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Articles 61 - 90 of 1688

Full-Text Articles in Translational Medical Research

Improving Empathy And Reducing Stigmatization In Pre-Clinical Physician Assistant Students Towards Patient Taking Opioids For Chronic Pain: The Feasibility Of A Perspective-Taking Peer Role-Play Intervention, Barbie Ann Seton Stephen Nov 2025

Improving Empathy And Reducing Stigmatization In Pre-Clinical Physician Assistant Students Towards Patient Taking Opioids For Chronic Pain: The Feasibility Of A Perspective-Taking Peer Role-Play Intervention, Barbie Ann Seton Stephen

Doctor of Philosophy in Translational Health Sciences Dissertations

Background: Empathy has been identified as a crucial skill for all healthcare providers who treat patients with chronic pain. It has been directly linked to higher patient satisfaction and improved health outcomes. It has also been linked to reduced burnout, fewer medical errors, and improved job satisfaction among healthcare providers. Despite the many interventions that have been developed to promote empathy, the decline of empathy in healthcare providers and trainees continues to be of great concern, especially in pain management and opioid prescribing, thus affecting the quality of care given to these patients. In physician assistant students, this decline has …


Rebound Bursting Selectively Enables Fast Dynamics In Dopamine Midbrain Neurons Projecting To The Dorsolateral Striatum, Strahinja Stojanovic, Christopher J. Knowlton, Richard Egger-Mackrodt, Johanna Mankel, Josef Shin, Stephan Lammel, Carmen C. Canavier, Jochen Roeper Oct 2025

Rebound Bursting Selectively Enables Fast Dynamics In Dopamine Midbrain Neurons Projecting To The Dorsolateral Striatum, Strahinja Stojanovic, Christopher J. Knowlton, Richard Egger-Mackrodt, Johanna Mankel, Josef Shin, Stephan Lammel, Carmen C. Canavier, Jochen Roeper

School of Graduate Studies Faculty Publications

Dopamine (DA) midbrain neurons are involved in a wide array of key brain functions including movement control and reward-based learning. They are also critical for major brain disorders such as Parkinson's disease or schizophrenia. DA neurons projecting to distinct striatal territories are diverse with regard to their molecular makeup and cellular physiology, which are likely to contribute to the observed differences in temporal DA dynamics. Among these regions, the dorsolateral striatum (DLS) displays the fastest DA dynamics, which might control the moment-to-moment vigor and variability of voluntary movements. However, the underlying mechanisms for these DLS-specific fast DA fluctuations are unresolved. …


Epdevatlas: Mapping Gabaergic Cells And Microglia In The Early Postnatal Mouse Brain, Josephine K. Liwang, Fae N. Kronman, Hyun-Jae Pi, Yuan-Ting Wu, Daniel J. Vanselow, Steffy B. Manjila, Deniz Parmaksiz, Donghui Shin, Yoav Ben-Simon, Michael Taormina, Sharon W. Way, Hongkui Zeng, Bosiljka Tasic, Lydia Ng, Yongsoo Kim Oct 2025

Epdevatlas: Mapping Gabaergic Cells And Microglia In The Early Postnatal Mouse Brain, Josephine K. Liwang, Fae N. Kronman, Hyun-Jae Pi, Yuan-Ting Wu, Daniel J. Vanselow, Steffy B. Manjila, Deniz Parmaksiz, Donghui Shin, Yoav Ben-Simon, Michael Taormina, Sharon W. Way, Hongkui Zeng, Bosiljka Tasic, Lydia Ng, Yongsoo Kim

School of Graduate Studies Faculty Publications

During development, brain regions follow encoded growth trajectories. Compared to classical brain growth charts, high-definition growth charts could quantify regional volumetric growth and constituent cell types, improving our understanding of typical and pathological brain development. Here, we create high-resolution 3D atlases of the early postnatal mouse brain, using Allen CCFv3 anatomical labels, at postnatal days (P) 4, 6, 8, 10, 12, and 14, and determine the volumetric growth of different brain regions. We utilize 11 different cell type-specific transgenic animals to validate and refine anatomical labels. Moreover, we reveal region-specific density changes in γ-aminobutyric acid-producing (GABAergic) neurons, cortical layer-specific cell …


Female Cardioprotection In A Mouse Model Of Alcohol-Associated Cardiomyopathy, Joshua M. Edavettal, Meagan Donovan, Nicholas R. Harris, Xavier R. Chapa-Dubocq, Keishla M. Rodríguez-Graciani, Janos Paloczi, Liz Simon, Bysani Chandrasekar, Jason D. Gardner Oct 2025

Female Cardioprotection In A Mouse Model Of Alcohol-Associated Cardiomyopathy, Joshua M. Edavettal, Meagan Donovan, Nicholas R. Harris, Xavier R. Chapa-Dubocq, Keishla M. Rodríguez-Graciani, Janos Paloczi, Liz Simon, Bysani Chandrasekar, Jason D. Gardner

School of Graduate Studies Faculty Publications

Chronic alcohol misuse is the leading cause of non-ischemic dilated cardiomyopathy, and the molecular mechanisms underlying the development of alcohol-associated cardiomyopathy (ACM), particularly regarding sex-specific susceptibility and mitochondrial contributions, are not fully known. In this study, we utilized a preclinical model of chronic + binge ethanol consumption to investigate sex differences in disease severity and mitochondrial function. Male and female C57BL/6J mice were fed ethanol or control liquid diets for 30 days, with 2 binge episodes on days 10 and 30. Cardiac morphology was assessed via echocardiography and cardiac function via left ventricular pressure-volume catheterization. Mitochondrial function was evaluated ex …


Proteomic Analysis Of Central Amygdala Systems Regulated By Mifepristone In The Context Of Alcohol Dependence, Stephanie S. Lee, Laura Monteagudo Romero, John W. Lammons, Jennifer M. Klein, Kimberly N. Edwards, Jessie J. Guidry, Scott Edwards Oct 2025

Proteomic Analysis Of Central Amygdala Systems Regulated By Mifepristone In The Context Of Alcohol Dependence, Stephanie S. Lee, Laura Monteagudo Romero, John W. Lammons, Jennifer M. Klein, Kimberly N. Edwards, Jessie J. Guidry, Scott Edwards

School of Graduate Studies Faculty Publications

Alcohol use disorder (AUD) is a psychiatric disorder characterized by escalated alcohol use and the emergence of negative affective symptoms. Studies have described a dysregulation of glucocorticoid receptor (GR) signaling in the context of AUD at the levels of the hypothalamic-pituitary-adrenal (HPA) axis and central amygdala (CeA). A functional increase in CeA GR activity occurs during alcohol withdrawal in alcohol-dependent animal models, and the GR antagonist mifepristone reduces alcohol-seeking and drinking behaviors in both rodents and humans. The aims of this study were to determine differential CeA protein expression in alcohol-dependent rats and examine the effects of mifepristone treatment in …


Pcornet’S Patient Advisory Councils Relevance To Research, Toni Hill Oct 2025

Pcornet’S Patient Advisory Councils Relevance To Research, Toni Hill

Mountain Plains Business Conference

This presentation will provide an overview of the UNMC award and UNK sub-award with the Patient-Centered Outcomes Research Network (PCORnet) specific to the research of patient and family-focused research using the Patient Advisory Council (PAC) framework. The UNMC PCORnet project is now in Phase 4 (2025 – 2029). This four-year, $13,500,000 project includes 14 partner organizations as part of the Great Plains Collaborative (GPC) with data from 8.9 million unique individuals across 14 states. This presentation will begin a discussion related to the uniqueness of patient engagement, community engagement, and Patient Advisory Council engagement.


Multimodal Reprogramming Of The Tumor Microenvironment By Mmr And Dual Checkpoint Blockade In Hepatocellular Carcinoma Models, Mulu Z. Tesfay, Aleksandra Cios, Khandoker Usran Ferdous, Randal S. Shelton, Bahaa Mustafa, Camila C. Simoes, Murat Gokden, Isabelle R. Miousse, Kimberly J. Krager, Marjan Boerma, Alicja Urbaniak, Anuradha Kunthur, Sri Obulareddy, Joshua M. Eichhorn, Steven R. Post, Jean Christopher Chamcheu, Omeed Moaven, Chiswili Y. Chabu, Dan G. Duda, Matteo Conti, Bruno Nardo, Rang Govindarajan, Martin E. Fernandez-Zapico, Lewis R. Roberts, Mitesh J. Borad, Martin J. Cannon, Alexei G. Basnakian, Bolni M. Nagalo Oct 2025

Multimodal Reprogramming Of The Tumor Microenvironment By Mmr And Dual Checkpoint Blockade In Hepatocellular Carcinoma Models, Mulu Z. Tesfay, Aleksandra Cios, Khandoker Usran Ferdous, Randal S. Shelton, Bahaa Mustafa, Camila C. Simoes, Murat Gokden, Isabelle R. Miousse, Kimberly J. Krager, Marjan Boerma, Alicja Urbaniak, Anuradha Kunthur, Sri Obulareddy, Joshua M. Eichhorn, Steven R. Post, Jean Christopher Chamcheu, Omeed Moaven, Chiswili Y. Chabu, Dan G. Duda, Matteo Conti, Bruno Nardo, Rang Govindarajan, Martin E. Fernandez-Zapico, Lewis R. Roberts, Mitesh J. Borad, Martin J. Cannon, Alexei G. Basnakian, Bolni M. Nagalo

School of Graduate Studies Faculty Publications

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide, thus, there is an urgent need to develop more effective therapeutic options for this dismal condition. Tumor-infiltrating lymphocytes (TILs) are associated with improved response to immune checkpoint blockade in HCC, but their low abundance in most cases limits their therapeutic efficacy. Here, we demonstrate, in mice, that low-dose intratumoral immunovirotherapy with the trivalent measles, mumps, and rubella vaccine (MMR) induces superior tumor-growth delay and extended host survival compared to individually administered vaccines for measles, mumps, or rubella viruses. Further, our results show that MMR therapy synergizes with PD-1 and …


Dual Membrane Receptor Degradation Via Folate Receptor Targeting Chimera, Zhen Wang, Zhixin Li, Jenny Högström, Hiroyuki Inuzuka, Rui Jing, Peiqiang Yan, Tao Hou, Yihang Qi, Daoyuan Huang, Jingchao Wang, Ting Wu, Xiaoying Shi, Bolin Liu, Taru Muranen, Dingpeng Zhang, Wenyi Wei Oct 2025

Dual Membrane Receptor Degradation Via Folate Receptor Targeting Chimera, Zhen Wang, Zhixin Li, Jenny Högström, Hiroyuki Inuzuka, Rui Jing, Peiqiang Yan, Tao Hou, Yihang Qi, Daoyuan Huang, Jingchao Wang, Ting Wu, Xiaoying Shi, Bolin Liu, Taru Muranen, Dingpeng Zhang, Wenyi Wei

School of Medicine Faculty Publications

Cancer drug resistance poses a significant challenge in oncology, often driven by intricate cross-talk among membrane-bound receptors that compromise mono-targeted therapies. We develop a dual membrane receptor degradation strategy leveraging Folate Receptor α (FRα) to address this issue. Folate Receptor α Targeting Chimeras-dual (FolTAC-dual) are engineered degraders designed to selectively and simultaneously degrade distinct receptor pairs: (1) EGFR/HER2 and (2) PD-L1/VISTA. Through modular optimization of modality configurations and geometries, we identify the “string” format as the most effective construct. Mechanistic studies demonstrate an ~85% increase in EGFR-binding affinity compared to the conventional knob-into-hole design, likely contributing to the improved efficiency …


Understanding Strategies To Translate Knowledge On Hookah Smoking: A Mixed Methods Study, Rabia Mir Oct 2025

Understanding Strategies To Translate Knowledge On Hookah Smoking: A Mixed Methods Study, Rabia Mir

Doctor of Philosophy in Translational Health Sciences Dissertations

Background: One tobacco trend of the 21 st century is smoking hookah or waterpipes. Hookah smoking is thriving on a false widespread belief that it is a safe alternate to smoking cigarettes when in fact it has adverse effects on health and is not safer. Hookah use has especially become popular for young adults and college students.

Study Objectives: The purpose of this study is to generate knowledge to inform university administration (health education personnel and campus policy makers) on what the psychosocial profile of a hookah smoker is, including risk factors, and how they can use messaging to reduce …


Chri Research Operations Summit Building Bridges Across Chri, Tina Freese Decker, Paula Schuiteman-Bishop, Surender Rajasekaran, Matthew Sims Sep 2025

Chri Research Operations Summit Building Bridges Across Chri, Tina Freese Decker, Paula Schuiteman-Bishop, Surender Rajasekaran, Matthew Sims

Website/Multimedia Contributions

The CHRI Research Operations Summit is the premier event for all research team members and leaders across CHRI. Our theme of Building Bridges highlights our commitment to strengthening connections, fostering collaboration, and unifying our efforts across all regions.


A Novel Scaffold-Based Model For Stage Ii Pressure Injury Simulation: Protocol Development And Future Directions In Tissue Engineering, Skyler B. Wrubleski Sep 2025

A Novel Scaffold-Based Model For Stage Ii Pressure Injury Simulation: Protocol Development And Future Directions In Tissue Engineering, Skyler B. Wrubleski

Undergraduate Research and Scholarship Symposium

This study developed a 3D tissue-engineered scaffold to mimic human sacral skin for modeling pressure injuries. The scaffold consisted of a composite hydrogel of sodium alginate, gelatin, and tannic acid, crosslinked with calcium chloride. Swelling tests showed moderate hydration capacity, while wound mimic formation using a custom 3D-printed apparatus produced consistent morphology and dimensions comparable to human dermal tissue. The scaffold maintained structural integrity under prolonged compressive forces, demonstrating viability for pressure injury studies. Future work will incorporate a bilayer model with keratinocytes and fibroblasts and introduce elastin to enhance elasticity and mechanical properties. This approach aims to improve in …


Tc-Ptp Enhances Cordycepin-Induced Apoptosis In Human Pancreatic Cancer Cells, Olivia Samaie, Rodrigo Vidales, Lindsey Shim, Murali M. Yallapu, Subhash C. Chauhan, Mushfiq Hassan Shaikh, Dae Joon Kim Sep 2025

Tc-Ptp Enhances Cordycepin-Induced Apoptosis In Human Pancreatic Cancer Cells, Olivia Samaie, Rodrigo Vidales, Lindsey Shim, Murali M. Yallapu, Subhash C. Chauhan, Mushfiq Hassan Shaikh, Dae Joon Kim

Research Colloquium

Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy marked by early metastasis, dense desmoplastic stroma, and profound resistance to conventional therapies. Despite the development of combination regimens such as gemcitabine and FOLFIRINOX, outcomes remain dismal, with median survival under one year for metastatic cases. This underscores the urgent need for novel therapeutic approaches that target multiple pathways simultaneously. T-cell protein tyrosine phosphatase (TC-PTP) is one of nonreceptor PTPs that negatively regulates oncogenic signaling pathways, particularly STAT3 and AKT, both of which are constitutively active in many solid tumors. Cordycepin, a nucleoside analogue derived from Cordyceps militaris, has …


Synthesis, Pharmacokinetic Studies, And Metabolite Analysis Of Meridianin C In Rats Using A Validated Ultra High Performance Liquid Chromatography-Tandem Mass Spectrometry Method, Liangyu Xu, Zhaogen Wu, Karna Ramachandraiah, Guihun Jiang, Guozhe Zhang Sep 2025

Synthesis, Pharmacokinetic Studies, And Metabolite Analysis Of Meridianin C In Rats Using A Validated Ultra High Performance Liquid Chromatography-Tandem Mass Spectrometry Method, Liangyu Xu, Zhaogen Wu, Karna Ramachandraiah, Guihun Jiang, Guozhe Zhang

School of Graduate Studies Faculty Publications

Introduction: Meridianin C (MC) is a marine-derived indole alkaloid that has demonstrated kinase inhibitory and anti-tumor activities. Despite its diverse biological properties, no previous reports have systematically evaluated the in vivo quantitative analysis of MC and its metabolites. Methods: In this study, MC was synthesized following a previously reported procedure with slight modifications. A sensitive, accurate, and reliable ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC–MS/MS) method was developed to simultaneously detect MC and its five major metabolites (MC-1-N-O-GluA, MC-1-N-O-SO3H, MC-2′-N-O-GluA, MC-2′-N-O-SO3H, and MC-O-GluA-didehydration) in rat plasma. Rats received a single oral dose of MC (100 mg/kg), and pharmacokinetic analysis was …


A Study On Nutritional Status Among Regular Gym Goers In And Around Chennai, India, Ettiyappan Thirumurugan, Kalpana Devi Venkatesan, Pavithra Tamilmani, Devika Preetha, Joyce Albert Princy Mariya Selvanathan, Dhanyasree Mohandas, Ameer Basha Sathik, Santhosh Kumar Manjunathan, Ashika Kannadhas Sheeba Aug 2025

A Study On Nutritional Status Among Regular Gym Goers In And Around Chennai, India, Ettiyappan Thirumurugan, Kalpana Devi Venkatesan, Pavithra Tamilmani, Devika Preetha, Joyce Albert Princy Mariya Selvanathan, Dhanyasree Mohandas, Ameer Basha Sathik, Santhosh Kumar Manjunathan, Ashika Kannadhas Sheeba

Makara Journal of Health Research

Background: The increasing sales of sports supplements indicate a concerning trend, as many gym-goers may misuse these products owing to misinformation and insufficient knowledge, potentially impacting their performance. This issue is further compounded by specific gym trainers who may lack comprehensive information and inadvertently influence their clients' choices. To address this concern, the present study evaluated dietary supplement practices and sports nutrition knowledge among regular gym-goers at fitness centers in Chennai, India.

Methods: A cross-sectional survey was conducted from November 2023 to May 2024 using a validated questionnaire distributed across Chennai, India. A total of 450 participants were …


Association Of Physical Activity And Neighborhood Deprivation With Extracellular Vesicle Characteristics In African American Women With Obesity, Anca D. Dobrian, Yvonne Baumer, Tiffany Powell-Wiley, Lizzy Aquino-Peterson, Noel Miller Aug 2025

Association Of Physical Activity And Neighborhood Deprivation With Extracellular Vesicle Characteristics In African American Women With Obesity, Anca D. Dobrian, Yvonne Baumer, Tiffany Powell-Wiley, Lizzy Aquino-Peterson, Noel Miller

Cardiovascular Research Symposium

Association of Physical Activity and Neighborhood Deprivation with Extracellular Vesicle Characteristics in African American Women with Obesity


Colostrum Extracellular Vesicle Are Neuroprotective In The Mptp Intoxicated Mouse Model Of Parkinson's Disease, Samia Akter Aug 2025

Colostrum Extracellular Vesicle Are Neuroprotective In The Mptp Intoxicated Mouse Model Of Parkinson's Disease, Samia Akter

Theses & Dissertations

Parkinson’s Disease (PD) is the second most common neurodegenerative disorder. Dopaminergic neuronal loss in the substantia nigra and the formation of Lewy bodies are the disease pathological hallmarks. We demonstrate that bovine colostrum extracellular vesicles (EVs) induce anti-inflammatory and neuroprotective activities during MPTP (methyl-4-phenyl-1,2,3,6-tetrahydropyridine) intoxication. Treatment these mice with colostrum EVs reduced the extent of activated microglia and neurodegenerative activities. RNA sequencing and transcriptomic analysis revealed a significant decrease in pro- inflammatory responses, as well as reduced recruitment and activation of immunocytes in affected brain tissues. Decreased expression of pro-inflammatory cytokines and chemokines, as well as suppressed canonical inflammasomes, was …


Hydrogen Sulfide Deficiency And Therapeutic Targeting In Cardiometabolic Hfpef: Evidence For Synergistic Benefit With Glp-1/Glucagon Agonism, Jake E. Doiron, Mahmoud H. Elbatreek, Huijing Xia, Xiaoman Yu, Natalie D. Gehred, Tatiana Gromova, Jingshu Chen, Ian H. Driver, Naoto Muraoka, Martin Jensen, Smitha Shambhu, W. H.Wilson Tang, Kyle B. Lapenna, Thomas E. Sharp, Traci T. Goodchild, Ming Xian, Shi Xu, Heather Quiriarte, Timothy D. Allerton, Alexia Zagouras, Jennifer Wilcox, Sanjiv J. Shah, Josef Pfeilschifter, Karl Friedrich Beck, Thomas M. Vondriska, Zhen Li, David J. Lefer Aug 2025

Hydrogen Sulfide Deficiency And Therapeutic Targeting In Cardiometabolic Hfpef: Evidence For Synergistic Benefit With Glp-1/Glucagon Agonism, Jake E. Doiron, Mahmoud H. Elbatreek, Huijing Xia, Xiaoman Yu, Natalie D. Gehred, Tatiana Gromova, Jingshu Chen, Ian H. Driver, Naoto Muraoka, Martin Jensen, Smitha Shambhu, W. H.Wilson Tang, Kyle B. Lapenna, Thomas E. Sharp, Traci T. Goodchild, Ming Xian, Shi Xu, Heather Quiriarte, Timothy D. Allerton, Alexia Zagouras, Jennifer Wilcox, Sanjiv J. Shah, Josef Pfeilschifter, Karl Friedrich Beck, Thomas M. Vondriska, Zhen Li, David J. Lefer

School of Graduate Studies Faculty Publications

Heart failure with preserved ejection fraction (HFpEF) presents significant treatment challenges. We assessed hydrogen sulfide (H2S) bioavailability in HFpEF patients and 2 animal models: the "2-hit" L-NAME + high-fat diet mouse model and ZSF1 obese rats. H2S levels were significantly reduced in patients and both models, linked to decreased cystathionine-γ-lyase expression and increased sulfide quinone oxidoreductase. Cystathionine-γ-lyase knockout worsened HFpEF, whereas pharmacological supplementation with an H2S donor improved diastolic function and reduced cardiac fibrosis. H2S supplement synergized with GLP-1/glucagon agonist and ameliorated HFpEF. These findings suggest that enhancing H2S bioavailability may provide a novel therapeutic strategy for HFpEF.


Therapeutic Potential Of Sglt2 Inhibitors In A Repeated Love Dose Cisplatin Model., Dianet C. Sanchez Aug 2025

Therapeutic Potential Of Sglt2 Inhibitors In A Repeated Love Dose Cisplatin Model., Dianet C. Sanchez

Electronic Theses and Dissertations

Cisplatin is a potent chemotherapeutic, thirty percent of patients develop Acute Kidney Injury (AKI). These patients are ten times more likely to develop chronic kidney disease (CKD). Sodium-glucose-cotransporter-2-inhibitors (SGLT2i), FDA approved for diabetes, has shown protection in multiple mouse models of AKI-CKD. We hypothesize SGLT2i can protect the kidney in a model of repeated low dose cisplatin with/without cancer. B6:129 mice with/without lung adenocarcinoma (Lung-adeno) were treated daily with SGLT2i dapagliflozin (10mg/kg)/vehicle control. After seven days, weekly cisplatin (7mg/kg)/vehicle control was initiated for 3-4 weeks. Following final cisplatin dose, kidney function, injury, fibrosis, inflammation was assessed. SGLT2i treatment attenuated alterations …


Sarcoplasmic Reticulum-Mitochondria Microdomains: Hugging And Kissing In The Heart, Bong Sook Jhun, Jin O-Uchi, Brian Rhee, Ameneh Ahrari, Nathan Demichaelis, Kye-Im Jeon, David M. Booth, Shey-Shing Sheu Aug 2025

Sarcoplasmic Reticulum-Mitochondria Microdomains: Hugging And Kissing In The Heart, Bong Sook Jhun, Jin O-Uchi, Brian Rhee, Ameneh Ahrari, Nathan Demichaelis, Kye-Im Jeon, David M. Booth, Shey-Shing Sheu

Center for Translational Medicine Faculty Papers

Endoplasmic reticulum (ER)-mitochondrial (ER-Mito) interface, termed mitochondrial-ER contacts (MERCs), plays significant roles in the maintenance of bioenergetics and basal cell functions via the exchange of lipids, Ca 2 þ , and reactive oxygen species (ROS) in various cell types/tissues. Genetic deletion of mitofusin 2 (Mfn2), one of the key components of ER-Mito tethering, in cardiomy- ocytes (CMs) in vivo revealed the importance of the microdomains between mitochondria and sarcoplasmic reticulum (SR), a dif- ferentiated form of ER in muscle cells, for maintaining normal mitochondrial Ca 2 þ (mtCa 2 þ ) handling and bioenergetics in the adult heart. However, key …


Impact Of S-Phase Kinase Protien 2 Blockades On Hematopoetic Stem Cell Metabolism, Nicole Elmaraghy Aug 2025

Impact Of S-Phase Kinase Protien 2 Blockades On Hematopoetic Stem Cell Metabolism, Nicole Elmaraghy

Electronic Theses, Projects, and Dissertations

Hematopoietic stem and progenitor cells (HSPCs) quiescence is vital for the success of bone marrow transplantation, as it preserves long term self- renewal and prevents premature exhaustion (Takubo et al., 2013; Wilson et al., 2008). However, bone marrow transplant (BMT) failure remains a clinical challenge, often due to lack of long-term engraftment and insufficient stress reliance. Both of these characteristics are tightly linked to disrupted stem cell quiescence and metabolic imbalance (Anso et al., 2017; Vannini et al., 2016). One key player is S-phase kinase protein (SKP2), an E3 ubiquitin ligase that targets cell cycle inhibitors, like p27, for proteosome …


Effects Of Maackia Amurensis Seed Lectin (Masl) On Oscc Cell Morphology, Pdpn Expression, Growth, And Motility In A Phase 1 Clinical Trial, Ariel C Yin, Cayla J Holdcraft, Tyler J Hellmig, Eamonn J Brace, David I Suster, Alan J Shienbaum, Dylan Roden, Evelyne Kalyoussef, Ghayoour Mir, Eugenio Capitle, Soly Baredes, Rabie M Shanti, Mika K Kaneko, Yukinari Kato, Hisataka Kobayashi, Aki Furusawa, Mahnaz Fatahzadeh, Gary S Goldberg Jul 2025

Effects Of Maackia Amurensis Seed Lectin (Masl) On Oscc Cell Morphology, Pdpn Expression, Growth, And Motility In A Phase 1 Clinical Trial, Ariel C Yin, Cayla J Holdcraft, Tyler J Hellmig, Eamonn J Brace, David I Suster, Alan J Shienbaum, Dylan Roden, Evelyne Kalyoussef, Ghayoour Mir, Eugenio Capitle, Soly Baredes, Rabie M Shanti, Mika K Kaneko, Yukinari Kato, Hisataka Kobayashi, Aki Furusawa, Mahnaz Fatahzadeh, Gary S Goldberg

Rowan-Virtua School of Osteopathic Medicine Departmental Research

BACKGROUND: Podoplanin (PDPN) has emerged as a functionally relevant biomarker and chemotherapeutic target expressed by OSCC cells. PDPN signaling can directly increase tumor cell invasion and metastasis, and also inhibit host lymphocyte activation and immune response. Accordingly, antibodies and Maackia amurensis seed lectin (MASL) can target the PDPN receptor to inhibit OSCC cell migration and viability. However, the effects of MASL on OSCC cells in oral cancer patients has not yet been reported.

METHODS: We conducted a Phase 1 human clinical trial to examine the effects of a single 100 mg oral dose of MASL on OSCC cell morphology, PDPN …


Nitric Oxide Does Not Improve Liver Mitochondrial Function 48 Hours After Cecal Ligation And Perforation In Experimental Sepsis, Pierre Eyenga, Shey-Shing Sheu Jul 2025

Nitric Oxide Does Not Improve Liver Mitochondrial Function 48 Hours After Cecal Ligation And Perforation In Experimental Sepsis, Pierre Eyenga, Shey-Shing Sheu

Center for Translational Medicine Faculty Papers

Nitric oxide (NO) has a dual effect on mitochondria. Incubating liver mitochondria with NO improves oxidative phosphorylation (OXPHOS) efficiency by decreasing state 4 respiration more than ATP synthesis and preventing mitochondrial permeability transition pore (mPTP) opening. We evaluated the effect of L-arginine (L-arg), an NO donor, on isolated liver mitochondrial respiration and mPTP in sepsis. Male mice were subjected to cecal ligation and perforation (CLP) with saline resuscitation or sham. After 8, 24, and 48 h, with and without L-arg, we measured isolated liver mitochondrial respiration and cytochrome c oxidase (COX) activity using polarographic methods and calcium retention capacity (CRC) …


Pilot Survey Of Attitudes Toward Xenotransplantation Among Nursing Students In London, Uk., Daniel Rodger, Luz A. Padilla, Daniel J. Hurst, David K C Cooper, Gilberto Buzzi, Antonio Ríos Jul 2025

Pilot Survey Of Attitudes Toward Xenotransplantation Among Nursing Students In London, Uk., Daniel Rodger, Luz A. Padilla, Daniel J. Hurst, David K C Cooper, Gilberto Buzzi, Antonio Ríos

Rowan-Virtua School of Osteopathic Medicine Departmental Research

BACKGROUND: Solid organ xenotransplantation has been approved for clinical trials in the United States. Because of the role of nurses in patient decision-making, it is important to understand the attitudes of the future nursing workforce toward xenotransplantation. This pilot study aimed to investigate the attitudes of adult nursing students toward xenotransplantation.

METHODS: A cross-sectional survey design was used. The online pilot survey was completed by 33 undergraduate adult nursing students at one university in London, England. A minority of the hospitals that students may have had a clinical placement in had a transplant unit. The protocol for this study was …


Profile Of Trna-Derived Short Non-Coding Rnas During Monocyte Differentiation And Their Role In Macrophage Survival, Anahita Jayaram, Sanjeev Galande, Soroush Sharbati, Deepak A. Deshpande, Phd, Kamlesh Pawar Jul 2025

Profile Of Trna-Derived Short Non-Coding Rnas During Monocyte Differentiation And Their Role In Macrophage Survival, Anahita Jayaram, Sanjeev Galande, Soroush Sharbati, Deepak A. Deshpande, Phd, Kamlesh Pawar

Center for Translational Medicine Faculty Papers

Monocytes, a type of leukocytes, are key players in immune responses, transitioning to macrophages at infection sites. Differentiation, which is crucial for macrophage survival and resistance to apoptosis, is a tightly regulated process. Based on our earlier findings implicating the 5'-fragment of tRNAHisGUG (5'-HisGUG) in macrophage biology, we specifically focused on these fragments to investigate its regulation during monocyte-to-macrophage differentiation and its role in macrophage survival. We performed small RNA sequencing during monocyte-to-macrophage differentiation using THP-1 cells and identified 5'-HisGUG as a prominently regulated tDR. Notably, transfection of 5'-HisGUG in macrophages decreased survival under apoptotic stress. We propose that 5'-HisGUG …


Muscle Rev-Erb Controls Time-Dependent Adaptations To Chronic Exercise In Mice, Jidong Liu, Fang Xiao, Abhinav Choubey, Udhaya Kumar S, Yanxiang Wang, Sungguan Hong, Tingting Yang, Husniye Gul Otlu, Ege Sanem Oturmaz, Emanuele Loro, Yuxiang Sun, Pradip Saha, Tejvir S Khurana, Li Chen, Xinguo Hou, Zheng Sun Jul 2025

Muscle Rev-Erb Controls Time-Dependent Adaptations To Chronic Exercise In Mice, Jidong Liu, Fang Xiao, Abhinav Choubey, Udhaya Kumar S, Yanxiang Wang, Sungguan Hong, Tingting Yang, Husniye Gul Otlu, Ege Sanem Oturmaz, Emanuele Loro, Yuxiang Sun, Pradip Saha, Tejvir S Khurana, Li Chen, Xinguo Hou, Zheng Sun

Center on Aging Staff Publications

The best time of the day for chronic exercise training and the mechanism underlying the timing effects is unclear. Here, we show that low-intensity, low-volume treadmill training in mice before sleep yields greater benefits than after waking for muscle contractile performance and systemic glucose tolerance. Baseline muscle performance also exhibits diurnal variations, with higher strength but lower endurance before sleep than after waking. Muscle-specific knockout of circadian clock genes Rev-erbα/β (Rev-MKO) in male mice eradicates the diurnal variations in both training and baseline conditions without affecting muscle mass, mitochondrial content, food intake, or spontaneous activities. Multi-omics and metabolic measurements reveal …


A Collective Case Study Of How Researchers Describe Their Experiences, Challenges, And Perceived Impact Of Patient Engagement, Lorna M. Richards Jun 2025

A Collective Case Study Of How Researchers Describe Their Experiences, Challenges, And Perceived Impact Of Patient Engagement, Lorna M. Richards

Doctor of Philosophy in Translational Health Sciences Dissertations

Background: Patient engagement (PE) in clinical research has become “extensively and internationally recognized as important and gained growing policy attention, supported by scientific evidence” (Al-Tannir et al., 2017, Background section). The proliferation of PE directives has driven the paradigm shift in drug development from a paternalistic approach to a more patient-centric approach influenced by regulatory agencies, funders, and academic initiatives (Bombak & Hanson, 2017). However, too often, PE activities are not well considered for discovering actionable insights but are merely an empty formality. For PE to be meaningful, patient involvement must be planned, supported, and valued by clinical researchers.

Objectives: …


Increasing Community Members' Engagement In Cancer Research: The Making Research Clear Program, Rebecca J. Melillo, Christiane J. El Khoury, Joshua Blanding-Godbolt, Q. Greene, Karen M. Bussard, Amy Leader Jun 2025

Increasing Community Members' Engagement In Cancer Research: The Making Research Clear Program, Rebecca J. Melillo, Christiane J. El Khoury, Joshua Blanding-Godbolt, Q. Greene, Karen M. Bussard, Amy Leader

Kimmel Cancer Center Faculty Papers

BACKGROUND: Despite the importance of engaging community members in research, multiple barriers from the perspective of the investigator and community member exist. The Making Research CLEAR (Community Learning and Experience about Research) Program aims to bridge the gap between research conducted at an NCI-designated cancer center and the community.

METHODS: Community members and a cancer center investigator were paired for a 6-month immersive research experience. Community members had at least one research experience per month with their investigator, while also attending cancer center activities such as Institutional Review Board (IRB) meetings, research lectures, protocol review meetings, and community outreach events. …


Mechanistic Insights Into The Flash Effect: The Role Of Oxygen And Radiation Chemistry In Ultra-High Dose Rate Radiation Therapy, Jacob Pierce Sunnerberg Jun 2025

Mechanistic Insights Into The Flash Effect: The Role Of Oxygen And Radiation Chemistry In Ultra-High Dose Rate Radiation Therapy, Jacob Pierce Sunnerberg

Dartmouth College Ph.D Dissertations

The development of new cancer therapies focuses on widening the therapeutic ratio between tumor control and normal tissue toxicity. Over the last decade, ultra-high dose rate (UHDR) radiation therapy, commonly known as FLASH radiotherapy (FLASH-RT), has shown promising potential to reduce normal tissue toxicity while maintaining tumor control. However, the underlying mechanisms of the FLASH effect remain poorly understood. This thesis explores the radiation-chemical basis of FLASH-RT, focusing on the role of oxygen and reactive oxygen species in modulating biological outcomes.

A comprehensive set of in vitro studies demonstrated that UHDR delivery significantly alters radiation chemistry compared to conventional dose …


Advancing Novel Contrast Agents For Applications In Fluorescence-Guided Neurosurgery Using Fluorescence Cryotomography, Augustino Vittorio Scorzo Jun 2025

Advancing Novel Contrast Agents For Applications In Fluorescence-Guided Neurosurgery Using Fluorescence Cryotomography, Augustino Vittorio Scorzo

Dartmouth College Ph.D Dissertations

Fluorescence guided surgery (FGS) is an emerging surgical technique that aims to help surgeons identify tissue types to assist in surgical decision making - ideally providing “cut-by-color” guidance. A primary application for this approach is the identification of tumor tissue to achieve more accurate and complete tumor removal while simultaneously minimizing damage to surrounding normal tissue. The cornerstone of tumor visualization for FGS is the administration of fluorescent contrast agents, or in some cases metabolic precursors, designed to accumulate specifically in tumor tissue, and a wide range of agents that use different targeting mechanisms are currently under investigation. Although these …


Measuring What Matters To Patients: A Multiple Methods Sequential Study Of Disease Burden, Quality Of Life, And The Alignment Of Patient-Reported Outcome Measurements For High-Risk Myelodysplastic Syndrome And Acute Myelogenous Leukemia Patients, Anthony J. Messina Jun 2025

Measuring What Matters To Patients: A Multiple Methods Sequential Study Of Disease Burden, Quality Of Life, And The Alignment Of Patient-Reported Outcome Measurements For High-Risk Myelodysplastic Syndrome And Acute Myelogenous Leukemia Patients, Anthony J. Messina

Doctor of Philosophy in Translational Health Sciences Dissertations

Background

High-risk myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are aggressive hematologic malignancies with poor prognoses, where extending survival often comes at the cost of substantial morbidity. This study was grounded in the quality of survival (QoS) framework, which emphasizes that treatment outcomes should balance longevity with the health-related quality of life (HRQoL) experienced during the period of survival. In this context, patient-reported outcomes are crucial to capturing what truly matters to patients. However, existing patient-reported outcome measures (PROMs) used in MDS/AML clinical trials may not fully reflect patient priorities. A complementary Wilson–Cleary model perspective, linking biological factors to …