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Targeting The Stat5 Pathway In Ph+ Acute Lymphoblastic Leukemia, Valentina Minieri, Marco De Dominici, Marja T. Nevalainen, Bruno Calabretta

Department of Cancer Biology Faculty Papers

No abstract provided.

Community Air Quality Monitoring, Russell Zerbo, Karl Koerner, Joseph Minott, Jonathan C. Li

Student Papers, Posters & Projects

Research Goals & Questions

What’s missing? / Overarching goal:

• Despite improving air quality as reported in the 2017 Community Health Assessment, asthma is still a major health problem in Philadelphia with some low-income communities affected significantly more than others.
• In North and West Philadelphia where child asthma hospitalization rates are highest, there is a lack of air monitors in these affected communities.
• Thus, the air quality information that is recorded on the city’s air monitors may not accurately reflect the air quality in these areas of Philadelphia with high asthma rates.

Questions:

1. Does ground level air quality differ in underserved …

A Mixed-Methods Refugee Community Health Needs And Assets Assessment, Eleni Florakis, Rickie Brawer, Phd, Mph, Mches, Abby Cabrera, Kaushal Desai, Saya Bery

Phase 1

Introduction:

Many factors may negatively affect the experience of refugees navigating the healthcare system in Philadelphia. These factors include, but are not limited to, lack of familiarity with the healthcare system, language and cultural barriers, limited health literacy, physical and transportation barriers, and fear and/or distrust of the healthcare system. In addition, there are a large proportion of United States refugees in Pennsylvania. According to usnews.com, Pennsylvania was ranked the top 6th state for taking in the most refugees in the year 2017.

Objective:

The primary objective is to assess the experiences of refugees within the healthcare system since resettlement …

Mental Health And Resilience In Adolescent Refugees Resettled In Philadelphia, Saya Bery, Pia Ghosh, Mph, Ellen Plumb, Md

Phase 1

Introduction: Mental health in adolescents has a large impact on physical health, academic achievement, and overall well-being; moreover, refugee youth are at an increased risk for mental health disorders. While growing evidence shows that positive youth development interventions can prevent health risk behaviors, there is need for further evaluation that shows how to tailor interventions to meet population-specific needs.

Objective: The aim is to assess how targeted interventions can enhance protective factors and reduce negative adult outcomes in vulnerable refugee adolescents. The goals are to understand the current status of mental health and access to resources among resettled adolescents in …

The Genomic Landscape Of Cutaneous Scc Reveals Drivers And A Novel Azathioprine Associated Mutational Signature., Gareth J. Inman, Jun Wang, Ai Nagano, Ludmil B. Alexandrov, Karin J. Purdie, Richard G. Taylor, Victoria Sherwood, Jason Thomson, Sarah Hogan, Lindsay C. Spender, Andrew P. South, Michael Stratton, Claude Chelala, Catherine A. Harwood, Charlotte M. Proby, Irene M. Leigh

Department of Dermatology and Cutaneous Biology Faculty Papers

Cutaneous squamous cell carcinoma (cSCC) has a high tumour mutational burden (50 mutations per megabase DNA pair). Here, we combine whole-exome analyses from 40 primary cSCC tumours, comprising 20 well-differentiated and 20 moderately/poorly differentiated tumours, with accompanying clinical data from a longitudinal study of immunosuppressed and immunocompetent patients and integrate this analysis with independent gene expression studies. We identify commonly mutated genes, copy number changes and altered pathways and processes. Comparisons with tumour differentiation status suggest events which may drive disease progression. Mutational signature analysis reveals the presence of a novel signature (signature 32), whose incidence correlates with chronic exposure …

The Dermatologist And Color, Andrzej Grzybowski, Lawrence Charles Parish

Department of Dermatology and Cutaneous Biology Faculty Papers

The idea for an issue on color and the skin was initiated by the 2017 exhibit “Breathing Color” that had been created by the new Design Museum in London, England. While variations in color may play a significant role in diagnosing a skin disease, little attention has been directed towards the influence that color may be used to identify a dermatologic disease and even monitor a therapeutic agent. The reader need only to recall how early dermatology atlases were hand colored to provide a more realistic picture of a disease.

Gene Therapy Reimbursement Models – A Stakeholder Assessment, Aaron Bholé, Matthew Luminais, Msc, B. A. Sillah, Md, Mba

Phase 1

Introduction: The first one-time curative gene therapy was approved in December 2017 with a list price of $850,000, and there is a historic increase in gene therapy clinical trials with 89 having reached phase III as of May 2018. Gene therapy’s high upfront cost will challenge the traditional reimbursement models which are well suited for common, chronic conditions.

Objective: This stakeholder assessment surveys groups to identify existing opinions and generate insights regarding gene therapies and their reimbursement models.

Methods: A 12 question survey was sent to 200 stakeholders with the list generated from author’s contacts. Stakeholder groups targeted were providers, …

Normalized Healthcare Utilization Among Refugees Resettled In Philadelphia, 2007-2016, Kaushal Desai, Mph, Colleen Payton, Phd, Mph, Ches, Kevin Scott, Md, Brandon George, Phd, Ms, Marc Altshuler, Md

Phase 1

Background/Purpose: About 70,000 new refugees are resettled in the United States each year, of which approximately 600 are resettled in Philadelphia. This project seeks to better understand the patterns of healthcare utilization, including primary care, emergency, and hospitalization, among refugees resettled in Philadelphia, PA, between 2007 and 2016.

Methods: Demographic and healthcare utilization data for 1,144 refugees seen at Jefferson Family Medical Associates were compiled from the Jefferson Longitudinal Refugee Health Registry. Descriptive statistics were used to describe the demographic characteristics of the refugee population. Negative binomial count regressions were used to test for significant correlations between major demographic variables …

Medication Assisted Treatment In The Primary Care Setting: A Prospective Review, Bridget M. Smith, Lara Weinstein, Md

Phase 1

Introduction: Project HOME Health Services (PHHS) initiated a Medication Assisted Treatment program for Opioid Use Disorder in a primary care setting that is the first of its kind in the city of Philadelphia. This study assesses the MAT program by evaluating the Quality of Life (QoL) of the participants as well as their perception of the program.

Objective: The purpose of this study is to assess the QoL of the participants in the MAT program at PHHS and to evaluate the participants’ satisfaction with the program.

Methods: The population includes patients enrolled in the MAT program at PHHS who consented …

Housing First For People With Opioid Use Disorder (Oud), Ashley Katzenstein, Lara C. Weinstein, Md, Mph, Drph

Phase 1

Introduction

Philadelphia’s opioid crisis has subsequently resulted in an increase in unsheltered individuals. Significant barriers in healthcare access exist for individuals experiencing homelessness and substance use disorders, often leading to poor health outcomes and significant disease burden.

Objective

This study’s purpose is to determine the prevalence of physical and mental illness among individuals with experiences of homelessness and OUD upon entry to a permanent supportive housing program through Pathways to Housing PA (PTHPA).

Methods:

This study is a cross-sectional analysis of physical and mental health conditions of individuals who entered PTHPA’s housing program by July 2018. All individuals included had …

Rethinking Emergency Response To Mass Casualty Incidents: Disaster Medicine Education And The Role Of Medical Students, Claire Zurlo, Edward Jasper, Md, Mph

Phase 1

Introduction: The threat of a mass casualty incident (MCI) is one that must be taken seriously and for which hospitals must be prepared. In the wake of a disaster, emergency departments are often taxed beyond their ability to handle the demands of incoming traumas. In response to this, Dr. Edward Jasper, an emergency physician at Thomas Jefferson Hospital, designed the Hospital Emergency Response Team (HERT) to alleviate the pressure on the ED during a MCI. The HERT is a team of nursing and medical students who are FEMA trained to respond in the event of a MCI.

Objective: The primary …

Signs Of Humanity: A Qualitative Exploration Of Panhandling In Philadelphia, Alyssa Tate, Rosemary Frasso, Phd, Msc, Cph, Willie Baronet, Mfa, Katherine Brierly, Steven Buffer, Kaela Edwards, Zach Fusfeld, Jenna Garret, Nisha George, Nichole Holmes, Emily Wei

Phase 1

People who participate in panhandling are those who ask for financial or other assistance on the street. In Philadelphia, it is known that a large portion of people who panhandle also experience housing insecurity or other hardship. Panhandlers are a very visible fraction of a city’s homeless population and their experiences are of particular interest because their cardboard signs can give insight into common hardships such as housing and food insecurity and substance abuse disorders. While panhandlers in Philadelphia have been surveyed in the past, there is not recent literature on their lived experiences and perspectives and information was not …

Emt- And Stroma-Related Gene Expression And Resistance To Pd-1 Blockade In Urothelial Cancer., Li Wang, Abdel Saci, Peter M. Szabo, Scott D. Chasalow, Mireia Castillo-Martin, Josep Domingo-Domenech, Arlene Siefker-Radtke, Padmanee Sharma, John P. Sfakianos, Yixuan Gong, Ana Dominguez-Andres, William K. Oh, David Mulholland, Alex Azrilevich, Liangyuan Hu, Carlos Cordon-Cardo, Hélène Salmon, Nina Bhardwaj, Jun Zhu, Matthew D. Galsky

Department of Cancer Biology Faculty Papers

Cancers infiltrated with T-cells are associated with a higher likelihood of response to PD-1/PD-L1 blockade. Counterintuitively, a correlation between epithelial-mesenchymal transition (EMT)-related gene expression and T-cell infiltration has been observed across tumor types. Here we demonstrate, using The Cancer Genome Atlas (TCGA) urothelial cancer dataset, that although a gene expression-based measure of infiltrating T-cell abundance and EMT-related gene expression are positively correlated, these signatures convey disparate prognostic information. We further demonstrate that non-hematopoietic stromal cells are a major source of EMT-related gene expression in bulk urothelial cancer transcriptomes. Finally, using a cohort of patients with metastatic urothelial cancer treated with …

Effect Of Differences In Metabolic Activity Of Melanoma Models On Response To Lonidamine Plus Doxorubicin., Kavindra Nath, Jeffrey Roman, David S. Nelson, Lili Guo, Seung-Cheol Lee, Stepan Orlovskiy, Kevin Muriuki, Daniel F. Heitjan, Stephen Pickup, Dennis B. Leeper, Ian A. Blair, Mary E. Putt, Jerry D. Glickson

Department of Radiation Oncology Faculty Papers

Lonidamine (LND), a metabolic modulator, sensitizes DB-1 human melanoma to doxorubicin (DOX) chemotherapy by acidifying and de-energizing the tumor. This report compares the effects of LND on two human melanoma lines, DB-1 and WM983B, which exhibit different metabolic properties. Using liquid chromatography mass spectrometry and Seahorse analysis, we show that DB-1 was more glycolytic than WM983B in vitro. ³¹P magnetic resonance spectroscopy (MRS) indicates that LND (100 mg/kg, i.p.) induces similar selective acidification and de-energization of WM983B xenografts in immunosuppressed mice. Over three hours, intracellular pH (pHi) of WM983B decreased from 6.91 ± 0.03 to 6.59 ± 0.10 (p …

Spaceoar To Improve Dosimetric Outcomes For Monotherapy High-Dose-Rate Prostate Implantation In A Patient With Ulcerative Colitis., Michael Trager, Benjamin Greenberger, Amy S. Harrison, James Keller, Robert B. Den

Department of Radiation Oncology Faculty Papers

High-dose-rate (HDR) brachytherapy is an attractive option for patients receiving definitive radiation therapy for prostate cancer with decreased overall dose to the pelvis. However, ulcerative colitis increases rectal toxicity risk and may be a contraindication. A synthetic hydrogel, SpaceOAR (Augmentix Inc., Waltham, MA, USA), can facilitate the use of HDR brachytherapy for patients where rectal toxicity is a limiting factor. SpaceOAR gel (13.19 cc) was utilized in a monotherapy HDR prostate treatment with Ir-192 under transrectal ultrasound guidance, with the intention of decreasing rectal dose. SpaceOAR gel was inserted transperineally into the patient 18 days prior to the procedure. The …

Sumo-Mediated Regulation Of Nlrp3 Modulates Inflammasome Activity., Rachael Barry, Sidonie Wicky John, Gianmaria Liccardi, Tencho Tenev, Isabel Jaco, Chih-Hong Chen, Justin Choi, Paulina Kasperkiewicz, Teresa Fernandes-Alnemri, Emad S Alnemri, Marcin Drag, Yuan Chen, Pascal Meier

Department of Biochemistry and Molecular Biology Faculty Papers

The NLRP3 inflammasome responds to infection and tissue damage, and rapidly escalates the intensity of inflammation by activating interleukin (IL)-1β, IL-18 and cell death by pyroptosis. How the NLRP3 inflammasome is negatively regulated is poorly understood. Here we show that NLRP3 inflammasome activation is suppressed by sumoylation. NLRP3 is sumoylated by the SUMO E3-ligase MAPL, and stimulation-dependent NLRP3 desumoylation by the SUMO-specific proteases SENP6 and SENP7 promotes NLRP3 activation. Defective NLRP3 sumoylation, either by NLRP3 mutation of SUMO acceptor lysines or depletion of MAPL, results in enhanced caspase-1 activation and IL-1β release. Conversely, depletion of SENP7 suppresses NLRP3-dependent ASC oligomerisation, …

The Single Mitochondrion Of The Kinetoplastid Parasite Crithidia Fasciculata Is A Dynamic Network., John Dimaio, Gordon Ruthel, Joshua J. Cannon, Madeline F. Malfara, Megan L. Povelones

Department of Medical Laboratory Sciences & Biotechnology Faculty Papers

Mitochondria are central organelles in cellular metabolism. Their structure is highly dynamic, allowing them to adapt to different energy requirements, to be partitioned during cell division, and to maintain functionality. Mitochondrial dynamics, including membrane fusion and fission reactions, are well studied in yeast and mammals but it is not known if these processes are conserved throughout eukaryotic evolution. Kinetoplastid parasites are some of the earliest-diverging eukaryotes to retain a mitochondrion. Each cell has only a single mitochondrial organelle, making them an interesting model for the role of dynamics in controlling mitochondrial architecture. We have investigated the mitochondrial division cycle in …

Capabilities Of Upper Extremity Test (Cue-T) V1.1 (Jul 2016) – Training Video, Ralph J. Marino

Department of Rehabilitation Medicine Training Videos and Materials

No abstract provided.

Trends And Costs Of External Electrical Bone Stimulators And Grafting Materials In Anterior Lumbar Interbody Fusion., Anthony D'Oro, Zorica Buser, Darrel Scott Brodke, Jong-Beom Park, Sangwook Tim Yoon, Jim Aimen Youssef, Hans-Joerg Meisel, Kristen Radcliff, Patrick Hsieh, Jeffrey Chun Wang

Rothman Institute Papers

STUDY DESIGN: Retrospective review.

PURPOSE: To identify the trends in stimulator use, pair those trends with various grafting materials, and determine the influence of stimulators on the risk of revision surgery.

OVERVIEW OF LITERATURE: A large number of studies has reported beneficial effects of electromagnetic energy in healing long bone fractures. However, there are few clinical studies regarding the use of electrical stimulators in spinal fusion.

METHODS: We used insurance billing codes to identify patients with lumbar disc degeneration who underwent anterior lumbar interbody fusion (ALIF). Comparisons between patients who did and did not receive electrical stimulators following surgery were …

A Cost Analysis Of Carpal Tunnel Release Surgery Performed Wide Awake Versus Under Sedation., Todd H. Alter, William J. Warrender, Frederic E. Liss, Asif M. Ilyas

Rothman Institute Papers

BACKGROUND: Hand surgery under local anesthesia only has been used more frequently in recent years. The purpose of this study was to compare perioperative time and cost for carpal tunnel release performed under local anesthesia ("wide-awake local anesthesia no tourniquet," or WALANT) only to carpal tunnel release performed under intravenous sedation.

METHODS: A retrospective comparison of intraoperative (operating room) surgical time and postoperative (postanesthesia care unit) time for consecutive carpal tunnel release procedures performed under both intravenous sedation and wide-awake local anesthesia was undertaken. All operations were performed by the same surgeon using the same mini-open surgical technique. A cost …

Etiology And Surgical Management Of Cervical Spinal Epidural Abscess (Sea):: A Systematic Review., Justin Iorio, Yusef Mosley, Md, Srinivas Prasad, Joshua Pelta-Heller, Jack Jallo, Soroush Shahrokh, James Harrop

Department of Medicine Faculty Papers

Study Design: Systematic analysis and review.

Objective: Evaluation of the presentation, etiology, management strategies (including both surgical and nonsurgical options), and neurological functional outcomes in patients with cervical spinal epidural abscess (SEA).

Methods: The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) criteria were used to create a framework based on which articles pertaining to cervical SEA were chosen for review following a search of the Ovid and PubMed databases using the search terms "epidural abscess" and "cervical." Included studies needed to have at least 4 patients aged 18 years or older, and to have been published within the …

Perioperative Aspirin And Long-Term Survival In Patients Undergoing Coronary Artery Bypass Graft., Qian Ding, Hong Liu, Zugui Zhang, Jordan E. Goldhammer, Eric Yuen, Zhongmin Li, Linong Yao, Nilas Young, Douglas Boyd, William Weintraub, Rohinton Morris, Jianzhong Sun

Department of Anesthesiology Faculty Papers

This study aimed to examine association between perioperative uses of aspirin and long-term survival in patients undergoing CABG. A retrospective cohort study was performed in 9,584 consecutive patients receiving cardiac surgery from three tertiary hospitals. Of all the patients, 4,132 patients undergoing CABG met inclusion criteria and were divided into four groups: with or without preoperative or postoperative aspirin respectively. 30-day postoperative and long-term mortality were compared with the use of propensity scores and inverse probability weighting adjustment to reduce the treatment-selection bias. The patients taking preoperative aspirin presented significantly more with comorbidities. However, the results of this study showed …

Levels Of Par-1 Kinase Determine The Localization Of Bruchpilot At The Drosophila Neuromuscular Junction Synapses., Kara R. Barber, Martin Hruska, Keegan M. Bush, Jade A. Martinez, Hong Fei, Irwin B. Levitan, Matthew B. Dalva, Yogesh P. Wairkar

Farber Institute for Neuroscience Faculty Papers

Functional synaptic networks are compromised in many neurodevelopmental and neurodegenerative diseases. While the mechanisms of axonal transport and localization of synaptic vesicles and mitochondria are relatively well studied, little is known about the mechanisms that regulate the localization of proteins that localize to active zones. Recent finding suggests that mechanisms involved in transporting proteins destined to active zones are distinct from those that transport synaptic vesicles or mitochondria. Here we report that localization of BRP-an essential active zone scaffolding protein in Drosophila, depends on the precise balance of neuronal Par-1 kinase. Disruption of Par-1 levels leads to excess accumulation of …

Traumatic Complications Of Inpatient Massage Therapy: Case Report And Literature Review, Ishna Sharma, D'Andrea Joseph, Orlando Kirton

Abington Jefferson Health Papers

No abstract provided.

A Word From The Writing Team (December 2018), Jennifer Wilson, Ms, Els, Pam Walter, Mfa

A Word From the Writing Team (Newsletter)

This issue includes:

• January Writing Retreat
• Find the Time Workshop

The Hungry Cancer Patient: A Case Of Money Ill Spent., Allison Zibelli

Kimmel Cancer Center Papers, Presentations, and Grand Rounds

No abstract provided.

Nkx2-1-As1 Negatively Regulates Cd274/Pd-L1, Cell-Cell Interaction Genes, And Limits Human Lung Carcinoma Cell Migration., Hasmeena Kathuria, Guetchyn Millien, Liam Mcnally, Adam C. Gower, Jean-Bosco Tagne, Yuxia Cao, Maria I. Ramirez

Center for Translational Medicine Faculty Papers

The function of most long noncoding RNAs (lncRNAs) is unknown. However, recent studies reveal important roles of lncRNAs in regulating cancer-related pathways. Human antisense lncRNA-NKX2-1-AS1 partially overlaps the NKX2-1/TTF1 gene within chromosomal region 14q13.3. Amplification of this region and/or differential expression of genes therein are associated with cancer progression. Herein we show higher levels of NKX2-AS1 and NKX2-1 in lung adenocarcinomas relative to non-tumor controls but no correlation between NKX2-1-AS1 and NKX2-1 levels across specimens, or with amplification of the 14q13.3 region, suggesting that NKX2-1-AS1 and NKX2-1 are independently regulated. Loss-and-gain of function experiments showed that NKX2-1-AS1 does not regulate …

Knowledge And Awareness Of Std Risk Perception Of Msm In Philadelphia, Timothy Chou, Nancy Brisbon, Md

Phase 1

There has been a rise in incidence of sexually transmitted diseases (STDs), in particularly in men who have sex with men (MSM). MSM were 106x as likely to have primary or secondary syphilis as compared to men who exclusively had sex with women (MSW). MSM account for large portion of antimicrobial resistant gonorrhea diagnoses and saw a 151% increase in incidence while compared to a 31.7% increase in MSW. This study examines what MSM in Philadelphia know about transmission methods and outcomes of syphilis and gonorrhea to better understand MSM risk perception of these diseases. A multiple-choice test was distributed …

Clinician Perspectives On Factors Affecting Shared Decision Making About Lung Cancer Screening, Mohammad Abubaker-Sharif, Melissa Dicarlo, Mph, Ms, Ronald E. Myers, Phd, Dsw

Phase 1

Background/Objective. In 2015, the Centers for Medicare and Medicaid Services (CMS) announced coverage for annual lung cancer screening (LCS) with low dose computed tomography (LDCT) for individuals who are 55 to 77 years of age, have > 30 pack years of smoking history, and undergo shared decision making (SDM) prior to screening. Most referrals for LCS are initiated in primary care. Currently, little is known about how primary care physicians view SDM and barriers in practice to SDM about LCS. This study aimed to gather information to help fill these knowledge gaps.

Methods. I worked with senior leadership in …

Knowledge, Attitudes, And Beliefs About Sexual Health And Behavior In Huye, Rwanda, Sara Charles, Lianna Drobatz, Ryan Dorey

Phase 1

Introduction: Pregnancy and its associated complication is the leading cause of death for women aged 15-19 worldwide. Teenage pregnancy is correlated with increased health complications, death, poverty, and societal stigma. Pregnancy in Rwanda has been documented at rates of 7% among teen women.

Objective: The objectives of this research study include assessing the attitudes, knowledge, and beliefs of adolescents in the Huye District of Rwanda regarding sexual health and behavior. We hypothesize that gaps in sexual health knowledge may exist and that differing beliefs among male and female adolescents affect adolescent sexual decision making, and, therefore, teenage pregnancy prevalence.

Methods: …