Medicine and Health Sciences Commons^™

Vesicle-Mediated Mitochondrial Clearance Presents An Actionable Metabolic Vulnerability In Triple-Negative Breast Cancer, Jody Vykoukal, Yihui Chen, Mingxin Zuo, Riccardo Ballarò, Monica J Hong, Hansini Krishna, Daniela B Rodriquez-Perera, Hiroyuki Katayama, Ehsan Irajizad, Ranran Wu, Ricardo A León-Letelier, Jennifer B Dennison, Angelica M Gutierrez, Adriana Paulucci-Holthauzen, Timothy C Thompson, Leona Rusling, Yining Cai, Fu Chung Hsiao, Soyoung Park, Banu Arun, Samir Hanash, Johannes F Fahrmann

Faculty, Staff and Student Publications

Selective autophagy of mitochondria is known to promote cancer cell survival and progression, including in triple-negative breast cancer (TNBC). Here, we apply an integrated multi-omics approach together with functional experimental analyses to investigate metabolic adaptations that support mitochondrial quality control in TNBC. We detail a mitochondrial quality control mechanism, complementary to mitophagy, that is enabled by a program of heightened extracellular sphingomyelin salvaging in TNBC coupled with extracellular vesicle-mediated intracellular clearance of mitochondrial damage. Targeting of this onco-metabolic pathway via repurposing of eliglustat, a selective small molecule inhibitor of glucosylceramide synthase, results in ceramide-mediated compensatory mitophagy and cancer cell death …

Accurate Imputation Of Pathway-Specific Gene Expression In Spatial Transcriptomics With Pasta, Ruoxing Li, Peng Yang, Mauro Di Pilato, Jianjun Zhang, Christopher R Flowers, Lulu Shang, Ziyi Li

Faculty, Staff and Student Publications

Mapping the entire transcriptome at single-cell resolution under its natural spatial context is essential for investigating the oncogenesis and progression of diseases. The recently emerged targeted in-situ technologies retain the spatial organization of cells at high resolution, although they remain limited in the number of genes that can be simultaneously measured. To overcome this obstacle, numerous computational methods have been developed to predict unmeasured gene expression in spatial transcriptomics data by leveraging scRNA-seq data. Most of these methods focus on the expression of individual genes and usually generate highly variable predictions. In this study, we introduce PASTA (PAthway-oriented Spatial gene …

Lung Adenocarcinoma Surfaceome Remodeling With Egfr Inhibitors Uncovers Placental Alkaline Phosphatase As A Target For Combination Therapy, Yihui Chen, Rongzhang Dou, Monica J Hong, Hanwen Xu, Jody Vykoukal, Ricardo A León-Letelier, Yining Cai, Soyoung Park, Ehsan Irajizad, Fu Chung Hsiao, Jennifer B Dennison, Edwin J Ostrin, Johannes F Fahrmann, Hiroyuki Katayama, Samir M Hanash

Faculty, Staff and Student Publications

Treatment of lung adenocarcinomas (LUADs) that exhibit activated epidermal growth factor receptor (EGFR) with EGFR tyrosine kinase inhibitors (TKIs) has limited efficacy. Assessment of the impact of EGFR TKI on the LUAD surfaceome remodeling reveals potential therapeutic targets. We identify placental type alkaline phosphatase (ALPP), which has restricted expression in normal tissues, among upregulated surface proteins following EGFR TKI treatment of both TKI sensitive as well as resistant cells. EGF treatment represses ALPP expression, whereas EGFR TKIs upregulate its expression through dephosphorylation and activation of FoxO3a, a transcriptional regulator that binds to the promoter region of ALPP. The combination of …

Quantitative Profiling Of Intratumor Immune Heterogeneity Identifies Loss Of Immune Diversity As A Hallmark Of Cancer Progression, Qiqi Lu, Jiangti Luo, Chia-Hao Tung, Xiaosheng Wang, Zhongming Zhao

Faculty, Staff and Student Publications

Immunological intratumor heterogeneity (ImTH) describes the variability in the types, spatial distribution, and functional states of immune cells within tumors. While evidence suggests that ImTH influences tumor progression and therapeutic response, few studies have provided a quantitative characterization of ImTH. Here, we present Scoring Immunological Intratumor Heterogeneity (ScImTH), a novel algorithm that quantifies ImTH by calculating the Shannon entropy of immune cell type proportions within the tumor microenvironment. Using bulk, single-cell, and spatial transcriptomic datasets, we show that reduced ScImTH scores are associated with unfavorable survival outcomes, tumor progression-related molecular and phenotypic features, immunosuppressive states, and resistance to immunotherapy across …

The Effects Of Grounding Techniques On Strength And Power In Division Ii Track And Field Athletes: A Pre/Post Cohort Study, Matthew Ronald Hall

Doctoral Dissertations and Projects

Grounding is the practice of connecting the human body to the Earth’s electrical surface. It has been proposed as a natural intervention capable of reducing inflammation, enhancing recovery, and improving physiological balance. While previous research has identified benefits for general health and recovery, limited evidence exists regarding its effects on athletic performance. This study investigated the effects of grounding interventions on strength and power among Division II track and field athletes. A five-week, pre/post randomized prospective cohort design was employed with thirty participants, stratified for men and women, which included three groups: grounding sheets, grounding pads, control. Athletes were assessed …

Successful Treatment Of Comorbid Sapho Syndrome And Hidradenitis Suppurativa With Upadacitinib, Deepika Narayanan, Tiffaney Tran, Valeria Duque-Clavijo, Hung Q Doan, Stephen K Tyring

Faculty, Staff and Student Publications

No abstract provided.

Intracellular Acinetobacter Baumannii Acts As A Transient Reservoir In Lung Infection Via A "Persist And Resist" Strategy, Manon Janet-Maitre, Gisela Di Venanzio, Clay D Jackson-Litteken, Nichollas E Scott, Mario F Feldman

2020-Current year OA Pubs

Although considered primarily extracellular,

Resident-Led Peer Support Groups In Emergency Medicine: A Pilot Framework For Peer Leader Training, Kyra D Reed, Alexandria P Weston, Alexandra E Serpe, Destiny D Folk, Jacob M Destrampe, Heather P Kelker, Aloysius J Humbert, Katie E Pettit, Julie L Welch

2020-Current year OA Pubs

Peer support has demonstrated efficacy in alleviating symptoms of anxiety and depression, while fostering empathy and mitigating burnout among healthcare professionals. Given the considerable demands of residency training, there is a strong rationale for resident-led peer support interventions. However, structured programs to train residents for such leadership roles remain limited. Our objective was to implement a peer support leader training program for residents, evaluate its perceived effectiveness, and identify common themes discussed in sessions. Between June 2021 and June 2023, we performed a longitudinal, prospective cohort survey study of Emergency Medicine (EM) and EM/Pediatrics (EM/P) residents participating in a novel …

A Proteogenomic Gene Signature Defines Prognostic Subgroups Highlighting Pi3k/Akt/Mtor Signaling Pathway As A Therapeutic Vulnerability In Myeloid Malignancies, Fan He, Shuyang Lin, Bei Gao, Varun Ramesh, Alexander B Kim, Tim Kong, Daniel A C Fisher, Christopher T Letson, Molly Brakhane, Mary Fulbright, Yanbo Yu, Marco Sardiello, Jorge Di Paola, Stephen M Sykes, Stephen T Oh

2020-Current year OA Pubs

INTRODUCTION: Myeloid malignancies, including acute myeloid leukemia (AML) and myeloproliferative neoplasms (MPN), exhibit overlapping pathophysiology. Chronic MPNs can transform into secondary AML (sAML), which is associated with poor prognosis and limited treatment options. However, the process and prognostic significance of leukemic transformation remain incompletely understood.

METHOD: Through a two-sample bidirectional Mendelian randomization (MR) analysis, we showed that genetic liability to MPN significantly predicts the risk of developing AML, establishing MPN as the precursor to leukemia. To identify mediators of this risk, we integrated population-level plasma proteomics data, identifying 55 proteins associated with MPN. Upon integrative analysis with the BEAT-AML cohort, …

Mbnl Loss Of Function In Smooth Muscle As A Model For Myotonic Dystrophy Associated Gastrointestinal Dysmotility, Janel A M Peterson, Jesus A Frias, Andrew N Miller, Krishnakant G Soni, Yi Zhang, Zheng Xia, John W Day, Geoffrey A Preidis, Thomas A Cooper

Faculty, Staff and Students Publications

Myotonic dystrophy type 1 (DM1) is the most common adult-onset muscular dystrophy and severely affects multiple organ systems, including the brain, heart, skeletal muscle, and gastrointestinal (GI) tract. Despite 80% of individuals with DM1 experiencing GI dysfunction that affects their daily life, the mechanisms of GI dysmotility in DM1 remain an understudied aspect of the disease. DM1 is caused by a CTG repeat expansion in the DMPK gene that, when expressed as an expanded CUG repeat RNA, sequesters and reduces the activity of the muscleblind-like (MBNL) RNA-binding protein family. We developed a mouse line with conditional, smooth muscle-specific knockout of …

Flawed Design And Selection Bias In Critical Care Randomized Controlled Trials (Rcts): The Patient Safety Risk Of The "Rct Mimic"., Lawrence A Lynn

Ambulatory and Primary Care Articles

Over three decades, randomized controlled trials (RCTs) for critical care syndromes such as acute respiratory distress syndrome (ARDS), sepsis, and community acquired pneumonia (CAP) have repeatedly produced non-reproducible results, at times leading to high-impact reversals of global protocols when later studies revealed harm. These trials enroll patients using expert-derived threshold sets intended to define the syndrome. This analytic review presents the first historical and formal methodological review and mathematical analysis of such RCT using causal symbolic modeling (cSM), directed acyclic graphs (DAGs), and do-calculus. The review includes landmark publications, task-force threshold sets, and case examples, including the 2025 REMAP-CAP corticosteroid …

The Impact Of Average Principal Diabetes Cost On Population Health Measures Within Homogeneous Demographics, Alvin Dwayne Binns

Doctoral Dissertations and Projects

The United States healthcare sector has encountered an increasing burden from diabetes health conditions and diabetes expenditures. Vulnerable populations are disproportionately affected, resulting in increased health mortality and morbidity. This quantitative retrospective, observational, cross-sectional cohort study identified the relationship between the average principal diabetes cost and population measures for Alabama Medicare beneficiaries living in homogeneous communities diagnosed with the principal diagnosis of diabetes. The theoretical framework guiding the study was the socio-ecological theory. Purposive sampling was applied to the secondary Mapping Medicare Disparities data population comprising 57 United States territories and 3,243 counties. Specifically, Medicare beneficiary participants diagnosed with the …

Nursing Faculty Attitudes Toward Artificial Intelligence: A Quantitative Causal-Comparative Cross-Sectional Study, Micaela Mcspadden

Doctoral Dissertations and Projects

The rapid growth of artificial intelligence (AI) in healthcare has highlighted the importance of understanding how nursing faculty perceive this technology. Although prior studies have explored public views, nurses’ perceptions, and faculty attitudes toward technology and curriculum change, limited research has focused on nursing faculty perspectives toward AI. Through the lens of the Theory of Reasoned Action (TRA) and the Technology Acceptance Model (TAM), this study examined factors that influence nursing faculty attitudes toward AI in nursing education. This study used a quantitative, causal-comparative, cross-sectional design with 263 nursing faculty participants from undergraduate pre-licensure programs in the United States. Participants …

Analysis Of The Health Access Initiatives Available For Newly Resettled Immigrants And Refugees In Charlotte, North Carolina, Yetunde Akinyelu

Doctoral Dissertations and Projects

The Health Access Initiative for Newly Arrived Immigrants and Refugees in Charlotte, North Carolina addresses the major obstacles which prevent these populations from obtaining vital healthcare services (P Iqbal., et al 2022). The research investigated healthcare difficulties faced by immigrant and refugee populations after their arrival in the United States while developing solutions to enhance their healthcare accessibility and results. The research employed qualitative methods to gather data through semi-structured interviews with immigrants and refugees who resided in Charlotte (Alkhawaldeh, et al., 2023). The research took place in community-based locations to create an environment where participants could freely discuss their …

Bridging The Gap: Optimizing Outpatient Care Delivery In Rural Kenya Through A Telemedicine Workflow Training Initiative, Elizabeth K. Bennett

Doctoral Dissertations and Projects

Access to timely, high-quality outpatient care in rural Kenya is constrained by workforce shortages, geographic barriers, and inefficiencies in care delivery. This Doctor of Nursing Practice project evaluated the impact of implementing a structured telemedicine workflow and training program for a regional mission hospital in the highlands of Western Kenya and its satellite outpatient clinic. Guided by the Iowa Model of Evidence-Based Practice, Kotter's Change Theory, and the reach, effectiveness, adoption, implementation, and maintenance (RE-AIM) framework, the project employed a quasi-experimental, pre-post design, with eight medical providers participating in structured workshops, interactive telemedicine simulations, and workflow integration exercises. Impacts were …

Improving Muscle Tonus Of “Weak” Muscles In Non-Specific Chronic Low Back Pain: A Case Series Addressing The Role And Impact Of Proprioceptive Response And Isolated Isometric Exercises, Jeffrey S. Tardiff

Doctoral Dissertations and Projects

Nonspecific chronic low back pain affects most people through-out the world at some point within their lives, negatively impacting 80%-90% of the overall population, their families, and their communities. Thus far, the outcome of most studies indicate that the best form of treatment for this specific problem is a form of resistance training exercises, core stability exercises, mobilization, manual therapy, and or proprioceptive training with no consensus on which provides the best outcomes. The purpose of this study was to explore an individualized approach in treatment utilizing methods shown to improve muscle tonus or “stability” in muscles of the abdomen, …

The Impact Of Street Medicine Programs On Addressing Poor Health Outcomes In Unhoused Populations, Lori R. Kelley

Doctoral Dissertations and Projects

The purpose of this phenomenological study was to understand the problem of poor health among unhoused populations based on the perspectives of outreach workers and shelter staff. This study was conducted in Monroe County, Indiana. The theory guiding this study was social ecological theory by Urie Bronfenbrenner. Social ecological theory was used to understand how social ecological layers impact poor health in unhoused populations. Hermeneutic phenomenology was used with purposive maximum variation sampling to gather seven study participants with lived experience of working with unhoused populations. Data collection included one-on-one interviews, observation, and documentation review. After data collection was completed, …

Workplace Violence: A Paradigm Shift, Ann Marie Hutchens

Doctoral Dissertations and Projects

Workplace violence (WPV) has reached epidemic proportions. WPV poses devastating results on the healthcare industry: affecting quality of care and patient outcomes, contribute to the development of physical and psychological conditions for nurses, and reduce the healthcare teams’ level of job satisfaction and organizational commitment. The United States is already facing a nursing shortage due to baby boomers retiring and an increase chronic disease and the elder population. Although strongly prevalent, WPV is significantly underreported. It is believed that the low rate of reporting is a consequence of apathy that violence is an occupational hazard, and that nothing will change. …

Molecular Effects Of Glucose On Mir503hg-Regulated Genes In Triple-Negative Breast Cancer, Victoria Reid, Barbara Yang, Kyle Russo, Melina J. Sedano, Ramesh Choudhari, Enrique I. Ramos, Shrikanth S. Gadad

School of Medicine Publications

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype, characterized by a lack of key hormone receptors in tumor cells. As there are limited treatment options for these patients, it is crucial to understand the underlying mechanisms by which TNBC constantly evolves and evades treatments. In this regard, the pervasive nature of transcription provides a potential reservoir of transcripts, including both coding and noncoding, that TNBC leverages to sustain a proliferative advantage and support tumor growth. TNBC is affected by energy sources such as glucose, which can have a profound impact on gene expression regulation mediated by various …

Neuropathic Pain And Related Depression In Mice: The Effect Of A Terpene And A Minor Cannabinoid In Combination, Jose Rios, Mohammed Alnoud, Mohammad Hussain, Zayd Ayas, Emmanuel Franco, Justin D. Mills, Joshua Nwose, Maria Sophia Malbas, Hiram L. Garcia, Manish Kumar Tripathi, Khalid Benamar

School of Medicine Publications

Background/Objectives: Neuropathic pain is one of the most severe types of chronic pain. Although it is difficult to manage, it often co-occurs with depression. Yet, no medication addresses the neuropathic pain and depression comorbidity. Therefore, developing integrated treatment strategies that address both pain and depression is a major public health priority and an unmet need affecting millions. Methods: In this study, we investigated the effect of combining a terpene, Beta-Caryophyllene (BCP), and cannabidiol (CBD) on neuropathic pain and associated depression. We employed a chronic constriction injury (CCI) neuropathic pain model and a series of behavioral tests to evaluate …

Clinical Practice Variation Among Pediatric Rheumatologists Treating Kawasaki Disease: Results Of A North American Survey, Daniel Ibanez, Bianca Lang, Julia Shalen, Ali Yalcindag, Linda Wagner-Weiner, Kenneth N Schikler, Shoghik Akoghlanian, Hulya Bukulmez, Kristen Hayward, Laura Berbert, Sivia Lapidus, Andrea A Ramirez, Cagri Yildirim-Toruner

Faculty, Staff and Students Publications

Background: The best treatment for children with KD who fail to respond to the first dose of IVIG (refractory KD) is currently unknown. The purpose of this study was to determine treatment practices of pediatric rheumatologists in North America who manage IVIG-refractory KD.

Methods: A 34-item web-based survey was sent to 102 randomly selected members of the Childhood Arthritis and Rheumatology Research Alliance (CARRA). The anonymous survey addressed the use of primary intensification as well as the treatment of IVIG-refractory KD.

Results: The response rate was 82%; 56% (all pediatric rheumatologists) completed the survey. Primary intensification was …

Wdfy4-Dependent Cross-Presentation Proceeds Via A Vacuolar Antigen-Processing Route, J Luke Postoak, Alyssa Koch, Sicong Shan, Ray A Ohara, Suin Jo, Jing Chen, Pritesh Desai, Feiya Ou, Magdalena Kraft, Michael S Diamond, Sunkyung Kim, Theresa L Murphy, Kenneth M Murphy

2020-Current year OA Pubs

The intracellular processing route used by type I conventional dendritic cells (cDC1) for cross-presentation of viral- or tumor-associated antigens remains controversial. One model proposes that captured antigens exit from damaged phagolysosomes and enter the cytosol, where they are processed for presentation by MHC class I molecules (MHC-I). This model relies on proteasomal degradation and TAP-dependent peptide transport into the endoplasmic reticulum (ER) for loading by the peptide loading complex (PLC). An alternative model proposes a vesicular route in which captured antigens are retained and processed within an endocytic compartment. A compelling argument favoring the cytosolic model is the dramatic loss …

The Inferred Functional Connectome Underlying Circadian Synchronization In The Mouse Suprachiasmatic Nucleus, K L Nikhil, Bharat Singhal, Daniel Granados-Fuentes, Jr-Shin Li, István Z Kiss, Erik D Herzog

2020-Current year OA Pubs

Circadian rhythms in mammals arise from the spatiotemporal synchronization of ~20,000 neuronal clocks in the suprachiasmatic nucleus (SCN). Although anatomical, molecular, and genetic approaches have revealed diverse SCN cell types, how network-level wiring enables their synchronization remains unclear. To overcome the challenges of inferring functional connectivity from fixed tissue, we developed Mutual Information & Transfer Entropy (MITE), an information-theoretic framework to infer directed cell-cell connections with high fidelity from long-term live-cell imaging. Recording and analyzing 3,290 h of clock gene expression from 8,261 SCN neurons across 17 mice, we uncovered a highly conserved, sparse SCN network organized into two asymmetrically …

Intracranial Injection Of Genetically Modified, Mosquito Non-Transmissible Zika Virus: Safety In Primates And Ramifications For Brain Tumor Therapy, Alec J Hirsch, Amanda De Andrade Costa, Emilie Russler-Germain, Ashwani Kesarwani, Yuping Li, Michael S Diamond, Milan G Chheda, Et Al.

2020-Current year OA Pubs

Glioblastomas (GBMs) are incurable brain tumors. Zika virus (ZIKV) has specificity in killing GBM stem cells, which drive treatment resistance. In mouse models of GBM, ZIKV also generates an anti-tumor inflammatory response and prolongs survival. To support clinical development and address safety concerns for intra-tumoral treatment, we assessed the effects of injection of an immune-sensitized ZIKV (Δ10 3'-UTR ZIKV), which cannot be transmitted by mosquitos, into non-tumor-bearing rhesus macaque brains. After injection, the primates showed no clinical signs of illness. Histologically, as expected, ZIKV infection elicited mild inflammation, which resolved within 2 weeks. No infectious virus was detected in the …

Exploiting Large Language Models For Diagnosing Autism Associated Language Disorders And Identifying Distinct Features, Chuanbo Hu, Wenqi Li, Mindi Ruan, Xiangxu Yu, Shalaka Deshpande, Lynn K Paul, Shuo Wang, Xin Li

2020-Current year OA Pubs

Diagnosing language disorders associated with autism is a complex challenge, often hampered by the subjective nature and variability of traditional assessment methods. In this study, we explored large language models (LLMs) to overcome the speed and precision obstacles by enhancing sensitivity and profiling linguistic features for autism diagnosis. This research utilizes natural language understanding capabilities of LLMs to simplify and improve the diagnostic process, focusing on identifying autism-related language patterns. We showed that the proposed method demonstrated improvements over the baseline models, with over a 10% increase in both sensitivity and positive predictive value in a zero-shot learning configuration. Combining …

Holter Monitor Qt Dispersion And Qtc-Dispersion In Pediatric Long Qt Syndrome And Development Of A Diagnostic And Arrhythmia Risk Prediction Model, Hadeel Allam, Na Le Dang, Edita Karasalihovic, Nathan Miller, Lisa Roelle, William B Orr, Dustin Nash, Anthony G Pompa, Jennifer N A Silva

2020-Current year OA Pubs

BACKGROUND: Holter monitors can provide temporal QT analysis, allowing for calculation of QT dispersion and corrected QT dispersion over time. We describe the results of the QT dispersion and corrected QT dispersion over a 24-hour period in pediatric patients with long QT syndrome (LQTS), compared with a normal cohort, and develop 2 new machine learning models for diagnosis and arrhythmia risk prediction in LQTS.

METHODS: A single-center retrospective case-control study was conducted comparing patients with congenital LQTS and normal controls who underwent a clinically indicated Holter between January 2022 and May 2024. After identifying patients with cardiac events, 2 neural …

Baseline Ecg And Cardiovascular Outcomes In People With Hiv: Insights From Reprieve, Aya Awwad, Shashwatee Bagchi, Et Al.

2020-Current year OA Pubs

BACKGROUND: With antiretroviral therapy, people with HIV (PWH) have an increased burden of cardiovascular disease. The REPRIEVE (Randomized Trial to Prevent Vascular Events in HIV) trial demonstrated that pitavastatin reduces major adverse cardiovascular events (MACEs) among PWH at low to moderate traditional atherosclerotic risk. Electrocardiographic abnormalities are common in PWH, but little is known about their association with MACEs. We sought to examine whether baseline electrocardiographic abnormalities are associated with increased MACE risk among a global primary cardiovascular disease prevention cohort of PWH in REPRIEVE.

METHODS: In this observational analysis, entry electrocardiographic abnormalities were adjudicated and classified as major or …

Addressing Challenges In Accessing Secondary And Tertiary Healthcare Services For Migrants And Refugees In Egypt, Noura Seada, Nehal El-Bakhshawangy, Heba Semary, Fatma Alzahraa Hassan, Ahmed Hammad

Papers, Posters, and Presentations

The growing number of vulnerable migrants and refugees worldwide presents a significant challenge to host countries, particularly in terms of accessing healthcare services. Egypt hosts over 9 million migrants and refugees, with 1.5 million in a vulnerable situation. Despite the country’s efforts in providing adequate healthcare to these vulnerable groups, some challenges persist. This paper addresses the barriers that vulnerable migrants and refugees face when seeking secondary and tertiary healthcare services in Egypt, analyzing the legal, economic, social, and health system factors that contribute to this problem.

In 2018, the Egyptian government began an ambitious journey to reform its healthcare …

Cv: Robert Sweet (Physical Therapy), Robert Sweet

Rehabilitation and Health Sciences Department Faculty Curricula Vitae

No abstract provided.

Cv: Maria Josefina Natividad (Medical Assistant, Pharmacy Technician), Maria Josefina Natividad

Rehabilitation and Health Sciences Department Faculty Curricula Vitae

No abstract provided.