Investigative Techniques Commons^™

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 …

Evaluating The Potential And Limitations Of Nanopore Adaptive Sampling For Targeted Transcriptome Sequencing, Nicole Debruyne, Feng Wang, Yang Xu, Lan Lin

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Long-read RNA sequencing is a powerful technology for transcriptomics, but low throughput and high cost pose challenges. Adaptive sampling, a feature of Oxford Nanopore Technologies, offers real-time enrichment by selectively ejecting non-target molecules. We evaluate adaptive sampling for human transcriptome analysis. Adaptive sampling modestly enriches target transcripts (1.3 × for cDNA sequencing, 1.9 × for direct RNA sequencing) while preserving gene expression and splicing profiles, but is significantly less effective than cDNA hybridization capture. Short read lengths and low sequencing quality limit performance. Adaptive sampling on direct RNA sequencing can boost target yield (~ 20%) within fixed run times, potentially …

Apostel-R Recommendations For Reporting Retinal Optical Coherence Tomography Studies In Rodents, Frederike Cosima Oertel, Delia Cabrera Debuc, Peter A. Calabresi, Mei Chen, Christian Cordano, Michael Dietrich, Nicolas Feltgen, Oliver Gramlich, Ari J. Green, Janos Groh, Su-Chun Huang, Benjamin Knier, Thomas Korn, Letizia Leocani, Anat Loewenstein, Christian Van Oterendorp, Tunde Peto, Sven Schippling, Leopold Schmetterer, Steffen Schmitz-Valckenberg, Mathias W. Seeliger, Kenneth S. Shindler, Joel Schuman, Mustafa Sindi, Adnan Tufail, Jui-Kai Wang, Sebastian Wolf, Yuyi You, Martin Zinkernagel, Wolf Lagrèze, Philipp Albrecht

Department of Medicine Faculty Papers

BACKGROUND AND OBJECTIVES: Retinal optical coherence tomography (OCT) in rodent models has been used to longitudinally image retinal changes, to define end points for more costly or time-consuming experiments, and to better understand the pathophysiology underlying OCT findings in human diseases. No standardization of rodent OCT reporting currently exists. Here, we aim to establish consensus recommendation for reporting results from retinal OCT studies in rodents.

METHODS: Initial recommendations were developed based on the APOSTEL criteria for quantitative OCT reporting in humans by a core team. Using a modified Delphi process, an expert panel of rodent OCT researchers (N = 31) …

Comparison Of Anterior And Posterior Surgical Approaches For Cervical Ossification Of The Posterior Longitudinal Ligament Stratified By Spinal Levels: A Systematic Review And Meta-Analysis, Seyed Danial Alizadeh, Sepehr Khosravi, Farzin Farahbakhsh, Vali Baigi, Moein Khormali, Mohsen Hajiqasemi, Zahra Eskandari, Mahgol Sadat Hassan Zadeh Tabatabaei, Amirmahdi Khayyamfar, Mohammad-Rasoul Jalalifar, Sepehr Armaghan, Masoud Pourghahramani Koltapeh, Zahra Ghodsi, Michael G. Fehlings, Alex R. Vaccaro, Vafa Rahimi-Movaghar

Rothman Institute Papers

OBJECTIVE: To compare the outcomes of anterior and posterior surgical approaches for treating cervical ossification of the posterior longitudinal ligament across multiple spinal levels, including 1-2 spinal levels, ≥ 3 levels, or studies that operated on both spinal levels, called mixed spinal levels.

METHODS: A search strategy using pertinent keywords was employed in the MEDLINE, Embase, Scopus, and Web of Science databases. Data on Modified Japanese Orthopaedic Association (mJOA) scores, radiographic outcomes, and complications were extracted. A random-effects meta-analysis, subgroup meta-analysis, and sensitivity analysis were performed.

RESULTS: Among 13 included studies, the anterior approach was statistically associated with improved C2-C7 …

Performing Dual Glucose Clamp Experiments In Sedated Farm Swine: A Practical Method, Marc Torjman, Winston Hamilton, Katherine Dillon, Channy Loeum, Jeffrey Joseph

Department of Anesthesiology Faculty Papers

The hyperinsulinemic-euglycemic clamp technique is considered the gold standard for measuring insulin sensitivity in large animals. We developed a practical method for conducting concurrent glucose clamp experiments in a pair of sedated farm swine positioned in a sling. Descriptions of customized equipment and central venous access surgical procedures for blood collection are provided. Personnel functions are described for execution of the clamp protocol. A total of 24 hyperinsulinemic-euglycemic clamp studies were performed over 6 weeks. Infusaports remained functional for 1454 blood samples. There were three CSII catheter occlusions during bolus administration, and the swine showed no signs of infection or …

Implementing A Pap Smear Tracking Tool For Increased Compliance, Meghan Marie Madea Msn, Cnm, Whnp-Bc, Katherine Ferrell Fouquier Phd, Cnm, Facnm, Bobby Bellflower Dnsc, Nnp-Bc, Faan, Faanp, Fnap

Doctor of Nursing Practice Projects

Purpose/Background

The Papanicolaou “pap” smear screens for cervical cancer in women ages 21-65 with a cervix. Inconsistent locations for lab results lead to a decrease in provider efficiency, and patients are unaware of results or recommended follow-up. This quality improvement project implemented a tracking tool within the electronic medical record (EMR) in a busy midwifery clinic. The outcomes are the identification of patients overdue for pap smears, scheduling the procedure, recording of results, and patient notification with recommended follow-up.

Methods

A one-month chart review was performed of fifty gynecology patients within a midwifery clinic. Results of pap smears were located …

The Science Of Sound: Studying The Cognitive, Emotional, And Physiological Effects Of Frequency, Genre, And Music, Jett Yarborough

Senior Honors Theses

Music influences emotion, physiology, and cognition, yet little is known about how the frequency it is tuned to affects these influences. Prior research has shown that music tuned to 432 Hz can reduce stress, lower blood pressure, and improve sleep. My colleagues and I conducted two studies to investigate this. Our research found that music tuned to 432 Hz promotes a significant increase in memory retention and induces a state of focus and relaxation. These results suggest that shifting from the standard tuning frequency of 440 Hz to 432 Hz could have a profoundly positive impact on our daily lives. …

A Comparative Evaluation Of Two Subharmonic-Aided Pressure Estimation (Shape) Analysis Methods, Hailee Mayer, Priscilla Machado, Trang Vu, Annalisa Berzigotti, Jaume Bosch, Elton Dajti, Antonina Antonenko, Kirk Wallace, Flemming Forsberg

Department of Radiology Faculty Papers

Pressure measurement in clinical practice is a valuable tool for diagnostic evaluation, especially in diseases such as portal hypertension. Currently, portal pressures are measured by invasive hepatic vein catheterization, posing risks to patients, and limiting how often measurements can be obtained. Subharmonic-aided pressure estimation (SHAPE) is an ultrasound-based technique that leverages ultrasound contrast agents (UCAs) to estimate changes in hydrostatic pressure. UCAs act as nonlinear oscillators when exposed to high enough acoustic pressures (typically > 200 kPa) and produce significant energy components ranging from subharmonics to higher harmonics. Tissues do not generate significant subharmonic components, thus making it the optimal component …

Introducing Patient-Centered Outcomes To Preceptors In Caate-Approved Athletic Training Programs, K. Judge

Clinical Practice in Athletic Training

The 2020 standards set by the Commission on Accreditation of Athletic Training Education (CAATE) now require the incorporation of the International Classification of Function and Patient-Centered Outcomes into professional practice. These standards can be introduced initially through simulation, but to develop a competent and culturally aware professional, outcome measures should be completed during clinical experiences under the guidance of approved preceptors. As this is a relatively new standard, many preceptors did not receive this as part of their education and may be uncomfortable integrating outcomes into their practice. This lack of integration can negatively affect the learning opportunities of athletic …

Incorporating Balance Training Into Ankle Sprain Injury Prevention Programs: An Evidence-To-Practice Review, David Tomchuk, Jacob Meyer, Kyle Schneider, Ben Fox

Clinical Practice in Athletic Training

Ankle sprains are among the most common injuries in sports and non-sporting activities. For patients, ankle sprains can result in multiple short and long-term hardships, such as financial burdens of evaluation and treatment, absenteeism from sport and physical activity, and diminished ankle and lower extremity function. However, athletic trainers and other stakeholders are also impacted by administrative and time burdens in caring for ankle sprains and how ankle sprains affect team dynamics and performance. The 2022 guiding systematic review evaluated the effectiveness of incorporating preventive balance training exercises on the incidence of ankle sprains in soccer athletes. The search performed …