Analytical, Diagnostic and Therapeutic Techniques and Equipment Commons^™

Predicting Survival Of Nsclc Patients Treated With Immune Checkpoint Inhibitors: Impact And Timing Of Immune-Related Adverse Events And Prior Tyrosine Kinase Inhibitor Therapy, Michael R. Sayer, Isa Mambetsariev, Kun-Han Lu, Chi Wah Wong, Ashley Duche, Richard Beuttler, Jeremy Fricke, Rebecca Pharaon, Leonidas Arvanitis, Zahra Eftekhari, Arya Amini, Marianna Koczywas, Erminia Massarelli, Moom Rahman Roosan, Ravi Salgia

Pharmacy Faculty Articles and Research

Introduction: Immune checkpoint inhibitors (ICIs) produce a broad spectrum of immune-related adverse events (irAEs) affecting various organ systems. While ICIs are established as a therapeutic option in non-small cell lung cancer (NSCLC) treatment, most patients receiving ICI relapse. Additionally, the role of ICIs on survival in patients receiving prior targeted tyrosine kinase inhibitor (TKI) therapy has not been well-defined.

Objective: To investigate the impact of irAEs, the relative time of occurrence, and prior TKI therapy to predict clinical outcomes in NSCLC patients treated with ICIs.

Methods: A single center retrospective cohort study identified 354 adult patients with NSCLC receiving ICI …

Chimeric Antigen Receptor T-Cell Therapy And Hematopoiesis, Bryanna Reinhardt, Patrick Lee, Joshua P. Sasine

School of Medicine Faculty Publications

Chimeric Antigen Receptor (CAR) T-cell therapy is a promising treatment option for patients suffering from B-cell- and plasma cell-derived hematologic malignancies and is being adapted for the treatment of solid cancers. However, CAR T is associated with frequently severe toxicities such as cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), macrophage activation syndrome (MAS), and prolonged cytopenias—a reduction in the number of mature blood cells of one or more lineage. Although we understand some drivers of these toxicities, their mechanisms remain under investigation. Since the CAR T regimen is a complex, multi-step process with frequent adverse events, ways …

Second Generation Phenyloxadiazolyl Methyl Sulfones For Thiol-Specific Bioconjugations, Guillaume Dewaele-Le Roi

Dissertations, Theses, and Capstone Projects

The role of antibody-based molecular agents for diagnosis and therapy of cancer has expanded significantly over the past decades. However, most of these constructs are synthesized using traditional bioconjugation methods based on the random ligations between the molecular cargo and lysine residues within the protein. These non-specific approaches can create poorly defined conjugates with suboptimal immunoreactivity and in vivo performance while Site-specific approaches to antibody bioconjugation based on ligations between maleimides and free cysteine residues have long stood as attractive alternatives. Yet the inherent instability of the thiol-maleimide linkage has fueled the search for new, more stable thiol-reactive prosthetic groups. …

Leveraging Bio-Inspired Molecules For Cancer Theranostics, Douglas S. Macpherson

Dissertations, Theses, and Capstone Projects

A variety of molecules can be radiolabeled and delivered to a cancer site for the purposes of diagnostics and therapy. Among the most promising of tumor targeting molecules are peptides and antibodies. These bio-inspired molecules can be designed and synthesized to target and respond to cancer cells based on the properties of those cells. Matrix metalloproteinase (MMP) enzymes are over-expressed by some metastatic cancers, in which they are responsible for the degradation and remodeling of the extracellular matrix. In recent years, MMPs have emerged as promising targets for enzyme-responsive diagnostic probes because oligopeptides can be designed to be selectively hydrolyzed …

Community Risks For Sars-Cov-2 Infection Among Fully Vaccinated Us Adults By Rurality: A Retrospective Cohort Study From The National Covid Cohort Collaborative, Alfred Jerrod Anzalone, Jing Sun, Amanda J. Vinson, William H. Beasley, William B. Hillegass, Kimberly Murray, Brian M. Hendricks, Melissa Haendel, Carol Reynolds Geary, Kristina L. Bailey, Corrine K. Hanson, Lucio Miele, Ronald Horswell, Julie A. Mcmurry, J. Zachary Porterfield, Michael T. Vest, H. Timothy Bunnell, Jeremy R. Harper, Bradley S. Price

School of Medicine Faculty Publications

Background While COVID-19 vaccines reduce adverse outcomes, post-vaccination SARS-CoV-2 infection remains problematic. We sought to identify community factors impacting risk for breakthrough infections (BTI) among fully vaccinated persons by rurality. Methods We conducted a retrospective cohort study of US adults sampled between January 1 and December 20, 2021, from the National COVID Cohort Collaborative (N3C). Using Kaplan-Meier and Cox-Proportional Hazards models adjusted for demographic differences and comorbid conditions, we assessed impact of rurality, county vaccine hesitancy, and county vaccination rates on risk of BTI over 180 days following two mRNA COVID-19 vaccinations between January 1 and September 21, 2021. Additionally, …

Identifying The Serious Clinical Outcomes Of Adverse Reactions To Drugs By A Multi-Task Deep Learning Framework, Haochen Zhao, Peng Ni, Qichang Zhao, Xiao Liang, Di Ai, Shannon Erhardt, Jun Wang, Yaohang Li, Jiianxin Wang

Computer Science Faculty Publications

Adverse Drug Reactions (ADRs) have a direct impact on human health. As continuous pharmacovigilance and drug monitoring prove to be costly and time-consuming, computational methods have emerged as promising alternatives. However, most existing computational methods primarily focus on predicting whether or not the drug is associated with an adverse reaction and do not consider the core issue of drug benefit-risk assessment-whether the treatment outcome is serious when adverse drug reactions occur. To this end, we categorize serious clinical outcomes caused by adverse reactions to drugs into seven distinct classes and present a deep learning framework, so-called GCAP, for predicting the …

Treatment Of Allergic Rhinitis: Diphenhydramine Vs. Fexofenadine, Lauren Setzer

Undergraduate Honors Theses

Allergic rhinitis is a growing allergic illness brought on by the inhalation of allergens, resulting in a list of symptoms, including sneezing, watery eyes, runny nose, etc. Among the many treatment options available, H1-antihistamines are a popular choice for allergic rhinitis sufferers. First-generation antihistamines were the first to hit the market and were later discovered to be lipophilic, causing blood-brain barrier penetration and cognitive impairment. Second-generation antihistamines were later developed with lipophobic properties to eliminate any form of cognitive impairment. Both generations are readily available over-the-counter in tablet form, including two commonly used ones: diphenhydramine (Benadryl®) and fexofenadine (Allegra®). These …

Analysis Of D- And L- Isomers Of (Meth)Amphetamine In Human K2edta Plasma, Brian Robbins, Jacob Perry, Mary Long, Rob E. Carpenter

Human Resource Development Faculty Publications and Presentations

Methamphetamine and its metabolite amphetamine are frequently abused drugs. Whether obtained legally or from clandestine laboratories it is of relevance to determine the chiral makeup of these drugs for investigative purpose. Although urine and oral fluid matrices are commonly offered, less available to independent laboratories are techniques to verify dextro (D-) or levo (L-) (meth)amphetamine from human K2EDTA plasma. This paper outlines the development and validation of a method that includes the addition of internal standard and a two-step liquid-liquid extraction to remove the analytes from human K2EDTA plasma by triple quadrupole mass spectrometry (LC-MS/MS). The assay was validated according …

An Acute Respiratory Distress Syndrome Drug Development Collaboration Stimulated By The Virginia Drug Discovery Consortium, John S. Lazo, Ruben M.L. Colunga-Biancatelli, Pavel A. Solopov, John D. Catravas

Bioelectrics Publications

The genesis of most older medicinal agents has generally been empirical. During the past one and a half centuries, at least in the Western countries, discovering and developing drugs has been primarily the domain of pharmaceutical companies largely built upon concepts emerging from organic chemistry. Public sector funding for the discovery of new therapeutics has more recently stimulated local, national, and international groups to band together and focus on new human disease targets and novel treatment approaches. This Perspective describes one contemporary example of a newly formed collaboration that was simulated by a regional drug discovery consortium. University of Virginia, …

Msdrp: A Deep Learning Model Based On Multisource Data For Predicting Drug Response, Haochen Zhao, Xiaoyu Zhang, Qichang Zhao, Yaohang Li, Jianxin Wang

Computer Science Faculty Publications

Motivation: Cancer heterogeneity drastically affects cancer therapeutic outcomes. Predicting drug response in vitro is expected to help formulate personalized therapy regimens. In recent years, several computational models based on machine learning and deep learning have been proposed to predict drug response in vitro. However, most of these methods capture drug features based on a single drug description (e.g. drug structure), without considering the relationships between drugs and biological entities (e.g. target, diseases, and side effects). Moreover, most of these methods collect features separately for drugs and cell lines but fail to consider the pairwise interactions between drugs and cell …

A Quality Improvement Project To Improve Management Of Urinary Tract Infections In A System Of Pediatric Urgent Care Centers, Benjamin Klick, Tammy Speerhas, Jessica Parrott, Jeffrey Bobrowitz, Anne Mcevoy, Debra Conrad, Theresa Guins

Ellmer School of Nursing Faculty Publications

Background and objective: Urinary tract infections (UTIs) are a common problem in pediatric urgent care medicine. There are multiple quality improvement (QI) projects related to the management of UTIs documented in the pediatric literature. We developed a project to decrease the prescribing of ultimately unneeded antibiotics for possible UTIs in a pediatric urgent care setting. A similar project has not been described in the pediatric literature.

Methods: We first reviewed the charts of patients presenting to a system of pediatric urgent care centers with a possible UTI over a 2-year period. We then launched a QI project with three plan, …

Proposing An Rna Interference (Rnai)-Based Treatment For Human Immunodeficiency Virus (Hiv) By Analyzing The Post-Transcriptional Gene Targeting Of Sars-Cov-2, Hepatitis C Virus, And A549 Lung Cancer Cells, Arjun Jagdeesh

UROP Posters

Human Immunodeficiency Virus (HIV) is a retrovirus that infects CD4+ T cell lymphocytes in humans, leading to the development of Acquired Immunodeficiency Syndrome (AIDS) if left untreated. While current treatment methods, including antiretroviral combination treatments, effectively limit HIV replication, HIV can evade these treatments due to its high mutation rate. Long-term antiretroviral treatment can also be toxic to patients, meaning patients would benefit from a new mechanism of HIV treatment. RNA interference (RNAi) is an antiviral pathway found in mammals, plants, and insects that involves a small-interfering RNA that is incorporated into a protein complex called the RNA-induced Silencing Complex …

Investigation Into The Potential For Acquired Cross Tolerances Of Amphetamines, Benjamin Weldon

CMC Senior Theses

In the United States, the treatment of ADHD through use of psychostimulants in adolescents is a growing reality that many people know today and many more will know in the coming years. Although the effectiveness of psychostimulants is a known asset, the benefits of these medications may not be a permanent solution, suggesting not only the presence of a tolerance build up, but as many stimulants are prescribed in a joint effort to combat ADHD, a possible cross tolerance between two prescribed medications. There are minimal studies published that have addressed the topic of cross stimulation tolerance buildup between prescription …

Sugar-Sweetened Beverages Intake, Abdominal Obesity, And Inflammation Among Us Adults Without And With Prediabetes—An Nhanes Study, Wei Ting Lin, Yu Hsiang Kao, Mirandy S. Li, Ting Luo, Hui Yi Lin, Chien Hung Lee, David W. Seal, Chih Yang Hu, Lei Shih Chen, Tung-Sung Tseng

School of Public Health Faculty Publications

Excessive sugar-sweetened beverages (SSB) consumption and abdominal obesity have been independently linked to numerous disorders, including diabetes and elevated C-reactive protein (CRP). This study aimed to explore the association between SSB intake, abdominal obesity, and inflammation in normal and prediabetic adults. Sugar intake from SSBs was calculated from 24-h dietary recalls and further classified into non-, medium-, and high-intake. The status of non- and prediabetes was identified based on hemoglobin A1c level. All analyses were performed under a survey module with appropriate sampling weights to control for the complex survey design. A total of 5250 eligible adults without diabetes were …

Therapies For Mitochondrial Disorders, Kayli Sousa Smyth, Anne Mulvihill

SURE Journal: Science Undergraduate Research Experience Journal

Mitochondria are cytoplasmic, double-membrane organelles that synthesise adenosine triphosphate (ATP). Mitochondria contain their own genome, mitochondrial DNA (mtDNA), which is maternally inherited from the oocyte. Mitochondrial proteins are encoded by either nuclear DNA (nDNA) or mtDNA, and both code for proteins forming the mitochondrial oxidative phosphorylation (OXPHOS) complexes of the respiratory chain. These complexes form a chain that allows the passage of electrons down the electron transport chain (ETC) through a proton motive force, creating ATP from adenosine diphosphate (ADP). This study aims to explore current and prospective therapies for mitochondrial disorders (MTDS). MTDS are clinical syndromes coupled with abnormalities …

Designing And Synthesizing A Warhead-Fragment Inhibitory Ligand For Ivyp1 Through Fragment-Based Drug Discovery, Samuel Moore

Symposium of Student Scholars

Fragment-based drug discovery (FBDD) is a powerful tool for developing anticancer and antimicrobial agents. Within this, magnetic resonance spectroscopy (NMR) provides a comprehensive qualitative and quantitative approach to screening and validating weak and robust binders with targeted proteins, making NMR among the most attractive strategies in FBDD. Inhibitor of vertebrate lysozyme (Ivyp1) of P. aeruginosa serves as an excellent target because of its active cellular location and implications in clinical prognosis for cystic fibrosis and immunocompromised patients. This study uses current NMR and biophysical techniques to develop a covalent, fragment-linked warhead inhibitor for Ivyp1 through synthetic methods, warhead linking, and …

Radioluminescence Based Biochemical Sensing And Imaging Strategies To Measure Local Drug Release And Ph, Gretchen B. Schober

All Dissertations

In this dissertation we describe methods for measuring infection relevant biochemical analytes using radioluminescent and ultrasound luminescent materials. Films and nanoparticles fabricated with europium doped gadolinium oxysulfide (Gd₂O₂S:Eu³⁺) are used to quantitatively measure radiolabeled pharmaceutical concentration, specifically tritium labeled vancomycin (³H-vancomycin). Europium and dysprosium doped strontium aluminate is used to fabricate an ultrasound modulated, pH sensing film. These methods are indicated for theranostic evaluation of implant associated infection. Bacterial biofilms are inherently resistant to traditional antibiotic treatment and can coat biomedical implants. These biofilm related infections are difficult or impossible to eradicate …

Thromboelastography Profiles Of Hemophilia A Patients On Emicizumab, Daniel J. Vanzweden, Meera Chitlur, Charity J. Stadler

Medical Student Research Symposium

Emicizumab is a new monoclonal antibody developed to dtreat people with Hemophilia A, especially those with antibodies. However, breakthrough bleeding can still occur in patients taking Emicizumab. TEG is a global coagulation assay which measures coagulability through viscosity. This study describes the use of tissue factor activated TEG in measuring bleeding profiles in patients taking Emicizumab. The goal of this prospective study is to determine if TEG can be used, which variables of TEG might be useful, and how much more useful it is than the current standard, aPtt. Findings include a 25% increased R time and 24% increased K …

Omarigliptin Attenuates Rotenone-Induced Parkinson's Disease In Rats: Possible Role Of Oxidative Stress, Endoplasmic Reticulum Stress And Immune Modulation, Shereen Mowaka, Haidy E. Michel, Mariam M. Tadros, Moataz S. Hendy, Bassam M. Ayoub

Pharmacy

The current study aimed to explore the potential neuroprotective effect of omarigliptin (OG), an antidiabetic drug that crosses the blood-brain barrier (BBB), in a Parkinson's disease (PD) rotenone-based rat-model. Results showed that OG attenuated motor impairment, histological aberrations, α-synuclein accumulation, and rescued the dopaminergic neurons in rotenone-administered rats. Furthermore, OG halted rotenone-induced oxidative stress; as shown by reduced lipid peroxidation, decline in the oxidative stress sensor (nuclear factor erythroid 2-related factor 2) and its downstream heme oxygenase-1. In addition, OG abrogated neuroinflammation and apoptosis in rotenone-treated rats. Moreover, OG ameliorated endoplasmic reticulum (ER) stress in rotenone-administered rats; as evidenced by …

Updates In The Pharmacologic Prophylaxis And Treatment Of Invasive Candidiasis In The Pediatric And Neonatal Intensive Care Units, James Hunter Fly, Seerat Kapoor, Kelly Bobo, Jeremy S. Stultz

Faculty Publications

Purpose of review The goal of this review was to provide an update on the prevention and treatment options for invasive candidiasis (IC) in the neonatal intensive care unit (NICU) and pediatric intensive care unit (PICU).

Recent findings Studies have further validated the use of fluconazole for IC prophylaxis among high-risk patients in the NICU. It remains unclear if prophylaxis leads to resistance development and the ideal dosage regimen is still not clear. Recent studies have been published comparing caspofungin and micafungin to amphotericin B and illustrated similar efficacy outcomes in the NICU. Micafungin now has approval from the United …

The Use Of Silica Nanoparticles For Controlled Drug Delivery Of Nicotine, Jennifer C. Iwenofu

Honors College Theses

Drug molecules can be administered in different ways to the human body. Nanotechnology stands out over other alternatives by delivering drugs to specific locations and reducing reactivity time. In this research, the hydrogen bond between silica nanoparticles and the drug molecule, nicotine, were studied to controllably deliver nicotine by varying pH values.

Cytotoxic Activity Of Non-Specific Lipid Transfer Protein (Nsltp1) From Ajwain (Trachyspermum Ammi) Seeds, Saud O. Alshammari, Taibah Aldakhil, Qamar A. Alshammari, David Salehi, Aftab Ahmed

Pharmacy Faculty Articles and Research

Background

Trachyspermum ammi, commonly known as Ajwain, is a member of the Apiaceae family. It is a therapeutic herbal spice with diverse pharmacological properties, used in traditional medicine for various ailments. However, all previous studies were conducted using small molecule extracts, leaving the protein’s bioactivity undiscovered.

Aim

The current study aimed to demonstrate the cytotoxic activity of Ajwain non-specific lipid transfer protein (nsLTP1) in normal breast (MCF10A), breast cancer (MCF-7), and pancreatic cancer (AsPC-1) cell lines. Also, to evaluate its structural stability in human serum as well as at high temperature conditions.

Methods

The cytotoxic activity of Ajwain nsLTP1 was …

What Motivates Patients To Enroll In A Naloxone Co-Prescribing Program?, Christina Kanagawa, David Aloisio, Eshani Choksi, Manasa Gowda, Tyler Klecha, Charles M. Defendorf

Rowan-Virtua Research Day

Patients were contacted via phone call to establish knowledge of and prescription status regarding naloxone. They were then invited to enroll in a research study consisting of two online surveys.

The patients who had been prescribed naloxone by the time the study had started ranked being persuaded by a medical professional as being the most important reason for accepting the naloxone prescription.

Insufficient data collected during the six-week time frame to draw statistically significant conclusions about what motivates patients to receive naloxone co-prescriptions.

Correlations seen in this study are interesting and warrant further investigation.

A Brief Literature Review On Heparin: To Bolus Or Not To Bolus, That Is The Question, Alex Gechlik, James Espinosa, Alan Lucerna, Kishan Patel

Rowan-Virtua Research Day

Heparin is an anticoagulant medication, used to inhibit the formation of thrombi that pose arteriolar and vein-occlusive risk. The choice between starting a heparin infusion with or without an initial bolus is case dependent based on whether a patient is already anticoagulated and if so, foregoing an initial bolus. In contrast, both anticoagulated and non-anticoagulated patients share the same goal when receiving Heparin for various thromboembolic syndromes, and that is to be within aPTT target range of 1.5-2.5 or 45 to 75 seconds. Falling below goal range leads to a 20-25% recurrence of VTE, and aPTT above goal range has …

Early Detection Of Atypical Motor And Neurobehavior Of Infants At Risk Secondary To Opioid Exposure: A Prospective Study, Kara Boynewicz

Electronic Theses and Dissertations

Prenatal opioid exposure has been studied in relation to infants' medical outcomes. However, large gaps exist in the literature supporting early identification of atypical neurobehavior and motor development of infants with prenatal opioid exposure. The purpose of the study was to investigate whether prenatal opioid exposure has a negative influence on a newborn infant’s neurobehavior and motor development to aid in the early identification of potential delays. Using a prospective quasi experimental design, infants motor development using the Test of Infant Motor Performance (TIMP) and neurobehavior using the NICU Neonatal Network Scale (NNNS) was assessed on 58 infants in a …

“Translation Of Hdac6 Pet Imaging Using [18f]Ekz-001 – Cgmp Production And Measurement Of Hdac6 Target Occupancy In Nhps” – A Review, Dania Rahal

Chemistry & Biochemistry Undergraduate Honors Theses

The inhibition of histone deacetylase 6 (HDAC6) has been reported to alleviate the effects of neurodegenerative diseases such as Alzheimer’s disease. The brain-penetrant PET radioligand [¹⁸F]EKZ-001 has high affinity and selectivity towards HDAC6 and therefore suggests great promise in therapeutic treatment studies and development for neurodegenerative diseases. “Translation of HDAC6 PET imaging using [¹⁸F]EKZ-001 – cGMP production and measurement of HDAC6 target occupancy in NHPs” has achieved an effective, fully automated method of producing [¹⁸F]EKZ-001 in compliance with current good manufacturing practices (cGMP) to support the translation of [¹⁸F]EKZ-001 PET for …

Synthesis, Structural Characterization, And In Vitro Biological Assessment Of Trans- Platinum (Ii) Thionate Complexes As Potent Anticancer Agents, Mia Alshami

Chemistry & Biochemistry Undergraduate Honors Theses

The content of this thesis has been originally reported in our published paper, “trans-Platinum (II) Thionate Complexes: Synthesis, Structural Characterization, and in vitro Biological Assessment as Potent Anticancer Agents” ChemPlusChem 2019 84, 1525-1535, DOI: 10.1002/cplu.201900394, in which I served as coauthor. Cancer caused 9.6 million deaths in 2018 worldwide, with 18.1 million new diagnoses during that same year.The most widely used metal in anticancer drugs is platinum (Pt), and these drugs are used to treat almost 50% of cancer patients. To optimize drug effectiveness, trans-configured Pt(II) complexes have been introduced as a strategy to potentially overcome the …

Estimating The Analytical Performance Of Raman Spectroscopy For Quantification Of Active Ingredients In Human Stratum Corneum, Hichem Kichou, Emilie Munnier, Yuri Dancik, Kamilia Kemel, Hugh Byrne, Ali Tfayli, Dominique Bertrand, Martin Soucé, Igor Chourpa, Franck Bonnier

Articles

Confocal Raman microscopy (CRM) has become a versatile technique that can be applied routinely to monitor skin penetration of active molecules. In the present study, CRM coupled to multivariate analysis (namely PLSR—partial least squares regression) is used for the quantitative measurement of an active ingredient (AI) applied to isolated (ex vivo) human stratum corneum (SC), using systematically varied doses of resorcinol, as model compound, and the performance is quantified according to key figures of merit defined by regulatory bodies (ICH, FDA, and EMA). A methodology is thus demonstrated to establish the limit of detection (LOD), precision, accuracy, sensitivity (SEN), and …

Succinic Semialdehyde Dehydrogenase Deficiency (Ssadhd): Qualitative Needs Assessment For Patients With A Rare Neurological Disorder, Cassandra Bovee, Kayla Woodring

Annual Research Symposium

No abstract provided.

Effectiveness Of Stabilized Hypochlorous Acid In Acute Peritonitis Treatment: A Murine Surgical Study, Benjamin Michael Pomeroy

Graduate Theses/Dissertations

Peritonitis is an inflammatory condition affecting the mesothelial cells that line the peritoneal cavity and is commonly induced by bowel perforations. This medical emergency is treated through antibiotic therapy and surgical intervention followed by tissue irrigation (lavage). Acute treatments aim to remove the bacterial burden, however recurring peritoneal infections occur at high rates and contribute to patient morbidity. These recurring infections are likely due to the inability of lavage solutions to remove the entire massive intra-abdominal bacterial load due to intestinal perforation. Numerous antiseptic solutions and antibiotic additives have been evaluated in their ability to improve source control by abdominal …