Therapeutics Commons^™

Functional Contribution Of Epithelial To Mesenchymal Transition Program On Krasg12d Targeting Efficacy In Pancreatic Cancer, Ana S. Maldonado

Dissertations and Theses (Open Access)

Functional contribution of epithelial to mesenchymal transition program on KRAS^G12D targeting efficacy in pancreatic cancer

Ana S. Maldonado, BS

Advisory Professor: Raghu Kalluri, M.D., Ph.D.

Pancreatic Ductal Adenocarcinoma (PDAC), a highly aggressive, metastatic, and therapeutically resistant form of pancreatic cancer has been projected to become the second-leading cause of cancer related mortality in the United States. This is driven by its detection difficulty, treatment efficacy, and asymptomatic nature, among other factors. PDAC is driven predominantly by KRAS^G12D mutations, which are responsible for the initial development of pancreatic intraepithelial neoplasia (Pan-IN) lesions, that are further maintained and progressed until …

Nanoparticle-Based Approaches To Brain Injury And Studies For Improved Detectability Toward Better Delivery Characterization, Hunter A. Miller

Dissertations and Doctoral Documents, University of Nebraska-Lincoln, 2023–

The clinical translation of nanoparticle (NP) therapeutics for brain injury has been slow despite preclinical promise. The causes of disconnect between preclinical and clinical outcomes is multifactorial, but insufficient delivery is noteworthy. Preclinical delivery characterization often lacks, obscuring mechanisms of failure, slowing development. Multimodal imaging is a promising strategy to improve delivery characterization, combining the strengths of various modalities. Magnetic resonance imaging (MRI) and luminescence imaging are a suitable combination for multimodal imaging, expanding the spatial and temporal resolution of either alone, but further material development is needed to enhance detectability. One problem is the interference of cellular autofluorescence in …

High-Dose Intravenous Vitamin C Combined With Docetaxel In Men With Metastatic Castration-Resistant Prostate Cancer: A Randomized Placebo-Controlled Phase Ii Trial, Channing Paller, Marianna Zahurak, Adel Mandl, Nicole Metri, Aliya Lalji, Elisabeth Heath, William Kelly, Christopher Hoimes, Pedro Barata, Jason Taksey, Dominique Garrison, Kartick Patra, Ginger Milne, Nicole Anders, Julie Nauroth, Jennifer Durham, Catherine Marshall, Mark Markowski, Mario Eisenberger, Emmanuel Antonarakis, Michael Carducci, Samuel Denmeade, Mark Levine

Department of Medicine Faculty Papers

UNLABELLED: High-dose intravenous vitamin C (HDIVC) administered to produce pharmacologic concentrations shows promise in preclinical models and small clinical trials, but larger prospective randomized trials are lacking. We evaluated the clinical benefit of combining HDIVC with docetaxel in patients with progressive metastatic castration-resistant prostate cancer (mCRPC). In this double-blind, placebo-controlled phase II trial, 47 patients were randomized 2:1 to receive docetaxel (75 mg/m2 i.v.) with either HDIVC (1 g/kg) or placebo. Coprimary endpoints were PSA50 response and adverse event rates. Secondary endpoints included overall survival, radiographic progression-free survival, and quality of life measured using the Functional Assessment of Cancer Therapy-Prostate …

Differential Effect Of An Evolving Amyloid And Tau Pathology On Brain Phospholipids And Bioactive Lipid Mediators In Rat Models Of Alzheimer-Like Pathology, Sonia Do Carmo, Marie Audrey I. Kautzmann, Surjyadipta Bhattacharjee, Bokkyoo Jun, Carolyn Steinberg, Joshua T. Emmerson, Janice C. Malcolm, Quentin Bonomo, Nicolas G. Bazan, A. Claudio Cuello

School of Graduate Studies Faculty Publications

Background: Brain inflammation contributes significantly to the pathophysiology of Alzheimer’s disease, and it is manifested by glial cell activation, increased production of cytokines/chemokines, and a shift in lipid mediators from a pro-homeostatic to a pro-inflammatory profile. However, whether the production of bioactive lipid mediators is affected at earlier stages, prior to the deposition of Aβ plaques and tau hyperphosphorylation, is unknown. The differential contribution of an evolving amyloid and tau pathology on the composition and abundance of membrane phospholipids and bioactive lipid mediators also remains unresolved. Methods: In this study, we examined the cortical levels of DHA- and AA-derived bioactive …

Potential Targeting Mechanisms For Bone-Directed Therapies, Betul Celik, Andrés Leal, Shunji Tomatsu

Department of Pediatrics Faculty Papers

Bone development is characterized by complex regulation mechanisms, including signal transduction and transcription factor-related pathways, glycobiological processes, cellular interactions, transportation mechanisms, and, importantly, chemical formation resulting from hydroxyapatite. Any abnormal regulation in the bone development processes causes skeletal system-related problems. To some extent, the avascularity of cartilage and bone makes drug delivery more challenging than that of soft tissues. Recent studies have implemented many novel bone-targeting approaches to overcome drawbacks. However, none of these strategies fully corrects skeletal dysfunction, particularly in growth plate-related ones. Although direct recombinant enzymes (e.g., Vimizim for Morquio, Cerezyme for Gaucher, Elaprase for Hunter, Mepsevii for …

Transcriptomic Features Associated To Neoadjuvant Chemotherapy Response In Four Molecular Breast Cancer Subtypes, Hedda Michelle Guevara-Nieto, Rafael Parra-Medina, Carlos Alberto Orozca, Alejandro Mejia-Garcia, Jovanny Zabaleta, Liliana Lopez-Kleine, Alba Lucia Combita-Rojas

School of Medicine Faculty Publications

12th Annual Symposium on Global Cancer Research, Virtual, May 5 - 9, 2024

Perceptions And Use Of The Athletic Training Milestones In Education: A Report From The Aate Research Network, Cailee E. Welch Bacon, Barton E. Anderson, Julie M. Cavallario, Bonnie L. Van Lunen, Lindsey E. Eberman

Clinical Practice in Athletic Training

The Athletic Training Milestones (AT Milestones) were developed as an evaluation tool to capture the breadth and depth of athletic training knowledge, skills, and behavior. However, it is unclear whether athletic training programs are implementing this tool or how they are implementing it to gauge the clinical progression of students or residents in athletic training. We aimed to explore the perceptions and use of the AT Milestones among educators in athletic training programs. We used a cross-sectional, web- based survey with open-ended questions to collect data from athletic training programs on if and how they implement the AT Milestones at …

The Value Of Using Validated Competency-Based Assessments Across The Career Span Of An Athletic Trainer, Matthew Drescher, Lindsey Eberman

Clinical Practice in Athletic Training

No abstract provided.

The Development, Implementation, And Value Of The Athletic Training Milestones For Assessing Progressive Clinical Behaviors, Hollie Walusz, Eric Sauers, Mark Laursen, Forrest Pecha

Clinical Practice in Athletic Training

No abstract provided.

Standardized Patient Evaluation Tool: A Valid Measure Of The Core Competencies, Lindsey E. Eberman, Jessica Edler Nye

Clinical Practice in Athletic Training

No abstract provided.

Enhancing Neoadjuvant Virotherapy's Effectiveness By Targeting Stroma To Improve Resectability In Pancreatic Cancer, Khandoker Usran Ferdous, Mulu Z. Tesfay, Aleksandra Cios, Randal S. Shelton, Conner Hartupee, Alicja Urbaniak, Jean Christopher Chamcheu, Michail N. Mavros, Emmanouil Giorgakis, Bahaa Mustafa, Camila C. Simoes, Isabelle R. Miousse, Alexei G. Basnakian, Omeed Moaven, Steven R. Post, Martin J. Cannon, Thomas Kelly, Bolni Marius Nagalo

School of Medicine Faculty Publications

About one-fourth of patients with pancreatic ductal adenocarcinoma (PDAC) are categorized as borderline resectable (BR) or locally advanced (LA). Chemotherapy and radiation therapy have not yielded the anticipated outcomes in curing patients with BR/LA PDAC. The surgical resection of these tumors presents challenges owing to the unpredictability of the resection margin, involvement of vasculature with the tumor, the likelihood of occult metastasis, a higher ratio of positive lymph nodes, and the relatively larger size of tumor nodules. Oncolytic virotherapy has shown promising activity in preclinical PDAC models. Unfortunately, the desmoplastic stroma within the PDAC tumor microenvironment establishes a barrier, hindering …

The Evolving Use Of Gold Nanoparticles As A Possible Reversal Agent For The Symptoms Of Neurodegenerative Diseases: A Narrative Review, Alan D. Kaye, Kelly R. Sala, Drew Dethloff, Matthew Norton, Corey Moss, Michael J. Plessala, Alyssa G. Derouen, Yair Lopez Torres, Julian Kim, Sridhar Tirumala, Sahar Shekoohi, Giustino Varrassi

School of Medicine Faculty Publications

Neurodegenerative diseases are broadly hallmarked by impaired energy metabolism and toxic intracellular accumulations such as damaged organelles or reactive oxygen species (ROS). Gold nanoparticles readily cross the blood-brain barrier and increase nicotinamide adenine dinucleotide + hydrogen (NADH) oxidation to nicotinamide adenine dinucleotide (NAD+), which is vital for intracellular energy generation, cellular repair, and protection from ROS. Thus, the use of gold nanoparticles to treat and potentially reverse cellular injury seen in neurodegenerative disease has been an area of ongoing research. This systematic review explores current literature regarding the use of gold nanoparticle therapy in the treatment of neurodegenerative diseases such …

Effect Of Transcranial Direct Current Stimulation And Narrow-Band Auditory Stimulation On The Intraoperative Electroencephalogram: An Exploratoratory Feasibility Study, Oliver G. Isik, Tuan Z. Cassim, Meah T. Ahmed, Matthias Kreuzer, Alice M. Daramola, Paul S. Garcia

SKMC Student Presentations and Publications

INTRODUCTION: During general anesthesia, frontal electroencephalogram (EEG) activity in the alpha frequency band (8-12 Hz) correlates with the adequacy of analgesia. Transcranial direct current stimulation (tDCS) and auditory stimulation, two noninvasive neuromodulation techniques, can entrain alpha activity in awake or sleeping patients. This study evaluates their effects on alpha oscillations in patients under general anesthesia.

METHODS: 30 patients receiving general anesthesia for surgery were enrolled in this two-by-two randomized clinical trial. Each participant received active or sham tDCS followed by auditory stimulation or silence according to assigned group (TDCS/AUD, TDCS/SIL, SHAM/AUD, SHAM/SIL). Frontal EEG was recorded before and after neuromodulation. …

Qualitative Interviews Exploring Adverse Event Mitigation Strategies In Adults Receiving Amikacin Liposome Inhalation Suspension, Juzar Ali, Jasmanda Wu, Mariam Hassan, Jui-Hua Tsai, Nancy Touba, Kelly Mccarrier, Mark Ballard, Anjan Chatterjee

School of Medicine Faculty Publications

Introduction: This study aimed to gain insight from patients with refractory Mycobacterium avium complex lung disease (MAC-LD) into strategies used to manage adverse events (AEs) associated with amikacin liposome inhalation suspension (ALIS). Methods: We conducted semi-structured interviews with US patients with refractory MAC-LD prescribed ALIS in a real-world setting. Interview transcripts were analyzed and coded to identify patterns in participants’ descriptions of their ALIS treatment experiences, including AEs and their disruptiveness, and AE mitigation strategies, including participants’ ratings of strategies’ effectiveness. Concept saturation was also assessed. Results: Twenty participants (mean age 48.7 years; 80% women; mean ALIS duration 5.45 months) …

Histopathology Imaging And Clinical Data Including Remission Status In Pediatric Inflammatory Bowel Disease, Chloe Martin-King, Ali Nael, Louis Ehwerhemuepha, Blake Calvo, Quinn Gates, Jamie Janchoi, Elisa Ornelas, Melissa Perez, Andrea Venderby, John Miklavcic, Peter Chang, Aaron Sassoon, Kenneth Grant

Food Science Faculty Articles and Research

The incidence of inflammatory bowel disease (IBD) is increasing annually. Children with IBD often suffer significant morbidity due to physical and emotional effects of the disease and treatment. Corticosteroids, often a component of therapy, carry undesirable side effects with long term use. Steroid-free remission has become a standard for care-quality improvement. Anticipating therapeutic outcomes is difficult, with treatments often leveraged in a trial-and-error fashion. Artificial intelligence (AI) has demonstrated success in medical imaging classification tasks. Predicting patients who will attain remission will help inform treatment decisions. The provided dataset comprises 951 tissue section scans (167 whole-slides) obtained from 18 pediatric …

Splenic Artery Embolization In The Treatment Of Blunt Splenic Injury: Single Level 1 Trauma Center Experience, Katelyn Gill, Sarah Aleman, Alexandra H. Fairchild, Bahri Üstünsöz, Dan Laney, Alison A. Smith, Hector Ferral

School of Medicine Faculty Publications

PURPOSE: To describe the experience of a single level 1 trauma center in the management of blunt splenic injuries (BSI). METHODS: This is a retrospective study with Institutional Review Board approval. The medical records of 450 patients with BSI treated between January 2016 and December 2022 were reviewed. Seventy-two patients were treated with splenic artery embolization (SAE), met the study criteria, and were eligible for data analysis. Spleen injuries were graded in accordance with the American Association for the Surgery of Trauma Organ Injury Scale. Univariate data analysis was performed, with P < 0.05 considered statistically significant. RESULTS: The splenic salvage rate was 90.3% (n = 65/72). Baseline demographics were similar between the groups (P > 0.05). Distal embolization with Gelfoam had similar rates …

Bridging The Gap: Psychopharmacologic Education And Side Effect Screening For Non-Prescribing Mental Health Professionals, Elaine Fitzgerald

Dissertations

Abstract

Problem: The United States is experiencing a growing demand for pediatric mental health support. Surges in mental health diagnoses and psychotropic medication prescriptions have occurred, compounded by a shortage of psychiatric providers. Non-prescribing mental health professionals are well-positioned to recognize psychotropic medication side effects. However, psychologists and counselors lack formal pharmacology education.

Methods: The quality improvement (QI) initiative was guided by the Plan-Do-Study-Act (PDSA) model. The evidence-based psychopharmacologic education for non-prescribers utilized a quasi-experimental pre- and post- test design. Data collected from clinicians included knowledge, confidence, and skill concerning psychotropic medications. The Psychotropic Medication Monitoring Checklist (PMMC) screen clients …

Emerging Treatments And Therapies For Autism Spectrum Disorder: A Narrative Review, Alan D. Kaye, Kaitlyn E. Allen, Van S. Smith Iii, Victoria T. Tong, Vivian E. Mire, Huy Nguyen, Zachary Lee, Maria Kouri, Carlo Jean Baptiste, Chizoba N. Mosieri, Adam M. Kaye, Giustino Varrassi, Sahar Shekoohi

School of Medicine Faculty Publications

The prevalence of autism spectrum disorder (ASD) has increased over the last decade. In this regard, many emerging therapies have been described as ASD therapies. Although ASD does not have a cure, there are several management options available that can help reduce symptom severity. ASD is highly variable and, therefore, standard treatment protocols and studies are challenging to perform. Many of these therapies also address comorbidities for which patients with ASD have an increased risk. These concurrent diagnoses can include psychiatric and neurological disorders, including attention deficit and hyperactivity disorder, anxiety disorders, and epilepsy, as well as gastrointestinal symptoms such …

Development Of A Durable And Low-Dose Universal Vaccine Against Swine Influenza A Virus, Erika Petro-Turnquist

Dissertations and Doctoral Documents, University of Nebraska-Lincoln, 2023–

Swine Influenza A Virus (IAV-S) imposes a significant burden on the pork industry and poses a great threat to public health due to its zoonotic potential. Susceptibility to human, avian, and swine influenza make pigs the ultimate mixing vessels for reassorted influenza A virus strains. Current vaccination strategies induce short-lived and strain-specific responses against IAV-S. Further, the substantial genetic diversity of IAV-S necessitates consistent revaccination and updating of commercial vaccines. Computational platforms have recently emerged as a promising strategy to develop new-age vaccines against infectious diseases in livestock animals. Here, we describe a computationally derived set of vaccine immunogens, called …

Data-Driven Drug Repurposing For Immune System-Related Diseases, Sabyasachi Mohanty

Department of Biochemistry: Dissertations, Theses, and Student Research

In this research, we explore a data-driven approach for drug repurposing to enhance the immunomodulatory effect by integrating pattern-based search and genome-scale metabolic modeling. This research helps to find a solution to the preexisting problems of drug discovery which includes expenses and a high amount of time consumption. By leveraging the pre-existing data of the approved drugs to identify the major metabolic pathway changes, we can find new drugs with similar effects with less off-target effects.

The focus on the immune system modulating drugs is due to the high prevalence of immune system-involved diseases and the growing demand for effective …