Analytical, Diagnostic and Therapeutic Techniques and Equipment Commons^™

Performance Of A Sars-Cov-2 Rt-Pcr Assay With Non-Traditional Specimen Types, Subathra Marimuthu, Holly Aliesky, Heather Ness, Daniya Sheikh, Sathya Rashmit, Dawn Balcom, Leslie A. Wolf

The University of Louisville Journal of Respiratory Infections

During the first two years of the coronavirus disease 2019 (COVID-19) pandemic, nasopharyngeal (NP) specimens were the gold standard for clinical diagnostic testing. As information about the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing the pandemic continued to be shared, it was clear that the virus could be detected in other specimen types during an active infection. The University of Louisville Infectious Diseases Laboratory accepted non-traditional specimen types, most without a paired, positive NP result, for research purposes only to support local epidemiology efforts. A real-time reverse transcription-polymerase chain reaction (RT-PCR) assay originally validated for NP specimens was used …

Novel Therapeutic Targets For Migraine, Areeba Nisar, Zubair Ahmed, Hsiangkuo Yuan

Department of Jefferson Headache Center Papers and Presentations

Migraine, a primary headache disorder involving a dysfunctional trigeminal vascular system, remains a major debilitating neurological condition impacting many patients’ quality of life. Despite the success of multiple new migraine therapies, not all patients achieve significant clinical benefits. The success of CGRP pathway-targeted therapy highlights the importance of translating the mechanistic understanding toward effective therapy. Ongoing research has identified multiple potential mechanisms in migraine signaling and nociception. In this narrative review, we discuss several potential emerging therapeutic targets, including pituitary adenylate cyclase-activating polypeptide (PACAP), adenosine, δ-opioid receptor (DOR), potassium channels, transient receptor potential ion channels (TRP), and acid-sensing ion channels …

Hemoglobinopathy Is Associated With Total Hip Arthroplasty Indication Even Beyond Sickle Cell Anemia, Maxwell J. Rakutt, Daniel N. Bracey, Anna Cohen-Rosenblum, Peter K. Sculco, Franco M. Sabatini, Cale A. Jacobs, Stephen T. Duncan, David C. Landy

School of Medicine Faculty Publications

Background: The extent to which hemoglobinopathies other than sickle anemia (HbSS) are associated with hip osteonecrosis is unknown. Sickle cell trait (HbS), hemoglobin SC (HbSC), and sickle/β-thalassemia (HbSβTh) may also predispose to osteonecrosis of the femoral head (ONFH). We sought to compare the distributions of indications for a total hip arthroplasty (THA) in patients with and without specific hemoglobinopathies. Methods: PearlDiver, an administrative claims database, was used to identify 384,401 patients aged 18 years or older undergoing a THA not for fracture from 2010 to 2020, with patients grouped by diagnosis code (HbSS N = 210, HbSC N = 196, …

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 …

Current And Emerging Therapies For Atherosclerotic Cardiovascular Disease Risk Reduction In Hypertriglyceridemia, Reed Mszar, Sarah Bart, Alexander Sakers, Daniel Soffer, Dean G. Karalis

Division of Cardiology Faculty Papers

Hypertriglyceridemia (HTG) is a prevalent medical condition in patients with cardiometabolic risk factors and is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD), if left undiagnosed and undertreated. Current guidelines identify HTG as a risk-enhancing factor and, as a result, recommend clinical evaluation and lifestyle-based interventions to address potential secondary causes of elevated triglyceride (TG) levels. For individuals with mild to moderate HTG at risk of ASCVD, statin therapy alone or in combination with other lipid-lowering medications known to decrease ASCVD risk are guideline-endorsed. In addition to lifestyle modifications, patients with severe HTG at risk of acute pancreatitis …

Deutj: An Imagej Plugin For Improved Automatic Masking And Segmentation Of Images From Confocal Microscopy, Sunny Cui

Independent Student Projects and Publications

Due to advances in microscopic imaging, there are a plethora of biological molecules that can now be tagged and subsequentially imaged from almost any cell, organism, or tissue. However, the ability of software to analyze these images remains to be a challenge. ImageJ is open source software that allows for the processing of these images, but faces challenges when dealing with images that show weak contrast between objects of interest and background. DeutJ is an ImageJ plugin that color corrects and brightness corrects gradients that inhibit segmentation in confocal microscopy images. It can analyze hundreds of images from a given …

Session 12: Active Learning To Minimize The Possible Risk From Future Epidemics, Kc Santosh

SDSU Data Science Symposium

In medical imaging informatics, for any future epidemics (e.g., Covid-19), deep learning (DL) models are of no use as they require a large dataset as they take months and even years to collect enough data (with annotations). In such a context, active learning (or human/expert-in-the-loop) is the must, where a machine can learn from the first day with minimum possible labeled data. In unsupervised learning, we propose to build pre-trained DL models that iteratively learn independently over time, where human/expert intervenes only when it makes mistakes and for only a limited data. In our work, deep features are used to …

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 …

Digital 3d Brain Mri Arterial Territories Atlas, Chin-Fu Liu, Johnny Hsu, Xin Xu, Ganghyun Kim, Shannon M. Sheppard, Erin L. Meier, Michael I. Miller, Argye E. Hillis, Andreia V. Faria

Communication Sciences and Disorders Faculty Articles and Research

The locus and extent of brain damage in the event of vascular insult can be quantitatively established quickly and easily with vascular atlases. Although highly anticipated by clinicians and clinical researchers, no digital MRI arterial atlas is readily available for automated data analyses. We created a digital arterial territory atlas based on lesion distributions in 1,298 patients with acute stroke. The lesions were manually traced in the diffusion-weighted MRIs, binary stroke masks were mapped to a common space, probability maps of lesions were generated and the boundaries for each arterial territory was defined based on the ratio between probabilistic maps. …

Deciphering Microbiota Of Acute Upper Respiratory Infections: A Comparative Analysis Of Pcr And Mngs Methods For Lower Respiratory Trafficking Potential, Sadia Almas, Rob E. Carpenter, Anuradha Singh, Chase Rowan, Vaibhav Tamrakar, Rahul Sharma

Human Resource Development Faculty Publications and Presentations

Although it is clinically important for acute respiratory tract (co)infections to have a rapid and accurate diagnosis, it is critical that respiratory medicine understands the advantages of current laboratory methods. In this study, we tested nasopharyngeal samples (n = 29) with a commercially available PCR assay and compared the results with those of a hybridization-capture-based mNGS workflow. Detection criteria for positive PCR samples was Ct < 35 and for mNGS samples it was >40% target coverage, median depth of 1X and RPKM > 10. A high degree of concordance (98.33% PPA and 100% NPA) was recorded. However, mNGS yielded positively 29 additional microorganisms (23 bacteria, 4 viruses, and …

Supporting Cardiac Perfusion By Preboa With Reduced Visceral Ischemia Despite Extended Occlusion, Paige Deville, John Hunt, Alan B. Marr, Lance Stuke, Patrick Greiffenstein, Jonathan Schoen, Alison Smith

School of Medicine Faculty Publications

No abstract provided.

Dissociating Statistically Determined Normal Cognitive Abilities And Mild Cognitive Impairment Subtypes With Dctclock., Emily F. Matusz, Catherine C. Price, Melissa Lamar, Rod Swenson, Rhoda Au, Sheina Emrani, Victor Wasserman, David J Libon, Louisa I. Thompson

Rowan-Virtua School of Osteopathic Medicine Departmental Research

OBJECTIVE: To determine whether the DCTclock can detect differences across groups of patients seen in the memory clinic for suspected dementia.

METHOD: Patients (n = 123) were classified into the following groups: cognitively normal (CN), subtle cognitive impairment (SbCI), amnestic cognitive impairment (aMCI), and mixed/dysexecutive cognitive impairment (mx/dysMCI). Nine outcome variables included a combined command/copy total score and four command and four copy indices measuring drawing efficiency, simple/complex motor operations, information processing speed, and spatial reasoning.

RESULTS: Total combined command/copy score distinguished between groups in all comparisons with medium to large effects. The mx/dysMCI group had the lowest total …

Optimization Of The Illumina Covidseq™ Protocol For Decentralized, Cost-Effective Genomic Surveillance, Rob E. Carpenter, Vaibhav Tamrakar, Sadia Almas, Aditya Sharma, Chase Rowan, Rahul Sharma

Human Resource Development Faculty Publications and Presentations

A decentralized surveillance system to identify local outbreaks and monitor SARS-CoV-2 Variants of Concern is one of the primary strategies for the pandemic’s containment. Although nextgeneration sequencing (NGS) is a gold standard for genomic surveillance and variant discovery, the technology is still cost-prohibitive for decentralized sequencing, particularly in small independent labs with limited resources. We have optimized the Illumina COVIDSeq™ protocol for the Illumina MiniSeq instrument to reduce cost without compromising accuracy. We slashed the library preparation cost by half by using 50% of recommended reagents at each step and normalizing the libraries before pooling to achieve uniform coverage. Reagent-only …

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. …

Quantifying 64 Drugs, Illicit Substances, And D- And L- Isomers In Human Oral Fluid With Liquid-Liquid Extraction, Brian Robbins, Rob E. Carpenter, Mary Long, Jacob Perry

Human Resource Development Faculty Publications and Presentations

Although human oral fluid has become more routine for quantitative drug detection in pain management, detecting a large scope of medications and substances is costly and technically challenging for laboratories. This paper presents a quantitative assay for 64 pain medications, illicit substances, and drug metabolites in human oral fluid. The novelty of this assay is that it was developed on an older model AB SCIEX 4000 instrument and renders obscure the need for more technical and expensive laboratory equipment. This method includes addition of internal standard and a 2-step liquid-liquid extraction and dry-down step to concentrate and clean the samples. …

Epigenetic Regulation Of Corneal Epithelial Differentiation By Tet2, Yuzuru Sasamoto, Siyuan Wu, Catherine A. A. Lee, Jason Y. Jiang, Bruce R. Ksander, Markus H. Frank, Natasha Y. Frank

Research outputs 2022 to 2026

Epigenetic DNA modification by 5-hydroxymethylcytosine (5hmC), generated by the Ten-eleven translocation (TET) dioxygenases, regulates diverse biological functions in many organ tissues, including the mammalian eye. For example, 5hmC has been shown to be involved in epigenetic regulation of retinal gene expression. However, a functional role of 5hmC in corneal differentiation has not been investigated to date. Here, we examined 5hmC and TET function in the human cornea. We found 5hmC highly expressed in MUC16-positive terminally differentiated cells that also co-expressed the 5hmC-generating enzyme TET2. TET2 knockdown (KD) in cultured corneal epithelial cells led to significant reductions of 5hmC peak distributions …

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 …

Synthesis And Biomedical Applications Of Hollow Iron Oxide Nanoparticles, Aloka S. Paragoda Arachchilage

Dissertations, Theses, and Capstone Projects

Nano-scale materials have gained much attention during the past few decades due to the stark differences in their properties compared to bulk material. Thus, they are being studied for a myriad of applications ranging from harnessing solar energy to diagnostics. This thesis focuses on the synthesis of hollow iron oxide nanoparticles using Galvanic replacement reactions and their application in drug delivery. Moreover, the use of a peptide precursor for the enhancement of exosomes is also discussed.

Chapter 1 discusses a simple and economical Galvanic approach used for the synthesis of hollow one-dimensional iron oxide nanotubes. In the initial reaction, the …

Electrochemical Sensors And Biosensors Of Biomarkers And Therapeutic Agents Detection, Mahmoud Abdelhakem

Theses and Dissertations

Electrochemical sensing is a pioneering tool amongst all other sensing techniques even though it had been started in the early 20th century. Due to their cost efficacy, accuracy, and real-time measurement, electrochemical sensing has been utilized in a vast of biomedical applications in therapeutic drug monitoring and biomarker detection. This thesis work concerned the monitoring of three therapeutic agents in spiked plasma, urine, dosage form, and interstitial skin fluid with high specificity and accuracy. Two of our sensing platforms utilized nanomaterials for sensing (sensors) of Cilostazol and Velpatasvir utilizing α-MnO2-V2O5 (metal oxide nanorods) and NH2- MIL-53 (Aluminum-based metal organic frameworks), …

Are College Students Interested In Family Health History Education? A Large Needs Assessment Survey Study, Ming Li, Oi Man Kwok, Ping Ma, Tung-Sung Tseng, Lei Shih Chen

School of Public Health Faculty Publications

Family health history (FHH) is an essential foundation for personalized disease prevention. As the incidence of early-onset chronic diseases is increasing among college students, it is important to provide them with the education required to learn about their FHH. This study aimed to assess college students’ interest in receiving FHH education, preferred topics, and desired learning methods. We invited college students to complete an online survey from a large research-intensive university. A total of 2276 college students completed the survey. Nearly half of the participants self-identified as non-Hispanic white (45.5%). Slightly more than half of the sample (53.9%) were not …