University of Nebraska Medical Center

University of Nebraska Medical Center Research: DigitalCommons@UNMC
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    Improving Information Literacy and Research Skill Instruction Through Peer Consultation

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    This is an abstract from the Spotlight on Scholarship event in 2025

    The Characterization of Per- and Polyfluoroalkyl Substances (PFAS) in Nebraska Drinking Water and Human Health Impacts

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    Per- and polyfluoroalkyl substances (PFAS) are synthetic compounds that have been detected in water sources of urban and rural environments with evidence of adverse human health effects from exposure. Humans are primarily exposed through ingestion of contaminated water and food. PFAS exposure has been linked to negative multi-system health outcomes (liver, kidneys, cardiovascular, reproductive, and immune). PFAS occur as persistent mixtures in environmental media with decades long consequences to water quality. While national agencies have launched large-scale PFAS water quality monitoring studies, limited data exists for contamination of rural water in Nebraska, especially private wells. The aims of this study were: 1) explore the spatial patterns and variations of PFAS across rural Nebraska; 2) determine the PFAS profile in drinking water and risk estimates to human health; 3) characterize human health effects of PFAS exposure and explore any other predictors of PFAS exposure in the study population. Our findings from Chapter II indicate varying geospatial patterns of PFAS across the state. The spatial pattern of PFAS was generally diffuse with non-point sources as a more important contributor than point sources to rural Nebraska PFAS-related water quality. Hot spots of predicted concentrations above 4 ng/L were identified at two of the sampling sites. These results indicate vulnerable areas in Nebraska that require further data collection or modeling of PFAS in drinking water and other environmental media. These insights can also extend beyond PFAS to other water contaminants because populations are often exposed to chemical mixtures. The findings in Chapter III identified the types of PFAS present and concentrations in drinking water. PFAS occurrence was common in rural Nebraska drinking water (98% detection frequency) but at low concentrations (\u3c 4 ng/L) with high variability of PFAS concentrations in private well water sources (max 108 ng/L). Town and water source were significant predictors of ∑PFAS concentrations. The PFAS risk profile from samples measured in this study represented minimal risk with a hazard index (HI) of 1.90. The estimated health risk resulting from our HI screening should be taken into consideration for future water quality monitoring efforts, but the HI values should be interpreted with extreme caution. Community specific recommendations should be provided given that the patterns and concentrations of PFAS contamination were inconsistent across the state. Chapter IV found there were no significant effects of PFAS concentrations in drinking water and the health outcomes of interest in this study. Age and years lived at residence could be related to other confounding variables that were not included in this study like bioaccumulation rate. Predictor variables to consider for future PFAS drinking water studies include bioaccumulation rate, length of exposure, tap water consumption rate, and dietary food quality. The positive correlation found between socioeconomic groups and ∑PFAS concentration deserves more attention in future studies to determine the influence of this variable in the context of rural communities. The results from this research provide a better understanding of the scope of PFAS contamination in rural Nebraska. This data will add to the growing body of PFAS water quality data in Nebraska, broadening the national surveillance of PFAS in drinking water

    Targeting FOXM1/Aurora Kinase B Axis Attenuates Small Cell Lung Cancer Growth, Metastasis and Chemoresistance

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    Small cell lung cancer (SCLC) is a deadly malignancy of the lung. Most SCLC patients show distant metastasis at the time of diagnosis, and consequently, the patients show dismal survival. Etoposide in combination with platinum-based chemotherapy has been used as the standard of care for SCLC patients for more than 30 years. This regimen shows a prominent anti-tumor response; however, nearly all patients encounter a disease relapse with inherent chemoresistance. The expeditious development of chemo-resistance causes SCLC patients to have a median overall survival of 12-16 months. Additionally, the lack of effective targeted therapies for SCLC has complicated the disease outcome. In search of promising molecular targets in SCLC, we analyzed publicly available single-cell RNA-sequencing (RNA-seq) data that revealed FOXM1 (Forkhead Box M1), an oncogenic transcription factor, is overexpressed in SCLC, which is recapitulated in SCLC tissues and cell lines. Interestingly, chemo-resistant SCLC showed a substantially higher level of FOXM1 expression relative to naive SCLC. Genetic silencing of FOXM1 or its targeting using pharmacological inhibitors revealed a substantial reduction in cell viability, colony formation, migration and sphere formation in naïve and chemo-resistant SCLC models. FOXM1 inhibition (by FDI-6 and NB-73) also induced cell cycle arrest and apoptosis in SCLC cells. Combining FOXM1 inhibitor with first-line chemotherapy showed synergistic anticancer effects in vitro as well as in xenograft and spontaneous mouse models (RPM: Rbfl/fl; Tp53fl/fl; LSL-MycT58A) of SCLC. Our RNA-seq studies revealed that FOXM1 inhibition significantly downregulated Aurora Kinase B signaling pathway, which is dysregulated in SCLC. Furthermore, we have found that FOXM1 inhibition enhances T cell activity and T cell-mediated killing of cancer cells. Altogether, these findings demonstrate that FOXM1 inhibition is a potential therapeutic strategy to combat SCLC

    Targeted Deletion of Cxcl1 in MSCs Regulates Osteogenesis and Suppresses Bone-Metastatic Prostate Cancer

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    Bone metastasis continues to be the greatest challenge in treating patients with prostate cancer despite ongoing research. In bone, prostate cancer tumors hijack normal bone remodeling processes to drive cancer progression. However, it is unclear how these interactions drive bone-metastatic prostate cancer growth in the bone environment. To understand the mechanisms associated with bone-metastatic prostate cancer regulation of mesenchymal stem cells (MSC), we previously identified that bone-metastatic prostate cancer induces MSC expression of the pro-inflammatory chemokine CXCL8 and its mouse functional homologue Cxcl1. To date, there has been little to no information about the role of CXCL1/8 in MSC biology and its impact in the tumor-bone environment. Using genetic deletion of Cxcl1, we discovered a novel role for Cxcl1/8 in regulating MSC osteoblast differentiation, such that targeted deletion of Cxcl1 enhanced MSC osteoblastogenesis. Despite the osteogenic nature of prostate cancer, co-injection of Cxcl1 knockout (KO) MSCs with bone-metastatic prostate cancer in bone significantly suppressed tumor growth compared with co-injection with scrambled control (non-targeting) MSCs, even in the presence of three times more prostate cancer to MSCs. Furthermore, bulk RNA sequencing revealed immune response pathways, both in Cxcl1-KO MSCs and bone-metastatic prostate cancer tumors containing Cxcl1-KO MSCs. In support of this, Cxcl1-KO MSCs reduced immature neutrophils in the bone environment, while increasing monocytes. These findings demonstrate the importance of MSC-derived Cxcl1 in the bone microenvironment and highlight the importance of Cxcl1 in bone-metastatic prostate cancer progression. IMPLICATIONS: MSC-derived Cxcl1 regulates prostate cancer progression in bone

    Clinic Emotions

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    This is a sketch of a woman walking into a clinic with her three children, being greeted by a member of the nursing staff. There are two additional staff members in the background. Overlaid on the sketch are acrylic paints representing the emotions of each person. For the mother holding her newborn, the dark blue around her represents sadness, the white represents isolation, and the purple represents detachment. Her toddler behind her, as well as the nurse greeting her, are both outlined in orange and light blue, representing happiness and calmness, respectively. Her newborn and the toddler at her hip are also enclosed in calmness. The nurse greeting her has a baseline of dark grey around her, representing confidence. The staff member in the background, whispering while looking at the approaching patient and facing the staff member to her left, is encircled in dark green, representing envy, as well as light pink, representing immaturity. The recipient of her whispers is encircled in dark, dark grey, representing anxiety, and dark pink, representing embarrassment. You may also notice that the mother has dark pink around her, representing embarrassment as well. These colors flow from the individuals to coat the clinic around them. The emotions patients bring into the clinic, and those with which staff members greet them, affect the entire environment.https://digitalcommons.unmc.edu/emet_posters/1051/thumbnail.jp

    Benefit-Risk Assessment of Rivaroxaban in Older Patients With Nonvalvular Atrial Fibrillation or Venous Thromboembolism

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    BACKGROUND: Both bleeding and adverse ischemic events increase with age, compounding the benefit-risk balance of anticoagulants in older patients. We present analyses using benefit-risk methods to better understand the age-dependence of the benefit-risk profile of rivaroxaban in patients with nonvalvular atrial fibrillation (NVAF) or venous thromboembolism (VTE). METHODS: Randomized controlled trial data from the ROCKET-AF (NVAF) and EINSTEIN DVT, EINSTEIN PE, EINSTEIN-Extension, and EINSTEIN CHOICE in (VTE) were used. For ROCKET-AF, benefits and risks were assessed with incidence rates for key thrombotic and bleeding endpoints and a net clinical benefit (NCB) measure. Cumulative incidences (estimated by the Kaplan-Meier method) were estimated at day 185 for EINSTEIN and EINSTEIN Extension and 1 year for EINSTEIN CHOICE. Incidence differences were calculated for the overall population and age subgroups of \u3c 65, 65-75, and \u3e 75 years. RESULTS: In ROCKET-AF, rate differences in the composite NCB outcome (vascular death, stroke, myocardial infarction, fatal bleeding, critical organ bleeding, and non-CNS systemic embolism) favored rivaroxaban overall and by age \u3c 65, 65-75, and \u3e 75 years (-84, -25, -61, and -150 cases per 10,000 patient-years, respectively). In the pooled EINSTEIN DVT and EINSTEIN PE studies, cumulative incidence differences for the composite NCB outcome (recurrent VTE and major bleeding) were -103, 3, -105, and -544 per 10,000 patients, respectively. For extended VTE treatment with rivaroxaban versus placebo in EINSTEIN-Extension, NCB results were -536, -492, -556, and -601 per 10,000 patients, respectively. In the EINSTEIN CHOICE analysis, NCB favored rivaroxaban 20 mg versus aspirin (-284, -255, -339, and -338, respectively) and rivaroxaban 10 mg versus aspirin (-339, -328, -485, and -80, respectively). CONCLUSIONS: This analysis demonstrated a positive benefit-risk profile with rivaroxaban versus trial comparators in older patients with NVAF or VTE, with benefit-risk increasingly favoring rivaroxaban with increasing age. CLINICAL TRIAL REGISTRATION: http://ClinicalTrials.gov , identifiers: NCT00403767 (ROCKET-AF), NCT00440193 (EINSTEIN DVT), NCT00439777 (EINSTEIN PE), NCT00439725 (EINSTEIN Extension), and NCT02064439 (EINSTEIN CHOICE)

    Evaluation of an External Urinary Device Protocol and Practices in Hospitalized Female Patients: A Quality Improvement Project at a Rural Midwestern Hospital

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    Aims and Objectives- 1: Describe and measure current implementation and management practices of the PureWick™. 2: Describe and measure current outcomes in the use of the PureWick™ device including mobility scores, skin breakdown, Braden scores, moisture-associated dermatitis, CAUTIs, PAUTIs, hospital LOS, HAIs and HPIs. 3: Measure the survey results from staff regarding the current PureWick™ practices. 4: Propose recommendations for an improved EB protocol for the PureWickTM. Background: Currently, the PureWickTM device has been utilized by facilities as an alternative to indwelling urinary catheters in an effort to reduce the incidence of CAUTI. Since the introduction of the device, there have been over 500 adverse events reported to the FDA. Design: This QI project was implemented using the Iowa Model. Methods-This project used a retrospective chart review (n=65) for data collection related to the use, management, and outcomes associated with the use of the PureWickTM device. In addition, staff surveys (n=59) were utilized to identify current perceptions, education deficits, and beliefs about the PureWickTM device. Results-HAPIs occurred in 22% of the studied patient population that used the device. Those patients that utilized the device and developed a HAPI had a statistically significant longer hospital stay. Patients that were considered mobile used the device almost as frequently as less mobile patients. 47% of staff surveyed reported that they feel that the PureWickTM device limits a patient’s mobility. 39% of staff members reported inadequate training on the device. 74% of charts were deficient in documentation pertaining to the device’s level of suction at any point during its use. Conclusions- A device that has been correlated to adverse patient outcomes in the literature review, FDA reporting, and through the results of the data collection from this QI project; warrants a proposal to seek best practices to prevent morbidity and mortality in the hospitalized, female patient with urinary incontinence. Relevance to clinical practice-In an era in which we seek to provide the best care, protocols to ensure the safety of the patient must be implemented. Each facility should work to develop an evidence-based protocol for the PureWickTM that aims to prevent a decline in baseline mobility. No Patient or Public Contribution- aside from patient chart reviews, no patients or public contributed to this project. What does this paper contribute to the wider global clinical community? The findings of this QI project should: · Create an awareness that this device, although appearing non-invasive, can result in patient injury when implemented and managed inappropriately. · Encourage future study of the device related to mobility. If the device is not utilized appropriately this device may contribute to a decline in baseline mobility. These outcomes should be studied on a larger population. · Highlight the importance of investigating the PureWickTM device on a larger scale to develop evidence-based recommendations for the implementation and management of the UI device in the hospitalized, female patient

    An Integrative Multi-Omics Approach for Enhanced Alzheimer\u27s Disease Diagnosis

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    Alzheimer’s disease (AD), the most common subtype of dementia, is characterized by a progressive decline in cognitive functions. Early diagnosis enables timely interventions to reduce or slow disease progression, preventing individuals from severe brain function decline. The current AD diagnosis framework depends on A/T/(N) biomarkers detection from cerebrospinal fluid or imaging, which are invasive and expensive. Meanwhile, the pathophysiological changes of AD accumulate in metabolism, neuroinflammation, etc., resulting in heterogeneity in newly registered patients. Recently, next-generation sequencing (NGS) technologies for blood samples have been found to be a non-invasive, cost-effective alternative for AD screening. However, most of the existing studies rely on single omics only. To address this, we develop WIMOAD, a stacking ensemble and weighted integration of multi-omics data for AD diagnosis. It leverages specialized classifiers for paired gene expression and methylation data, followed by meta learning for performance enhancement during classification. The prediction results of two distinct meta models were weighted for final decision-making. Remarkably, WIMOAD outperforms single-omics models and existing integration methods, highlighting its ability to effectively discern intricate patterns in multi-omics data and their correlations with clinical diagnosis results. In addition, WIMOAD also stands out as a biologically interpretable model by leveraging the SHapley Additive exPlanations (SHAP) to elucidate the contributions of genes from each omics to the model output. We believe WIMOAD is a very promising tool for accurate AD diagnosis and effective biomarker discovery across different cognitive stages, which eventually will have consequential impacts on early treatment intervention and personalized therapy design on AD

    Empowering Women\u27s Health and Wellness: The Role of Holistic Occupational Therapy

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    Background: Nearly two-thirds of women were unaware that pelvic floor rehabilitation is an available treatment for pelvic floor dysfunction (Burkhart et. al., 2021). Students, clients, and practitioners need supplemental, easily accessible resources for this broad emerging practice area of women’s health (Jones et. al., 2020). This Pressbook is a free, open-access, interactive educational resource for students, patients, and practitioners to improve understanding of holistic occupational therapy (OT) in women\u27s health. It highlights OT\u27s unique role in addressing the physical, emotional, and psychosocial needs of women. Method: Current OT students report a lack of resources and desire more support. A survey of 22 OT students at one doctoral-level university revealed a significant gap in women\u27s health education, with 100% of students reporting minimal curriculum focus. Despite this, 96.5% of students expressed interest in further learning about this practice area. A survey of 5 holistic occupational therapists highlighted common health concerns among female clients in women’s health. The needs analysis suggested a freely available, online, interactive publication would meet student, client, and practitioner desires. Before developing the publication, competence was established through continuing education courses, following media platforms by experts in the field, and a capstone focused in this practice area. Competence was gained for prenatal and postpartum care, pelvic dysfunction, and wellness. The evidenced-based publication was developed combining literature, continuing education, clinician feedback, and faculty review. The publication addresses areas of physical, emotional, and psychosocial needs of women’s health. Interactions and exercises in the publication reinforce content retention while additional resources, including videos and handouts, guide supplemental learning. Students explored the publication for 30-minutes in class. Student surveys and therapist questionnaires collected quantitative and qualitative feedback on the publication. Results: Students (n = 26) completed the publication feedback survey. A student survey showed a 99.2% satisfaction rate for the publication\u27s ease of use and organization. Insights into women\u27s health through holistic occupational therapy received a 96.2% satisfaction rate. Additionally, 96.2% of students expressed they are likely to use the publication again. Students found the publication graphics, pictures, and key takeaways to be most engaging. Therapists (n = 8) valued the content and reported ease of implementation in clinics. They were motivated to share it with clients to enhance their understanding of their condition. Conclusion: This freely available, online resource offers education on a variety of women’s health and wellness topics that are within the scope of OT practice. This supports OT programs, OT students, clients, and healthcare providers desiring to increase knowledge in this practice area. In a packed OT curriculum, OT programs may offer this resource for students who want to dive deeper in this practice area. Practitioners at clinical sites may also use this resource as onboarding or training materials for students going into a women’s health practice setting. This resource serves as a means to close the gap in women’s health services. References: Burkhart, R., Couchman, K., Crowell, K., Jeffries, S., Monvillers, S., & Vilensky, J. (2021). Pelvic floor dysfunction after childbirth: Occupational impact and awareness of available treatment. OTJR: Occupational Therapy Journal of Research, 41(2), 108-115. https://doi.org/10.1177/1539449220970881 Jones, J. Domanico, J., Peek, H., Lee, T. E., & Kern, L. A. (2020, July 23). Promoting women’s health and wellness. American Occupational Therapy Association. https://www.aota.org/publications/ot-practice/ot-practice-issues/2020/womens-healt

    Building Empathy Through Storytelling: A Living Library Program Focused on Women’s Health

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    An academic health sciences library hosted a grant-funded living library program titled “Bringing Stories of Women’s Health to the Forefront.” With a campus that is increasingly focused on incorporating the humanities into medical education, the library added to this momentum by offering a program which encouraged empathy through the art of storytelling. The program was delivered via three routes: an in-person event for the city’s metro community, a virtual event for the university community and their clinical partners, and oral interview video recordings that are hosted on the library website. In order to host a successful event that met the needs of numerous audiences, the library pulled in the expertise of individuals from across campus, the community, and clinical partners. One key partner was the university’s gender and sexuality resource center (GSRC). The coordinator of the GSRC brought their knowledge and mastery of topics surrounding the medical humanities and gender advocacy work to the program planning committee. This program allowed the library to tap into current trends and social conversations about women’s healthcare experiences that challenge traditional understandings of healthcare like the popularity of social media stories about medical gaslighting and narratives about understudied illnesses largely affecting women. The recorded narratives are valuable as they provide local, visible connections to and examples of these broader trends. The narratives shared during the event went beyond the women’s healthcare topics that are typically shared in these types of spaces such as breast cancer and pregnancy. While those narratives were addressed, others also shared their experiences surrounding topics such as gender-affirming care, autism, urinary incontinence, lymphoblastic leukemia, living with dissociative identity disorder, etc. The living books shared stories from multiple perspectives such as their experience as a patient, as a healthcare professional providing care, as a researcher, and as a parent of a child receiving a diagnosis. These narratives can be used in a variety of ways to meet common pedagogical goals in health sciences education like understanding patient perspectives, gaining familiarity with disease discourse, and recognizing health disparities. The library recognized that past programming had been intended mainly for internal university and clinical partner audiences. This living library sought to reach a wider and more diverse crowd. The goal was to reach both existing and new audiences across the state. To do this an omnichannel marketing approach was utilized to promote the program and engage the community. This marketing approach drew on the expertise of a marketing and communications specialist and was built intentionally so that it could be replicated in future efforts to deliver successful programs. Success of the program was measured via survey responses and observations

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