Digital Commons Network^™

Correction To: Small Molecule Kras Agonist For Mutant Kras Cancer Therapy., Ke Xu, Dongkyoo Park, Andrew T Magis, Jun Zhang, Wei Zhou, Gabriel L Sica, Suresh S Ramalingam, Walter J Curran, Xingming Deng

Articles, Abstracts, and Reports

An amendment to this paper has been published and can be accessed via the original article.

Commencement, Philadelphia (2020), Philadelphia College Of Osteopathic Medicine

Commencements

Philadelphia Campus Commencement program, Class of 2020. Degrees include Doctorate in Osteopathic Medicine.

Zinc Finger Rna-Binding Protein Zn72d Regulates Adar-Mediated Rna Editing In Neurons., Anne L Sapiro, Emily C Freund, Lucas Restrepo, Huan-Huan Qiao, Amruta Bhate, Qin Li, Jian-Quan Ni, Timothy J Mosca, Jin Billy Li

Department of Neurology Faculty Papers

Adenosine-to-inosine RNA editing, catalyzed by adenosine deaminase acting on RNA (ADAR) enzymes, alters RNA sequences from those encoded by DNA. These editing events are dynamically regulated, but few trans regulators of ADARs are known in vivo. Here, we screen RNA-binding proteins for roles in editing regulation with knockdown experiments in the Drosophila brain. We identify zinc-finger protein at 72D (Zn72D) as a regulator of editing levels at a majority of editing sites in the brain. Zn72D both regulates ADAR protein levels and interacts with ADAR in an RNA-dependent fashion, and similar to ADAR, Zn72D is necessary to maintain proper neuromuscular …

Correlations Of Calf Muscle Macrophage Content With Muscle Properties And Walking Performance In Peripheral Artery Disease, Kate Kosmac, Marta Gonzalez-Freire, Mary M. Mcdermott, Sarah H. White, R. Grace Walton, Robert L. Sufit, Lu Tian, Lingyu Li, Melina R. Kibbe, Michael H Criqui, Jack M. Guralnik, Tamar S. Polonsky, Christiaan Leeuwenburgh, Luigi Ferrucci, Charlotte A. Peterson

Physical Therapy Faculty Publications

Background

Peripheral artery disease (PAD) is a manifestation of atherosclerosis characterized by reduced blood flow to the lower extremities and mobility loss. Preliminary evidence suggests PAD damages skeletal muscle, resulting in muscle impairments that contribute to functional decline. We sought to determine whether PAD is associated with an altered macrophage profile in gastrocnemius muscles and whether muscle macrophage populations are associated with impaired muscle phenotype and walking performance in patients with PAD.

Methods and Results

Macrophages, satellite cells, and extracellular matrix in gastrocnemius muscles from 25 patients with PAD and 7 patients without PAD were quantified using immunohistochemistry. Among patients …

Tfeb Regulates Murine Liver Cell Fate During Development And Regeneration, Nunzia Pastore, Tuong Huynh, Niculin J Herz, Alessia Calcagni', Tiemo J Klisch, Lorenzo Brunetti, Kangho Ho Kim, Marco De Giorgi, Ayrea Hurley, Annamaria Carissimo, Margherita Mutarelli, Niya Aleksieva, Luca D'Orsi, William R Lagor, David D Moore, Carmine Settembre, Milton J Finegold, Stuart J Forbes, Andrea Ballabio

Faculty, Staff and Students Publications

It is well established that pluripotent stem cells in fetal and postnatal liver (LPCs) can differentiate into both hepatocytes and cholangiocytes. However, the signaling pathways implicated in the differentiation of LPCs are still incompletely understood. Transcription Factor EB (TFEB), a master regulator of lysosomal biogenesis and autophagy, is known to be involved in osteoblast and myeloid differentiation, but its role in lineage commitment in the liver has not been investigated. Here we show that during development and upon regeneration TFEB drives the differentiation status of murine LPCs into the progenitor/cholangiocyte lineage while inhibiting hepatocyte differentiation. Genetic interaction studies show that …

Knowledge Of Autism Spectrum Disorder In Medical Students And Residents, Laura Katherine Hansen, Tammy D. Barry

Research Days

No abstract provided.

Allosteric Inhibitor Of Β-Catenin Selectively Targets Oncogenic Wnt Signaling In Colon Cancer., Anton Cheltsov, Natsuko Nomura, Venkata Mahidhar Yenugonda, Jatin Roper, Rajesh Mukthavaram, Pengfei Jiang, Nam-Gu Her, Ivan Babic, Santosh Kesari, Elmar Nurmemmedov

Articles, Abstracts, and Reports

Abnormal regulation of β-catenin initiates an oncogenic program that serves as a main driver of many cancers. Albeit challenging, β-catenin is an attractive drug target due to its role in maintenance of cancer stem cells and potential to eliminate cancer relapse. We have identified C2, a novel β-catenin inhibitor, which is a small molecule that binds to a novel allosteric site on the surface of β-catenin. C2 selectively inhibits β-catenin, lowers its cellular load and significantly reduces viability of β-catenin-driven cancer cells. Through direct binding to β-catenin, C2 renders the target inactive that eventually activates proteasome system for its removal. …

Investigating Birth Outcomes Among Deaf Mothers: Hospital Vs. Home Births, Aashni Kamra

Undergraduate University Honors Capstones

This study examined birth outcomes among Deaf mothers who have given birth in a hospital setting versus a home setting. Deaf individuals are often marginalized in healthcare due to lack of accessibility, and therefore, the right to make their own informed decisions. This marginalization leads to inequality in health care, and oftentimes individuals within the Deaf community, with added intersectionalities, face even more discrimination. Deaf women face more health disparities in comparison to hearing women due to a variety of factors which include; lack of accessibility, medical professionals’ lack of cultural competency, and lack of inclusion in their healthcare decisions. …

Childhood Absence With Polyspike Ictal-Onset, Sherouk A. Abdelmoity

Research Days

No abstract provided.

Feasibility Of Using Cerner Health Facts To Characterize Comorbid Down Syndrome And Autism Spectrum Disorder, Michael Slogic

Research Days

No abstract provided.

Correlation Between Zinc And Hemoglobin F, Oluwaseun Olaiya, Ashley K. Sherman, Nazia Tabassum, Gerald Woods

Research Days

No abstract provided.

Angiopoietin 1 Protects Against Lps-Induced Acute Lung Injury And Alveolar Remodeling In Neonatal Mice, Umar Salimi

Research Days

No abstract provided.

Transcriptional Analyses Of Adult And Pediatric Adamantinomatous Craniopharyngioma Reveals Similar Expression Signatures Regarding Potential Therapeutic Targets., Eric Prince, Ros Whelan, Andrew Donson, Susan Staulcup, Astrid Hengartner, Trinka Vijmasi, Chibueze Agwu, Kevin O Lillehei, Nicholas K Foreman, James M Johnston, Luca Massimi, Richard C E Anderson, Mark M Souweidane, Robert P Naftel, David D Limbrick, Gerald Grant, Toba N Niazi, Roy Dudley, Lindsay Kilburn, Eric M Jackson, George I Jallo, Kevin Ginn, Amy Smith, Joshua J Chern, Amy Lee, Annie Drapeau, Mark D Krieger, Michael H Handler, Todd C Hankinson, Advancing Treatment For Pediatric Craniopharyngioma Consortium

Manuscripts, Articles, Book Chapters and Other Papers

Adamantinomatous craniopharyngioma (ACP) is a biologically benign but clinically aggressive lesion that has a significant impact on quality of life. The incidence of the disease has a bimodal distribution, with peaks occurring in children and older adults. Our group previously published the results of a transcriptome analysis of pediatric ACPs that identified several genes that were consistently overexpressed relative to other pediatric brain tumors and normal tissue. We now present the results of a transcriptome analysis comparing pediatric to adult ACP to identify biological differences between these groups that may provide novel therapeutic insights or support the assertion that potential …

Proteolysis-Targeting Chimera (Protac) For Targeted Protein Degradation And Cancer Therapy, Xin Li, Yongcheng Song

Faculty, Staff and Students Publications

Proteolysis-targeting chimera (PROTAC) has been developed to be a useful technology for targeted protein degradation. A bifunctional PROTAC molecule consists of a ligand (mostly small-molecule inhibitor) of the protein of interest (POI) and a covalently linked ligand of an E3 ubiquitin ligase (E3). Upon binding to the POI, the PROTAC can recruit E3 for POI ubiquitination, which is subjected to proteasome-mediated degradation. PROTAC complements nucleic acid-based gene knockdown/out technologies for targeted protein reduction and could mimic pharmacological protein inhibition. To date, PROTACs targeting ~ 50 proteins, many of which are clinically validated drug targets, have been successfully developed with several …

Maternal Inflammatory Markers For Chorioamnionitis In Preterm Prelabour Rupture Of Membranes: A Systematic Review And Meta-Analysis Of Diagnostic Test Accuracy Studies, Angela Koech, Geoffrey Omuse, Abraham Mukaindo, Marleen Temmerman

Obstetrics and Gynaecology, East Africa

Background: There is no consensus on the role of inflammatory markers in identifying chorioamnionitis in preterm prelabour rupture of membranes (PPROM). We set out to evaluate the accuracy of maternal blood C-reactive protein (CRP), procalcitonin and interleukin 6 (IL6) in diagnosis of histological chorioamnionitis and/or funisitis (HCA/Funisitis) in PPROM.

Methods: We searched MEDLINE, EMBASE and The Cochrane Library from inception to January 2020 for studies where maternal blood CRP, procalcitonin or IL6 was assessed against a reference standard of HCA/Funisitis in PPROM. The Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool was used to assess methodological quality. Hierarchical summary …

Safety And Activity Of Varlilumab, A Novel And First-In-Class Agonist Anti-Cd27 Antibody, For Hematologic Malignancies., Stephen M Ansell, Ian Flinn, Matthew H Taylor, Branimir I Sikic, Joshua Brody, John Nemunaitis, Andrew Feldman, Thomas R Hawthorne, Tracey Rawls, Tibor Keler, Michael J Yellin

Articles, Abstracts, and Reports

CD27, a costimulatory molecule on T cells, induces intracellular signals mediating cellular activation, proliferation, effector function, and cell survival on binding to its ligand, CD70. Varlilumab, a novel, first-in-class, agonist immunoglobulin G1 anti-CD27 antibody, mediates antitumor immunity and direct killing of CD27+ tumor cells in animal models. This first-in-human, dose-escalation, and expansion study evaluated varlilumab in patients with hematologic malignancies. Primary objectives were to assess safety and the maximum tolerated and optimal biologic doses of varlilumab. Secondary objectives were to evaluate pharmacokinetics, pharmacodynamics, immunogenicity, and antitumor activity. In a 3 + 3 dose-escalation design, 30 patients with B-cell (n = …

Planning And Facilitating The Training Of Emergency Medical Services On The Safe Transport Of Patients With Highly Infectious Diseases, Mohammed Alhallaf

Theses & Dissertations

Emergency Medical Services (EMS) personnel are the first line of treatment and are the first exposed health care workers to infectious diseases (IDs). Consequently, the EMS setting is a relatively vulnerable environment for disease transmission and cross-contamination. Also, serious and emerging IDs, such as highly pathogenic viral hemorrhagic fevers and novel Coronaviruses, in a time of increased globalization, require comprehensive EMS training and preparedness. This project had the objective of identifying best practices for the EMS transport of patients with IDs. The methods for this project were done in two phases. In the first stage, we …

Development Of Fluorescent Hyaluronic Acid Nanoparticles For Intraoperative Tumor Detection, Nicholas E. Wojtynek

Theses & Dissertations

Surgical resection remains to be the primary treatment for the majority of solid tumors, including breast cancer. The complete removal of the primary tumor, local metastases, and metastatic lymph nodes dramatically improve a patient’s treatment outcome and prognosis. Nevertheless, surgeons are limited to tactile and visual cues in distinguishing malignant and healthy tissue. This can result in a positive surgical margin (PSM), which occurs when tumor goes undetected and is left behind in the surgical cavity. PSMs decreases a patient’s prognosis and necessitate additional treatment in the form of surgery, radiation, and chemotherapy. An emerging imaging modality, known as fluorescence-guided …

The Effects Of Alpha-Tocopherol And Ascorbic Acid On Metastatic Breast Cancer Cells, Scout Treadwell

Honors Theses

Breast cancer is a multifaceted, complex disease that affects hundreds of thousands of patients every year. Although there has a been a decline in the mortality rate of this disease, it is still vital to investigate and discover new possible treatments. One area of research involves the generation of reactive oxygen species (ROS) in cancer cells and the possibility of ROS-induced apoptosis. Antioxidants such as Vitamin C and Vitamin E have been shown to serve as pro-oxidants. Instead of detoxifying the cell from damaging ROS, these compounds can stimulate ROS production, triggering an apoptotic cascade in the cell. In this …

An Examination Of The Association Between State Medicaid Perinatal Services And Birth Outcomes, Joy Morgan Myers

Honors Theses

This thesis investigated the connection between socioeconomic status, healthcare coverage, and birth outcomes. The research question that was posed specifically looked at twenty perinatal services that states covered under Medicaid to varying degrees to see their association, if any, with premature birth rates and low birthweight rates. State-level and Mississippi county-level data were compiled regarding preterm birth rates, low birthweight rates, presumptive eligibility adoption, and coverage of twenty different perinatal services. Using these data, the correlation between state Medicaid expansion status and birth outcomes was first calculated in order to determine if variation in birth outcomes was associated with expanded …

Characterization Of A Plasmid-Based Dna Vaccine For Simian Immunodeficiency Virus, Priya Sanipara

Honors Theses

Described as one of the world’s worst pandemics, HIV (Human Immunodeficiency Virus) infects millions of people each year and is the cause for AIDS (Acquired Immunodeficiency Syndrome). Despite the development of vaccines for numerous infectious diseases such as polio, small pox, and influenza, a vaccine for HIV remains elusive due to the virus’s high mutation rate and ability to evade the immune system. HIV causes depletion of CD4+ lymphocytes, resulting in a weakened immune system. However, the development of a plasmid-based DNA vaccine approach may help revolutionize vaccine development for HIV due to its ability to confer cellular and humoral …

Correlation Of Inflammation In Arthritis With The Myelination In The Brain, Anna Spears

Honors Theses

This study was conducted to investigate whether the influence of arthritis has an effect on the cerebral white matter. The project was performed at the South Oxford Campus, where diffusion tensor imaging (DTI) data was obtained from the Nathan Kline Institute-Rockland Sample (NKI- RS). Image processing was conducted using Functional Magnetic Resonance Imaging of Brain Software Library in which we obtained raw data to formulate Apparent Diffusion Coefficient (ADC), Axial Diffusivity (AD), Radial Diffusivity (RD), and Fractional Anisotropy. A one way Analysis of Covariance (ANCOVA) was performed to determine the significant difference between the history of arthritis on each of …

Integrating Geriatric Assessment And Genetic Profiling To Personalize Therapy Selection In Older Adults With Acute Myeloid, Vijaya R. Bhatt

Theses & Dissertations

Integrating geriatric assessment for patient profiling and genetic profiling of leukemic cells represents an innovative approach to personalize therapy selection in older adults with acute myeloid leukemia (AML). We report results of a pre-planned interim analysis of a pragmatic phase II trial that utilized this strategy to personalize therapy. Patients ≥60 years with a new diagnosis of AML underwent geriatric assessment prior to initiation of treatment. Geriatric assessment of physical function, cognitive function and comorbidity burden were used to determine fitness for chemotherapy. Patients with good or intermediate-risk AML received intensive chemotherapy such as anthracycline and cytarabine (7+3) if determined …

Scald Injury-Induced T Cell Dysfunction Can Be Mitigated By Gr1+ Cell Depletion And Blockage Of Cd47/Cd172a Signaling, Nadine Beckmann, Franziska Huber, Marc Hanschen, Barbara St. Pierre Schneider, Vanessa Nomelli, Charles C. Caldwell

Nursing Faculty Research

Infection is a common and severe complication of burn injury: Sepsis accounts for 47% of postburn mortality. Burn-induced T cell suppression likely contributes to the increased infection susceptibility in burn patients. However, little is known about the kinetics of T cell dysfunction after burn and its underlying mechanisms. In this study, we show in a murine scald injury model that T cell activation of both CD4+ and CD8+ T cells as well as T cell cytokine production is suppressed acutely and persistently for at least 11 days after burn injury. Purified T cells from scald-injured mice exhibit normal T cell …

Endorepellin Evokes An Angiostatic Stress Signaling Cascade In Endothelial Cells., Aastha Kapoor, Carolyn G Chen, Renato V Iozzo

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Endorepellin, the C-terminal fragment of the heparan sulfate proteoglycan perlecan, influences various signaling pathways in endothelial cells by binding to VEGFR2. In this study, we discovered that soluble endorepellin activates the canonical stress signaling pathway consisting of PERK, eIF2α, ATF4, and GADD45α. Specifically, endorepellin evoked transient activation of VEGFR2, which, in turn, phosphorylated PERK at Thr980 Subsequently, PERK phosphorylated eIF2α at Ser51, upregulating its downstream effector proteins ATF4 and GADD45α. RNAi-mediated knockdown of PERK or eIF2α abrogated the endorepellin-mediated up-regulation of GADD45α, the ultimate effector protein of this stress signaling cascade. To functionally validate these findings, we utilized an ex …

Laryngotracheal Stenosis, Kelsey Stuckey

Doctor of Nursing Practice Projects

Laryngotracheal stenosis (LTS) is the luminal compromise at the laryngeal, subglottic, or tracheal level (Gelbard et al., 2014). Various etiologies for LTS exist. Endotracheal cuff over-inflation, inappropriately sized endotracheal tubes, and sudden movements of the tube contribute to injury, as well as anatomical differences(Cardillo et al., 2010; Divatia & Bhowmick, 2005; Medina et al., 2009; Miñambres et al., 2009; Nikolovski et al., 2019; Zaghi et al.,2016). The influence of estrogen may contribute to the development of LTS in women during the third through fifth decades Dedo & Catten, 2001; Poetker et al., 2006; Valdez & Shapshay, 2002). The project goal …

The Society For Immunotherapy Of Cancer Perspective On Regulation Of Interleukin-6 Signaling In Covid-19-Related Systemic Inflammatory Response, Fernanda I. Arnaldez, Steven J. O'Day, Charles G. Drake, Bernard A Fox, Bingqing Fu, Walter Urba, Vincenzo Montesarchio, Jeffrey S. Weber, Haiming Wei, Jon M. Wigginton, Paolo Antonio Ascierto

Articles, Abstracts, and Reports

The pandemic caused by the novel coronavirus SARS-CoV-2 has placed an unprecedented burden on healthcare systems around the world. In patients who experience severe disease, acute respiratory distress is often accompanied by a pathological immune reaction, sometimes referred to as ‘cytokine storm’. One hallmark feature of the profound inflammatory state seen in patients with COVID-19 who succumb to pneumonia and hypoxia is marked elevation of serum cytokines, especially interferon gamma, tumor necrosis factor alpha, interleukin 17 (IL-17), interleukin 8 (IL-8) and interleukin 6 (IL-6). Initial experience from the outbreaks in Italy, China and the USA has anecdotally demonstrated improved outcomes …

A Goldenbraid Cloning System For Synthetic Biology In Social Amoebae, Peter Kundert, Alejandro Sarrion-Perdigones, Yezabel Gonzalez, Mariko Katoh-Kurasawa, Shigenori Hirose, Peter Lehmann, Koen J T Venken, Gad Shaulsky

Faculty, Staff and Students Publications

GoldenBraid is a rapid, modular, and robust cloning system used to assemble and combine genetic elements. Dictyostelium amoebae represent an intriguing synthetic biological chassis with tractable applications in development, chemotaxis, bacteria-host interactions, and allorecognition. We present GoldenBraid as a synthetic biological framework for Dictyostelium, including a library of 250 DNA parts and assemblies and a proof-of-concept strain that illustrates cAMP-chemotaxis with four fluorescent reporters coded by one plasmid.

Immunity And Field Efficacy Of Type 2-Containing Polio Vaccines After Cessation Of Trivalent Oral Polio Vaccine: A Population-Based Serological Study In Pakistan, Arie Voorman, Atif Habib, Imtiaz Hussain, Rana Muhammad Safdar, Jamal A. Ahmed, William C. Weldon, Imran Ahmed, Muhammad Umer, Jeffrey Partridge, Sajid Bashir Soofi

Department of Paediatrics and Child Health

Background: In Pakistan and other countries using oral polio vaccine (OPV), immunity to type 2 poliovirus is now maintained by a single dose of inactivated polio vaccine (IPV) in routine immunization, supplemented in outbreak settings by monovalent OPV type 2 (mOPV2) and IPV. While well-studied in clinical trials, population protection against poliovirus type 2 achieved in routine and outbreak settings is generally unknown.
Methods: We conducted two phases of a population-based serological survey of 7940 children aged 6-11 months old, between November 2016 and October 2017 from 13 polio high-risk locations in Pakistan.
Results: Type 2 seroprevalence was 50% among …

How Can We Stop Cancer?, Joseph R. Current

The Review: A Journal of Undergraduate Student Research

Cancer is a disease that humans have been struggling to combat for centuries. It originates from the accumulation of several mutations over the life of a cell that causes it to evade cell death and multiply rapidly. It can affect any tissue in the body and can spread to other parts of the body through metastasis. Cancer comes in numerous shapes and sizes with different levels of aggression, growth speeds, and health risks. Many treatments for cancer exist today, three of the most popular being surgery, chemotherapy, and radiation therapy, which can be used in combinations with other treatments to …