.195), family income (p=0.008; OR=1.000012), ED disposition-observation (p=0.007; OR=0.502), and length of stay (p< 0.001; OR=1.084). Specifically, in-hospital surgical complications were significantly associated with family income (p=0.046; OR=1.0000013), obesity (p=0.047; OR=3.031), length of stay (p< 0.001; OR=1.070). Conclusion: This study addresses a research gap on post-discharge surgical complications and the influence of SDOH, highlighting opportunities for SDOH integration into institutional practices and medical education.
Copyright (c) 2026 Olivia Strube, Jonathan Guerrero, Baraka Muvuka, Kyle Gospodarek, Joshua Mangum http://creativecommons.org/licenses/by/4.0
Shifts in Pediatric Urinary Stone Composition from 2012 to 2023: A Retrospective Cohort Analysis
Background: Multiple studies have noted shifts in urinary stone composition amongst adult populations in recent decades, often attributed to changing diets and rising obesity rates3 . These trends are less studied in the pediatric population. Therefore, in this study, we investigate if shifts in urinary stone composition also existed in the pediatric population over the span of 12 years. Methods: A retrospective chart review of our institutional database for stone events from 2012 to 2023 was conducted. A list of pediatric patients was compiled with ICD codes for primary diagnosis of nephrolithiasis. For each year, we collected 20 stone analyses, which overall equated to 240 distinct stone analyses from 233 patients across 2012 to 2023. To increase the power of the study, we decided to create 3 cohorts (each with 80 stone analyses): 2012-2015, 2016-2019, 2020-2023. Stones were categorized based on the predominant composition. Various demographic data (e.g. age, gender) as well as clinical data (e.g. underlying conditions, stone characteristics) were collected. A Chi-square analysis was also performed to evaluate statistical significance. Results: A total of 233 pediatric patients were identified with the average age being 12.0 years. Calcium oxalate and calcium phosphate were by far the most common stone types in all three cohorts. Struvite stones did show an upward trend although a larger sample would be needed to draw any conclusions. Chi-square test comparing the three cohorts resulted in χ² (14, N=240) = 17.732, p = .2193. Conclusion: There was no statistically significant shift in stone composition within this pediatric cohort over the 12-year study period. Some limitations of this study were its retrospective design, potential loss of patients due to spontaneous stone passage without follow-up, and the data coming from a single institution. Further studies should be conducted to confirm these findings and to explore different time frames and pediatric populations.
Copyright (c) 2026 Saad Sualeh, Ashorne Mahenthiran, Pankaj Dangle http://creativecommons.org/licenses/by/4.0
Synthesizing Stable Matrices from the HS-5 Bone Marrow Stromal Cell Line
Background/Objective: Our lab is focused on investigating the physical and biochemical mechanisms through which the bone marrow extracellular matrix (ECM) regulates musculoskeletal and hematopoietic homeostasis. Previously, we showed that primary cells from young and aging bone produce matrices which recapitulate aging-related remodeling of the bone marrow microenvironment. Among these changes is a significant depletion of CCN matricellular proteins. However, isolating the impact of CCNs from the variety of aging-associated changes, requires producing ECMs from immortalized bone marrow stromal cell lines, in which individual CCNs may be deleted without disturbing other matrix components. However, matrices produced by immortalized stromal lines are highly susceptible to damage by decellularization. Methods: A 9-day matrix production protocol was performed with HS-5 bone marrow stromal cells maintained on a variety of commercially-available substrates/surfaces. Briefly, the procedure consisted of ascorbic acid induction on day 5 and decellularization on day 8, followed by ECM collection and analysis/imaging with Coomassie Blue stain. Substrates evaluated included tissue culture plastic (TCP), Cell-Tak, Collagen, PDL, CellBind, Silane, Supra, UpCell; with and without fibronectin coating. Results: While HS-5 cells readily produced matrix on several substrates, plates coated with Collagen I, further supplemented with fibronectin, most consistently supported the preparation of a wellanchored matrix, which remained intact following decellularization. Conclusion and Potential Impact: Producing stable ECMs from HS-5 bone stromal cells will allow our lab to specifically modify and study proteins of interest, including CCN1 and CCN2, which have been suggested to play important roles related to the aging-associated remodeling of the bone marrow niche. When coated with fibronectin, UpCell (Corning) supported stable matrix anchoring, while also allowing for detachment from the culture surface, suggesting potential applications in manufacturing of orthobiologic implants.
Copyright (c) 2026 Noah Theobald, Piper Wilburn, Conner Quinlan, Sonali Karnik, Milos Marinkovic http://creativecommons.org/licenses/by/4.0
Mesenchymal-to-Epithelial Transition in the Oral Cavity: Highlighting Migration Dynamics During Wound Healing
Background: Oral cancers are particularly aggressive due to their propensity for early invasion into adjacent lymphatic and vascular structures. Consequently, a significant proportion of cases are diagnosed at advanced stages, underscoring the need to further elucidate mechanisms of metastasis. Given the established parallels between wound healing and tumor progression, we utilized a gingival injury model to investigate cellular migratory dynamics that may inform oral cancer metastatic behavior. Methods: K5/GFP transgenic mice were injected with Tamoxifen to induce GFP expression in Keratin 5- positive epithelial cells, followed by surgical extraction of the first molar to simulate oral tissue injury. Tissue was collected and processed for immunohistochemistry. Co-staining for Keratin 5 and GFP was used to track epithelial cell lineage, while additional co-staining with mesenchymal and microenvironmental markers was performed to further characterize cellular identity and tissue architecture. Results: Select regions within intact gingival epithelium lacked Tamoxifen-induced GFP signal, suggesting a non-epithelial cell lineage, with this pattern further exacerbated by tooth extraction surgery. The integrity of the basement membrane was maintained in GFP-negative regions as evidenced by ITGB1 staining. Keratin 17 expression in both GFP-positive and GFP-negative regions highlighted that GFP loss was not stress induced. Notably, Vimentin and Collagen I showed highly specific expression within GFP-negative zones, suggesting the epithelial cells present were mesenchymal in origin. Furthermore, WNT5a, known to promote the Mesenchymal-to-Epithelial Transition (MET), was prominently expressed in these GFP-negative areas, indicating its potential role in facilitating mesenchymal cell integration into the epithelium. Conclusion: The detection of mesenchymal markers within epithelial regions, along with the absence of GFP in these infiltrating cells, provides evidence for MET in oral mucosa. Our data indicate this cellular transition in oral mucosa may contribute to the highly metastatic nature of oral cancers by facilitating cellular plasticity and invasion processes.
Copyright (c) 2026 Tyler Thompson, Carson Walton, Sofia Syed, Xue Yuan http://creativecommons.org/licenses/by/4.0
From Scalpel to Slide: The Effects of Air Exposure and Histologic Processing on Surgical Margin Assessment in a Murine Model
Background: Accurate measurement of surgical margins is essential to confirm complete tumor excision and to guide appropriate postoperative oncologic treatment. However, post-resection tissue shrinkage, resulting from factors such as air exposure and histologic processing, can lead to underestimation of true margins. This distortion may contribute to overtreatment with unnecessary adjuvant therapies. This study aimed to evaluate the impact of various post-resection factors on the accuracy of margin measurement. Methods: Seventeen euthanized mice had their arms, thighs, and legs dissected. Specimens were either processed immediately or exposed to ambient air for three or 24 hours. Micro-CT imaging was performed on arm specimens to measure cross-sectional muscle area and calculate radius at humeral mid-diaphysis. Lower limbs were processed using frozen sectioning, paraffin embedding after formalin fixation and EDTA demineralization, or MMA embedding with or without demineralization. Muscle fiber cross-sectional areas were measured from histology sections using ImageJ. Statistical analysis was performed using GraphPad PRISM version 10.5.0. Results: Arm mass decreased by 15.7% at three hours (p < 0.0001) and 57.3% at 24 hours (p < 0.0001). Thigh and leg specimens showed similar time-dependent reductions in mass. Micro-CT analysis revealed a 25.5% decrease in muscle area at three hours (p = 0.0199) and 67.3% at 24 hours (p < 0.0001), corresponding to reductions in calculated radius of 14.2% and 43.2%, respectively. Differences were observed in muscle fiber area of paraffin embedded specimens only at 24 hours (p=0.0178). No differences were observed in muscle fiber area between frozen vs paraffin embedded thighs at zero, three, or 24 hours (p=0.4848, 0.3095, 0.4206) or between nondemineralized and demineralized legs (2261.4 vs 1940.4 um2 , p= 0.0649). Conclusions: Air exposure causes significant tissue and margin shrinkage. Early changes likely result from interstitial fluid loss rather than muscle atrophy. Clinical processing and demineralization do not likely affect margin size. Adjustments for air exposure are therefore necessary to improve margin accuracy and provide appropriate post-surgical cancer patient care. Future research will confirm these effects in clinical specimens.
Copyright (c) 2026 Camren Toole, Anoushka Poduval, Johanna Koothur, Anuradha Kambrath, Laura Warmke, L. Daniel Wurtz, Christopher Collier http://creativecommons.org/licenses/by/4.0
Social Determinants of Health and Emergency Department Utilization for Genitourinary Complications in Patients with Genitourinary Cancers: A Retrospective Cohort Study
Background: Genitourinary (GU) complications are a common reason for emergency department (ED) visits, particularly among patients with GU cancers who represent approximately 1 in 16 cancerrelated ED encounters. Urinary tract infections (UTIs) are the leading GU complication, accounting for over 3% of cancer-related ED visits. Patients with GU malignancies often experience overlapping complications, such as infections, obstruction, or postprocedural issues, reflecting underlying disparities in access to care and coordination. To our knowledge, this study is the first to examine this issue in Northwest Indiana (NWI), focusing on demographic, clinical, and social factors associated with ED presentation for GU complications. The goal is to inform community-based interventions targeting cancer disparities in NWI. Methods: This retrospective cohort study included patients with GU cancers who presented to the ED at three NWI hospitals from January 2021 to March 2025. GU cancers and complications were identified using ICD-10. The primary outcome was ED presentation for GU complications (yes/no). Data were extracted from EPIC. Analyses included descriptive statistics, bivariate analysis (Chi-square, Kruskal-Wallis), and binary logistic regression using SPSS 31.0 (p< 0.05). The study was IRB-exempt (IRB #14040) through Indiana University. Results: Among 534 patients, bivariate analysis showed significant (p< 0.05) associations between GU complications and age, sex, ethnicity, insurance type, smoking status, ED disposition, and return visits (30-day and 90-day). Multivariate analysis revealed increased age (OR=1.034, p< 0.001) and 90-day return visits (OR=3.603, p=0.001) were associated with higher odds of ED presentation. Hispanic ethnicity (OR=0.557, p=0.049) and current smoking (OR=0.369, p=0.002) were associated with lower odds of ED presentation. Conclusion: Multiple sociodemographic and clinical factors were independently associated with ED presentation for GU complications. These findings may guide targeted interventions, risk stratification, and future research aimed at addressing structural inequities and care coordination among patients with GU cancer.
Copyright (c) 2026 Carly Waite, Baraka Muvuka, Jonathan Guerrero, Joshua Mangum http://creativecommons.org/licenses/by/4.0
Infection Rates of Initial and Exchanged Peripherally-Inserted Central Catheters in Pediatric Patients
Background/Objective: Peripherally-inserted central catheters (PICCs) act as modes of longterm access to the bloodstream in patients who would otherwise need frequent needle sticking to obtain intravenous access. PICCs are beneficial because they allow for efficient access to the bloodstream to administer medications such as chemotherapy, antibiotics, total parenteral nutrition, and pain control through a single long-term access point. This allows for less pain and discomfort for patients (especially pediatric patients), minimizes waste, and allows for convenient access to the bloodstream for delivery of medications or sampling of blood for testing which allows for better long-term care. However, PICC replacement procedures are associated with increased risk of introducing infections and thrombosis. We hypothesize that patients who do not receive PICC exchanges will have lower rates of infection than those who do receive an exchange. Methods: For this quality improvement retrospective study, we examined one year worth of PICC placement/exchange procedures in pediatric patients at a single academic hospital through their electronic medical records in Cerner. Infections were documented by positive blood cultures at the PICC site within 30 days of the procedure and were corroborated through clinical documentation to ensure the PICC was the origin of the infection, rather than just a site of infection spread. Results: In the year 2024, pediatric patients displayed significantly higher infection rates in PICC exchanges at 1.97%, compared to 0.40% in initial PICC placements (p=0.040). Clinical Implications and Conclusion: The data from this investigation supports previously identified infection rates in the pediatric patient population. The results from this project will help support and guide future guidelines regarding clinical decision making in pediatric patients who require long-term intravenous access.
Copyright (c) 2026 Charlie Walker, Sean Pfaff http://creativecommons.org/licenses/by/4.0
Prevalence and Geographic Distribution of Elevated Blood Lead Levels in Pregnant Women in Indiana
Background: Prenatal lead exposure increases the risk of pregnancy complications and results in fetal neurodevelopmental damage. Despite well-documented risks, most clinicians predominantly rely on risk-based screening rather than on universal lead testing. The study aim was to measure whole blood lead levels (BLL) in pregnant women from parts of Indiana and explore associations with maternal age, residential zip code, and median household income (MHI). Methods: Remnant whole blood (WB) samples collected during routine antenatal care and submitted to Indiana University Health Pathology Laboratory between May - July 2025 were analyzed. Samples were prepared by mixing 20 µL of WB with 1 mL of solution A (1% ethanol, 0.5% ammonium hydroxide, 0.02% TritionX-100, and 0.01% nitric acid). The mixture was then vortexed and further diluted with 3.98 mL of solution B (0.5% nitric acid) followed by analysis on Inductively Coupled Plasma Mass Spectroscopy (ICP-MS). A BLL of ≥1 ug/dL was classified as elevated. Age and zip codes were extracted from electronic health records. Results: Among 548 samples analyzed, 37 (6.8%) had BLL >1 µg/dL; two samples were between 3.6 to 5 µg/dL, and four samples were >5 µg/dL. The following table shows BLL >5 µg/dL with corresponding zip codes, county names, and MHI. BLL (µg/dL) Zip Code County Name MHI ($) 6.67 46902 Howard County 59,548 6.71 47581 Martin County 56,864 10.55 46040 Hancock County, with overlap into Hamilton County & Madison County 144,834 15.96 46074 Hamilton County 123,580 Participants were also grouped by age, and higher age was positively correlated with lead levels (ANOVA p < 0.05). Conclusion: Nearly seven percent of the sampled population had elevated BLL. Our findings suggest that Indiana clinicians should continue to surveil for lead exposure and increase communication with their patients about potential sources of lead exposure in the environment.
Copyright (c) 2026 Ashley Weaver, Rejwi Dahal http://creativecommons.org/licenses/by/4.0
Predicting Patient-Initiated Procedural Stoppages during Focused Ultrasound Thalamotomy for Essential Tremor
Magnetic resonance imaging-guided focused ultrasound thalamotomy (FUS) is an incisionless neurosurgical technique to treat medically refractory essential tremor and parkinsonian tremor, often serving as an alternative to deep brain stimulation. FUS uses precisely targeted ultrasound energy to heat and ablate brain tissue. The procedure is performed in stages, known as sonications, lasting 10-30s with the patient awake inside an MRI scanner; with each sonication, it becomes more difficult to achieve the temperatures required for tissue ablation. During treatment, the patient can voluntarily halt the procedure if adverse effects, such as headache/head pressure, vertigo, and nausea, become intolerable. These patient-initiated procedural stoppages (PIPS) challenge treatment completion and may result in suboptimal outcomes. This study aims to develop a predictive model for risk of PIPS using variables available to the operator preoperatively or prior to each sonication. A retrospective analysis was conducted on 50 patients who underwent FUS at IU, each with multiple treatment sonications. The primary outcome was whether a procedure was voluntarily halted due to sonication effects. Pretreatment factors include age, sex, skull density ratio, skull area available for treatment, and number of ultrasound transducer elements; intraoperative factors include sonication number, prescribed power and duration, maximum lesion temperature achieved, and dose area. A multivariate logistic regression was created using a bidirectional stepwise selection fitted for the Akaike Information Criterion. Model performance was evaluated using receiver operating characteristic (ROC). Increased input duration was significantly associated with increased odds of PIPS (OR 1.14, 95% CI: 1.05-1.22, p < 0.001), while higher maximum lesion temperature approached significance for a risk-reducing effect (OR = 0.84, 95% CI: 0.71-1.00, p =0.051). ROC analysis revealed an AUC of 0.85 (95% CI: 0.74-0.95), indicating strong predictive accuracy. As a preliminary model, further data collection and validation are needed to improve stability and confirm clinical applicability.
Copyright (c) 2026 Robert Woodburn IV, David Purger http://creativecommons.org/licenses/by/4.0
Holistic Care and Respect for Persons: Exploring the Motivations and Concerns of Pregnant Women When Considering HIV Research Engagement
Background: The ethical principle, respect for persons, suggests investigators must design research that is responsive to participants’ preferences and concerns. This is especially important when engaging vulnerable populations, such as pregnant or recently pregnant women with HIV (PWHIV). This qualitative study aimed to explore the understanding and prioritization of holistic care by PWHIV when considering research participation. Methods: This study was conducted within the Academic Model Providing Access to Healthcare in Eldoret, Kenya. We performed 45 semi-structured interviews between January and September 2024. Interview participants were currently or recently pregnant [29 with HIV, 16 without HIV] participating in HIV research with their infants. Interviews were audio-recorded, transcribed, translated, and analyzed by coders using a priori coding, constant comparison, axial coding, and triangulation. Results: Holistic care was a major motivation facilitating longitudinal participation. Dimensions of holistic care included monitoring of their children’s health and development, increased access to referrals and healthcare, reimbursement, and learning about topics including parenting, HIV, prevention of perinatal HIV transmission, and child health. Most participants viewed contact with the research team as an opportunity for positive healthcare interactions without stigma where PWHIV felt cared for, free to ask questions, accepted, and empowered. Participants identified actions for investigators engaging PWHIV in research that promote respect and holistic care. These included return and explanation of all tests results, dynamic reimbursement based on burden of participation, availability of a supportive visit environment, communication with participants between visits, and offering educational resources, referrals, and guidance. Participants expressed concerns regarding how they will navigate the loss of support when study participation ends and desired clear communication about what should be expected at that time. Conclusion: Holistic engagement and understanding of the factors affecting participation of this population will help researchers promote respect for participants, prevent harm, and uplift PWHIV and their children.
Copyright (c) 2026 Grace White, Eric Masese, Daniel Kinyanjui, Edwin Were, Colin Halverson, Mary Ott, James Carlucci, John Humphrey, Esther Wahome, Dennis Munyoro, Amira Nafiseh, Kristen Cunningham, Madeline Cory, Mark Nyalumbe, Roselyne Ananda Ombitsa, Megan McHenry http://creativecommons.org/licenses/by/4.0
Can Clusterin Target Mutant Human GNAQ in Sturge-Weber Syndrome to Alleviate Ocular Hypertension?
Background/Objective: Sturge Weber Syndrome (SWS) results from a somatic mosaic mutation of GNAQ, which encodes the alpha subunit of Gaq. This R183Q mutation disables the G-protein from exchanging ATP for ADP, restricting the receptor to its active conformation. Chronic activation results in angiomas, or benign vascular overgrowths, in the leptomeningeal, cutaneous facial, and orbital regions. Patients with SWS therefore commonly present with a characteristic port wine birthmark, focal seizures, developmental delay, and glaucoma. Management of glaucoma is particularly difficult, as SWS patients are often resistant to traditional medications and surgeries are complicated by the risk of angioma rupture. It is predicted that similar mechanisms may relieve ocular hypertension in patients with SWS. We investigated the role of the GNAQR183Q in glaucoma pathogenesis and potential downregulatory molecular interventions using clusterin. Materials/Methods: Analyzed data of the protein profile from total and ECM enriched fraction. To generate adenovirus human GNAQ, we received mutant and wild-type human GNAQ from Dr. Doug Marchuk, Duke University, which were cloned into Adeno-X adenoviral plasmids and replicated in Stellar competent E. coli. Isolated plasmids were linearized via PacI digestion and transfected into HEK-293 cells for amplification. Results: In the proteomics data, we found a significant decrease in AdCLU lowered G-proteins including GNAQ, GNB1, and GNG12, and Ras-related RRAS2. The downregulation of wild-type GNAQ expression by chaperone protein clusterin as well as pharmacological inhibitors of GNAQ leading to decreased intraocular pressure. In the process of cloning the mutant adenovirus, we have the virus which will be transduced in trabecular meshwork and tested for the effectiveness of clusterin to lower the mutant GNAQ. Potential Impact: This GNAQ adenovirus developed will allow to mimic the underlying pathophysiology of SWS in human and mouse tissues ex vivo and in vivo. The expression of these genes/proteins will be used for investigation into potential pharmaceutical interventions aiming to noninvasively preserve these patients’ vision.
Copyright (c) 2026 Forrest Wade, Rodahina Pasteurin, Avinash Soundararajan, Padmanabhan Pattabiraman http://creativecommons.org/licenses/by/4.0
School Staff Perspectives on Building Healthier School Communities
Background: School staff spend significant time with students, positioning schools as key settings for shaping health behaviors. The Patachou Foundation’s PataSchool program partners with two Indianapolis charter schools to promote health equity through scratch-cooked meals and staff training. However, little research exists on school staff perspectives regarding community health and wellness. Project Method: 36 staff members, including teachers, administrators, and cafeteria staff, participated in interviews or focus groups. Transcripts were standardized and uploaded to NVivo for qualitative thematic analysis. Descriptive analysis focused on staff health definitions, motivations, barriers, and perceptions of healthy school environments. Results: Staff defined health as a balance of physical, mental, and emotional well-being, with motivation grounded in personal and family experiences with illness. Common barriers included fatigue and time, with staff stating “By the time we get home… I’m drained out.” Staff emphasized schools’ responsibility in promoting student health beyond academics, emphasizing how “schools have very important roles to try and just promote the overall health and well-being of kids, not just academic[s].” Staff’s perceived barriers to student health included food insecurity, limited access to fresh food, and lack of consistent health education for both students and parents. Several staff also described that new programming should use strategies that are interactive, visually-engaging, and family-inclusive. Potential Impact: Given staff’s emphasis on schools as key environments for well-being, future wellness strategies should reinforce schools’ role in modeling and supporting healthy behaviors. To address barriers such as fatigue, time, and inconsistent health education, programming should include visually engaging, hands-on health education that extends beyond students to staff and families. New partnerships that expand staff wellness support and incorporating these facets may help create healthier school communities and strengthen the impact of programs like PataSchool across Indianapolis schools.
Copyright (c) 2026 Viha Bynagari, Julie Pike, Jondea Mon-Romero, Mathew Feltrop, Bryan Daniel, Tamara Hannon http://creativecommons.org/licenses/by/4.0
Hematological and Inflammatory Biomarkers Associated with Pain in Sickle Cell Disease
Background and Objective: Pain is the hallmark of sickle cell disease (SCD). Clinically, SCD is characterized by a steady-state phase with chronic pain and a vaso-occlusive crisis (VOC) phase marked by unpredictable, severe pain episodes often requiring hospitalization and opioids. VOCs, caused by the adhesion and obstruction of sickled red blood cells in microvasculature, are among the most debilitating manifestations of the disease. VOCs have four clinically defined phases: prodromal, initial, established, and resolving. We observed abnormal elevation of inflammatory biomarkers in SCD compared to healthy controls at baseline and changes throughout the VOC stages. The goal of this exploratory project of our clinical trial (ClinicalTrial.gov ID: NCT05045820) is to evaluate the inflammatory biomarker-based immunological mechanism associated with pain and acupuncture analgesia in SCD. Methods: Peripheral blood samples are collected at baseline and at each VOC phase. Hematological testing (complete blood count with white blood cell differential, hemoglobin electrophoresis, and reticulocyte count) is performed while serum, plasma, and peripheral blood mononuclear cells are simultaneously isolated, aliquoted, and stored for future analyses. Inflammatory markers are assessed with immune assays and cell activation analyses. Patient-reported outcome measures are collected using validated instruments to assess pain, neuropathic symptoms, physical dysfunction, emotional well-being, and quality of life. Samples and data are collected before, during, and after the treatment. Results: Our published results have demonstrated significant differences in patient-reported outcome measures and hematological and inflammatory biomarkers in SCD as compared to healthy controls. Additional analytical work is ongoing. Conclusion and Potential Impact: Published and preliminary data demonstrate robust clinical outcomes of acupuncture treatment and biomarker-based mechanistic findings related to inflammation in SCD. This project has strong clinical relevance as it investigates biomarker-based mechanisms of pain in SCD and aims to identify therapeutic targets to improve pain management and quality of life.
Copyright (c) 2026 Abbie Clay, Caitlyn Carpenter, Lina Houran, Candice Debats, Andrew Pucka, Ying Wang http://creativecommons.org/licenses/by/4.0
Functional Connectivity Differences Across the Alzheimer’s Disease Continuum: A Neural ROI-Based Analysis in Relation to Depression
Background: Alzheimer’s disease (AD) is a neurodegenerative disease characterized by β-amyloid plaques and tau tangles, leading to symptoms like memory loss, agnosia, and apraxia. A common AD comorbidity includes depression. While some studies identify midlife depression as a risk factor for AD development, others interpret depression as a manifestation of AD itself. Though emerging literature supports both models, the underlying mechanisms linking the two remain poorly understood. We hypothesized that functional connectivity in the default-mode network (DMN), somatomotor network (SMN), and salience network (SN) would be reduced in association with both AD and depression. Methods: 178 participants (ages 65-90, positive β-amyloid) fMRI datasets collected, split into 68 ROIs per the Desikan-Killiany atlas. Depressive symptoms were assessed via the NPI and GDS questionnaires. Participants were subdivided into 4 groups: preclinical AD patients without depressive symptoms; preclinical AD patients with depressive symptoms; prodromal and AD patients without depressive symptoms; and prodromal and AD patients with depressive symptoms. This data was residualized to correct for age and sex, then analyzed via non-parametric tests, e.g., Kruskal-Wallis. Results: Six significantly different functional connectivity regions were found across groups: p < 0.001, bankssts; 0.001 < p < 0.01, precentral, postcentral, and superiortemporal; and 0.01 < p < 0.05, lateralorbitofrontal and paracentral. Post hoc tests revealed that preclinical AD patients had greater connectivity relative to prodromal + AD patients, with and without depression. Depression specific regions included the paracentral and lateralorbitofrontal ROIs. Conclusion: The DMN and SMN are implicated in AD development through the bankssts & superiortemporal regions, and the pre-, post-, & paracentral regions, respectively, in patients both with and without depression. The SN and DMN are implicated in depression through the lateralorbitofrontal region, in preclinical AD. And lastly, the SMN and SN are implicated in depression through the paracentral region, specifically in AD patients.
Copyright (c) 2026 Luka Cvijanovic, Meiheng Liang, Meichen Yu http://creativecommons.org/licenses/by/4.0
Preliminary Results Characterizing the Role of Megakaryocytes in Pain Behavior and Fractured Healing
Introduction: Bone is a heterogeneous tissue regulated by both a complex interconnected biological and mechanical response. Megakaryocytes play an integral role in the biological signaling of this response by increasing bone formation through osteoblast upregulation and osteoclast downregulation. Megakaryocytes may also have a significant role in pain amplification through the release of platelet derived growth factor. The aim of this study is to characterize the role of megakaryocytes in fractured healing and pain behavior. Methods: PF4Cre;iDTR male and female mice were separated into two groups. One group received diphtheria toxin (DT), adjusted for weight, every four to five days to ablate the natural megakaryocyte population. The control group received isovolumetric saline injections at the same time points. A complete, nondisplaced fracture was created in the right hind femoral shaft. Weekly saphenous blood samples and twice weekly in vivo x-rays were collected. Weekly behavior testing, including Von-Frey mechanical sensitivity test, was conducted. At twenty-two days post fracture, the mice were euthanized. Surgical and contralateral femurs were collected for later analysis. Results: DT mice had a significantly lower body platelet count compared to the control group. Body weight remained constant in both treatment groups. Preliminary pain and radiographic results did not show a difference in pain behavior response or healing. However, this was a small sample size (n = 5-6 per group), and only two analyses were completed at this point in the study. Future Direction: In addition to doubling the current sample size, we plan to analyze blood samples, μCT scans, biomechanical torsional testing, and four different behavior responses. Through gaining a greater understanding of the extent of megakaryocyte involvement in fracture healing signaling, we may discover new targets for pain management and methods to improve fracture outcomes.
Copyright (c) 2026 Muira Fontaine, Amy Creecy, Jiliang Li, Upasana Ganguly, Spencer Britton, Sonali J. Karnik, Rachel J. Blosser, Kuldeep Yadav, Sarah L. Mostardo, Melissa A. Kacena http://creativecommons.org/licenses/by/4.0
Is the Social Vulnerability Index Related to Outcomes in Pregnancies Complicated by Type 2 Diabetes?
Background: Type 2 diabetes (T2D) is associated with increased risk for adverse maternal and fetal outcomes. Using the Social Vulnerability Index (SVI), a measure developed by the CDC, studies show that women in areas of higher social vulnerability face challenges achieving recommended glycemic targets. We investigated whether pregnancies complicated by T2D and higher social vulnerability have increased adverse perinatal outcomes. Methods: We performed a retrospective cohort study looking at pregnancies complicated by T2D who delivered at Eskenazi and IU Health from January 2018 to December 2020. Demographic, medical history, and pregnancy outcome data were abstracted. We used the Census Geocoder Tool to match each patient's address with the respective census tract and SVI value. SVIs were divided into tertiles (< 0.492, 0.492 - 0.7792, > 0.7792). We compared demographic and perinatal outcomes using chi-square test and ANOVA as indicated across SVI tertiles. Results: The SVI was calculated for 349/371 (94%) participants. Those in the highest tertile of SVI were less likely to initiate prenatal care in the first trimester compared to those in the lowest tertiles (79 vs 70 vs 59%, p=0.005). HbA1c values were similar across SVI groups. The proportion of those with T2D who received prenatal care at Eskenazi Health increased across SVI tertiles (21 vs 34 vs 58%, p<0.001). Unexpectedly, birth weight, preterm birth, hypertensive disorders, and neonatal morbidity did not differ among groups. Conclusions: The SVI identifies individuals at increased risk for initiation of prenatal care after the first trimester. Rates of adverse outcomes were high among all individuals with T2D and did not vary significantly by SVI tertile. To better understand the impact of public health support provided by Eskenazi on perinatal outcomes among those with T2D and a high SVI, data abstraction from 2021 to 2024 is ongoing.
Copyright (c) 2026 Claudia Linczer Kabele, Christina Scifres, MD http://creativecommons.org/licenses/by/4.0
Effects of Gastrokine-1 in Bacterial Biofilm Formation
Background and hypothesis: Gastrokine-1 (GKN1) is produced and secreted by the epithelial cells of the gastric mucosa. It is highly expressed in normal gastric mucosa, and it plays a role in gastric mucosal protection, anti-inflammatory processes and epithelial cell proliferation. While GKN-1 is typically absent in the colon, emerging evidence suggests it may have a protective effects in intestinal inflammatory conditions, such as colitis. Adherent-Invasive Escherichia coli (AIEC) is a gut pathobiont associated with Crohn’s disease that invades intestinal epithelial cells and can form biofilms. Citrobacter rodentium, a murine pathogen, serves as a model for enteropathogenic E. coli-induced colitis. We hypothesize that GKN1 treatment will inhibit or reduce bacterial biofilm formation on intestinal epithelial cells. Experimental design: Human colorectal carcinoma cell line HCT-116 was cultured on circular glass coverslips (1.8 cm diameter). Cells were pre-treated with recombinant GKN1 before incubation with bacterial suspensions of either AIEC or C. rodentium. The co-culture was maintained overnight (24 hours) under static conditions. A parallel set of samples was prepared without GKN1 treatment as a control. Post-incubation, cells were stained for biofilm and bacterial visualization, mounted, and imaged using fluorescence and confocal microscopy. The experiment was extended to 48 hours in an attempt to amplify observable differences between treated and untreated conditions. Results: To date, microscopy analysis has not revealed a discernible difference in fluorescence signal or bacterial presence between GKN1-treated and untreated HCT-116 cells. This was consistent across both 24-hour and 48-hour incubation periods, using both fluorescence and confocal imaging. Conclusion and potential impact: Although our results did not support the original hypothesis, this experiment highlights the challenge of translating known gastric effects of GKN1 to colonic cell models. GKN1 is well-documented to maintain gastric epithelial integrity and modulate mucin production, yet its role in intestinal epithelial–bacterial interactions remains poorly defined. The lack of observed biofilm inhibition suggests several possible explanations, including cell line limitations, protein activity loss, or ineffective localization of GKN1 in this in vitro setup. These findings warrant further investigation, such as testing different cell lines, using in vivo colitis models, or exploring dose and timing variations of GKN1 application. Despite the inconclusive outcome, this study provides a valuable starting point for exploring GKN1 as a therapeutic or modulatory agent in the context of intestinal infections and inflammation.
Copyright (c) 2026 Alexander Mehreteab, Arpitha Rajashekara, David Boone http://creativecommons.org/licenses/by/4.0
Association Between Semaglutide Use and Mood Disorders in Patients with Type 2 Diabetes
Background and Objective: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been approved for blood glucose management and weight loss since 2005 with the FDA approval of exenatide. However, research has shown mixed results concerning effects on mood. The aim of this study is to investigate whether the use of the GLP-1 RA semaglutide, specifically Ozempic, is associated with mood disorder diagnoses, particularly depression and anxiety. Methods: A retrospective study was conducted using data from the IU School of Medicine-Evansville RWEdataLab (CRC/Sidus Insights) national Real-World psychiatry and cardiology databases containing de-identified EHR information. The databases were searched for patients with type 2 diabetes. Odds ratios were calculated to compare the occurrence of depressive episodes, major depression, or anxiety after 2018 given at least one documented prescription of Ozempic. Results: A total of 660,523 patients with type 2 diabetes were identified from 5,316,216 patients in the psychiatric database. 187,838 patients were identified from 3,396,429 patients in the cardiac database. The psychiatric database demonstrated semaglutide was significantly associated with higher odds of mood disorder diagnoses: anxiety (OR 2.323; 95% CI: 2.277–2.370), depressive episodes (OR 2.029; 95% CI: 1.988–2.071), and major depression (OR 1.449; 95% CI: 1.406–1.493). The cardiac database demonstrates similar trends: anxiety (OR 1.967; 95% CI: 1.792–2.159), depressive episodes (OR 1.585; 95% CI: 1.398–1.797), and major depression (OR 1.660; 95% CI: 1.317–2.092). Conclusion and Potential Impacts: Our findings suggest that in patients with T2DM, semaglutide prescription is likely positively associated with a mood disorder diagnosis. Limitations of the database include a lack of dosage information and potential over- and underrepresentation of the true prevalence of mood diagnoses. Additionally, the observational nature of the study means causality cannot be implied. However, our findings suggest increased vigilance for depression and anxiety is appropriate in patients prescribed semaglutide.
Copyright (c) 2026 Uday Lomada, Jonathan Rusche, Steven Wu, Gattadahalli Seetharam http://creativecommons.org/licenses/by/4.0
Penile Plication for Severe Peyronie’s Disease Deformities: A Retrospective Review of Patient Characteristics and Surgical Outcomes
Background and Objective: Peyronie's disease (PD) is a fibrotic disorder of the penile tunica albuginea leading to penile curvature, pain, and reduced quality of life. Penile plication (PP) is an established surgical procedure to correct curvatures up to 60 degrees. However, data on outcomes for more severe curvatures remain limited, largely due to concerns about penile length loss or inadequate curvature correction. Current options to correct severe curvature, such as plaque incision/excision with grafting or penile prosthesis, require highly trained surgeons and carry increased complication risks. Our study aimed to assess the efficacy and safety of PP for severe PD deformities. Methods: We conducted a retrospective chart review of patients who underwent PP for severe curvature, defined as either uniplanar curvature ≥60 degrees or biplanar curvature ≥35 degrees. Patient demographics, comorbidities, satisfaction, and post-operative outcomes were analyzed. Results: Fifty-one heterosexual men, with a median age of 58 years, underwent PP for severe PD deformity. Concomitant PD and erectile dysfunction (ED) were present in 61% of cases. Preoperatively, the median primary curvature was 70 degrees, and for the twenty-five patients with biplanar deformity, the median secondary curvature was 20 degrees. Postoperatively, both the median primary and secondary curvatures were 0 degrees, with a median change from baseline of 65 and 20 degrees, respectively. At a median follow-up of 7 months, 92% of patients reported satisfaction with surgical outcomes. Penile shortening was subjectively reported by 6 patients, and 3 developed new-onset ED. Curvature recurrence occurred in 3 patients, with a mean time to recurrence of 6.3 months. Conclusion and Impact: PP is a safe and effective procedure for men with severe PD curvature, yielding high patient satisfaction, excellent curvature correction and low complication rates. These findings reinforce the role of PP as a valuable surgical option for severe PD deformities.
Copyright (c) 2026 James Malony, Katherine Snook, Lucas Amorim, Jeremiah Dallmer, Thairo Pereira, Helen Bernie http://creativecommons.org/licenses/by/4.0
Defining Pharmacodynamic Gene Markers and the Biological Processes of INPP5D Modulation Across Experimental Models
Background Alzheimer’s disease (AD) is a progressive neurodegenerative disorder marked by the accumulation of extracellular amyloid-β plaques and intracellular neurofibrillary tau tangles. Microglia respond to these pathological features but often become functionally impaired as the disease advances. INPP5D (also known as SHIP1), a phosphatase broadly expressed in hematopoietic cells and restricted to microglia within the brain, plays a key inhibitory role in regulating microglial activity. It acts through receptors such as TREM2, Dectin-1, and FcγR via the PI3K/AKT signaling axis. Preclinical studies suggest that inhibiting INPP5D enhances microglial function and reduces AD-related pathology. To advance INPP5D-targeted therapies, it is essential to characterize the downstream transcriptional effects of inhibition. Identifying consistent gene expression changes across experimental models can help establish pharmacodynamic markers and clarify biological pathways to guide therapeutic development. Methods We investigated transcriptomic alterations associated with INPP5D inhibition using four models: (1) primary mouse microglia from Inpp5d haplodeficient versus wild-type mice (in vitro), (2) TAD32-treated versus vehicle-treated primary microglia (in vitro), (3) TAD32-treated versus vehicle-treated C57BL/6J mice (in vivo), and (4) INPP5D-targeting siRNA versus scrambled RNA-treated C57BL/6J mice (in vivo). Gene expression was profiled using Nanostring’s neuroinflammation and glial panels. Differentially expressed genes (DEGs) were compared across models to identify shared molecular signatures, and enrichment analysis was performed. Results Despite a limited overlap of individual DEGs, we observed consistent enrichment of key biological pathways related to phagocytosis (including FcγR signaling, lysosomal function, and complement activation), inflammatory regulation (TLR, IL-17, and TNF signaling), and PI3K/AKT signaling. These findings suggest that INPP5D inhibition elicits conserved functional effects across diverse experimental contexts. Conclusion Our findings identify convergent transcriptional and biological responses to INPP5D inhibition that may serve as pharmacodynamic indicators. These results support the utility of INPP5D modulation in therapeutic development, offering potential biomarkers for drug selection and efficacy monitoring across preclinical models.
Copyright (c) 2026 Roma Matharu, Disha Soni, Peter Lin, Isaac Caballero-Floran, Bruce Lamb, Claudia Rangel-Barajes, Adrian Oblak http://creativecommons.org/licenses/by/4.0
Retrospective Review of Pediatric Polypectomy Cases at Riley Hospital for Children
Background: Despite advances in adult polypectomy research — particularly favoring cold snare polypectomy (CSP) over cold forceps polypectomy (CFP) for polyps <10 mm — pediatric adoption has lagged due to the absence of pediatric-specific studies and formal guidelines. Pediatric endoscopists often rely on expert opinions and extrapolate from adult guidelines despite important differences in polyp pathology, procedural training, and safety considerations. In adults, CSP is associated with lower recurrence rates than CFP, lower delayed bleeding than hot snare polypectomy (HSP), and a higher risk of immediate bleeding. We aimed to assess whether similar patterns of techniques and complications were observed in a pediatric cohort. Methods: We conducted a retrospective review of 395 polypectomy cases at Riley Hospital for Children from 2/2012 to 7/2025. Demographic, procedural, and post-polypectomy outcomes were collected and analyzed – with the latter category being our primary focus. Results: Of the 395 procedures, HSP was used in 237 cases, CFP in 171, and CSP in 78 (some procedures used more than one technique). Immediate bleeding requiring intervention occurred in 15 cases (3.8%), most commonly following CSP (7/78; 9.0%) and HSP (5/237; 2.1%). Delayed bleeding requiring hospitalization occurred in 4 cases (1.0%), all following HSP (4/237; 1.7%) with 2 requiring repeat endoscopy (0.8%). Polyp recurrence was identified in 4 cases (1.0%), all after CFP (4/171; 2.3%). Discussion/Implications: In this single-center retrospective review, our post-procedural findings align with adult data: the highest immediate bleeding rates occurred after CSP; the highest delayed bleeding rates occurred after HSP; and each polyp recurrence case occurred after CFP. These results suggest that adult findings may be applicable to pediatric practice, despite differences in polyp morphology, pathology, and procedural context. However, pediatric-specific evidence and formal guidelines are lacking; and multicenter or prospective studies are needed to better characterize complication risk, recurrence, and optimal polypectomy strategies in children.
Copyright (c) 2026 Matt Murray, Brett Hoskins http://creativecommons.org/licenses/by/4.0
Evaluating the Management of Ectopic Pregnancies at a Tertiary Teaching Hospital in Western Kenya to Build Minimally Invasive Gynecologic Surgery
Background/Objectives: Minimally invasive surgery (MIS) offers clinical and economic benefits over laparotomy which are critical in low- and middle-income countries (LMICs) like Kenya. Most efforts to expand MIS in LMICs have focused on surgical training, while systems-level barriers remain under-addressed. As part of a larger quality improvement (QI) initiative to expand minimally invasive gynecologic surgery (MIGS) at Moi Teaching and Referral Hospital (MTRH), this subproject of preliminary data focused on evaluating MIGS implementation for ectopic pregnancy using time-based analysis and outcome comparison. Methods: To assess change over time, we used a run-sequence plot to track rates of laparoscopic management of ectopic pregnancy, overlaying Plan, Do, Study, Act (PDSA) cycles to identify interventions and setbacks. We also compared clinical outcomes between laparotomy and laparoscopy groups, focusing on estimated blood loss (EBL), and length of hospital stay. Insights from a MIS Leaders Committee (LCom) interpreted these findings. Results: Laparoscopic management of ectopic pregnancies increased from an average of 2.8% to 6% after targeted interventions. The run chart revealed both progress and barriers to MIGS adoption. Preliminary data showed reduced EBL in laparoscopic cases but no difference in hospital stay. LCom feedback suggested selection bias in patient acuity and norms around post-op discharge practices as possible explanations. Additional challenges include case identification by OBGYN registrars and equipment, space, and staff availability. Conclusion: While some progress has been made, systems-level challenges continue to limit MIGS uptake. The ongoing QI project will focus on improvements needed to meet the target of 20% laparoscopic management of ectopic pregnancies and expand MIGS capacity at MTRH. Potential Impact: This work supports development of a context-specific MIS implementation toolkit for use across similarly resourced Kenyan hospitals. Improving MIS access advances surgical equity, strengthens health systems, and aligns with global health priorities shared by U.S. and Kenyan partners.
Copyright (c) 2026 Elena Rogers, Etoroabasi Ekpe, Doreen Gati, Peter Itsura, Wycliffe Kosegei, Richard Mogeni, Veran Mokua, Wan-Ju Wu http://creativecommons.org/licenses/by/4.0
A Regional Analysis of Air Quality and Respiratory Health Outcomes in the Northwest Indiana and Chicagoland Area
Background: Northwest Indiana (NWI) houses three of seven coal-based steel factories in the US and other major industries that contribute to air pollution in NWI and Chicagoland. Pollutants such as ozone, PM2.5, and PM10 are associated with respiratory disease onset and exacerbation. The American Lung Association has assigned failing air pollution grades to most NWI and Chicagoland counties. While respiratory diseases are prevalent locally, there is limited research on air pollution’s role. This study investigated air pollution exposures and associations with respiratory outcomes in NWI and Chicagoland. Methods: This retrospective study analyzed data from the Chicago Multiethnic Prevention and Surveillance Study (COMPASS), with social determinants of health, demographic, and environmental data for adults from 2013-2023. Additional air quality data were obtained from the Environmental Protection Agency and Washington University in St. Louis. Descriptive, bivariate (Chi-Square; Mann Whitney U, Kruskal Wallis, Spearman Rank), and multivariate (Binary Logistic Regression; Linear Regression, p<0.05) analyses were conducted using SPSS 31.0 (p<0.05). This study was IRB-exempt (Indiana University IRB #27779). Results: This study included 2,971 participants with respiratory conditions including asthma (94.4%), COPD (6.5%), chronic bronchitis (7.4%), and lung cancer (1.0%), with 8.5% residing near a pollution source. Among participants with respiratory conditions, exposure to one pollution source was associated with fewer hospitalizations (B=-.823), while clinic visits predicted more hospitalizations (B=.749). For asthma, less than high school education (OR=2.4), some college education (OR=3.3), exposure to one (OR=2.1) and multiple pollution sources (OR=2.7) increased the odds of ED visits. Contrastingly, exposure to one pollution source (B=-.830, p=.003) was associated with fewer hospitalizations. Former smoking was associated with older age (B=7.620) of asthma diagnosis. Conclusion: Air pollution and SDOH were associated with increased ED utilization for asthma, reflecting their combined impact. NWI is heavily industrialized but underrepresented in environmental research, warranting further environmental justice research and interventions.
Copyright (c) 2026 Elizabeth Sullivan, Baraka Muvuka http://creativecommons.org/licenses/by/4.0
Generation of CRISPR-Cas9 Engineered OPTNE478G Human Embryo Stem Cell Line for Investigation into Mitophagy Defects
Background: Optineurin (OPTN) is a mitophagy adaptor protein linking damaged, ubiquitinated mitochondria to autophagosomes for lysosomal degradation. The E50K and E478G OPTN mutations are associated with normal tension glaucoma and ALS, respectively. Currently, it is unknown whether the E50K mutation selectively affects retinal ganglion cells and the E478G mutation selectively affects motor neurons. Given OPTN’s role in mitophagy, investigating the mitophagy defects in human stem cell-differentiated (hRGCs) and induced motor neurons (iMNs) harboring these mutations provides an avenue to explore the cellular mechanisms of these diseases. Methods: This project generated a OPTN-E478G human embryonic stem cell (hESC) line through CRISPR-Cas9 gene editing. gRNA oligomers were annealed and cloned via transformation of DH5ɑ cells. Following sequencing, the gRNA-Cas9-GFP plasmid and donor plasmid with E478G insert were transfected into H7-WT-hESCs. The CRISPR-Cas9 system cut and repaired the double stranded break by homology-directed repair introducing the E478G mutation. GFP-positive colonies were isolated, expanded, and screened by PCR and restriction enzyme digestion. Western blot analysis of E50K and E478G mutants for hRGCs and iMNs were performed following introduction of the mitochondrial uncoupler CCCP, inducing mitophagy. Results: Insertion of the gRNA into the Cas9-GFP plasmid was confirmed by sequencing. The hESCs were successfully transfected with the E478G plasmid as confirmed by restriction enzyme digestion of SapI and BspHI. Isolation of this stem cell population is ongoing and will be screened with restriction enzymes prior to sequencing. Western blots of NBR1 showed increased levels in WT-hRGCs and iMNs (E50K and E50K corrected), but not in E50K-hRGCs, indicating impaired mitophagy. Conclusions: Our study reveals distinct mitophagy defects seen in the OPTN mutations E50K and E478G for the RGCs and iMNs. This project lays the groundwork for further studies, including live cell imaging, OPTN activation, and LC3b lipidation, to further define the implications of these mutations on mitophagy.
Copyright (c) 2026 Maverick Tebbe, Saajid Kathri, Michelle Surma, Arupratan Das http://creativecommons.org/licenses/by/4.0
Modeling Inflammaging of the Bone Marrow Microenvironment Stimulates Multiple Myeloma Associated Stem Cells
Background: Multiple Myeloma (MM) is a malignancy of mature plasma cells, primarily affecting patients over 65, with a 5-year survival rate of ~62%. Aging alters the bone marrow (BM) microenvironment, including remodeling of the extracellular matrix (ECM), which may promote tumor-supportive functions of mesenchymal stromal cells (MSCs) and hematopoietic stem cells (HSCs). However, determining the impact of aging-related matrix remodeling on MM onset/progression remains challenging due to the absence of microphysiological systems that preserve the tumorigenic phenotype of MM cells in vitro. We hypothesize that recapitulating aged BM ECM may overcome these limitations by providing a physiologically relevant microenvironment that sustains MM cell behavior and models tumor-supportive functions. Additionally, we expect that interleukin-6 (IL-6), an inflammatory cytokine elevated in both the inflammaging BM microenvironment and MM, preferentially expands MM-associated MSCs without affecting HSCs. Methods: Cryopreserved tumor-associated MSCs and HSCs were cultured on tissue culture plastic (TCP), young ECM (≤25 y/o), or aged ECM (≥60 y/o), in either α-MEM or IMDM media, with or without IL-6. HSC cluster formation was observed, and cells were analyzed using Cytospin with Giemsa-May-Grünwald staining. Results: MM-derived HSCs, cultured on aged ECM, but not young, exhibited myelopoietic skewing. In contrast, young ECM supplemented with IL-6 promoted MSC expansion, suggesting a synergistic effect in developing patient-derived stromal models. Adherent MSCs were harvested and expanded on TCP to produce ECM. Conclusion: ECM-based microphysiological systems offer a promising, scalable approach for recapitulating aging- and MM-associated remodeling of the BM microenvironment. Understanding how aged ECM drives myeloid skewing may reveal therapeutic targets to delay/prevent MM progression. The observed myeloid bias in MM-derived HSCs cultured on aged ECM may reflect physiologically relevant disruptions in immunoregulatory cell populations. Future work will test whether ECM from MM patient-derived MSCs preserves tumor-specific phenotypes to advance translational models for MM drug discovery.
Copyright (c) 2026 Krishi Thaker, Piper Wilburn, Conner Quinlan, Noriyoshi Kurihara, Attaya Suvannasankha, Miloš Marinković http://creativecommons.org/licenses/by/4.0
Understanding Patient-Centered Factors of Percutaneous Electrical Nerve Field Stimulation (PENFS)
Background: Disorders of gut-brain interaction (DGBI) affect approximately 25% of U.S. children and include conditions like functional dyspepsia and irritable bowel syndrome. Percutaneous Electrical Nerve Field Stimulation (PENFS) like IB-Stim shows promise in reducing pain, nausea, and disability in pediatric DGBI cases. This study explores how patient-level factors like demographics, diagnoses, and orders relate to IB-Stim usage and aims to identify barriers to care and guide patient-centered treatment strategies. Methods: We conducted a retrospective cohort study of 60 patients (8-21 years) who received IB-Stim through the IU Health/Riley Pediatric Gastroenterology department between July 2021 and June 2025. Patient data was extracted from the IU Health Cerner EMR with support from Children’s Health Services Research. Collected variables included demographics, diagnoses, medications, insurance type, and other clinical information. We performed a univariate analysis between the demographics (age, gender, income, insurance type), diagnoses, and types of orders. Chi-squared tests were performed between gender and insurance type and the other data elements. T-tests were performed between age and income and those data elements. Results: Descriptive analysis findings show that more females undergo IB-Stim treatment. Patients tend to receive treatment in their mid-teenage years (M=15.8 yrs., SD=2.4, Median=16.2 (14.7-17.8)). Univariate analysis did not show clear patterns on any variations among demographic information and treatment usage. Conclusions and Potential Impact: The lack of variation may occur because all patients received treatment within the same practice. This finding indicates that differences in demographics—such as age, insurance type, and income—do not dictate whether or not a patient is offered IB-Stim treatment at Riley Hospital. Gender and age distribution suggest other factors influence IB-Stim usage. Further research on these patient-centered factors will be conducted in a qualitative study, in which participants will partake in a semi-structured interview and answer questions about their experiences and expectations with IB-Stim.
Copyright (c) 2026 Priyanka Thomas, William Bennett Jr. http://creativecommons.org/licenses/by/4.0
Ex Vivo Neurite Outgrowth of Sensory Neurons Derived from Patients Suffering from Taxane-Induced Peripheral Neuropathy
Introduction: Taxane-induced peripheral neuropathy (TIPN) is a devastating side effect commonly seen in African American women being treated with chemotherapy for breast cancer and can cause significant dose reduction or cessation of treatment. EAZ171, a first NCI sponsored clinical trial focusing only on African American women with breast cancer, demonstrated that docetaxel clinically caused significantly less TIPN than paclitaxel. In the current project, we have investigated the impact of two taxanes, paclitaxel and docetaxel, on the morphology of neurons derived from EAZ171 patients. Methods: Using an ex vivo model of induced pluripotent stem cell-derived sensory neurons (iPSC-dSNs) derived from peripheral blood of EAZ171 TIPN case and control patients, we measured neurite outgrowth of the induced neurons treated with vehicle or taxane. The change in neurite outgrowth was analyzed between vehicle- and taxane-treated groups. Differences in taxane induced neurite outgrowth between patients who experienced TIPN (cases) and those who did not (controls) were assessed for the differential impact of paclitaxel vs docetaxel. Results: Taxane treatment significantly reduced the neurite outgrowth of iPSC-dSNs in a combined analysis and an analysis stratified by taxane type. Compared to the iPSC-dSNs derived from their control counterparts, iPSC-dSNs derived from paclitaxel therapy cases had a greater reduction in neurite outgrowth than that from docetaxel therapy cases. Conclusions: The differences between paclitaxel and docetaxel in this model mirror the clinical differences in EAZ171 and provide an opportunity for unraveling mechanistic differences in this ex vivo model system. Further investigation involving fluorescence-based calcium imaging, whole transcriptome sequencing, methylation analysis, and ATAC-Seq can uncover differences between taxane types and factors that predispose patients to TIPN.
Copyright (c) 2026 Zane York, Erica Cantor, Fei Shen, Santosh Philips, Bryan Schneider http://creativecommons.org/licenses/by/4.0
Evaluation of a Multicomponent ED-based Intervention for Increasing Rates of Lung Cancer Screening: a Randomized Controlled Trial
Background/Objective While lung cancer screening (LCS) is a promising means to decreasing mortality from lung cancer among high-risk populations, as few as 6% of those who are eligible are screened. This is especially true for emergency department (ED) patients, who have a greater tendency towards tobacco smoking and lack of primary care compared to the general population. Thus, the ED represents an opportune setting in which to increase awareness of and access to LCS. The goal of this study is to determine the efficacy, acceptability, and feasibility of a multicomponent ED-based LCS intervention. Methods Patients complete a pre-survey including background information as well as knowledge about LCS and beliefs about lung cancer and its risks. The control group receives a brochure on LCS, a discharge diagnosis of tobacco use, and a referral to primary care. The intervention group interacts with LungTalk, completes a follow-up survey on the acceptability of the intervention, and is referred to the LCS clinic at Eskenazi Health. Feasibility is defined as ≥50% enrollment among approached eligible patients, and acceptability is defined as ≥70% of patients responding positively to the follow-up survey. Results/Conclusion Preliminary data show a trend confirming the acceptability of the intervention. A majority of patients report no delays or disruptions in medical care, and intention to screen after using LungTalk was expressed in a majority of the intervention. Almost all responded that they would recommend LungTalk to a friend. As for feasibility, enrollment among patients who were approached and found to be eligible is currently 46%. Impact and Implications This study will provide data for a future large-scale trial to be done across multiple affiliated EDs to assess generalizability of results. Importantly, it will allow for optimization of the intervention design and delivery to target the underserved and marginalized populations that make up the majority of ED patients.
Copyright (c) 2026 Peter Mayfield, Nicholas Pettit http://creativecommons.org/licenses/by/4.0
Isolation and Quantification of Microplastics from Pediatric Tonsils
Background: Microplastics have been identified in nearly every organ system, posing an increasing and poorly characterized threat to human health. This project aims to isolate and quantify environmentally acquired microplastics in pediatric tonsil samples. Tonsils provide a unique opportunity for the isolation of microplastics. Not only are they highly vascularized, but they are also exposed to microplastics through eating, drinking, and breathing. Methods: Pediatric tonsils, removed as standard of care, were obtained from a Stanford University collaborator on an approved IRB protocol. Samples were digested in 10% KOH at 50C for 48hrs with 30mins of ultrasonication at 24hrs (42kHz). Enzymatic digestion followed using collagenase (1mg/mL), DNase (100μg/mL), and proteinase K (250μg/mL) for 24hrs. Post-digestion, samples were stained with Nile Red (30μg/mL) to selectively visualize microplastics and filtered via 0.2μm aluminum oxide filters in an all-glass vacuum apparatus. Filters were imaged under brightfield, Texas Red (ex-560nm), and CY3 (ex-540nm) fluorescence channels. Image quantification was performed using R-statistical software to assess particle count, diameter, and area. Results: The digestion protocol effectively degraded tissue while preserving suspected microplastics. Filters captured fluorescently labeled particles larger than 0.2μm. Preliminary analyses revealed fluorescently labeled particles in every sample (n=6). Across samples there was a mean particle count of 268±274 and a median particle diameter ranging from 13.0μm to 15.6μm. No observed correlation between tonsil mass (78.3±39.4mg) and particle number. In the tissue free negative control, 39 particles were identified. Conclusion/Impact: Despite growing evidence of systemic microplastic contamination and an ever-increasing exposure to plastics, reliable methods for isolating and characterizing environmentally acquired microplastics remain limited. This work establishes an optimized protocol for non-destructive isolation and quantification of microplastics from human tissue. The tonsil-isolated microplastics will undergo further particle typing and be used in subsequent tissue culture models to better understand microplastic exposure implications to human health.
Copyright (c) 2026 http://creativecommons.org/licenses/by/4.0