Chemicals and Drugs Commons^™

A Scoping Review Of Population Diversity In The Common Genomic Aberrations Of Clear Cell Renal Cell Carcinoma, Sean S. Kumar, Ninad Khandekar, Komal Dani, Saina R. Bhatt, Vinay Duddalwar, Anishka D' Souza

Department of Medicine Faculty Publications

Introduction: Previous literature has shown that clear cell renal cell carcinoma (ccRCC) is becoming a more prevalent diagnosis and that the incidence and mortality differ both regionally and racially. While the molecular profiles for ccRCC are studied regionally through biopsy and sequencing techniques, the genomic landscape and ccRCC diversity data are not well studied. We conducted a review of the known genomic data on 6 of the most clinically relevant DNA biomarkers in ccRCC: von Hippel-Lindau (vHL), Polybromo-1 (PBRM1), Breast Cancer Gene 1-Associated Protein 1 (BAP1), Histone-Lysine N-Methyltransferase Domain-Containing 2 (SETD2), Mammalian Target of Rapamycin (mTOR), and Lysine-Specific Demethylase 5C …

Psychedelic Minimalism: The Case Against Music In Psychedelic Therapy Settings, Samir A. Nader

Department of Medicine Faculty Publications

[Introduction: reframing the role of setting] In recent years, renewed attention has been given to the centrality of set and setting in psychedelic-assisted therapy. The Reporting of Setting in Psychedelic Clinical Trials (ReSPCT) guidelines reflect an evolving consensus: therapeutic outcomes are not solely pharmacologically determined but are heavily shaped by both the environment and the psychological state of the participant (2). Within this evolving paradigm, music has assumed a privileged role, framed as a therapeutic constant, typically curated to be emotionally supportive or evocative, and especially emphasized during peak psychedelic states (3). The prevailing assumption is that music facilitates safety, …

Her2 Alterations Across Solid Tumors: Implications For Comprehensive Testing, Ahmed Ismail, Chimay Jani, Nusrat Jahan, Malla Midhun, Arnab Basu, Garima Gupta, Bassel El-Rayes, Sejong Bae, Tyler Mattox, Cyntanna Hawkins, Rebecca C. Arend, Mehmet Akce, Yanis Boumber, Aakash Desai

Department of Medicine Faculty Publications

Purpose

ERBB2 (HER2) alterations (e.g., overexpression, amplification, and mutations) are known to drive tumor progression. These changes, particularly in non-breast and gastric/gastroesophageal cancers, remain poorly characterized. With pan-tumor approval of HER2-targeted therapies like Trastuzumab deruxetecan (T-DXd), understanding ERBB2 alterations across diverse cancers is crucial.

Methods

HER2 analysis was conducted on 653 solid tumor specimens at the University of Alabama, using immunohistochemistry (IHC), copy number (CN) variation (CNV) assessment, and mutational profiling. The correlation between CN amplification and IHC expression was evaluated using Somers' D ordinal association.

Results

Of the 653 cases, HER2 IHC scores were distributed as 3 + (3.1%), …

Fibrinolysis For Apical Thrombus As A Bridge To Emergent Valve-In-Valve Transcatheter Aortic Valve Replacement, Nicholas J. Valle, Omar A. Saleh, Mani C. Akunuri, Parth K. Parikh, Joshua A. Cohen, Deepak R. Talreja, Matthew R. Summers

Department of Medicine Faculty Publications

Background

Left ventricular (LV) thrombus is traditionally a contraindication to transcatheter aortic valve replacement due to embolic risk. Consequently, management of valvular cardiogenic shock complicated by LV thrombus identifies unique challenges that require innovative strategies.

Case Summary

A 58-year-old woman with critical bioprosthetic aortic stenosis, cardiogenic shock, and large LV thrombus (2.8 × 2.6 cm) underwent successful valve-in-valve transcatheter aortic valve replacement after systemic fibrinolysis bridge therapy.

Why Beyond the Guidelines

Current guidelines contraindicate transcatheter aortic valve replacement in patients with LV thrombus. This case demonstrates the novel use of low-dose, slow infusion tissue plasminogen activator as a bridge therapy …

Automating The Amino Acid Identification In Elliptical Dichroism Spectrometer With Machine Learning, Ridhanya Sree Balamurugan, Yusuf Asad, Tommy Gao, Dharmakeerthi Nawarathna, Umamaheswara Rao Tida, Dali Sun

Electrical & Computer Engineering Faculty Publications

Amino acid identification is crucial across various scientific disciplines, including biochemistry, pharmaceutical research, and medical diagnostics. However, traditional methods such as mass spectrometry require extensive sample preparation and are time-consuming, complex and costly. Therefore, this study presents a pioneering Machine Learning (ML) approach for automatic amino acid identification by utilizing the unique absorption profiles from an Elliptical Dichroism (ED) spectrometer. Advanced data preprocessing techniques and ML algorithms to learn patterns from the absorption profiles that distinguish different amino acids were investigated to prove the feasibility of this approach. The results show that ML can potentially revolutionize the amino acid analysis …

Biomedical Mxene-Polymer Nanocomposites: Advancing Photothermal Therapy, Antibacterial Action, And Smart Drug Delivery: A Review, Ali Mohammad Amani, Lobat Tayebi, Ehsan Vafa, Mohammad Javad Azizli, Milad Abbasi, Ahmad Vaez, Hesam Kamyab, Daniel Simancas-Racines, Shreeshivadasan Chelliapan

Electrical & Computer Engineering Faculty Publications

MXenes are hydrophilic, conductive, tunable, and biocompatible two-dimensional ceramic materials prepared by etching the 'A' layer from their precursor MAX phases. Although MXenes show exceptional promise in photothermal therapy, biosensing, and regenerative medicine, they face challenges such as oxidative instability in physiological environments, limited drug-loading capacity, and unpredictable immune responses. To address these limitations, MXene/polymer nanocomposites incorporating both synthetic polymers (e.g., polyethylene glycol (PEG), polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP), and polylactic-co-glycolic acid (PLGA)) and natural biopolymers (e.g., cellulose nanofiber, gelatin, chitosan, hyaluronic acid, and soybean phospholipids) have been developed. These composites enhance functionality for biomedical applications such as photothermal cancer …

Enhancing Bone Regeneration Using Kaempferol As An Osteoprotective Compound: Signaling Mechanisms, Delivery Strategies, And Potential Applications, Mojdeh Salehi Namini, Sanam Mohandesnezhad, Sadaf Mohandesnezhad, Vahid Mansouri, Lobat Tayebi, Nima Beheshtizadeh

Electrical & Computer Engineering Faculty Publications

Various plants, including fruits, vegetables, and spices, contain kaempferol, a bioflavonoid compound with diverse medicinal effects, such as antioxidant, antibacterial, and anti-inflammatory characteristics. Furthermore, this compound exhibits multiple health-promoting properties, including osteoprotection and osteogenesis, primarily by modulating various cell-signaling pathways. This review aims to illustrate the medical advantages of kaempferol and its role in regulating bone metabolism through cell signaling mechanisms. Numerous studies have demonstrated the bone-protective properties of kaempferol and its encapsulated form. Further research is needed to clarify the optimal dosages, toxicity, safety, and other potential mechanisms of action. This review demonstrates that several signaling pathways, including nuclear …

Interaction Of Cardiac Leiomodin With The Native Cardiac Thin Filament, Madison Little, Cristina M. Risi, Tania M. Larrinaga, Mason D. Summers, Tyler Nguyen, Garry E. Smith Jr., Jennifer Atherton, Carol C. Gregorio, Alla S. Kostyukova, Vitold E. Galkin

Department of Biomedical and Translational Sciences Faculty Publications

Every heartbeat depends on cyclical contraction-relaxation produced by the interactions between myosin-containing thick and actin-based thin filaments (TFs) arranged into a crystalline-like lattice in the cardiac sarcomere. Therefore, the maintenance of thin filament length is crucial for myocardium function. The thin filament is comprised of an actin backbone, the regulatory troponin complex and tropomyosin that controls interactions between thick and thin filaments. Thin filament length is controlled by the tropomodulin family of proteins; tropomodulin caps pointed ends of thin filaments, and leiomodin (Lmod) promotes elongation of thin filaments by a “leaky-cap” mechanism. The broader distribution of Lmod on the thin …

Reduced Slow Wave Sleep Is Associated With Increased Risk Of Short Stature In Children: A Cross-Sectional Study, Zhaohua Chen, Yuan Shi, Fei Lei, Xujun Feng, Lu Tan, Taomei Li, Junying Zhou, Yuanfeng Sun, Jiamin Liao, Yun Li, Zhoulong Yu, Jian Jiao, Yanyan Wang, Larry D. Sanford, Michael V. Vitiello, Ye Zhang, Rong Ren, Xiangdong Tang

Department of Biomedical and Translational Sciences Faculty Publications

Objective: Although growth hormone was shown to be specifically released during slow wave sleep (SWS), no population-based evidence has demonstrated the association between sleep quality and childhood height. To address this gap, our study aims to investigate the relationship between SWS and height of children.

Methods: We analyzed polysomnography data and z-scores for height in 2527 suspected obstructive sleep apnea (OSA) children (537 non-OSA children and 1990 OSA children) collected over the past 16 years. Different grades of z-scores for height and SWS were classified by the quartile method, and the lowest z-scores for height quartile defined short stature as …

Swinging Lever Mechanism Of Myosin Directly Shown By Time-Resolved Cryo-Em, David P. Klebl, Sean N. Mcmillan, Cristina Risi, Eva Forgacs, Betty Virok, Jennifer L. Atherton, Sarah A. Harris, Michele Stofella, Donald A. Winkelmann, Frank Sobott, Vitold E. Galkin, Peter J. Knight, Stephen P. Muench, Charlotte A. Scarfi, Howard D. White

Department of Biomedical and Translational Sciences Faculty Publications

Myosins produce force and movement in cells through interactions with F-actin¹. Generation of movement is thought to arise through actin-catalysed conversion of myosin from an ATP-generated primed (pre-powerstroke) state to a post-powerstroke state, accompanied by myosin lever swing²,³. However, the initial, primed actomyosin state has never been observed, and the mechanism by which actin catalyses myosin ATPase activity is unclear. Here, to address these issues, we performed time-resolved cryogenic electron microscopy (cryo-EM)⁴ of a myosin-5 mutant having slow hydrolysis product release⁵,⁶. Primed actomyosin was predominantly captured 10 ms after …

Mobile Health Intervention Tools Promoting Hiv Pre-Exposure Prophylaxis Among Adolescent Girls And Young Women In Sub-Saharan Africa: Scoping Review, Alex Emilio Fischer, Homaira Hanif, Jacob B. Stocks, Aimee E. Rochelle, Karen Dominguez, Eliana Gabriela Armora Langoni, H. Luz Mcnaughton Reyes, Gustavo F. Doncel, Kathryn E. Muessig

Department of Obstetrics & Gynecology Faculty Publications

Background:

In 2022, 3100 adolescent girls and young women in sub-Saharan Africa experienced new HIV infections each week. HIV pre-exposure prophylaxis (PrEP) is effective at preventing HIV but has limited uptake and persistence. Mobile health (mHealth) interventions can improve medication adherence; however, their utility to improve PrEP adherence among adolescent girls and young women is not well established.

Objective:

This scoping review synthesizes evidence supporting mHealth for PrEP among adolescent girls and young women in sub-Saharan Africa and identifies strategies for further evaluation.

Methods:

We searched PubMed and Google Scholar databases, expert referrals, and reference lists using the following eligibility …

American Heart Association Blood Pressure Classification And Subsequent Risk Of Preeclampsia, Rebecca Horgan, Erkan Kalafat, Elena Sinkovskaya, Alfred Abuhamad, George Saade

Department of Obstetrics & Gynecology Faculty Publications

Background: In 2017, the American Heart Association (AHA) and American College of Cardiology updated their hypertension guidelines for the nonpregnant population, lowering the diagnostic thresholds to systolic blood pressure ≥130 mmHg or diastolic blood pressure ≥80 mmHg. This reclassification has raised important questions regarding whether blood pressure (BP) values previously considered within the normal range in pregnancy may, in fact, confer an increased risk for hypertensive disorders of pregnancy (HDPs).

Objective: To evaluate the association between first-trimester BP classified by AHA thresholds and the subsequent development of HDPs.

Study design: This was a secondary analysis of a prospective, multicenter cohort …

Optimization Of Serum And Salivary Cortisol Interpolation For Time-Dependent Modeling Frameworks In Healthy Adult Males, Nathaniel T. Berry, Travis Anderson, Christopher K. Rhea, Laurie Wideman

Rehabilitation Sciences Faculty Publications

Cortisol is an important marker of hypothalamic-pituitary-adrenal function and follows robust circadian and diurnal rhythms. However, biomarker sampling protocols can be labor-intensive and cost-prohibitive. Objectives: Explore analytical approaches that can handle differing biological sampling frequencies to maximize these data in more detailed and time-dependent analyses. Methods: Healthy adult males [N = 8; 26.1 (±3.1) years; 176.4 (±8.6) cm; 73.1 (±12.0) kg)] completed two 24 h admissions: one at rest and one including a high-intensity exercise session on the cycle ergometer. Serum and salivary cortisol were sampled every 60 and 120 min, respectively. Six alternative sampling profiles were defined by downsampling …

Cath-Ddg: Towards Robust Mutation Effect Prediction On Protein-Protein Interactions Out Of Cath Homologous Superfamily, Guanglei Yu, Xuehua Bi, Teng Ma, Yaohang Li, Jianxin Wang

Computer Science Faculty Publications

Motivation: Protein-protein interactions (PPIs) are fundamental aspects in understanding biological processes. Accurately predicting the effects of mutations on PPIs remains a critical requirement for drug design and disease mechanistic studies. Recently, deep learning models using protein 3D structures have become predominant for predicting mutation effects. However, significant challenges remain in practical applications, in part due to the considerable disparity in generalization capabilities between easy and hard mutations. Specifically, a hard mutation is defined as one with its maximum TM-score < 0.6 when compared to the training set. Additionally, compared to physics-based approaches, deep learning models may overestimate performance due to potential data leakage.

Results: We propose new training/test splits that mitigate data leakage according to the CATH homologous superfamily. Under the constraints of physical …

A Survey On Deep Learning For Drug-Target Binding Prediction: Models, Benchmarks, Evaluation, And Case Studies, Kusal Debnath, Pratip Rana, Preetam Ghosh

Computer Science Faculty Publications

Conventional drug discovery is expensive, time-consuming, and prone to failure. Artificial intelligence has become a potent substitute over the last decade, providing strong answers to challenging biological issues in this field. Among these difficulties, drug-target binding (DTB) is a key component of drug discovery techniques. In this context, drug-target affinity and drug–target interaction are complementary and essential frameworks that work together to improve our comprehension of DTB dynamics. In this work, we thoroughly analyze the most recent deep learning models, popular benchmark datasets, and assessment metrics for DTB prediction. We look at the paradigm shift in the development of drug …

Deepssetracer 2.0: Improved Deep Learning Model Performance For Protein Secondary Structure Segmentation From Cryo-Em Maps, Bryan Hawickhorst, Thu Nguyen, Willy Wriggers, Jiangwen Sun, Jing He

Computer Science Faculty Publications

DeepSSETracer is a method for segmenting protein secondary structure from medium-resolution (5-10Å) cryogenic electron microscopy (cryo-EM) density maps. We conducted experiments and ablation studies to examine the effects of normalization methods, max-pooling, activation functions, and loss calculation region on DeepSSETracer. By combining multiple technical improvements, the performance of the new version, DeepSSETracer 2.0, was significantly enhanced compared to DeepSSETracer 1.1. On a set of 77 test cases, the weighted average per-voxel F1 score increased from 62.1% to 70.3% for helix detection, and from 47.8% to 62.5% for β-sheet detection. While each of the five modifications in the network enhanced the …

Synthesis Of Small Molecules As Therapeutic Candidates, Savia Boyer

Electronic Theses & Dissertations (2024 - present)

RNA plays a critical role in many biological functions, such as normal cellular functions or disease-related processes. Regulating biological processes through RNA-based therapeutics can be employed by the reversible photoregulation of oligonucleotides. Azobenzene, a light-responsive compound that changes conformation when exposed to ultraviolet (UV) or visible light, is attached to cytidine phosphoramidite to be incorporated in a series of RNA oligonucleotides. The reversibility of the nucleoside and oligonucleotide is verified through UV melting point experiments. The modified oligonucleotide can change conformation upon light irradiation to stop reverse transcription (RT) in the presence of many different reverse transcriptase enzymes. This technique …

Optimizing Endogenous Glp-1 Holistically: A Nursing Led Approach To Sustainable Weight Loss Without Glp-1 Agonist Use, Taylee A. Carscadden

Nursing | Senior Theses

The increase in off-label Glucagon-like peptide-1 (GLP-1) receptor agonist drugs, such as semaglutide (Ozempic), for weight loss has sparked concern in regards to the not fully understood drug outcomes and safety. GLP-1 agonists were originally developed to manage Type 2 Diabetes Mellitus, but have been widely prescribed for obesity management despite minimal research on prolonged use in non-diabetic patients. This study explores how off-label use of GLP-1 agonist drugs exacerbate various adverse health outcomes, highlighting gastrointestinal complications, and the very possible dependency on drugs for weight management. It will also examine the efficacy of nursing-led education on the implementation of …

Medical-Grade Honey And Standard Dressings In Burn Wound Care: Evaluating Effectiveness, Cost, And Patient Outcomes, Andrew Golonka, Chloe Shin

Nursing | Senior Theses

Background: Burn injuries burden the healthcare system globally as silver sulfadiazine (SSD) is the standard treatment even though it delays healing and is highly costly. Medical-grade honey (MGH) demonstrates superior antimicrobial and anti-inflammatory properties, however, there are still evidence gaps when comparing effectiveness, cost efficiency, and patient centered outcomes. Purpose: This study aims to compare MGH and SSD amongst these gaps to inform evidence based burn care. Methods:A randomized controlled trial will enroll 100 people between 25-50 years of age with first and second degree burns, < 20% total body surface area within two hospital burn units. Participants will be assigned to either MGH or SSD treatment. The study will be a single blind design where dermatologists evaluating the wound photographs will not know the treatment given. Primary outcomes include wound healing time, infection rates, and patient reported pain scores. Secondary outcomes will focus on cost effectiveness analyses and patient quality of life. Standardized protocols will be implemented for data collection, wound assessment, and safety monitoring. Results: We anticipate that MGH will have lower infection rates, promote faster wound …

Ribosome Hibernation In Mycobacterium Abscessus And Its Effect On Antibiotic Resistance, Ryan Treen

Electronic Theses & Dissertations (2024 - present)

Non-tuberculosis mycobacteria (NTM) represent a diverse repertoire of species, most of which are ubiquitous in the environment. Some NTM species, such as Mycobacterium abscessus, can cause life-threatening infections in people with underlying medical conditions. The clinical incidence of such infections is on the rise, posing an emerging threat to public health. M. abscessus is characterized by intrinsic and acquired antibiotic resistance, complicating treatment strategies. Most chemotherapeutic approaches for M. abscessus infection target the bacterial ribosome, necessitating a better understanding of the physiological processes which confer this resistance. Multiple mycobacterial species respond to zinc-limiting conditions by inducing remodeling and hibernation …