Investigative Techniques Commons^™

Presenteeism Among Health Care Personnel With Covid-19, James C. Crosby, Eliezer Santos Leon, Brian Chinnock, Karisa K. Harland, Anusha Krishnadasan, Nicholas M. Mohr, Ian D. Plumb, Melissa Briggs Hagen, Kelli Wallace, David A. Talan, Project Prevent Network, Anne Zepeski, Tracy Young, Howard A. Smithline, Lilly C. Lee, Stephen C. Lim, Et Al

School of Medicine Faculty Publications

IMPORTANCE: Presenteeism-defined as continuing to work during an illness-poses a public health risk in the workplace and is especially hazardous within health care institutions where vulnerable patients may be exposed to nosocomial infections. Understanding the frequency and characteristics of health care personnel (HCP) who report presenteeism while ill with COVID-19 may help mitigate SARS-CoV-2 spread in hospitals and other health care institutions. OBJECTIVES: To determine the frequency of presenteeism among HCP with symptomatic COVID-19, and to evaluate the demographic, occupational, and clinical factors associated with it. DESIGN, SETTING, AND PARTICIPANTS: This is an observational cohort study that uses data from …

Per Se Driving Under The Influence Of Cannabis Statutes And Blood Delta-9-Tetrahydrocannabinol Concentrations Following Short-Term Cannabis Abstinence, Robert L. Fitzgerald, Anya Umlauf, Raymond T. Suhandynata, David J. Grelotti, Marilyn A. Huestis, Kyle F. Mastropietro, Igor Grant, Thomas D. Marcotte

Institute of Emerging Health Professions Faculty Papers

BACKGROUND: Several US states have per se laws using 2 or 5 ng/mL of delta-9-tetrahydrocannabinol (THC) as cutpoints for driving under the influence of cannabis, while some have zero-tolerance statutes. These cutpoints are considered prima facia evidence of driving impairment.

METHODS: In a cohort of people who regularly use cannabis (N = 190) we measured baseline concentrations of THC after instructing participants to abstain from cannabis for at least 48 hours. Baseline driving performance was evaluated using a driving simulator. We also measured blood THC concentrations serially following a smoking session (placebo or active cannabis).

RESULTS: Forty-three percent of the …

Point-Of-Care Ultrasound (Pocus): Measuring Inferior Vena Cava (Ivc) Diameter And Collapsibility In The Preoperative Setting, Jordan Parker, Dakota Kilpatrick

Doctoral Projects

Among the many aspects of preparation required for patients undergoing general anesthesia, preoperative optimization is key. One goal of preoperative optimization is the establishment of adequate preoperative intravascular fluid volume. Inadequate fluid volume can increase surgical risks and lead to adverse patient outcomes. Evidence has demonstrated that using point-of-care ultrasound (POCUS) to assess preoperative surgical patients can diminish the consequences associated with altered fluid status and increase the likelihood of hemodynamic stability. One of the varying methods of POCUS is the point-of-care focused cardiac ultrasound (FOCUS). Using FOCUS, the practitioner can measure the IVC diameter and collapsibility index to determine …

Dual-Task Interaction Between Vestibular Function And Cognitive Processing Using The P300 Event-Related Potential, Laurel Elise Money-Nolan

Graduate Theses and Dissertations (2019 - present)

Previous research has established links between vestibular function and cognitive processing, aging and cognitive function, and aging and vestibular function. Theories of cognitive resource allocation discuss how cognitive resources, such as attention, are devoted towards and divided between tasks when multitasking. This dual-task study, utilizing a balance task and a listening/cognitive task, across the young- and middle-aged adult age range, aimed to evaluate potential relationships between vestibular function, cognition, and age, and to examine how cognitive resources might be allocated under dual-task conditions.

The dual-task protocol in this study utilized an oddball paradigm with tonal stimuli to measure the P300 …

Detection Of Phase-Binning And Interpolation Artifacts In 4-Dimensional Computed Tomography Imaging Using Deep Learning And Rule-Based Approaches, Jorge Cisneros, Nathan H. Feldt, Yevgeniy Vinogradskiy, Richard Castillo, Edward Castillo

Department of Radiation Oncology Faculty Papers

BACKGROUND: Four-dimensional computed tomography (4DCT) imaging is a crucial component to lung cancer radiotherapy planning and enables CT-ventilation-based functional avoidance planning to mitigate radiation toxicity. However, 4DCT scans are frequently impaired by acquisition artifacts that corrupt downstream analyses that depend on lung segmentation and deformable image registration, such as CT-ventilation and dose accumulation.

PURPOSE: This study develops 3D deep learning models to identify phase-binning artifacts at the voxel level and a heuristic, rule-based method to identify interpolation slices within 4DCT images.

METHODS: We introduce a generator that systematically inserts synthetic phase-binning and interpolation artifacts into any artifact-free breathing phase obtained …

Benchmarking Dna Foundation Models For Genomic And Genetic Tasks, Haonan Feng, Lang Wu, Bingxin Zhao, Chad Huff, Jianjun Zhang, Jia Wu, Lifeng Lin, Peng Wei, Chong Wu

School of Medicine Faculty Publications

The rapid evolution of DNA foundation models promises to revolutionize genomics, yet comprehensive evaluations are lacking. Here, we present a comprehensive, unbiased benchmark of five models (DNABERT-2, Nucleotide Transformer V2, HyenaDNA, Caduceus-Ph, and GROVER) across diverse genomic and genetic tasks including sequence classification, gene expression prediction, variant effect quantification, and topologically associating domain (TAD) region recognition, using zero-shot embeddings. Our analysis reveals that mean token embedding consistently and significantly improves sequence classification performance, outperforming other pooling strategies. Model performance varies among tasks and datasets; while general purpose DNA foundation models showed competitive performance in pathogenic variant identification, they were less …

Liver-Directed Base Editing Of Abcc6 Prevents Ectopic Calcification In A Variant-Humanized Mouse Model Of Pseudoxanthoma Elasticum, Lauren C. Testa, Dora Obiri-Yeboah, Hooda Said, Ping Qu, Michael A. Levine, Mohamad-Gabriel Alameh, Kiran Musunuru, Qiaoli Li, Xiao Wang

Department of Biochemistry and Molecular Biology Faculty Papers

Pseudoxanthoma elasticum (PXE) is an autosomal recessive connective tissue disorder characterized by ectopic calcification of elastic fibers throughout the skin, retina, and arteries. It is caused by pathogenic variants in ABCC6 , which encodes a transmembrane transporter that primarily localizes to hepatocytes. Loss of ABCC6 function in hepatocytes leads to systemic deficiency of inorganic pyrophosphate (PPi), a potent inhibitor of calcification; such depletion of PPi from the circulation is responsible for multisystemic ectopic calcification seen in PXE. Therefore, liver-targeted variant correction by genome editing and subsequent restoration of systemic PPi may offer a one-and-done therapeutic approach for PXE. The ABCC6 …

Association Of Obesity Severity With Cardiometabolic And Renal Disease Burden In The United States, Florina Corpodean, Michael Kachmar, Shengping Yang, Steven B. Heymsfield, Peter T. Katzmarzyk, Philip R. Schauer, Michael W. Cook, Vance L. Albaugh

School of Medicine Faculty Publications

Objective This study examined the association between obesity severity and cardiometabolic and renal disease, using BMI as a surrogate for obesity severity. Methods This is a cross-sectional study using data from the United States Behavioral Risk Factor Surveillance System (BRFSS), 2011–2023. Survey-weighted logistic regression estimated odds ratios (OR) for the diagnosis of diabetes, hypertension, hyperlipidemia, kidney disease, myocardial infarction, stroke, and coronary artery disease among increasing BMI categories. Results Higher BMI was associated with increased odds of all conditions. For BMI ≥ 50 kg/m2, odds were notably elevated for diabetes (OR 8.32; 95% CI: 7.78–8.91), hypertension (OR 6.07; 95% CI: …

Promising Effects Of Car T-Cell Therapy In Refractory Stiff Person Syndrome And A Hopeful Future For All Neuroautoimmunities, Marinos Dalakas

Department of Neurology Faculty Papers

Chimeric antigen receptor (CAR) T cells are genetically modified T cells expressing CARs, initially developed to recognize tumor antigens and kill cancer cells that evade T-cell recognition. Because of their impressive success in hemato-oncologic malignancies, CAR T cells are being repurposed with redesigned constructs for safety and sustained efficacy to target refractory systemic autoimmune or neurologic diseases. The CD19 CAR T cells-targeting those CD19-positive, antibody-secreting, long-lived plasma cells, and plasmablasts-are now extensively explored in refractory neuroautoimmunities with promising benefits based on case series in patients with myasthenia gravis (MG), stiff person syndrome (SPS), neuromyelitis, myositis, and multiple sclerosis; some patients …

Intercellular Signaling And Synaptic Deconstruction Uncovered By Single-Cell And Spatial Transcriptomics In An Ad Tauopathy Model, Jeff X. Ji, Brian L. Giles, Surjyadipta Bhattacharjee, Marie-Audrey I. Kautzmann, Alasdair P. Masson, Sonia Do Carmo, A Claudio Cuello, Nicolas G. Bazan

School of Medicine Faculty Publications

Alzheimer's disease (AD) is the leading cause of dementia in elderly individuals worldwide; however, all mechanisms leading to disease onset and progression are not well understood. Here, we report brain single-cell multiome and spatial transcriptomics in a transgenic rat model of human-like tauopathy. We have identified new markers of tau-driven AD pathology and provided single-cell evidence for genes implicated in AD. Our findings reveal how tau hyperphosphorylation and aging alter ligand-receptor communication, transcription factor regulatory networks, and specific cellular networks. Notably, we found intriguing changes in cell communication involving glutamatergic transmission and Netrin signaling as a taupathy consequence. Overall, this …

Latent Classification Of Time-Dependent Transition Rates In Longitudinal Binary Outcome Data, Joonha Chang, Wenyaw Chan

School of Public Health Faculty Publications

Continuous-time Markov chain (CTMC) models and latent classification methods are commonly used to analyze longitudinal categorical outcomes in medical research. While CTMC models are popular for their simplicity and effectiveness, their assumption of constant transition rates presents limitations in capturing dynamic behaviors. To address this, non-homogeneous continuous-time Markov chains (NH-CTMCs) have been developed, incorporating time-varying transition rates to enhance model flexibility. In this study, we leverage closed-form transition probabilities for a fully ergodic two-state NH-CTMC model and propose a latent class clustering approach to identify heterogeneous transition rate patterns within the population. We emphasize the potential advantages of these models …

Editorial: Bridging Inflammation, Oxidative Stress, And Metabolic Dysfunction In Brain Disorders, Ansab Akhtar

School of Medicine Faculty Publications

We present this Special Issue of Brain Sciences, titled "Role of Inflammation, Oxidative Stress, and Metabolic Dysfunction in Neurodevelopmental and Neurodegenerative Diseases: Pharmacological Targets and Therapeutic Interventions", which brings together research and review articles that explore the molecular crosstalk between neuroinflammatory, oxidative stress, and metabolic pathways underlying both neurodegenerative and neurodevelopmental disorders [...].

In Situ-Generated Volumetric Dried Plasma Spots For The Analysis Of Edaravone And Metabolites In Animal Models, Michele Protti, Roberta Di Lecce, Jiri Adamec, Luca G. Regazzoni, Valeria Valsecchi, Claudia Volpi, Roberto Mandrioli, Laura Mercolini

School of Graduate Studies Faculty Publications

In this study, for the first time rat plasma microsampling was carried out by means of in situ-generated volumetric dried plasma spot (vDPS) technology and applied to the determination of the neuroprotective agent edaravone and its sulphate and glucuronide metabolites. Sampling was performed using Telimmune® plasma separation cards (vPSC), which allow the formation of volumetrically accurate dried plasma spots (3 µL) from blood drops deposited on them. After accelerated forced drying and solvent extraction in methanol, drying and redissolution, analytes were baseline separated and quantified through an original HPLC-MS/MS analytical method. Validation assays provided excellent results, with detection limits between …

Impact And Effectiveness Of Phq-9 Training For School Counselors On Mental Health Referrals For High School Students, Sherikee Dorice Grim Bsn, Rn, Ja’Quay Brister Dnp, Pmhnp-Bc, Margaret Harvey Phd, Aprn, Acnp, Chfn, Fhrs

Doctor of Nursing Practice Projects

Purpose/Background

Adolescents' mental health has worsened and become a public health issue, with depression being a primary concern. There is an urgent need for early screening, school-based referral pathways, and interventions to address common problems in high schools. Patient Health Questionnaire-9 (PHQ-9) is a validated, evidence-based tool for detecting depression; however, its systematic use in school-based counseling settings through organized training has not been studied for implementation in high schools. This review assesses the current literature on the impact and effectiveness of PHQ-9 training for school counselors on mental health referrals among high school students, with a focus on early …

Real-World Impact Of Amiodarone On Apixaban Population Pharmacokinetics In Hospitalized Patients, Samantha Kolowrat, Chazmyn Riley, Kevin Lam, Lynda Thomson, Douglas F. Stickle, Walter K. Kraft

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Despite common coadministration in nonvalvular atrial fibrillation (NVAF), there is minimal evidence regarding the impact of concomitant amiodarone use on apixaban pharmacokinetics (PK). We described the population PK of apixaban (2.5 and 5mg twice daily) in 106 hospitalized patients with and without concomitant amiodarone administration at steady state. Apixaban PK was reasonably described by a one-compartment model with first-order absorption and linear elimination. Aside from the receipt of amiodarone, age was retained as a statistically significant covariate on apparent clearance. Model-based simulations depicted concomitant amiodarone use increasing AUCT for both 2.5mg (1.58, 90% CI [1.28, 1.87]) and 5mg (1.12, 90% …

Sensitivity And Specificity Of The Cobas Liat Ct/Ng/Mg Nucleic Acid Test In A Clinical Laboratory Setting And Point-Of-Care Location, B Van Der Pol, R Arcenas, C Boraas, S Chavoustie, L L. Crane, N D'Empaire, A C. Ermel, G Harnett, F Hinestrosa, S House, Rebecca A. Lillis, J Miller, A Mills, R Poblete, S A. Young

School of Medicine Faculty Publications

Sexually transmitted infections, e.g., Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and Mycoplasma genitalium (MG), present with similar signs/symptoms and are often treated empirically due to delays in receiving diagnostic test results. This study evaluated the clinical performance of the Cobas Liat CT/NG/MG nucleic acid amplification test (NAAT) in detecting these pathogens in a point-of-care (POC) setting. This non-interventional, multicenter study recruited symptomatic/asymptomatic participants from 13 geographically diverse POC sites across the USA. Prospective clinician- and self-collected specimens (urine/vaginal swabs) were used to determine the sensitivity and specificity of the Cobas Liat CT/NG/MG test relative to the composite reference standard (CRS), …

Long-Term Liver-Targeted Aav8 Gene Therapy For Mucopolysaccharidosis Iva, Shaukat A. Khan, Eliana Benincore-Florez, Fnu Nidhi, Jose Victor Álvarez, Dione A. Holder, Shunji Tomatsu

Department of Pediatrics Faculty Papers

Mucopolysaccharidosis IVA (MPS IVA) is a lysosomal storage disease with an autosomal recessive trait caused by the deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS) enzyme, which leads to the accumulation of chondroitin-6-sulfate and keratan sulfate, primarily in cartilage and its extracellular matrix, resulting in a direct impact on cartilage and bone development, as well as subsequent systemic skeletal dysplasia. ERT and HSCT are current treatment options, but they have a limited effect on bone lesions. In this article, we investigated liver-specific AAV8 vectors with a thyroxine-binding globulin promoter in the MPS IVA murine model to evaluate the long-term (24 weeks in males …

Validation Of A Prognostic Nomogram For Locally Advanced Oropharyngeal Carcinoma Treated With Intensity-Modulated Radiotherapy With/Without Systemic Therapy, P. Bossi, R. Gili, S. Calza, L. Licitra, M. Maddalo, A. Bacigalupo, L. Belgioia, J. Cacicedo, N. Facchinetti, A. Garcia Castano, M. Oliva, P. Bonomo, G. Sanguineti, P. Franco, A. Argiris, A. Psyrri, E. Orlandi

Kimmel Cancer Center Faculty Papers

BACKGROUND: Head and neck squamous-cell carcinoma (HNSCC), particularly oropharyngeal cancer (OPC), exhibits diverse prognostic factors influenced by demographic and lifestyle variables. Prognostic nomograms, such as the one developed by Fakhry et al., incorporate clinical and biological markers to predict overall survival (OS) and progression-free survival (PFS) in OPC patients. However, their applicability to European populations remains unverified. This study aimed to externally validate Fakhry's prognostic nomogram in a large European cohort of locally advanced OPC patients treated with definitive intensity-modulated radiotherapy (IMRT) with or without systemic therapy.

METHODS: This is a retrospective external validation study conducted on 805 OPC patients …

Overview Of Exosomal Non-Coding Rnas In Cardiovascular Disease Using High Throughput Sequencing, Mortaza Eivazi, Leila Abkhooie, Kamran Hosseini, Parnia Mobasheran, Tahereh Ebrahimi, Vahideh Tarhriz, Eric Lazartigues

School of Graduate Studies Faculty Publications

Non-coding RNAs including miRNAs, long-ncRNAs, and circular RNAs play crucial roles in cell-to-cell communication and epigenetic regulation. They control gene expression at multiple levels, including transcriptional, post-transcriptional, and translational, thereby influencing associated signaling pathways. Encapsulated within exosomes, micro-vesicles, and apoptotic bodies, ncRNAs can be transported between cells while being protected from harsh environmental conditions. Studies have shown various expression patterns across different cell types and in various physiological and pathological states. However, the precise correlations and extent of their contribution to diseases are still under investigation. Recent studies have reported the involvement of extracellular vesicle-associated ncRNAs in the pathogenesis of …

Discriminative Accuracy Of Cha2ds2-Vasc Score, And Development Of Predictive Accuracy Model Using Machine Learning For Ischemic Stroke Risk In Cardiac Amyloidosis And Atrial Fibrillation, Waqas Ullah, Abhinav Nair, Eric Warner, Salman Zahid, Mansoor Rahman, Palwasha Khan, Indranee Rajapreyar, Sridhara S. Yaddanapudi, M. Chadi Alraies, Said Ashraf, Jeffery Van Hook, Yegeny Brailovsky

Department of Medicine Faculty Papers

BACKGROUND: CHA2DS2-VASc score in cardiac amyloidosis (CA) with atrial fibrillation (AF) is believed to underestimate ischemic stroke risk, necessitating a better predictive model.

METHODS: Data were obtained from the National Readmission Database (NRD). Outcomes between CA-AF and no-CA-AF were compared using multivariate regression analysis to calculate adjusted odds ratios (aORs). AutoScore, an interpretable machine learning framework, was used to develop a stroke risk prediction model, and its predictive accuracy was evaluated with an area under the curve (AUC) using the receiver operating characteristic analysis.

RESULTS: A total of 11,860,804 (CA-AF 22,687 (0.19%) and no-CA-AF 11,838,117) patients were identified from 2015 …