Medicine and Health Sciences Commons^™

Young Transposable Elements Rewired Gene Regulatory Networks In Human And Chimpanzee Hippocampal Intermediate Progenitors, Sruti Patoori, Samantha M Barnada, Christopher Large, John I Murray, Marco Trizzino

Department of Biochemistry and Molecular Biology Faculty Papers

The hippocampus is associated with essential brain functions, such as learning and memory. Human hippocampal volume is significantly greater than expected compared with that of non-human apes, suggesting a recent expansion. Intermediate progenitors, which are able to undergo multiple rounds of proliferative division before a final neurogenic division, may have played a role in evolutionary hippocampal expansion. To investigate the evolution of gene regulatory networks underpinning hippocampal neurogenesis in apes, we leveraged the differentiation of human and chimpanzee induced pluripotent stem cells into TBR2 (or EOMES)-positive hippocampal intermediate progenitor cells (hpIPCs). We found that the gene networks active in hpIPCs …

Large Retroperitoneal Mass, Ryan Lamm, Wilbur B. Bowne

Department of Surgery Faculty Papers

No abstract provided.

Reducing Time To Antibiotics In Patients With Neutropenic Fever On A Bone Marrow Transplant Unit, Regina Mcguire, Christopher Anand Gardner, Jordan Villars, William O'Hara, Jessica Radicke, Felicia Rivera, Jill Cristiano, Joanne E. Filicko-O'Hara, Usama Gergis, Adam F. Binder

Student Papers, Posters & Projects

Background/Methods: Timely administration of antibiotics in patients with neutropenic fever (NF) is essential for reducing morbidity and mortality among oncology patients. The optimal time to antibiotics (TTA) for patients with NF is unclear, but IDSA/ASCO guidelines recommend a median TTA within one hour of documented fever. This study focused on identifying barriers at a single academic institution to timely antibiotic administration for patients admitted to the inpatient Bone Marrow Transplant (BMT) unit, and implemented new processes to reduce median TTA to less than 60 minutes.

Methods: Chart reviews were performed to identify causes for delays in antibiotics (abx). Based on …

Anxiolytics For Bronchodilation: Refinements To Gaba, Ajay P Nayak, Steven S An

Department of Medicine Faculty Papers

No abstract provided.

Impact Of Adjuvant Radiation Therapy After Definitive Surgery In Senior Adults >80 Years Old With Advanced Head And Neck Squamous Cell Carcinoma On Overall Survival., Joann M Butkus, Meghan Crippen, Voichita Bar-Ad, Adam Luginbuhl

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

Background: Adjuvant radiotherapy (RT) following surgical resection confers a survival benefit for adult patients with locally advanced head and neck squamous cell carcinoma (HNSCC). We aim to investigate if adjuvant RT provides a similar survival advantage to patients ages 80+ through a national curated database.

Methods: This retrospective cohort study queried the National Cancer Database (NCDB) for all cases of HNSCC between 2004-2016. Patients treated with surgical resection alone were compared to those treated with surgery plus adjuvant RT. Overall survival (OS) was compared within adult (age <80 >years) and senior adult (age ≥80 years) cohorts using Kaplan-Meier analysis. Hazard ratios …

Functional Assessment Of Missense Variants In The Abcc6 Gene Implicated In Pseudoxanthoma Elasticum, A Heritable Ectopic Mineralization Disorder., Luke Kowal, Jianhe Huang, Hongbin Luo, Jagmohan Singh, Adam E Snook, Jouni Uitto, Qiaoli Li

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Pseudoxanthoma elasticum, a heritable multisystem ectopic mineralization disorder, is caused by inactivating mutations in the ABCC6 gene. The encoded protein, ABCC6, a transmembrane transporter, has a specialized efflux function in hepatocytes by contributing to plasma levels of inorganic pyrophosphate, a potent inhibitor of mineralization in soft connective tissues. Reduced plasma inorganic pyrophosphate levels underlie the ectopic mineralization in pseudoxanthoma elasticum. In this study, we characterized the pathogenicity of three human ABCC6 missense variants using an adenovirus-mediated liver-specific ABCC6 transgene expression system in an Abcc6

D121 Located Within The Dry Motif Of P2y12 Is Essential For P2y12-Mediated Platelet Function., Carol Dangelmaier, Benjamin Mauri, Akruti Patel, Satya P Kunapuli, John C Kostyak

Department of Medicine Faculty Papers

Platelets are anucleate cells that mediate hemostasis. This occurs via a primary signal that is reinforced by secreted products such as ADP that bind purinergic receptors (P2Y1 and P2Y12) on the platelet surface. We recently identified a human subject, whom we termed platelet defect subject 25 (PDS25) with a platelet functional disorder associated with the P2Y12 receptor. PDS25 has normal blood cell counts and no history of bleeding diathesis. However, platelets from PDS25 have virtually no response to 2-MeSADP (a stable analogue of ADP). Genetic analysis of P2Y12 from PDS25 revealed a heterozygous mutation of D121N within the DRY motif. …

Hypoglossal Nerve Injury With C1 Lateral Mass Screw Placement: A Case Report And Review Of The Literature, Maria De Abreu Pineda, Elias Atallah, John Wainwright, Joseph Schaefer, Aria Mahtabfar, James S Harrop, Srinivas Prasad, Joshua Pelta-Heller, Ashwini Sharan, Ahilan Sivaganesan, Jack Jallo

Department of Neurosurgery Faculty Papers

We report the case of a 62-year-old man who presented with a progressive myelopathy secondary to spinal cord compression from an odontoid process fracture and subaxial central canal stenosis. The patient underwent a C1-T2 posterior decompression and instrumented fusion (PCDF) and did well immediately postoperatively. However, on POD1, he developed a right hypoglossal nerve (HN) palsy attributed to direct mechanical compression or injury from the C1 lateral mass screw (LMS), which improved following a revision and screw replacement. While HN injury is a known complication of high anterior and anterolateral cervical spine approaches as well as transcondylar screw fixation, this …

Medical Student Sensitivity Training On The Differences In Sex Development, Paul Endres, Deborah Ziring, Dimitrios Papanagnou

Student Papers, Posters & Projects

No abstract provided.

Diffusing Alpha-Emitters Radiation Therapy In Combination With Temozolomide Or Bevacizumab In Human Glioblastoma Multiforme Xenografts, Yossi Nishri, Maayan Vatarescu, Ishai Luz, Lior Epstein, Mirta Dumančić, Sara Del Mare, Amit Shai, Michael Schmidt, Lisa Deutsch, Robert Den, Itzhak Kelson, Yona Keisari, Lior Arazi, Tomer Cooks, Vered Domankevich

Department of Radiation Oncology Faculty Papers

Glioblastoma multiforme (GBM) is at present an incurable disease with a 5-year survival rate of 5.5%, despite improvements in treatment modalities such as surgery, radiation therapy, chemotherapy [e.g., temozolomide (TMZ)], and targeted therapy [e.g., the antiangiogenic agent bevacizumab (BEV)]. Diffusing alpha-emitters radiation therapy (DaRT) is a new modality that employs radium-224-loaded seeds that disperse alpha-emitting atoms inside the tumor. This treatment was shown to be effective in mice bearing human-derived GBM tumors. Here, the effect of DaRT in combination with standard-of-care therapies such as TMZ or BEV was investigated. In a viability assay, the combination of alpha radiation with TMZ …

Enhanced Membrane Binding Of Oncogenic G Protein Αqq209l Confers Resistance To Inhibitor Ym-254890, Clinita E. Randolph, Morgan B. Dwyer, Jenna L. Aumiller, Alethia J. Dixon, Asuka Inoue, Patrick Osei-Owusu, Philip B. Wedegaertner

Department of Biochemistry and Molecular Biology Faculty Papers

Heterotrimeric G proteins couple activated G protein-coupled receptors (GPCRs) to intracellular signaling pathways. They can also function independently of GPCR activation upon acquiring mutations that prevent GTPase activity and result in constitutive signaling, as occurs with the αqQ209L mutation in uveal melanoma. YM-254890 (YM) can inhibit signaling by both GPCR-activated WT αq and GPCR-independent αqQ209L. Although YM inhibits WT αq by binding to αq-GDP and preventing GDP/GTP exchange, the mechanism of YM inhibition of cellular αqQ209L remains to be fully understood. Here, we show that YM promotes a subcellular redistribution of αqQ209L from the plasma membrane (PM) to the cytoplasm. …

Global Current Practice Patterns For The Management Of Hyphema, Sarah C Miller, Prajna Meeralakshmi, Michael J Fliotsos, Grant A Justin, Yoshihiro Yonekawa, Ariel Chen, Annette K Hoskin, Richard J Blanch, Kara M Cavuoto, Rebecca Low, Ximin Li, Matthew Gardiner, T Y Alvin Liu, Ankoor S Shah, James D Auran, Rupesh Agrawal, Fasika A Woreta, International Globe And Adnexal Trauma Epidemiology Study (Igates)

Wills Eye Hospital Papers

Purpose: Hyphema is a sequela of ocular trauma and can be associated with significant morbidity. Management of this condition is variable and can depend on individual institutional guidelines. We aimed to summarize current practices in hyphema management across ophthalmological institutions worldwide.

Methods: A cross-sectional online survey was conducted across North America, Asia, South America, Africa, Europe, and Australia from August 2020 to January 2021. The survey assessed the existing practices in the management of hyphema at each institution.

Results: For layered hyphema, topical steroids were routinely administered by 34 (of 36 respondents, 94.4%) institutions, of which prednisolone was the preferred …

Routine Use Of Closed Suction Drains Following Revision Arthroplasty May Not Be Necessary, Farideh Najafi, Jonah M. Stein, Nicholas V. Peterson, Michael Meghpara, Matthew B. Sherman, Camilo Restrepo, Javad Parvizi

Department of Orthopaedic Surgery Faculty Papers

BACKGROUND: There are numerous studies demonstrating that closed suction drainage (CSD) usage after primary total joint arthroplasty (TJA) has little to no benefit. There are little data on the role of CSDs after revision TJA. The purpose of our study was to evaluate whether there is any clinical advantage to CSD usage after revision TJA.

METHODS: This retrospective study evaluated the clinical records of 2,030 patients undergoing revision TJA between 2007 and 2021. CSD was used in 472 patients and not used in 1,558 patients. Primary outcome was blood transfusion rate and secondary outcomes included total blood loss (TBL), as …

Assessing The Effect Of Four Types Of Direct Mail Messages To Promote The Uptake Of Residential Lead Remediation Funds, H. Okatch, B. Nkala, J. Beltrami, E. Poy, D. Parmer, J. Nkala, F. Olawole

College of Population Health Faculty Papers

Objective

To examine the efficacy of direct mailing using four types of messaging on promoting the uptake of residential lead remediation (RLR) funds in Lancaster, PA, USA.

Study design

We designed a quasi-experiment to assess the effect of 4 RLR messages sent to households in Lancaster, PA by direct mail between September and December 2020: a brief flyer (F); a detailed brochure + the flyer (BF); a health infographic + the flyer (IF); and an application form + the flyer (AFF).

Methods

Mailers were sent to addresses in four census tracts; each census tract received a different message. Both English …

Sterile Setup Table In The Operating Room Is Not So Sterile, Farideh Najafi, Diana Fernández-Rodríguez, Javad Parvizi

Department of Orthopaedic Surgery Faculty Papers

BACKGROUND: One of the important factors for surgical site infection prevention is the implementation of an ultraclean operating room. This study was designed to evaluate back-table sterility during total joint arthroplasty.

METHODS: This prospective study includes 52 patients undergoing primary total joint arthroplasty between November 2021 and January 2022. A total of 4 swabs (2 air swabs and 2 table swabs) were obtained for each case, at the conclusion of surgery and prior to the takedown of drapes. One swab from each set was sent for culture, and the other was sent for next-generation sequencing (NGS) analysis.

RESULTS: Among 104 …

Predicting At-Risk Opioid Use Three Months After Ed Visit For Trauma: Results From The Aurora Study, Brittany E. Punches, Uwe Stolz, Caroline E. Freiermuth, Rachel M. Ancona, Samuel A. Mclean, Stacey L. House, Francesca L. Beaudoin, Xinming An, Jennifer S. Stevens, Donglin Zeng, Thomas C. Neylan, Gari D. Clifford, Tanja Jovanovic, Sarah D. Linnstaedt, Laura T. Germine, Kenneth A. Bollen, Scott L. Rauch, John P. Haran, Alan B. Storrow, Christopher Lewandowski, Paul I. Musey Jr., Phyllis L. Hendry, Sophia Sheikh, Christopher W. Jones, Michael C. Kurz, Nina T. Gentile, Meghan E. Mcgrath, Lauren A. Hudak, Jose L. Pascual, Mark J. Seamon, Erica Harris, Anna M. Chang, Claire Pearson, David A. Peak, Roland C. Merchant, Robert M. Domeier, Niels K. Rathlev, Brian J. O'Neil, Leon D. Sanchez, Steven E. Bruce, Robert H. Pietrzak, Jutta Joormann, Deanna M. Barch, Diego A. Pizzagalli, Jordan W. Smoller, Beatriz Luna, Steven E. Harte, James M. Elliott, Ronald C. Kessler, Kerry J. Ressler, Karestan C. Koenen, Michael S. Lyons

Department of Emergency Medicine Faculty Papers

OBJECTIVE: Whether short-term, low-potency opioid prescriptions for acute pain lead to future at-risk opioid use remains controversial and inadequately characterized. Our objective was to measure the association between emergency department (ED) opioid analgesic exposure after a physical, trauma-related event and subsequent opioid use. We hypothesized ED opioid analgesic exposure is associated with subsequent at-risk opioid use.

METHODS: Participants were enrolled in AURORA, a prospective cohort study of adult patients in 29 U.S., urban EDs receiving care for a traumatic event. Exclusion criteria were hospital admission, persons reporting any non-medical opioid use (e.g., opioids without prescription or taking more than prescribed …

Case Report: The Promising Application Of Dynamic Functional Connectivity Analysis On An Individual With Failed Back Surgery Syndrome, Jingya Miao, Isaiah Ailes, Laura Krisa, Kristen Fleming, Devon Middleton, Kiran Talekar, Peter Natale, Feroze B. Mohamed, Kevin Hines, Caio M. Matias, Mahdi Alizadeh

Department of Neurosurgery Faculty Papers

Failed back surgery syndrome (FBSS), a chronic neuropathic pain condition, is a common indication for spinal cord stimulation (SCS). However, the mechanisms of SCS, especially its effects on supraspinal/brain functional connectivity, are still not fully understood. Resting state functional magnetic resonance imaging (rsfMRI) studies have shown characteristics in patients with chronic low back pain (cLBP). In this case study, we performed rsfMRI scanning (3.0 T) on an FBSS patient, who presented with chronic low back and leg pain following her previous lumbar microdiscectomy and had undergone permanent SCS. Appropriate MRI safety measures were undertaken to scan this subject. Seed-based functional …

Smoking And Other Determinants Of Covid Severity Among Cancer Patients, Sameh Gomaa, Lindsay Wilde, Md, Tara Rakiewicz, Kuang-Yi Wen

Department of Medical Oncology Posters

Introduction

• Cancer patients might be more susceptible to COVID-19 infection.
• With a higher incidence of acute complications, severe disease and higher mortality rates.
• Identifying factors contributing to severe disease remains essential to avoid the risk of severe and often fatal COVID-19 exposure.
• We report on the predisposing factors for severe COVID-19 and increased hospitalization burden in cancer patients at the Sidney Kimmel Cancer Center (SKCC) in Philadelphia.

Intrinsic Disorder In Bap1 And Its Association With Uveal Melanoma., Mak B Djulbegovic, David J Taylor, Vladimir N Uversky, Anat Galor, Carol L Shields, Carol L Karp

Wills Eye Hospital Papers

BACKGROUND: Specific subvariants of uveal melanoma (UM) are associated with increased rates of metastasis compared to other subvariants. BRCA1 (BReast CAncer gene 1)-associated protein-1 (BAP1) is encoded by a gene that has been linked to aggressive behavior in UM.

METHODS: We evaluated BAP1 for the presence of intrinsically disordered protein regions (IDPRs) and its protein-protein interactions (PPI). We evaluated specific sequence-based features of the BAP1 protein using a set of bioinformatic databases, predictors, and algorithms.

RESULTS: We show that BAP1's structure contains extensive IDPRs as it is highly enriched in proline residues (the most disordered amino acid; p-value < 0.05), the average percent of predicted disordered residues (PPDR) was 57.34%, and contains 9 disorder-based binding sites (ie. molecular recognition features (MoRFs)). BAP1's intrinsic disorder allows it to engage in a complex PPI network with at least 49 partners (p …