Therapeutics Commons^™

Pancreatic Cancer Tumor Microenvironment Is A Major Therapeutic Barrier And Target, Conner Hartupee, Bolni Marius Nagalo, Chiswili Y. Chabu, Mulu Z. Tesfay, Joycelynn Coleman-Barnett, John T. West, Omeed Moaven

School of Medicine Faculty Publications

Pancreatic Ductal Adenocarcinoma (PDAC) is projected to become the 2nd leading cause of cancer-related deaths in the United States. Limitations in early detection and treatment barriers contribute to the lack of substantial success in the treatment of this challenging-to-treat malignancy. Desmoplasia is the hallmark of PDAC microenvironment that creates a physical and immunologic barrier. Stromal support cells and immunomodulatory cells face aberrant signaling by pancreatic cancer cells that shifts the complex balance of proper repair mechanisms into a state of dysregulation. The product of this dysregulation is the desmoplastic environment that encases the malignant cells leading to a dense, hypoxic …

De Novo Drug Design Using Transformer-Based Machine Translation And Reinforcement Learning Of An Adaptive Monte Carlo Tree Search, Dony Ang, Cyril Rakovski, Hagop S. Atamian

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

The discovery of novel therapeutic compounds through de novo drug design represents a critical challenge in the field of pharmaceutical research. Traditional drug discovery approaches are often resource intensive and time consuming, leading researchers to explore innovative methods that harness the power of deep learning and reinforcement learning techniques. Here, we introduce a novel drug design approach called drugAI that leverages the Encoder–Decoder Transformer architecture in tandem with Reinforcement Learning via a Monte Carlo Tree Search (RL-MCTS) to expedite the process of drug discovery while ensuring the production of valid small molecules with drug-like characteristics and strong binding affinities towards …

Cd133-Dependent Activation Of Phosphoinositide 3-Kinase /Akt/Mammalian Target Of Rapamycin Signaling In Melanoma Progression And Drug Resistance, Naji Kharouf, Thomas W. Flanagan, Abdulhadi A. Alamodi, Youssef Al Hmada, Sofie Yasmin Hassan, Hosam Shalaby, Simeon Santourlidis, Sarah Lilly Hassan, Youssef Haikel, Mossad Megahed, Robert T. Brodell, Mohamed Hassan

School of Medicine Faculty Publications

Melanoma frequently harbors genetic alterations in key molecules leading to the aberrant activation of PI3K and its downstream pathways. Although the role of PI3K/AKT/mTOR in melanoma progression and drug resistance is well documented, targeting the PI3K/AKT/mTOR pathway showed less efficiency in clinical trials than might have been expected, since the suppression of the PI3K/mTOR signaling pathway-induced feedback loops is mostly associated with the activation of compensatory pathways such as MAPK/MEK/ERK. Consequently, the development of intrinsic and acquired resistance can occur. As a solid tumor, melanoma is notorious for its heterogeneity. This can be expressed in the form of genetically divergent …

Antimicrobial And Synergistic Effects Of Syzygium Cumini, Moringa Oleifera, And Tinospora Cordifolia Against Different Candida Infections, Adedayo O. Adelakun, Ayoola Awosika, Uzochukwu Adabanya, Adekunle E. Omole, Akinyode I. Olopoda, Emmanuel T. Bello

School of Medicine Faculty Publications

Introduction The burden of multiple drug resistance in human pathogens has necessitated the search for and development of antimicrobial agents with a wide range of structural classes and potentials to selectively act on the several mechanisms of actions exhibited by the pathogens. However, most synthetic antimicrobial agents have been linked with adverse side effects and high costs, furthering the need to explore more options. Syzygium cumini, Moringa oleifera, and Tinospora cordifolia are three medicinal plants used in traditional medicine systems for various infectious diseases. They contain various phytochemicals that exhibit antimicrobial activities against various bacteria, fungi, and parasites. The mechanisms …

Mechanisms Of Melanoma Progression And Treatment Resistance: Role Of Cancer Stem-Like Cells, Youssef Al Hmada, Robert T. Brodell, Naji Kharouf, Thomas W. Flanagan, Abdulhadi A. Alamodi, Sofie Yasmin Hassan, Hosam Shalaby, Sarah Lilly Hassan, Youssef Haikel, Mosaad Megahed, Simeon Santourlidis, Mohamed Hassan

School of Medicine Faculty Publications

Melanoma is the third most common type of skin cancer, characterized by its heterogeneity and propensity to metastasize to distant organs. Melanoma is a heterogeneous tumor, composed of genetically divergent subpopulations, including a small fraction of melanoma-initiating cancer stem-like cells (CSCs) and many non-cancer stem cells (non-CSCs). CSCs are characterized by their unique surface proteins associated with aberrant signaling pathways with a causal or consequential relationship with tumor progression, drug resistance, and recurrence. Melanomas also harbor significant alterations in functional genes (BRAF, CDKN2A, NRAS, TP53, and NF1). Of these, the most common are the BRAF and NRAS oncogenes, with 50% …

Microsphere Core Technology Boosts Innovation Of Biopharmaceutical Industry Chain, Jie Wu, Weiqing Zhou, Lan Zhao, Guanghui Ma

Bulletin of Chinese Academy of Sciences (Chinese Version)

Advancements in life science and biotechnology have boosted the evolution of the biopharmaceutical industry with the continual emergence of biomedical products for disease prevention, diagnosis, and treatment. Microspheres, as crucial functional materials, play a significant role in the discovery, preparation, separation, and delivery of biological drugs due to their flexible size, morphology, structure, and function. This study reviews recent significant advancements in microspheres and their applications in cell culture, chromatographic separation, drug delivery, and as vaccine adjuvants. Additionally, it proposes future trends for the development of microspheres.

Nonhormonal Pharmacotherapies For The Treatment Of Postmenopausal Vasomotor Symptoms, Taylor Witten, Julia Staszkiewicz, Logan Gold, Mallory A. Granier, Rachel J. Klapper, Gabriel Lavespere, Bradley Dorius, Varsha Allampalli, Shahab Ahmadzadeh, Sahar Shekoohi, Alan D. Kaye, Giustino Varrassi

School of Medicine Faculty Publications

An average of 60-80% of all menopausal women experience bothersome vasomotor symptoms (VMSs), such as flushing and sweating, within the first seven years of onset. However, despite increasing prevalence, these hot flashes remain hard to treat and have a negative effect on the quality of life. Though hormone replacement therapy is commonly utilized as a standard treatment for VMSs, this therapy is not recommended for all women. Specifically, the oral form of hormone replacement therapy is associated with several contraindications, including a history of thromboembolic disease, migraine headache with aura, liver failure, heart disease, and hormone-dependent cancers. For women with …

Digital Phobia: An Inquiry For Mapping The Unseen Dimension Of New Digital Anxiety, The ‘Digiphobia’, Amarjit Kumar Singh ,Library Assistant, Md. Arshad Ali , Professional Assistant, Dr. Pankaj Mathur, Deputy Librarian,

Library Philosophy and Practice (e-journal)

Background: As technology continues to advance, individuals' interactions with digital platforms have become integral to daily life. Amidst this technological evolution, a novel concern emerges—Digital Phobia, hereafter referred to as “Digiphobia.” This phenomenon, although not previously explored in scholarly literature, necessitates an in-depth investigation due to its potential impact on individuals' well-being. Our research employs a two-step methodology to investigate its existence, implications, and manifestations.

Introduction: This research paper introduces and proposes the term "Digiphobia" as a comprehensive conceptualization of anxiety arising from interactions with digital spaces, applications, and environments. The proliferation of digital technologies has led to the emergence …

The Effects Of Physical Activity On Experimental Models Of Vascular Dementia; A Systematic Review And Meta-Analysis, Ifechukwude J. Biose, Wesley H. Chastain, Rebecca J. Solch-Ottaiano, Viktoriya S. Grayson, Hanyun Wang, Somdeb Banerjee, Gregory J. Bix

School of Medicine Faculty Publications

Background; Physical activity is associated with improved brain health and cognition in humans. However, the validity, range, and quality of evidence for the beneficial outcomes linked to exercise in experimental models of vascular dementia (VaD) have not been evaluated. We performed a systematic review and meta-analysis of studies that assessed the effect of exercise intervention on models of VaD to provide an unbiased and comprehensive determination of the cognitive function and brain morphology benefits of exercise. Summary; A systematic search in three databases as well as study design characteristics and experimental data extraction were completed in December 2021. We investigated …

Role Of Plasmapheresis: A Tale Of Two Thyroid Storms, Zhiwei Zhang, Sam Joseph, Donald Eagerton

South Atlantic Division GME Research Day 2024

No abstract provided.

Polypharmacy And Potentially Inappropriate Prescribing In Geriatric Population, Maryam Burney, Barry Brown, Victoria Nguyen, Garrett Furth, Ambreen I. Ahmed, Abigail Hulsizer

North Texas GME Research Forum 2024

Polypharmacy is a ubiquitous concern among patients, especially geriatric patients, who are at a higher risk of clinical burden. It is associated with an increase in healthcare costs, decreased functional status, and adverse drug events, contributing to geriatric syndromes, such as falls, cognitive decline, and urinary retention. Geriatric care is multi-tiered, requiring assistance and care from a thorough physician who is attune to the potential risks of medications that are commonly prescribed. Smaller communities, often with less resources and clinical providers and with an aging population, especially at the hospital setting, are vulnerable to oversights when it comes to medication …

Managing The Side Effects Of Aml Induction Therapy: A Case Report, Kristen Stovall, Taylor Frazier, Kaylee Brown, Jessica Waite

South Atlantic Division GME Research Day 2024

No abstract provided.

Comparative Analysis Of Inpatient And Outpatient Total Hip Arthroplasty: Cost, Rehabilitation, And Complexity, Kam Maghazehe

MUSC Theses and Dissertations

Background: Osteoarthritis in the hip joint leads to worn or damaged cartilage, resulting in bones scraping against each other. This scraping creates rough surfaces, causing significant pain and limiting mobility in daily activities. THA becomes necessary when other less invasive options fail to alleviate symptoms such as pain, stiffness, swelling, and reduced range of motion. Due to high out-of-pocket costs and the rapid spread of COVID-19, CMS took a substantial stride in healthcare policy by introducing the CMS-1736-FC ruling in December 2020. This ruling, effective from January 2021, facilitated the reclassification of eleven procedures, including Total Hip Arthroplasties (THAs), from …

Applying The Evidence: Taste Manipulation As A Dysphagia Management Strategy, Ross M. Westemeyer, Angela M. Dietsch, Rachel W. Mulheren

Department of Special Education and Communication Disorders: Faculty Publications

Purpose: This narrative review aims to summarize the evidence regarding taste manipulation as a dysphagia management strategy within the evidence-based practice framework, with a focus on clinical application for speech-language pathologists.

Method: First, we present background information on the physiology of taste and swallowing. A summary of research evidence on the effect of taste on swallowing is presented, followed by suggested methods for incorporating taste into swallowing evaluation and intervention. An overview of individual factors that can impact taste perception is provided. Finally, we discuss methods of clinical application and future directions for clinicians.

Conclusions: Although taste …

The Unequal Distribution Of Social Risk For Black Men Across The Life-Span. A Novel Framework., Waleed Y. Sami

Adultspan Journal

This conceptual overview offers a comprehensive overview of systemic pathways that negatively impact the mental health of Black Men throughout their lives. Our argument highlights the importance for counselors and mental health professionals to utilize a thorough social risk assessment that considers these pathways in order to effectively address the mental health needs of Black Men while fostering positive working relationships. This overview strongly advocates for the use of context and structural determinants when evaluating mental health symptoms. Without an appropriate understanding of social risk and determinants, counselors may inadvertently perpetuate disparities by decontextualizing symptomology, and reproducing racist discourse.

Sprtn Metalloprotease As A Target To Sensitize Cancer Cells To Crosslinking Chemotherapy, Cole J. Turner

Honors Theses

Bifunctional alkylating agents have demonstrated high clinical utility as a chemotherapeutic strategy against cancer. These compounds have been well-characterized for their capacity to exert cytotoxicity via interstrand DNA crosslinking. However, the same electrophilic chemistry can also form DNA-protein crosslinks (DPCs) whose contributions to these drugs’ antitumor effects have been less well-defined. Recently, the metalloprotease SPRTN has been implicated as a predominant mediator of DPC repair in mammalian cells. Previous work has demonstrated that SPRTN deficiency increases the sensitivity of cancer cells to DPC-inducing agents such as formaldehyde and cisplatin, but these findings have yet to be translated more broadly across …

The Ethical Concerns Of Improper Semaglutide Administration After Acquisition From A Compounded Pharmacy, Syed Basit Haider, Renu Thomas, E’Joven Reed, Aneesha Shaju, Bushra Bangash, Jakob Schnell, Edrianna Mae Ablola

Gulf Coast Division GME Research Symposium 2024

No abstract provided.

Heterogeneity In The Role Of Emergency Physicians And Treatment Of Acute Atrial Fibrillation In Emergency Departments— Results Of The International Atrial Fibrillation Background (Afib) Study, Markus Holmberg, Ville Hällberg, Hjalti M. Björnsson, Timothy H. Rainer, Colin A. Graham, Marc B. Sabbe, Wilhelm Behringer, Gayle Galletta, Hans Domanovits, Harri Pikkarainen, Bruce M. Lo, Christopher Laurent, Pascal Vanelderen, Ari Palomäki

Department of Emergency Medicine Faculty Publications

The consept of emergency departments (EDs) with specialized teams of emergency physicians originated in the United Kingdom and the United States during the 1970s and was expanded across most European countries in the twenty-first century. Among the various cardiac arrhythmias encountered in EDs, atrial fibrillation (AF) is the most prevalent, contributing to ED congestion. Existing guidelines offer multiple treatment options for acute-onset AF occurring within 48 hours. The aim of The Atrial Fibrillation Background Study is to evaluate treatment strategies, practices and the role of emergency physicians in managing acute-onset AF in Western medical tradition across Europe, the United States …

Inhibiting Pi3k/Akt To Enhance Brain Uptake Of Anticancer Agents In Glioblastoma, Louis Rodgers

Theses and Dissertations--Pharmacy

Glioblastoma (GBM) is the deadliest and most common malignant CNS tumor. Despite advances in understanding its biology and the development of targeted therapies, effective treatment options remain limited. As a result, patient survival rates are dismal, with a 5-year survival rate of only 6.8% and an overall survival of less than two years. This poor outcome is partly due to our inability to treat GBM cells that infiltrate the whole brain. Focal treatments like surgery and radiotherapy alone are insufficient due to these invasive tumor cells. Therefore, chemotherapy following resection and irradiation of the primary tumor is essential to eliminate …

Hsp70 Is A Critical Regulator Of Hsp90 Inhibitor's Effectiveness In Preventing Hcl-Induced Chronic Lung Injury And Pulmonary Fibrosis, Ruben M. L. Colunga Biancatelli, Pavel A. Solopov, Tierney Day, Betsy Gregory, Michael Osei-Nkansah, Christiana Dimitropoulou, John D. Catravas

Bioelectrics Publications

Exposure to hydrochloric acid (HCl) can provoke acute and chronic lung injury. Because of its extensive production for industrial use, frequent accidental exposures occur, making HCl one of the top five chemicals causing inhalation injuries. There are no Food and Drug Administration (FDA)-approved treatments for HCl exposure. Heat shock protein 90 (HSP90) inhibitors modulate transforming growth factor-β (TGF-β) signaling and the development of chemical-induced pulmonary fibrosis. However, little is known on the role of Heat Shock Protein 70 (HSP70) during injury and treatment with HSP90 inhibitors. We hypothesized that administration of geranylgeranyl-acetone (GGA), an HSP70 inducer, or gefitinib (GFT), an …