bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing the Self-Rating Scale Item as a Measure for Lactulose Adherence
Authors: Tam Stacey , Garcia Nicole , Orman Eric
Published: January 2024

Background/Objective:Hepatic encephalopathy (HE) is a defining complication of end-stage liver disease. The standard treatment is lactulose, but adherence is difficult due to complex dosing regimens and side effects. We adapted a single item self-reported adherence measure - the Self Rating Scale Item (SRSI) - for lactulose use and examined its relationship with clinical events, cognition, and quality of life.
Methods:We performed a cross-sectional study of patients with cirrhosis and HE seen at Indiana University Hospital 5/31/2023-7/14/2023. Clinical history and demographic information were collected through electronic health records and patient interviews. Patients provided the SRSI, which reflects their self-perceived ability to take lactulose, bowel movement frequency, perception of missing doses, and quality of life (PROMIS-29+2). Cognition was measured using the Animal Naming Test (ANT). The relationship between the SRSI and other measures was assessed.
Results:42 patients met eligibility criteria and enrolled. The median age was 59, and 55% were female. Patients were divided across SRSI categories: ≤good, very good, and excellent. Patients with better adherence were more likely to have ascites, but other demographics were similar between groups. Ascites was present in 43%, 64%, and 93% of ≤good, very good, and excellent categories, respectively. A higher SRSI score was associated with fewer missed doses and more days achieving bowel movement targets. 79% in the ≤good category skipped lactulose doses compared to 29% and 21% in very good and excellent groups. SRSI was not associated with HE-related hospitalizations or ANT. Higher SRSI was associated with improved sleep and cognitive function, with a trend towards decreased fatigue and pain.
Conclusion/Potential Impact:The SRSI is associated with other measures of lactulose adherence and quality of life and may be a promising tool to measure lactulose adherence. Adopting the SRSI may be a useful way to improve lactulose dosing, adherence, and health outcomes.
Prenatal Predictors of Survival, Pulmonary Hypertension, and ECMO in Isolated CDH Undergoing Expectant Management, A Systematic Review and Meta-analysis
Authors: Thiel Meera A. , Tofte Alena N. , Khalil Asma , Mustafa Hiba J.
Published: January 2024

Background and Hypothesis: Congenital diaphragmatic hernia (CDH) is a severe developmental defect affecting 1-4 per 10,000 births, characterized by left/right-sided defect, or mixed with herniation of abdominal contents into thorax, with resultant lung hypoplasia and persistent pulmonary hypertension (PHTN). The study investigates prenatal predictors of survival to hospital discharge, PHTN and the need for ECMO in fetuses with isolated CDH undergoing prenatal expectant management.
Project Methods: We performed a systematic literature review on prenatal diagnostic tests in fetuses with isolated CDH undergoing expectant management. Primary outcomes included survival-to-hospital discharge, persistent PHTN within 28 days, and ECMO need. Newcastle Ottawa Scale assessed quality of studies. Meta-analysis performed when two or more studies reported on the same test. Subgroup analysis performed according to CDH side.
Results: 161 full-text articles between 2000-2022 were assed for eligibility; 48 met inclusion criteria. 45 reported on survival, 12 on ECMO need, 8 on PHTN; quality of studies was moderate. Studies included were retrospective (81%) or prospective (19%) regarding fetuses undergoing expectant management (77%), or mixed tracheal occlusion and expectant management (20%). Most studies included mixed (41%) or left-sided (47%) CDH. Survival predicted by TFLV, o/e-TFLV, o/e-TFLV <30%, LiTR, o/e-LHR, o/e-LHR <25%, percentage herniated liver, MSA, stomach position in mid-chest, and liver up. ECMO need predicted by o/e-TFLV, o/e-LHR, and PPLV. These results were confirmed through subgroup analysis of only left-sided lesions. PHTN was predicted by presence of intrathoracic liver (OR-1.96, 95%CI 1.14,3.37, I2-0%); this was not significant after left-sided subgroup analysis.
Conclusion and Potential Impact: In fetuses with CDH, FLV and presence/percentage of intrathoracic liver predict survival. FLV measurements predict ECMO need. Presence of intrathoracic liver may predict persistent PHTN; further studies are needed. Accurate prognostication of CDH severity would aid patient triage, resource mobilization, and identification of high-risk CDH infants in need of advanced treatment including ECMO or identification of candidates for fetal intervention procedures.
SSRI Efficacy in Treating Major Depressive Disorder: Preliminary Findings
Authors: Desiron Samantha , York Brian
Published: January 2024

Background: Conflicting evidence on the relative effectiveness of second-generation antidepressants has made initial management of major depressive disorder (MDD) complex and frequently results in a trial-and-error-based approach to treatment. With recent literature suggesting serotonin plays no significant role in the etiology of depression, further investigation of selective serotonin reuptake inhibitors (SSRIs) as a firstline treatment of MDD is warranted.
Methods: A retrospective chart review of patients 18 years or older visiting the Fort Wayne Family Medicine Center and completing a Patient Health Questionnaire (PHQ) or Generalized Anxiety Disorder scale (GAD) from January 2020 through May 2023 was performed. Comparative analysis of PHQ and GAD scores was performed to determine if any differences in treatment management outcomes were present between SSRI therapy and other treatment approaches.
Results: 1,502 patients met the inclusion criteria. Due to time constraints, a sample of 45 patients (10 males, 35 females) was selected and preliminary results are as follows: After initiating treatment with an SSRI, 14 (42.4%) PHQ scores and 7 (24.1%) GAD scores demonstrated improved disease severity. After initiating treatment with another antidepressant class, 10 (31.3%) PHQ scores and 17 (48.6%) GAD scores demonstrated improved disease severity. There was no significant difference (p=0.351) in treatment outcomes between antidepressant class in terms of PHQ results, but a significant difference (p=0.044) was found between groups with regards to GAD results.
Conclusions: This study describes preliminary findings on the current patterns of care for mental health within a primary care setting and demonstrates antidepressant classes appear equally efficacious in treating depression. However, anxiety management outcomes appear to be influenced by antidepressant class administered. Future analysis will include the entire available dataset and produce more robust results from which to improve patient-specific and community health outcomes.
Clinician Perspectives on Risks and Benefits of Sharing Cardiovascular Implanted Electronic Device (CIED) Data with Patients
Authors: Tran Brandon , Daley Carly , Pruitt Stephanie , Shirazi Jonathan , Allmandinger Tina , Toscos Tammy , Mirro Michael
Published: January 2024

Background and Objective: Cardiovascular implantable electronic devices (CIEDs) are critical, life-saving devices that are essential for the clinical decision-making process due to the data they collect. Because not all patients have ready access to their device data, there may be a clinical care gap where the CIED data are not being used most effectively in the care of patients with CIEDs. However, sharing CIED data may risk harming clinician-patient relationships and necessitates further study into clinician’s perspectives on CIED data sharing. The objective of this study was to explore clinicians’ perspectives on sharing CIED data with their patients and explore the perceived benefits and concerns.
Methods: Clinicians involved in CIED care in the United States were recruited for semi-structured phone interviews. Participants were asked questions regarding their experiences and perspectives in sharing CIED data, and were presented scenarios to assess how they would leverage the CIED data in particular situations. Responses from the participants were analyzed by one researcher using thematic analysis.
Results: Of the 28 clinicians interviewed in this study, the majority were white (85.7%) and located in the midwestern United States (67.9%). Participants included cardiac device clinic nurses and electrophysiology nurses (28.6%), electrophysiologists (25%), electrophysiology advanced practice providers (APPs) (17.9%), cardiologists (14.3%), and cardiology APPs (14.3%). The following themes were identified: (1) Patient engagement with healthcare, (2) Patient selfadvocacy, (3) Patients cannot interpret CIED data, (4) One size does not fit all.
Conclusion and Potential Impact: Clinicians perceived both potential benefits and harms from CIED data sharing. Clinicians noted that CIED data sharing has the potential to increase patient participation in their healthcare, but it also can cause increased patient anxiety due to insufficient patient education. This study demonstrated some of the ways CIED data sharing may affect clinical practice involving CIEDs and the challenge of sharing complex data elements with patients.
Clinical Characteristics of Pre-pubescent Patients with Systemic Lupus Erythematosus (SLE)
Authors: Zagales Ruth , Tarvin Stacey E. , Rodriguez Martha
Published: January 2024

Background:
Systemic Lupus Erythematosus (SLE) is a chronic autoimmune condition that affects multiple organ systems, including cutaneous, renal, neurological, and hematological disorders. Pediatric SLE (pSLE) has a prevalence of 3.3-8.8 cases per 100,000 children. Children with SLE (cSLE) have higher disease severity than adults, but the evidence on cSLE is mostly from pubertal patients, and the reasons for the variation on presentation is unclear. There is limited data on prepubertal SLE, as SLE rarely affects pre-pubescent patients. This study aims to outline the clinical characteristics, disease activity and organ damage of pre-pubescent patients with SLE.
Methods:
A retrospective study was performed on prospectively collected multi-center data from 2005-2015. Patient data, including race, ethnicity, sex, age of presentation and diagnosis, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, and Systemic Lupus International Collaborating Clinics (SLICC) damage index was collected using REDcap.
Results:
This study included 43 pre-pubescent SLE patients, with an average age at diagnosis of 9.7 years and 10.7 years at the study's start. Organ systems with the highest prevalence rates were musculoskeletal (Arthritis – 69.77%) and cutaneous (Malar rash – 58.14%). The organ systems with the highest involvement frequency, according to the SLICC damage index, were skin (alopecia - 9.3%), ocular (retinal changes/optic atrophy/cataracts - 9.3%), gastrointestinal (pancreatic insufficiency – 4.65%), neuropsychiatric (cognitive impairment – 4.65%), and renal (reduced glomerular filtration rate – 4.65%). Throughout the study, all patients had SLEDAI scores ranging from no activity to high activity, with 55.8% having mild activity, 27.9% having moderate activity, and 14% having high activity.
Conclusion:
Similar to SLE studies on pediatric populations, our study found that cutaneous, gastrointestinal, and renal manifestations were common. However, we found a high prevalence of damage in prepubertal patients, in particular ocular and cognitive impairment. This highlights the need to prioritize ocular exams and cognitive assessments in patients with prepubertal SLE.
Identifying Socio-Demographic and Behavioral Predictors of Prolonged Hospital Stay in an Urban Hospital in Northwest Indiana
Authors: Yallourakis Michael , Gonsiorowski Eric , Muvuka Baraka , Guerrero Jonathan E.
Published: January 2024

Background: Hospital length of stay (LOS) is a crucial metric that impacts patient outcomes, healthcare resource utilization, and financial burden. In 2019 the CDC reported the average LOS in community hospitals was 5.4 days. Prolonged LOS is associated with an increased risk of hospital-acquired infections, decreased hospital bed availability limiting patient access to care, and cognitive impairment, particularly among the elderly. This indicates the importance of addressing LOS as a healthcare priority. This study examined the relationship between LOS and social determinants of health (SDOH), patient demographics, health behaviors, and health outcomes as part of a long-term Community Based Participatory Research partnership between IUSM-NW and St. Mary Medical Center (SMMC).
Methods: This retrospective study analyzed EPIC™-generated data for adult inpatient visits at an urban hospital in Northwest Indiana from January 2021 to March 2023. Data analysis was performed using SPSS 28.0, consisting of descriptive statistics, bivariate analysis (One-way ANOVA, Independent T-tests, Kruskal Wallis H; p<0.05), and Simple Linear Regression. This study was granted an exemption by the Indiana University Human Research Protection Program (IRB #14040).
Results: The sample comprised of 10,916 predominantly white (77.7%) patients with a median age of 65 (IQR=22) and a median LOS of 4 days (IQR= 5). Bivariate analysis revealed LOS was significantly associated with age (p<0.001), race (p<0.033), sex (p<0.012), insurance type (p<0.001), physical inactivity (p<0.001), and smoking tobacco (p<0.001). After controlling for all factors in the multivariate analysis, age (p<0.020), physical inactivity (p<0.013), and insurance type (p<0.013) retained their significance.
Conclusions: These findings highlight the significance of demographic, behavioral, and social factors in relation to hospital LOS. Understanding these factors holds immense potential to guide the development of targeted interventions and healthcare strategies to optimize patient care and reduce LOS.
“There’s Healing in Music”: Veteran Perceptions of Music Interventions for Their Chronic Musculoskeletal Pain
Authors: Whalen Claire , Story K. Maya , Bair Matthew J.
Published: January 2024

Background/Objective: For veterans suffering from chronic musculoskeletal pain, finding alternative treatments to analgesics is critical for safer, more effective pain management. While music interventions have shown promise for acute pain, their acceptability for chronic pain and telehealth delivery needs more rigorous examination.
Methods: The Feasibility and Acceptability of Music Imagery and Listening Interventions for Analgesia (FAMILIA) study randomized 60 veterans with chronic musculoskeletal pain to receive usual care, telehealth music listening (ML), or telehealth music imagery (MI). ML involved independent listening to songs of each participant’s choosing, while MI consisted of one-on-one music therapist-led sessions combining ML, imagery, and verbal processing. To complement quantitative analysis of patient-reported outcomes, qualitative interviews of participants were conducted to understand perceived benefits, acceptability, barriers, and facilitators of study interventions. We analyzed 15 interviews using thematic analysis to assess acceptability of the music interventions.
 
Results: All interviewees perceived mental-emotional benefits and almost all experienced physical pain relief during their music listening or therapy sessions. However, many noted that the pain relief was short term, and for some veterans randomized to ML, certain songs evoked negative associations. Participants also benefited from study participation and its formal structure, in contrast to their prior informal music listening experiences. Planned study activities like participant check-ins with staff and interactions with therapists fostered a deeper understanding of how music can be therapeutic and increased veterans’ confidence in their own ability to use music therapeutically. Study acceptability was further evidenced by interviewees’ intention to continue using music listening and imagery techniques after study completion and their strong support for expanding access to music interventions to other veterans.
Conclusion/Implications:  The FAMILIA study not only supports telehealth music interventions as acceptable treatments for chronic musculoskeletal pain, but the reported physical pain and mental-emotional benefits necessitate a larger, fully powered study.
Ethanol Induces Blood Brain Barrier Dysfunction in Healthy and Familial Alzheimer’s Blood Brain Barrier Models
Authors: Wetzel Abby M. , Bell Kameron T. , Hughes Jason M. , Canfield Scott G.
Published: January 2024

Background/Objective:
The blood brain barrier (BBB) is a highly selective semipermeable membrane between the blood and brain. Active efflux transporters such as PGP, MRP-1, and BCRP and localized tight junction proteins ensure barrier integrity. Interestingly, both alcohol consumption and Alzheimer’s disease (AD) suppress barrier functions independently. Furthermore, alcohol use can lead to or worsened neurodegenerative disorders, including AD. In this study, human stem-cell derived healthy and AD BBB models with near in vivo properties are used to investigate the effects of alcohol on critical BBB properties such as barrier tightness and efflux transporter activity.
Methods:
Induced pluripotent stem cells (iPSCs) from healthy (IMR90) and Familial Alzheimer’s (APP, PSEN1, PSEN2) cell lines were differentiated into brain microvascular endothelial cells (BMECs).  BMECs were treated with varying ethanol concentrations (5, 25, 50, and 100 mM) for one hour. Following ethanol treatment several barrier properties were assessed: trans-endothelial electrical resistance (TEER), sodium fluorescein permeability, tight junction localization, and efflux transporter activity.
Results:
Moderate to severe ethanol concentrations (25 mM and 50 mM) reduced TEER and delocalized tight junctions in healthy and AD-derived BMECs, indicating a disruption in barrier integrity. AD-derived BMEC cell lines also show an increased susceptibility to ethanol-induced barrier dysregulation at lower concentrations of ethanol (5 mM). Interestingly, our preliminary data shows that ethanol exposure seems to reduce BCRP efflux transporter activity in APP and PSEN1 AD cell lines.
Conclusion and Scientific Impact and Implications:
This study is novel in elucidating the enhanced disruption of BBB properties in familial AD-derived BMEC cell lines following ethanol exposure and provides insight into the potential harm of alcohol consumption in the development and/or exacerbation of BBB dysfunction in Alzheimer’s disease. Further studies will also unveil the possibility of ethanol-induced reduction of BCRP efflux transporter activity in APP and PSEN1 AD.
MR1/MAIT Cell Axis Impacts Innate Immunity and Synaptic Proteins in 5XFAD Mice
Authors: Warren Jalyn , Johnson Season , Ackley Samantha , Afifi Reham , Shrinivasan Rashmi , Brutkiewicz Randy R.
Published: January 2024

Background:
Amyloid beta (Aβ)-induced synaptic dysfunction and inflammation are features of Alzheimer’s disease (AD). One contributor to inflammation is mucosal-associated invariant T (MAIT) cells, an innate T cell that recognizes antigens presented by the MR1 molecule. Previously, we found increased MR1 expression in microglia near plaques and the loss of MR1/MAIT cell axis slowed the progression of Aβ pathology. This study aimed to determine contributions of the MR1/MAIT cell axis to immunity and synaptic proteins in the 5XFAD AD model mouse.
Methods:
We crossed 5XFAD mice with MR1-deficient mice (which lack MR1 and MAIT cells). At 2-, 4-, 6-, and 8-months of age, hippocampal and cortical brain tissue from wild-type, MR1KO, 5XFAD, and 5XFAD/MR1KO mice were analyzed by Western blot. Protein levels were analyzed with antibodies against GFAP (astrocytes), complement C3, and postsynaptic density protein (PSD)95. Additionally, Novel Object Recognition, Open Field, and Barnes Maze behavioral tests were performed in the 5XFAD mice to measure memory deficits.
Results:
Region-specific results were obtained for the hippocampus and cortex. The expression levels of PSD95 and C3 were significantly upregulated in the hippocampus of 5XFAD/MR1KO compared to 5XFAD mice at 6-8 months of age; in the cortex, GFAP levels were also significantly increased in 5XFAD/MR1KO mice. Finally, compared to wildtype C57BL/6 mice, 5XFAD mice showed memory deficits.
Conclusions and Potential Impact:
Approximately 6.7 million Americans are living with AD. This number is expected to double by 2050. Without any currently demonstrated therapy against AD, there is a need for therapeutic target(s) as part of novel treatment paradigms. Our results demonstrate an impact of the MR1/MAIT cell axis on postsynaptic proteins and consequent AD pathology. Thus, understanding the contribution of this axis could help reveal the role of innate immunity in AD and potentially serve as a future therapeutic target in AD patients.
Exploring Differentiation and TEAD Inhibition in NF2-Knockdown NES Cells
Authors: Badar Sidrah , Burket Noah , Tailor Jignesh
Published: January 2024

Background: The NF2 gene is a tumor suppressor encoding gene on chromosome 22 that is a known regulator of the Hippo pathway. When the mammalian version of the pathway is inactive, such as with a loss of NF2, downstream proteins YAP/TAZ remain unphosphorylated, enter the nucleus to form a complex with TEAD 1/2/3/4, and begin transcription. Hyperactivation of theYAP/TAZ-TEAD complex has been observed in many cancers, allowing for targeting with TEAD inhibitors. Here, we assess how the loss of NF2 in human neuroepithelial stem (NES) cells affect their differentiational development. We also seek to understand the effects of TEAD inhibition on wildtype (WT) and NF2-knockdown NES cells.
Materials and Methods: Differentiation. WT and NF2-knockdown cells were grown in media without growth factors to differentiate them. TEAD Inhibition. Non-differentiating and differentiating WT and NF2-knockdown cells were treated with TEAD Inhibitor 690 (TEADi). During both conditions, cells were harvested at 5 points throughout the growth period.
Results: Decreased NF2 in cells promoted retention of an earlier cell morphology compared to WT, which appeared to develop neuronal features, such as axons. WT cells exhibited elevated expression of genes characteristic of NES differentiation when compared to NF2-knockdown cells. Following the addition of TEADi, cell culture imaging revealed seemingly increased cell death in WT cell populations compared to NF2-knockdown cells. Interestingly, differentiating NF2-knockdown cells adhere to one another to form clusters, but with TEADi, these clusters are formed to a much lesser extent.
Conclusion: Although more experimentation is needed, these are early steps in demonstrating how NF2 loss appears to halt the differentiation of NES cells. Additionally, TEAD inhibition seems to reduce the clustering seen in differentiating NF2-knockdown cells; however, experimental concentrations need to be explored in the future. Further work is needed to understand the effects of TEAD inhibition on NF2-knockdown cells.
Artificial Intelligence in the Detection of Fatty Liver Disease
Authors: Catron Evan J. , Passarelli Robert P. , Wilmes Danielle , Griesemer Alex , Wei Barry , Le Minh-Uyen T. , Li Ping , Zhang Wenjun , Lin Jingmei , Mihaylov Plamen V. , Kubal Chandrashekhar A. , Mangus Richard S. , Ekser Burcin
Published: January 2024

Background: The current gold standard for quantification of the fat content of the liver (i.e., nonalcoholic fatty liver disease, NAFLD) is the visual microscopic inspection of liver biopsies by pathologists. Percentage of macrosteatosis (%MaS), used in determining NAFLD diagnosis, is vital in determining the transplant suitability of a donor liver. A major limitation of this method is inevitable human error which causes interobserver variability and overestimation of %MaS which could cause a potential discard of donor livers. We hypothesize that artificial intelligence (AI) can assist pathologists in providing a more objective and accurate measure of %MaS.
Methods: Our literature review identified HALO (image analysis) and U-Net (deep-learning) as AI programs currently available for high-accuracy %MaS calculation in liver biopsies. We compared the pathologist-reported %MaS from de-novo liver transplant (LT) biopsy samples taken 2h post-reperfusion to the %MaS calculated by HALO and/or U-Net (Fig. 1). 250 patients had undergone de novo LT at Indiana University between 2019-2020, and 211 of these patients had sufficient data (liver enzyme tests, biopsy results) to be included. Each biopsy sample was digitized into 5 random non-overlapping tiles at 20x magnification using a Leica microscope. Early allograft dysfunction (EAD) is defined by the presence of at least one of the following: (i) INR >1.6 on postoperative day (POD) 7, (ii) total bilirubin >10 mg/dL on POD7, or (iii) AST/ALT >2000 IU/L within the first 7 days following LT.
Results: Our literature review identified that both HALO and U-Net estimated the %MaS in liver allograft biopsies significantly lower than pathologists' estimation (Fig.1). Of 211 included patients, 46 (21.8%) had EAD. In this ongoing project, we found U-Net to have a 97.3% training accuracy with eight epochs (2000 biopsy images each). Tiles from the first ten patients are being analyzed by HALO and/or U-Net to calculate an average %MaS for each patient. These calculations will be compared to the %MaS estimation made by pathologists.
Conclusions: The rapidly evolving field of AI is emerging as a promising method in the quantification of the fat content of the liver with increased accuracy. AI will therefore help pathologists and transplant surgeons to determine liver transplant viability and better predict EAD in transplant patients.
Ineffectiveness of mitoTEMPO on Cardiomyocyte S-phase Activity in TNNI3K-expressing Mice
Authors: Chahoud Elias , Reuter Sean , Field Loren
Published: January 2024

Background and Hypothesis: The limited regenerative capacity of the mammalian adult myocardium is a significant roadblock for therapeutic approaches in cardiovascular disease. Cell cycle arrest following S-phase is widely considered a primary contributor to the reduced proliferative capacity of adult cardiomyocytes. Recently, expression of troponin I-interacting kinase (Tnni3k) was shown to increase cardiomyocyte S-phase activity in mice. Tnni3k was previously shown to enhance ROS formation and adverse cardiac remodeling following injury. Our primary hypothesis was that TNNI3K-induced cardiomyocyte DNA synthesis resulted from enhanced ROS signaling. To test this, cardiomyocyte S-phase activity in TNNI3K-expressing mice was compared between those treated with the ROS scavenging agent mitoTEMPO and untreated mice.
Project Methods: Transgenic mice expressing TNNI3K were subjected to 14 days infusion with mitoTEMPO (experimental group) or vehicle (control group). The mice were also subjected to 14 days infusion with bromodeoxyuridine (BrdU) to identify DNA synthesis during S-phase (all mice carried a cardiomyocyte-restricted nuclear-localized transgenic reporter to aid in cardiomyocyte nuclei identification). The proportion of cardiomyocytes in S-phase was determined and mean S-phase activity was compared between treatment groups. Ploidy analysis was also conducted to determine if cardiomyocytes completing S-phase progressed through karyokinesis.
Results: The percentage of cardiomyocytes in S-phase in the control and mitoTEMPO treated group were 0.819% ± 0.163% and 0.855% ± 0.138%, respectively (mean ± SEM, p=0.873). Ploidy analysis revealed no overt difference in DNA content in S-phase-positive cardiomyocyte nuclei between the groups. Hence, we have shown that there is no appreciable difference in cell cycle induction or progression in cardiomyocytes from control vs. mitoTEMPO treated mice expressing TNNI3K.
Conclusion and Potential Impact: These data suggest that (a) TNNI3K-induced cardiomyocyte S-phase activity is not secondary to elevated ROS activity, and (b) reduction of ROS activity does not relax the cell cycle block between S-phase and karyokinesis in adultcardiomyocytes.
Probing Brain Magnetic Susceptibility Alterations in a Mouse Model of Multiple Sclerosis
Authors: Gaughan Adrienne , Wang Nian , Maharjan Surendra , Wallace Abigail
Published: January 2024

Multiple sclerosis (MS) is an increasing cause of disability in the United States, characterized by autoimmune demyelinating events in the central nervous system. MS patients can present with a varying range of symptoms and disability due to the chronic inflammatory and relapsing events associated with the disease, such as impaired mobility, slowed cognitive processing, and high probability of disease progression.
MS can be morphologically characterized by the damage to the myelin sheath that surrounds axons, oligodendrocytes that produce myelin, and axons that transmit information to different neurons. Due to the complicated mechanism of MS, the advanced MRI methods which can provide both sensitive and specific assessment of MS tissue injury hold the promise to provide critical mechanistic guidance of MS and serve as robust imaging biomarkers for MS. Several animal models have been established to understand the distinct aspects of the disease. Cuprizone, a copper chelator, creates demyelination events comparable to MS, allowing the mouse model to be a representation QSM’s ability to accurately distinguish between and predict acute and chronic demyelination events. Recently, we have demonstrated that the novel quantitative susceptibility mapping (QSM) can identify between the demyelination andremyelination process in the corpus callosum of mice treated with cuprizone. However, how early QSM can detect brain alterations has not been investigated.
We acquired high-resolution in vivo whole-brain QSM, T-2 weighted, and magnetization transfer ratio (MTR) images at 0, 2, and 4 weeks after cuprizone administration. The corpus callosum exhibited significant changes in T2-weighted and MTR images at 4 weeks after cuprizone administration. In contrast, QSM decreased significantly in QSM at 2 weeks after cuprizone administration. Since dramatic demyelination only starts after oligodendrocytes depletion (3 weeks after cuprizone treatment), QSM may be able to detect the alteration of oligodendrocytes and serve as a sensitive biomarker even before demyelination occurs.
Effect of Oxygen Tension on Glioblastoma Cell Growth
Authors: Jackson Luke , Muller Jack , O’Herron Elise , Cooper Scott , Richardson Angela
Published: January 2024

Background and Hypothesis:Glioblastoma (GBM) is an aggressive primary malignancy of the CNS with a dismal prognosis (~15-20 months) despite standard of care therapies. The poor prognosis of GBM despite ongoing research may be due to inaccuracies in preclinical models of the disease. Cell lines typically used to study GBM are exposed to ambient air containing 21% oxygen (normoxia compared to physiologic oxygen tension, physoxia, ~5%). In extracranial tumors, exposure to the oxygen in ambient air triggers epigenetic changes that alter cell growth, metabolism, and treatment responsiveness. The aim of this study is to obtain preliminary data on the impact ofphysiologic oxygen tensions on primary glioma cell growth in vitro.
Experimental Design:Growth of primary glioma cell lines (GB43, GB10, GB001) and one immortalized cell line (293T HEK) was assessed in normoxia and physoxia. All cell lines were plated at 10,000 cells per well. Cells were harvested and counted in triplicate on days 2, 4, 6, 8, 10, 12. On each day the cells were counted, the media in the remaining wells was changed. This experiment was repeated three times. Wound healing assays with all cell lines were also performed at normoxia and physoxia.
Results:Cells line growth curves were plotted and showed consistent exponential growth after counting on day two. From these graphs, the cell doubling time was calculated over a period of four days during which the cells were undergoing exponential growth.
Conclusions:Current results indicated that primary glioblastoma cell lines grow at different rates at differing oxygen tensions. In ongoing studies, we are exploring the effect of low oxygen tensions on functional assays such as wound-healing. Future work will assess rates of growth and functional consequence of physoxia in tumor samples never exposed to ambient air to most accurately recapitulate the in-situ environment.
Blood Product Utilization Among Adolescent and Young Adult Patients with Acute Lymphoblastic Leukemia: A Single Center Ex
Authors: Knobelsdorf Jacquelyn , Althouse Sandra K. , Batra Sandeep
Published: January 2024

Background: Adolescent and young adult (AYA, 15-39 years old) patients with acute lymphoblastic leukemia (ALL) often experience pancytopenia and severe immunosuppression. Particularly during intensive phases of chemotherapy, allogeneic blood transfusion support is essential in their care. The utilization of both red blood cell (RBC) and platelet transfusions, as well as the thresholds used to determine when transfusions are needed, are poorly described in this population. The objective of this study is to describe blood product utilization in AYA patients with ALL treated at our institution.
Methods: A cohort of 20 AYA patients with ALL treated at Riley Hospital for Children from October 2020 to July 2023 were identified for data collection. Pre- and post-transfusion laboratory values, transfusion totals, comorbid events or complications, transfusion reactions, and minimal residual disease (MRD) values were collected and analyzed. All values reported are mean ± standard deviation for continuous variables and n (%) for categorical variables. Values were calculated individually for each patient for each phase of therapy and averaged across all patients.
Results: Patients studied had varying needs for transfusions throughout their therapy (50.75 ± 48.06), with an average of 22.95 ± 15.65 RBC transfusions and 25.60 ± 29.65 platelet transfusions. Patients being treated with standard chemotherapy protocols required moretransfusions during induction (14.13 ± 21.56) and delayed intensification (14.07 ± 24.29) phases compared to other phases. Patients with MRD positive status required more transfusions (69.14 ± 58.14) than patients with MRD negative status (40.92 ± 40.84).
Conclusions and Potential Impacts: This study helped to elucidate the need for transfusions among the AYA ALL patient population, throughout the different phases of treatment. These findings hold implications for establishing guidelines that could clarify when transfusions should be given in this population, helping physicians provide the best care to future patients.
Group Prenatal Care Models, Experiences, and Outcomes: An Integrative R
Authors: LaTurner Michelle , Muvuka Baraka
Published: January 2024

Background:The United States (US) has the highest maternal and infant mortality rates among developed countries. Indiana has the third highest maternal mortality rate in the US. Group Prenatal Care (GPC) was piloted in the early 1990s to improve perinatal experiences and outcomes through enhanced social support and education. Further research is needed as GPC is increasingly implemented in diverse contexts. This study critically synthesized current evidence on GPC models, experiences, and perinatal outcomes in the US to inform a Community Based Participatory Research Partnership between Indiana University School of Medicine-Northwest and Community HealthNet.
Methods:This integrative review utilized PRISMA guidelines to conduct a systematic search in Embase, CINAHL, and PubMed. Two researchers screened articles for inclusion criteria and quality. Studies were included if they were empirical research or meta-analyses conducted in the US and published in English between January 2013 and June 2023. Data synthesis utilized a qualitative analytical approach that sorted findings thematically.
Results:We retained 98 articles, including 8 meta-analyses, 4 randomized trials, 3 cluster randomized trials, 3 quasi-experimental studies, 4 prospective cohort studies, 12 observational studies, 19 qualitative studies, and 46 retrospective cohort studies. There were several GPC models adapted to high-risk groups such as persons living with HIV, gestational diabetes, pre-existing or pregnancy-induced hypertension, and substance use disorders. GPC was associated with decreased preterm births among low-income and minority women, with more significant reductions when attending 5 or more GPC sessions. GPC improved psychosocial outcomes including satisfaction with care, empowerment, and social connectedness. It was also associated with increased breastfeeding rates in adolescents and African Americans, and increased contraception use among adolescents.
Conclusions:Engaging in GPC may have benefits for high-risk pregnancies, adolescents, low-income, and minority populations. More studies are needed to evaluate GPC’s impacts on perinatal experiences and outcomes among high-risk women.
Blood Culture Contaminations: Interventions and Culture Characteristics
Authors: Lee Aimee , Schwieterman Vanessa , Motzkus Christine
Published: January 2024

Background/Objective:Blood cultures are collected in patients with serious illnesses who are at risk of bacteremia. However, some blood cultures are contaminated which may lead to adverse health outcomes for patients such as an increased length of stay and the unnecessary utilization of antibiotics. The emergency department (ED) has been found to be a frequent source of blood culture contamination. We aimed to identify characteristics and consequences of blood culture contamination at IUH Bloomington.
Methods:Chart review of blood cultures collected at IUH Bloomington in January 2023 was utilized to extract variables including intravenous location and hospital location of blood draw, number and identification of antibiotics given, length of stay, and organisms identified in the blood cultures. Data were securely maintained in REDCap.
Results:The median length of stay for individuals with contaminated cultures in January was found to be 4 days which was comparable to individuals with negative cultures. Most commonly, contamination occurred from the ED with it being responsible for 33/34 contaminated cultures. The most frequently utilized antibiotic across all groups was vancomycin – with both the positive and contaminated groups having a greater percentage of individuals receiving a course of the antibiotic with a mean course of 3.43 days. The most common contaminant was found to be coagulase negative Staphylococcus.
Conclusion and Implications:Lower rates of blood culture contamination may contribute to lower length of stay and improved antibiotic de-escalation strategy. Identification of culture characteristics may guide future endeavors in infection control policies.
The Relationship Between Intensive Care Unit (ICU) Delirium Severity and 2-Year Mortality
Authors: Lehman Rachel , Jawaid Samreen , Lindroth Heidi , Meeker Jared , Perkins Anthony J. , Wang Sophia , Gao Sujuan , Khan Sikandar H. , Khan Babar A.
Published: January 2024

Background:Delirium is an acute brain dysfunction characterized by altered cognition, attention, and level of consciousness. The presence of delirium is associated with increased risk of mortality, neurocognitive decline, and physical impairment; however, the role of ICU delirium severity in long-term health outcomes is less understood.
Objective:Characterize the relationship between delirium severity and mortality risk in ICU survivors 2-years after discharge.
Methods:A secondary analysis was performed on patient data collected in two randomized controlled trials (Pharmacological Management of Delirium and Deprescribing in the Pharmacologic Management of Delirium, 2009-2015). Participants received delirium assessments twice daily during hospitalization via the Confusion Assessment Method for the ICU (CAM-ICU-7). Patients enrolled at Eskenazi Hospital with complete mortality data were included in this study. Mean delirium severity was categorized as rapidly resolving (0-2), mild to moderate (2.1-5), or severe (>5). Cox proportional hazard model was used to quantify mortality risk associated with delirium severity. Analyses were adjusted for patient demographics, comorbidities, and severity-of-disease.
Results:The cohort (n=434) was 54.6% female and 48.6% African American with an average age of 59.8 (SD 16.4). The admission diagnosis was acute respiratory failure/sepsis in 47.9% of patients across medical (n=272), progressive (n=52), and surgical (n=110) ICU types. Approximately one third of the original cohort (n=143) died within 2 years of index discharge. In the multivariate analysis, patients with severe delirium (>5) had nearly twice the adjusted hazard ratio for 2-year mortality compared to patients with mild-moderate delirium (aHR 2.1 [95% CI, 1.3-3.4] and aHR 1.1 [95% CI, 0.7-1.6], p=0.008).
Conclusion:Severe delirium during ICU stay was significantly associated with increased 2-year mortality risk in comparison to mild-moderate (subsyndromal) delirium.
Impact:The relationship between delirium severity and 2-year mortality underscores the need for further research on the mechanisms underlying ICU delirium and specific interventions to improve long-term outcomes.
Exploring Community-Based Strategies to Overcome Barriers to Hypertension Education and Management in Underserved Areas
Authors: Adindu Ugonna , Witty Lynn
Published: January 2024

Objective:In the United States, there are over 119.9 million adults who have been diagnosed with hypertension, representing nearly half of the adult population. Of this population with high blood pressure, 75% of Americans’ hypertension remains uncontrolled. Such control rates are significantly lower among individuals of racial and ethnic minorities as compared to their white counterparts, especially those in underserved areas. We hypothesize that the identification of community-based interventions and strategies to combat barriers to hypertension treatment and education could improve management in these populations.
Project Methods:In this study, we looked through various peer reviewed articles on community-based care and hypertension rates among minorities, exploring study design and limitations to develop a questionnaire focused on access to hypertension education. This survey was distributed randomly during outreach events around Muncie, Indiana to anyone who wished to participate, non-minority groups included. The questionnaire asked about various hypertension and healthcare barrier identification factors with a final question of whether said participant would benefit from a hypertension education course.
Results:The participants’ responses were across the board. Regarding hypertension knowledge, participants were asked about their diagnosis, as well as their level of knowledge of hypertension and its management; participants exhibited varying levels of knowledge. Understanding key aspects of management, including medication adherence, diet, physical activity, and potential complications and warning signs, also varied among participants. Overall, these preliminary survey results highlight the diverse characteristics and experiences of participants related to hypertension, access to healthcare, and hypertension knowledge.
Potential Impact:This study could provide information for those looking to establish community-based organizations in underserved areas. Increasing the magnitude of such teams and advocating for more interventions against barriers to hypertension education could increase not only the health of those in such communities, but also the overall wellbeing of all people in the United States.
Investigating Post-Operative Refractive Outcomes in Patients Undergoing Cataract Surgery to Assess the Potential Impact of a Concurrent Diagnosis of Dry Eye Disease (DED)
Authors: Almalahi Ateik , Schroeder Barbara
Published: January 2024

Cataract surgery is one of the most performed surgical procedures in the world. A cataract is defined as opaqueness in the interior of the ocular lens2. The exact etiology of cataracts is multifactorial ranging from environmental conditions to biochemical changes induced by aging3. The Intraocular lens (IOL) power calculation is an essential part of the pre-operative planning for cataract surgery as it determines the specific IOL that should be utilized for a patient. Keratometry measurements are required for this IOL power calculation, however, DED has been shown to cause inaccurate keratometry measurements4,5. We hypothesize that patients with DED undergoing cataract surgery will have a larger deviation from the predicted spherical equivalent (SE) post-operatively.
Patients who were over the age of 18 and underwent cataract surgery were included. Patients who had a diagnosis of glaucoma, Herpes Simplex Keratitis, punctual plugs, undergone Laser-Assisted in Situ Keratomileusis (LASIK) surgery, Radial Keratometry, or any form of corneal scarring were excluded from this study as they can negatively impact keratometry measurements.
The DED sample had a statistically significant larger SE deviation from the predicted SE compared to the healthy sample (p=0.037). The DED sample also had a statistically significant larger percentage of patients with an SE deviation of 0.50 D or greater (p=0.002). Finally, the DED had a statistically significant older age than the healthy group (p=0.028).
The significant difference in age between the healthy sample and the DED sample confirms the significant correlation between age and prevalence of DED the literature has described6. The statistically significant increased post-operative SE deviation from predicted SE within the DED sample can be the result of the increased variability in the tear film associated with DED. This can lead to inaccurate keratometry measurements, thus leading to incorrect IOL power calculations.
Older Adults and their Experience with Interfacility Transfer
Authors: Bille Dillon , Glober Nancy
Published: January 2024

Background/Objective:Interfacility transfers are an integral part of integrated systems of care in modern healthcare. Many transferred patients are older adults, a particularly vulnerable patient population. Unfortunately, interfacility transfers can result in discomfort during the transport, increased distance from family and home, a significant bill for the ambulance ride, and risk of an accident occurring during transport.
Methods:To better understand the experiences of older adults before, during, and after interfacility transfer, cognitive interviews were performed with patients and their caregivers at the bedside of the receiving hospital. A standard set of questions was used to assess multiple aspects of the interfacility transfer process including the consent process at the sending hospital, experience with the transfer, and perceived benefits/harms resulting from the transfer.
Results:21 patients and 14 caregivers were interviewed in this study and five themes were present throughout these conversations. These themes included, a perceived lack of participation in the decision to be transferred, failed expectations at the receiving hospital, and greater trust in trauma centers like Methodist Hospital.
Conclusion:Our interviews demonstrate a greater need for thorough consent for transfer at sending hospitals discussing the realistic outcomes and risks that can be expected from interfacility transfer. With these conversations patients and their caregivers can be empowered to make informed decisions about their care and will likely be more satisfied with the care that they receive and know what to expect during their treatment.