Medicine and Health Sciences Commons^™

Insights Into Genome Recoding From The Mechanism Of A Classic +1-Frameshifting Trna., Howard Gamper, Haixing Li, Isao Masuda, D. Miklos Robkis, Thomas Christian, Adam B. Conn, Gregor Blaha, E. James Petersson, Ruben L. Gonzalez, Ya-Ming Hou

Department of Biochemistry and Molecular Biology Faculty Papers

While genome recoding using quadruplet codons to incorporate non-proteinogenic amino acids is attractive for biotechnology and bioengineering purposes, the mechanism through which such codons are translated is poorly understood. Here we investigate translation of quadruplet codons by a +1-frameshifting tRNA, SufB2, that contains an extra nucleotide in its anticodon loop. Natural post-transcriptional modification of SufB2 in cells prevents it from frameshifting using a quadruplet-pairing mechanism such that it preferentially employs a triplet-slippage mechanism. We show that SufB2 uses triplet anticodon-codon pairing in the 0-frame to initially decode the quadruplet codon, but subsequently shifts to the +1-frame during tRNA-mRNA translocation. SufB2 …

Specification Of The Patterning Of A Ductal Tree During Branching Morphogenesis Of The Submandibular Gland., Janice L Walker, Weihao Wang, Edith Lin, Alison Romisher, Meghan P Bouchie, Brigid Bleaken, A Sue Menko, Maria A Kukuruzinska

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The development of ductal structures during branching morphogenesis relies on signals that specify ductal progenitors to set up a pattern for the ductal network. Here, we identify cellular asymmetries defined by the F-actin cytoskeleton and the cell adhesion protein ZO-1 as the earliest determinants of duct specification in the embryonic submandibular gland (SMG). Apical polarity protein aPKCζ is then recruited to the sites of asymmetry in a ZO-1-dependent manner and collaborates with ROCK signaling to set up apical-basal polarity of ductal progenitors and further define the path of duct specification. Moreover, the motor protein myosin IIB, a mediator of mechanical …

Assessment Of Narcotic Use In Management Of Post-Op Pain After Functional Endoscopic Sinus Surgery., Kurren S. Gill, Chandala Chitguppi, Michelle Haggerty, Tawfiq Khoury, Judd Fastenberg, Gurston Nyquist, Elina Toskala, Marc Rosen, Mindy Rabinowitz

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

Objectives: Pain and analgesic requirements after functional endoscopic sinus surgery (FESS) vary widely. This study aims to quantify pain after routine FESS and determine the most commonly used pain management regimen.

Methods: Retrospective chart review of 100 patients who underwent FESS from Oct 2017 to May 2019. Patients prospectively completed a daily pain diary and reported pain levels that were categorized into no pain (0), mild (1-3), moderate (4-7), or severe (8-10). Patients were categorized into narcotics, non-narcotics, combination, or none based on type of analgesic used.

Results: Sixty-nine patients were included. Majority of patients reported either mild (39%) or …

Myc Regulates Ribosome Biogenesis And Mitochondrial Gene Expression Programs Through Its Interaction With Host Cell Factor-1., Tessa M. Popay, Jing Wang, Clare M. Adams, Gregory Caleb Howard, Simona G. Codreanu, Stacy D. Sherrod, John A. Mclean, Lance R. Thomas, Shelly L. Lorey, Yuichi J. Machida, April M. Weissmiller, Christine M. Eischen, Qi Liu, William P. Tansey

Department of Cancer Biology Faculty Papers

The oncoprotein transcription factor MYC is a major driver of malignancy and a highly validated but challenging target for the development of anticancer therapies. Novel strategies to inhibit MYC may come from understanding the co-factors it uses to drive pro-tumorigenic gene expression programs, providing their role in MYC activity is understood. Here we interrogate how one MYC co-factor, host cell factor (HCF)-1, contributes to MYC activity in a human Burkitt lymphoma setting. We identify genes connected to mitochondrial function and ribosome biogenesis as direct MYC/HCF-1 targets and demonstrate how modulation of the MYC-HCF-1 interaction influences cell growth, metabolite profiles, global …

Cergc And Vision Loss From Traumatic Optic Neuropathy Indud By Repetitive Closed Head Trauma Is Dependent On Timing And Force Of Impact., Reas S. Khan, Ahmara G. Ross, Puya Aravand, Kimberly Dine, Evan B. Selzer, Kenneth S. Shindler

Student Papers, Posters & Projects

Purpose: Traumatic optic neuropathy (TON) is often caused by blunt head trauma and has no currently effective treatment. Common animal models of TON induced by surgical crush injury are plagued by variability and do not mimic typical mechanisms of TON injury. Traumatic head impact models have recently shown evidence of TON, but the degree of head impact necessary to consistently induce TON is not well characterized, and it is examined here.

Methods: Traumatic skull impacts to C57BL/6J mice were induced using an electromagnetic controlled impact device. One impact performed at two depths (mild and severe), as well as three and …

The Mitochondrial Permeability Transition: Nexus Of Aging, Disease And Longevity., Hagai Rottenberg, Jan B. Hoek

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The activity of the mitochondrial permeability transition pore, mPTP, a highly regulated multi-component mega-channel, is enhanced in aging and in aging-driven degenerative diseases. mPTP activity accelerates aging by releasing large amounts of cell-damaging reactive oxygen species, Ca²⁺ and NAD⁺. The various pathways that control the channel activity, directly or indirectly, can therefore either inhibit or accelerate aging or retard or enhance the progression of aging-driven degenerative diseases and determine lifespan and healthspan. Autophagy, a catabolic process that removes and digests damaged proteins and organelles, protects the cell against aging and disease. However, the protective effect of autophagy …

A Randomized Trial Of Manual Phone Calls Versus Automated Text Messages For Peripheral Nerve Block Follow-Ups., Gavyn Ooi, Eric S. Schwenk, Marc C. Torjman, Kent Berg

Department of Anesthesiology Faculty Papers

Mobile phone applications (apps) have been used for patient follow-up in the postoperative period, specifically to assess for complications and patient satisfaction. Few studies have evaluated their use in regional anesthesia. The objective of this study was to compare follow-up response rates using manual phone calls versus an automated patient outreach (APO) app for peripheral nerve block patients. We hypothesized that the response rate would be higher in the APO group. A mobile app, "JeffAnesthesia," was developed, which sends notifications to patients to answer survey questions in the app. We randomly assigned patients who received peripheral nerve blocks for postoperative …

Detecting Anterior Cruciate Ligament Tears And Posterolateral Corner Injuries On Magnetic Resonance Imaging, Paul Woloszyn, Vishal Desai, Md, Simukayi Mutasa, Md, Tiffany D’Souza, Dominick Battistini, Sasha Mitts, Bryan Sadler

Phase 1

Introduction: Anterior Cruciate Ligament (ACL) tears are an extremely common orthopedic injury, with an incidence ranging from 39-52 per 100,000. Knee Magnetic Resonance Imaging (MRI) scans are the gold standard for diagnosing ACL tears and their comorbidities, such as posterolateral corner injuries; the results of these scans determine the appropriate treatment needed for patients. There is evidence that machine learning can be used to automate the detection of pathology on MRI, and we hypothesize that we can train a neural network machine learning model to accurately interpret ACL injuries and posterolateral corner injuries.

Methods: We will be analyzing over 1000 …

Creation Of A Web-Based Tool To Facilitate Community Connectivity, Andrew Zeiger, Victoria Gulick, Tejal U. Naik

Phase 1

Introduction: Although medical schools are implementing programs to promote student scholarship, few programs exist to informally promote inter-student collaboration. Considering many medical students are early in the process of deciding what they want to spend their lives pursuing, and high levels of social connection and engagement may reduce burnout, we sought to evaluate medical students’ attitudes about inter-student collaboration.

Methods: Approximately 1000 medical students in all classes at Sidney Kimmel Medical College (SKMC) were invited to complete a questionnaire. Data collection remains active. Survey questions included a rank order choice on how respondents would use a tool to learn about …

Jefferson Digital Commons Quarterly Report: October-December 2020, Kelsey Duinkerken, Msi, Larissa Gordon, Mslis, Med, Ma

Jefferson Digital Commons Reports

This quarterly report includes:

• Articles
• Departmental Reports
• Dissertations
• Doctorate of Occupational Therapy (OTD) Capstones
• Educational Materials
• Grand Rounds and Lectures
• JCPH Capstone Presentations
• Journals and Newsletters
• Library Presentations
• Posters
• The Big in Big Data Symposium
• What People are Saying About the Jefferson Digital Commons

Targeting Accuracy Considerations For Simultaneous Tumor Treating Fields Antimitotic Therapy During Robotic Hypofractionated Radiation Therapy., Sharmi Biswas, Irina Kapitanova, Sabrina Divekar, Jimm Grimm, Ian J Butterwick, Daniel Garren, Lawrence R Kleinberg, Kristin J Redmond, Michel Lacroix, Anand Mahadevan, Kenneth M Forster

College of Health Professions Faculty Papers

Purpose: Tumor treating fields (TTFields) is a novel antimitotic treatment that was first proven effective for glioblastoma multiforme, now with trials for several extracranial indications underway. Several studies focused on concurrent TTFields therapy with radiation in the same time period, but were not given simultaneously. This study evaluates the targeting accuracy of simultaneous radiation therapy while TTFields arrays are in place and powered on, ensuring that radiation does not interfere with TTFields and TTFields does not interfere with radiation. This is one of several options to enable TTFields to begin several weeks sooner, and opens potential for synergistic effects of …

New Insights On The Role Of The Mesenchymal-Hematopoietic Stem Cell Axis In Autologous And Allogeneic Hematopoiesis., Tatiana D. Zorina

College of Health Professions Faculty Papers

Cytoreductive protocols are integral both as conditioning regimens for bone marrow (BM) transplantation and as part of therapies for malignancies, but their associated comorbidities represent a long-standing clinical problem. In particular, they cause myeloablation that debilitates the physiological role of mesenchymal stem and precursor cells (MSPCs) in sustaining hematopoiesis. This review addresses the damaging impact of cytoreductive regimens on MSPCs. In addition, it discusses prospects for alleviating the resulting iatrogenic comorbidities. New insights into the structural and functional dynamics of hematopoietic stem cell (HSC) niches reveal the existence of "empty" niches and the ability of the donor-derived healthy HSCs to …

Machine Learning Models For 6-Month Survival Prediction After Surgical Resection Of Glioblastoma, Jeffrey Gray, Lohit Velagapudi, Michael Baldassari, Bryan Sadler, David Vuong

Phase 1

Introduction: The role of surgical resection for the treatment of glioblastoma multiforme is well established. Survival analysis after resective surgery in the literature comprises mostly of traditional statistical models. Machine learning models offer powerful predictive and analytical capability for varied datasets and offer improved generalizability and scalability. We analyzed survival data of patients with glioblastoma with various machine learning algorithms and compared it to binary logistic regression.

Methods: We retrospectively identified cases of glioblastoma treated with surgical resection at our institution from 2012-2018. Feature scaling and one-hot encoding was used to better fit the models to the data and used …

Cryo Vs Rf P-Wave Characteristics Comparative Analysis, John Schanz, Waleed Khan, Behzad B. Pavri

Phase 1

Introduction: Atrial fibrillation (AF) is the leading cause of stroke. Patients with drug-refractory AF are managed with Radiofrequency (RF) or Cryoballoon (Cryo) pulmonary vein isolation (PVI). Approximately 30% of PVIs result in AF recurrences. There is clinical utility in identifying patients at higher risk of AF recurrence with readily available ECG parameters.

Methods: This retrospective study analyzed the ECG characteristics and AF recurrence of 86 paroxysmal AF patients who underwent PVI. Baseline characteristics were collected by chart review and p-wave parameters were measured with electronic calipers in the MUSE (GE) ECG database. AF recurrence was defined as any documented atrial …

Patient Tolerance To Virtual Reality-Based Vestibular Rehabilitation: A Scoping Review, Michael Knapp, Tejal Naik

Phase 1

Introduction: Virtual reality-based therapy (VRBT) using head-mounted devices (HMDs) is being explored as a novel treatment modality for rehabilitation of vestibular disorders. We hypothesize there may exist unique risks and side effects to VRBT using HMDs in the vestibular patient population which no previous studies have directly explored. This scoping review compiles all currently published data concerning vestibular patient tolerance to this treatment modality and provides preliminary interpretation of overall risks.

Methods: An exhaustive list of search terms covering virtual reality, HMDs, vestibular disorders, side effects, and adverse events were submitted to six different databases. Returned papers were uploaded to …

Provider Perceptions Of Virtual Reality As A Therapeutic Tool, Margaret Eberts, Christine Vincent, Tejal U. Naik, Md, Virginia O'Hayer

Phase 1

Introduction: Virtual reality (VR) shows significant potential as a healthcare tool, especially in the management of anxiety disorders and pain. However, despite recent studies demonstrating the effectiveness of VR, there continues to be limited use among providers. A lack of resources and understanding of the feasibility of clinical VR use may present a significant barrier for VR implementation. Through studying the perceptions of providers using VR clinically, this study aims to understand the achievability of VR as a standardized therapy.

Methods: Researchers distributed an online, self-administered questionnaire to healthcare providers identified on VR application websites. The questionnaire consisted of five …

Provider Perceptions Of Virtual Reality As A Therapeutic Tool, Christine Vincent, Margaret Eberts, Tejal U. Naik, C. Virginia O'Hayer

Phase 1

Introduction: Virtual reality (VR) can be an effective healthcare tool, particularly applied to anxiety and pain management. Despite significant interest in VR, lack of resources and knowledge regarding feasibility are barriers to implementation. This study aims to understand the current clinical usage of VR and the achievability of VR as a standardized therapy, by assessing VR healthcare providers.

Methods: An online, self-administered questionnaire with five sections—respondent demographics, VR value, onboarding, billing, and clinical use—was distributed. Providers, identified on VR application websites, were contacted via email. Inclusion criteria was providers in the United States using VR actively or in the past …

Readmission Risk Assessment Tool For Stroke Patients, Simran Rahi, Sasha Mitts, Dominick Battistini, Tiffany D’Souza, Bryan Sadler, Krista Mar, Maureen Deprince, Deborah Murphy, Diana Tzeng, Md

Phase 1

Introduction: Strokes are one of the leading causes of morbidity and mortality in the world and its cost of management has vastly increased; an effective prediction tool that utilizes artificial intelligence to lower the rate of stroke-related readmissions has the potential to lower healthcare costs and increase the quality of provider care. We hypothesize that machine learning techniques are superior to traditional statistics when determining the likelihood of 30-day readmission for Jefferson’s stroke patients.

Methods: Jefferson’s existing data on stroke patients were cleaned, aggregated, and prepared to be split into train and test sets. Using the train sets, machine learning …

Impact Of Algorithmic Bias On Hospital Risk Stratification Scores Among Insurance Recipients, Peter Zdunek, Sarah Reed, Saima Anis, J. Alex Wrem

Phase 1

Introduction: Artificial intelligence-based modelling has created an opportunity to improve upon existing hospital readmission risk score systems by redefining priority and uncovering new criteria, but inherent systematic errors known as algorithmic bias can impact applicability. This study evaluated whether there is racial bias for unplanned readmission risk scores in a novel model prepared for the CMS AI challenge.

Methods: The study population provided by the CMS challenge included Medicare recipients from 2012 (unique beneficiaries n=1,667,362, total claims n=34,233,260). Risk scores for unplanned hospital readmissions were projected on the basis of clinical and demographic criteria, including age, sex, comorbidities, and prior …

Apixaban Discontinuation For Invasive Or Major Surgical Procedures (Adios): A Prospective Cohort Study., Geno J. Merli, Walter K. Kraft, Luis H. Eraso, Taki Galanis, Lynda J. Thomson, Geoffrey O. Ouma, Eugene Viscusi, Jerald Z. Gong, Edwin Lam

Department of Medicine Faculty Papers

Background

Apixaban pharmacokinetic properties and some clinical reports suggest cessation 48 hours prior to surgery is safe, but this has not been demonstrated in a naturalistic setting. We sought to measure the residual apixaban exposure in patients who had apixaban held as part of standard of care peri-operative management.

Methods

This was a prospective, observational study of patients in whom apixaban plasma concentration and anti-Xa activity were measured while at steady state apixaban dosing and again immediately prior to surgery. Clinical management of cessation and resumption of apixaban was at the discretion of the treating physician.

Results

One hundred and …

Risk Factors For Poor Outcomes Among Patients With Extensively Drug-Resistant Tuberculosis (Xdr-Tb): A Scoping Review., Karan Varshney, Beverly Anaele, Matthew Molaei, Rosemary Frasso, Vittorio Maio

College of Population Health Faculty Papers

In recent years, there has been an upsurge in cases of drug-resistant TB, and strains of TB resistant to all forms of treatment have begun to emerge; the highest level of resistance is classified as extensively drug-resistant tuberculosis (XDR-TB). There is an urgent need to prevent poor outcomes (death/default/failed treatment) of XDR-TB, and knowing the risk factors can inform such efforts. The objective of this scoping review was to therefore identify risk factors for poor outcomes among XDR-TB patients. We searched three scientific databases, PubMed, Scopus, and ProQuest, and identified 25 articles that examined relevant risk factors. Across the included …

N2 Year In Review, Josep Dalmau, Marinos Dalakas, Dennis L Kolson, Friedemann Paul, Scott S Zamvil

Department of Neurology Faculty Papers

No abstract provided.

Trsper: A Web-Based Application For Archimedes Spiral Analysis, Rogan Magee, Benjamin Yang, Jeff Ratliff

Department of Neurology Faculty Papers

Background: We built a web-based application of the Archimedes spiral exam that implements clinically validated spiral metrics and tested drawing instructions to define a clinical workflow.

Methods: We designed an HTML5 and Javascript implementation of the spiral exam to run on mobile touchscreen devices. We then recruited 10 volunteers each for 2 experiments designed to validate the programmed spiral metrics and assess how instructions or drawing implement affect the results. In task one, volunteers drew 5 spirals each while following 6 different instruction sets (n=30 spirals each, n=300 spirals total) that varied by support of the drawing hand and tracing …

Lateral Modified Brandt-Daroff Exercises: A Novel Home Treatment Technique For Horizontal Canal Bppv, Michael T. Teixido, Ryan Casserly, Lauren E Melley

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

OBJECTIVES: Brandt-Daroff exercises (BDEs) are commonly used as an at-home treatment for posterior canalithiasis, but their efficacy in the treatment of benign paroxysmal positional vertigo (BPPV) of the horizontal canal (HC-BPPV) has not been previously studied. Using biomechanical model simulation, we investigated modifications that may optimize BDE use for HC-BPPV treatment.

MATERIALS AND METHODS: The BPPV Viewer, a three-dimensional model of the human labyrinth, was used to analyze BDE for HC-BPPV treatment. While moving the model through sequential BDE positions, the expected position of otoliths was demonstrated. Treatment steps were adjusted to maximize otolith movement around the canal circumference without …

Does Smoking Status Influence Health-Related Quality Of Life Outcome Measures In Patients Undergoing Acdf?, John J Mangan, Dhruv K C Goyal, Srikanth N Divi, Daniel R Bowles, Kristen J Nicholson, Victor E Mujica, Thomas J Lee, Rosalie V Depaola, Austin Saline, Taolin Fang, Matthew S Galetta, I David Kaye, Mark F Kurd, Barrett I Woods, Kris E Radcliff, Jeffery A Rihn, D Greg Anderson, Alan S Hilibrand, Christopher K Kepler, Alexander R Vaccaro, Gregory D Schroeder

Rothman Institute Papers

STUDY DESIGN: Retrospective comparative study.

OBJECTIVE: Whereas smoking has been shown to affect the fusion rates for patients undergoing an anterior cervical discectomy and fusion (ACDF), the relationship between smoking and health-related quality of life outcome measurements after an ACDF is less clear. The purpose of this study was to evaluate whether smoking negatively affects patient outcomes after an ACDF for cervical degenerative pathology.

METHODS: Patients with tumor, trauma, infection, and previous cervical spine surgery and those with less than a year of follow-up were excluded. Smoking status was assessed by self-reported smoking history. Patient outcomes, including Neck Disability Index, …

Burnout Among Healthcare Providers Of Covid-19; A Systematic Review Of Epidemiology And Recommendations, Mehrdad Sharifi, Ali Akbar Asadi-Pooya, Razieh Sadat Mousavi-Roknabadi

Department of Neurology Faculty Papers

Introduction: In the current systematic review, we intended to systematically review the epidemiology of burnout and the strategies and recommendations to prevent or reduce it among healthcare providers (HCPs) of COVID-19 wards, so that policymakers can make more appropriate decisions.

Methods: MEDLINE (accessed from PubMed), Science Direct, and Scopus electronic databases were systematically searched in English from December 01, 2019 to August 15, 2020, using MESH terms and related keywords. After reading the title and the abstract, unrelated studies were excluded. The full texts of the studies were evaluated by authors, independently, and the quality of the studies was determined. …

Functional Seizures Are Not Less Important Than Epilepsy, A A Asadi-Pooya, Francesco Brigo, Benjamin Tolchin, Kette D. Valente

Department of Neurology Faculty Papers

Functional seizures (FS) are frequently encountered in neurology clinics, often affect young adults, and have significant negative impacts on many aspects of a person's life. In the current narrative review, we searched the literature regarding some of the consequences of FS (i.e., psychiatric comorbidities, social consequences, costs that are associated with the condition, cognitive impairment in patients with FS, the quality of life of the people with FS, and the increased risk of mortality that is associated with FS). Evidence shows that FS have significant negative consequences, comparable in their magnitude to those affecting patients with epilepsy. The clinical and …

Ifn-Β Acts On Monocytes To Ameliorate Cns Autoimmunity By Inhibiting Proinflammatory Cross-Talk Between Monocytes And Th Cells., Javad Rasouli, Giacomo Casella, Larissa Ishikawa, Rodolfo Thome, Alexandra Boehm, Adam Ertel, Carolina R Melo-Silva, Elisabeth R. Mari, Patrizia Porazzi, Weifeng Zhang, Dan Xiao, Luis J. Sigal, Paolo Fortina, Guang-Xian Zhang, A M Rostami, Bogoljub Ciric

Department of Neurology Faculty Papers

IFN-β has been the treatment for multiple sclerosis (MS) for almost three decades, but understanding the mechanisms underlying its beneficial effects remains incomplete. We have shown that MS patients have increased numbers of GM-CSF+ Th cells in circulation, and that IFN-β therapy reduces their numbers. GM-CSF expression by myelin-specific Th cells is essential for the development of experimental autoimmune encephalomyelitis (EAE), an animal model of MS. These findings suggested that IFN-β therapy may function via suppression of GM-CSF production by Th cells. In the current study, we elucidated a feedback loop between monocytes and Th cells that amplifies autoimmune neuroinflammation, …

Collagen Structure-Function Mapping Informs Applications For Regenerative Medicine., James D San Antonio, Olena Jacenko, Andrzej Fertala, Joseph P R O Orgel

Department of Orthopaedic Surgery Faculty Papers

Type I collagen, the predominant protein of vertebrates, assembles into fibrils that orchestrate the form and function of bone, tendon, skin, and other tissues. Collagen plays roles in hemostasis, wound healing, angiogenesis, and biomineralization, and its dysfunction contributes to fibrosis, atherosclerosis, cancer metastasis, and brittle bone disease. To elucidate the type I collagen structure-function relationship, we constructed a type I collagen fibril interactome, including its functional sites and disease-associated mutations. When projected onto an X-ray diffraction model of the native collagen microfibril, data revealed a matrix interaction domain that assumes structural roles including collagen assembly, crosslinking, proteoglycan (PG) binding, and …

Enlightening Ways To Relax Airway Smooth Muscle: Opsins., Vera P. Krymskaya, Raymond B. Penn

Center for Translational Medicine Faculty Papers

No abstract provided.