Medicine and Health Sciences Commons^™

Stereotactic Mr-Guided On-Table Adaptive Radiation Therapy (Smart) For Borderline Resectable And Locally Advanced Pancreatic Cancer: A Multi-Center, Open-Label Phase 2 Study, Michael Chuong, Percy Lee, Daniel Low, Joshua Kim, Kathryn Mittauer, Michael Bassetti, Carri Glide-Hurst, Ann Raldow, Yingli Yang, Lorraine Portelance, Kyle Padgett, Bassem Zaki, Rongxiao Zhang, Hyun Kim, Lauren Henke, Alex Price, Joseph Mancias, Christopher Williams, John Ng, Ryan Pennell, M Raphael Pfeffer, Daphne Levin, Adam Mueller, Karen Mooney, Patrick Kelly, Amish Shah, Luca Boldrini, Lorenzo Placidi, Martin Fuss, Parag Jitendra Parikh

Department of Radiation Oncology Faculty Papers

BACKGROUND AND PURPOSE: Radiation dose escalation may improve local control (LC) and overall survival (OS) in select pancreatic ductal adenocarcinoma (PDAC) patients. We prospectively evaluated the safety and efficacy of ablative stereotactic magnetic resonance (MR)-guided adaptive radiation therapy (SMART) for borderline resectable (BRPC) and locally advanced pancreas cancer (LAPC). The primary endpoint of acute grade ≥ 3 gastrointestinal (GI) toxicity definitely related to SMART was previously published with median follow-up (FU) 8.8 months from SMART. We now present more mature outcomes including OS and late toxicity.

MATERIALS AND METHODS: This prospective, multi-center, single-arm open-label phase 2 trial (NCT03621644) enrolled 136 …

Rapidiron Trial Follow-Up Study - The Rapidiron-Kids Study: Protocol Of A Prospective Observational Follow-Up Study, Richard Derman, Roopa Bellad, Mrutyunjaya Bellad, Jesse Bradford-Rogers, Michael Georgieff, Zubair Aghai, Simal Thind, Michael Auerbach, Rupsa Boelig, Benjamin Leiby, Vanessa Short, S. Yogeshkumar, Umesh Charantimath, Manjunath Somannavar, Ashalata Mallapur, Ramesh Pol, Umesh Ramadurg, Radha Sangavi, Basavaraj Peerapur, Nasima Banu, Praveen Patil, Amaresh Patil, Subarna Roy, Phaniraj Vastrad, Dennis Wallace, Hemang Shah, Shivaprasad Goudar

Global Health Articles

BACKGROUND: Anemia is a worldwide problem with iron deficiency being the most common cause. When anemia occurs in pregnancy, it increases the risk of adverse maternal, fetal, and postnatal outcomes. It induces preterm births and low birth weight (LBW) deliveries, long-term neurodevelopmental sequelae, and an increased risk of earlier onset of postnatal iron deficiency. Anemia rates are among the highest in South Asia, and India's National Family Health Survey (NFHS-5) for 2019-2021 indicated that over half of pregnant women, and more than 65% of children, in the country are classified as anemic (Sciences IIfP, National Family Health Survey-5, 2019-21, India …

The 50 Most Cited Papers On Rugby Since 2000 Reveal A Focus Primarily On Strength And Conditioning In Elite Male Players, Katherine J. Hunzinger, Eric Schussler

Department of Exercise Science Faculty Papers

We sought to conduct a bibliometric analysis and review of the most cited publications relating to rugby since 2000 in order to identify topics of interest and those that warrant further investigations. Clarivate Web of Science database was used to perform a literature search using the search term "rugby." The top 200 papers by citation count were extracted and reviewed for the inclusion criteria: all subjects were rugby players. The top 50 manuscripts were included for analysis of author, publication year, country of lead authors, institution, journal name and impact factor, topic, participant sex, and level of rugby. The total …

The Pharmacological Deprescription In Elderly Patients, Chelsey Ali, Daniel Huang, Charlene Tugwete, Stefano Del Canale, Vittorio Maio

College of Population Health Faculty Papers

No abstract provided.

Extended-Synaptotagmin-1 And -2 Control T Cell Signaling And Function, Nathalia Benavides, Claudio G. Giraudo

Department of Microbiology and Immunology Faculty Papers

Upon T-cell activation, the levels of the secondary messenger diacylglycerol (DAG) at the plasma membrane need to be controlled to ensure appropriate T-cell receptor signaling and T-cell functions. Extended-Synaptotagmins (E-Syts) are a family of inter-organelle lipid transport proteins that bridge the endoplasmic reticulum and the plasma membrane. In this study, we identify a novel regulatory mechanism of DAG-mediated signaling for T-cell effector functions based on E-Syt proteins. We demonstrate that E-Syts downmodulate T-cell receptor signaling, T-cell-mediated cytotoxicity, degranulation, and cytokine production by reducing plasma membrane levels of DAG. Mechanistically, E-Syt2 predominantly modulates DAG levels at the plasma membrane in resting-state …

Needle Biopsy Accelerates Pro-Metastatic Changes And Systemic Dissemination In Breast Cancer: Implications For Mortality By Surgery Delay, Hiroyasu Kameyama, Priya Dondapati, Reese Simmons, Macall Leslie, John Langenheim, Yunguang Sun, Misung Yi, Aubrey Rottschaefer, Rashmi Pathak, Shreya Nuguri, Kar-Ming Fung, Shirng-Wern Tsaih, Inna Chervoneva, Hallgeir Rui, Takemi Tanaka

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

ncreased breast cancer (BC) mortality risk posed by delayed surgical resection of tumor after diagnosis is a growing concern, yet the underlying mechanisms remain unknown. Our cohort analyses of early-stage BC patients reveal the emergence of a significantly rising mortality risk when the biopsy-to-surgery interval was extended beyond 53 days. Additionally, histology of post-biopsy tumors shows prolonged retention of a metastasis-permissive wound stroma dominated by M2-like macrophages capable of promoting cancer cell epithelial-to-mesenchymal transition and angiogenesis. We show that needle biopsy promotes systemic dissemination of cancer cells through a mechanism of sustained activation of the COX-2/PGE₂/EP2 feedforward loop, …

Treatment Response Of Gingival Squamous-Cell Carcinoma To Palliative Intent Immunotherapy, Natalia Trehan, Angelina Debbas, Mykaihla Sternick, Jennifer Johnson, James Gates

Department of Medical Oncology Faculty Papers

The use of PD-1 immune checkpoint inhibitor medications has become a common practice in the treatment of recurrent and metastatic head and neck squamous-cell carcinomas. Success in this setting has led to the investigation of their efficacy in locally advanced cases as a part of first-line therapy. In this report, we detail the treatment response to palliative intent immunotherapy of three geriatric patients with mandibular gingival squamous-cell carcinoma who decided against surgical intervention. Patient #1 was treated with pembrolizumab, a PD-1 inhibitor, and displayed complete clinical and radiologic response of the gingival mass after three months of treatment, which is …

Interprofessional Perspectives On School-Wide Mental Health Interventions For Enhancing Resilience In Adolescents, Danielle Costanzo, Ms, Otr/L

Post-Professional Occupational Therapy Doctorate Culminating Presentations

Introduction: There is a significant crisis in adolescent mental health (American Academy of Pediatrics, 2021; Radhakrishnan et al., 2022) that have been compounded by traumatic experiences experienced during the COVID-19 pandemic (Substance Abuse and Mental Health Services Administration, 2022) and widespread fear of violence in schools (Silver et al., 2021). The crisis and resulting vulnerability has led to a dire need to focus on overcoming mental health challenges and moving forward in the face of adversity, which calls for a focus on resilience to promote overall life outcomes (Fenwick-Smith et al., 2019; Ijadi-Maghsoodi et al., 2022; Steiner et al., 2019). …

New Jersey’S Web-Based Parent-Engaged Developmental Monitoring Information: Mapping And Critical Appraisal, Danielle Catalano, Ms, Otr/L

Post-Professional Occupational Therapy Doctorate Culminating Presentations

Caregivers use web-based information to make decisions about their children’s health and development. Due to the state’s high prevalence of developmental delays, New Jersey has developed numerous web-based early childhood initiatives to promote parent engagement. However, the quality of those resources is unknown. This critical appraisal evaluated the quality, readability, and accessibility of New Jersey’s commonly used web-based information on parent-engaged developmental monitoring in children aged 0-3. A systematic web search yielded 112 results. Thirty-six webpages were reviewed by three independent reviewers using four standardized assessment tools. Reviewers found that most information was written at a twelfth-grade reading level, two …

Evaluating Hope: A Trauma-Informed Sensory Training For Early Childhood Educators, Andrea Houtras, Otd, Otr/L

Post-Professional Occupational Therapy Doctorate Culminating Presentations

Introduction: Adverse childhood experiences create challenges in sensory integration (Perry, 2006) impacting preschoolers’ participation and occupational performance (May-Benson, 2016). Professional development in trauma-informed sensory training is essential to support early childhood educators working with this population (Loomis, 2018; Perry, 2006).

Objectives: To develop a trauma-informed sensory training and evaluate its validity and usefulness for early childhood educators.

Methods: We used a modified Delphi method to evaluate the training’s adherence to Ayres Sensory Integration® and trauma-informed care principles of practice and usefulness for early childhood educators. A convenience sample of three expert groups reviewed the training and completed surveys to …

Drug-Free Noninvasive Thermal Nerve Block: Validation Of Sham Devices, Michael Fishman, Ahish Chitneni, Alaa Abd-Elsayed, Samuel Grodofsky, Ashley Scherer, Brendan Schetzner, Malvina Klusek, Stephen Popielarski, Stephen Meloni, Steven Falowski, Philip Kim, Konstantin Slavin, Stephen Silberstein

Department of Jefferson Headache Center Papers and Presentations

Headache is a leading cause of disability and suffering. One major challenge in developing device treatments is demonstrating their efficacy given devices' often-high placebo rate. This paper reviews the importance of validating sham devices as part of finalizing the design for larger-scale prospective randomized controlled trials in patients with chronic headache as well as the results of a prospective, single-blind trial to validate two potential sham noninvasive thermal nerve block devices. Study participants were trained to self-administer thermal nerve block treatment using sham devices in an office visit. Two different sham systems with different temperature profiles were assessed. Devices were …

Pkcε Activator Protects Hippocampal Microvascular Disruption And Memory Defect In 3×Tg-Alzheimer's Disease Mice With Cerebral Microinfarcts, Huaixing Wang, Zongxiu Zhang, Jarin Hongpaisan

Center for Translational Medicine Faculty Papers

BACKGROUND: Current evidence suggests that microvessel disease is involved in Alzheimer's disease (AD). Cerebrovascular disease correlates with cardiovascular disease and is complicated in ≈40% of AD patients. The protein kinase C (PKC) ε activator DCPLA can stimulate human antigen (Hu) R that prevents degradation and promotes the translation of mitochondrial Mn-superoxide dismutase (MnSOD) and vascular endothelial growth factor-A (VEGF) mRNAs.

METHODS: To induce brain microinfarcts, we injected triple transgenic (3×Tg) and wild-type (WT) control mice with microbeads (20 μm caliber) into common carotid arteries, with or without the DCPLA-ME (methyl-ester) for 2 weeks. After water maze training, mice at 16 …

Utility Of T-Cell Immunosequencing In Distinguishing Mycosis Fungoides Progression From Treatment Related Cutaneous Adverse Events, Safiyyah Bhatti, Daniel Joffe, Lauren Banner, Sahithi Talasila, Jenna Mandel, Jason Lee, Pierluigi Porcu, Neda Nikbakht

Department of Dermatology and Cutaneous Biology Faculty Papers

Cutaneous adverse events of both topical and systemic drugs in patients with mycosis fungoides (MF) present a diagnostic challenge as it is often difficult to distinguish drug associated rash from disease progression in the skin. Mogamulizumab and mechlorethamine gel are approved treatments for MF, both of which can cause treatment related cutaneous adverse events. It can often be challenging to distinguish mogamulizumab associated rash (MAR) and mechlorethamine gel associated hypersensitivity dermatitis from MF progression both clinically and histologically. High-throughput sequencing (HTS) of the T-cell receptor (TCR), also known as immunosequencing, can be used to assess T-cell clonality to support a …

Implementation Of Multipronged Approach In Patients With Chest Trauma Reduces Vap And Unplanned Admission To The Icu, Julie Donnelly, Msn, Rn, Trcn, Kristen Firely, Msn, Rn, Nicole Olszewski, Bsn, Rn, Jessica Byrne, Msn, Rn-Bc, Tiffani Stanley, Cstr, Joshua A. Marks, Md, Facs, Fccm, George Koenig

Department of Surgery Posters

Problem

The incidence of pulmonary complications in trauma patients with chest trauma has been reported to be as high as 49% (Ruibel L, 2022). However, all trauma patients are at risk for developing pulmonary complications due to a multitude of factors some pre-existing while others injury related sequela. Within our institution, we observed an increase in pulmonary complications through review of our TQIP (Spring 2020) and state registry data.

A Review Of Slipping Rib Syndrome: Diagnostic And Treatment Updates To A Rare And Challenging Problem, Isheeta Madeka, Sneha Alaparthi, Marisa Moreta, Shawn Peterson, Jeffrey Mojica, Johanes Roedl, Olugbenga Okusanya

Department of Surgery Faculty Papers

Slipping rib syndrome (SRS) is a disorder that occurs when one or more of the eighth through tenth ribs become abnormally mobile. SRS is a poorly understood condition leading to a significant delay in diagnosis and therapeutic management. History and a physical exam are usually sufficient for a diagnosis of SRS. The utility of dynamic ultrasounds has also been studied as a useful diagnostic tool. Multiple surgical techniques for SRS have been described within the literature. Cartilage rib excision (CRE) has been the most common technique utilized. However, the literature has shown a high rate of recurrence and associated risks …

Iron Oxide-Coupled Crispr-Ncas9-Based Genome Editing Assessment In Mucopolysaccharidosis Iva Mice, Andrés Leal, Betul Celik, Nidhi Fnu, Shaukat Khan, Shunji Tomatsu

Department of Pediatrics Faculty Papers

Mucopolysaccharidosis (MPS) IVA is a lysosomal storage disorder caused by mutations in the GALNS gene that leads to the lysosomal accumulation of keratan sulfate (KS) and chondroitin 6-sulfate, causing skeletal dysplasia and cardiopulmonary complications. Current enzyme replacement therapy does not impact the bone manifestation of the disease, supporting that new therapeutic alternatives are required. We previously demonstrated the suitability of the CRISPR-nCas9 system to rescue the phenotype of human MPS IVA fibroblasts using iron oxide nanoparticles (IONPs) as non-viral vectors. Here, we have extended this strategy to an MPS IVA mouse model by inserting the human GALNS cDNA into the …

Evaluating The Efficacy Of A Thermoresponsive Hydrogel For Delivering Anti-Collagen Antibodies To Reduce Posttraumatic Scarring In Orthopedic Tissues., Andrzej Steplewski, Jolanta Fertala, Lan Cheng, Mark Wang, Michael Rivlin, Pedro K Beredjiklian, Andrzej Fertala

Department of Orthopaedic Surgery Faculty Papers

Excessive posttraumatic scarring in orthopedic tissues, such as joint capsules, ligaments, tendons, muscles, and peripheral nerves, presents a significant medical problem, resulting in pain, restricted joint mobility, and impaired musculoskeletal function. Current treatments for excessive scarring are often ineffective and require the surgical removal of fibrotic tissue, which can aggravate the problem. The primary component of orthopedic scars is collagen I-rich fibrils. Our research team has developed a monoclonal anti-collagen antibody (ACA) that alleviates posttraumatic scarring by inhibiting collagen fibril formation. We previously established the safety and efficacy of ACA in a rabbit-based arthrofibrosis model. In this study, we evaluate …

Master Transcription Factor Reprogramming Unleashes Selective Translation Promoting Castration Resistance And Immune Evasion In Lethal Prostate Cancer, Sandra Santasusagna, Shijia Zhu, Vijayakumar Jawalagatti, Marc Carceles-Cordon, Adam Ertel, Saioa Garcia-Longarte, Won-Min Song, Naoto Fujiwara, Peiyao Li, Isabel Mendizabal, Daniel P. Petrylak, William Kevin Kelly, E. Premkumar Reddy, Liguo Wang, Matthew J. Schiewer, Amaia Lujambio, Jeffrey Karnes, Karen E. Knudsen, Carlos Cordon-Cardo, Haidong Dong, Haojie Huang, Arkaitz Carracedo, Yujin Hoshida, Veronica Rodriguez-Bravo, Josep Domingo-Domenech

Department of Medical Oncology Faculty Papers

Signaling rewiring allows tumors to survive therapy. Here we show that the decrease of the master regulator microphthalmia transcription factor (MITF) in lethal prostate cancer unleashes eukaryotic initiation factor 3B (eIF3B)-dependent translation reprogramming of key mRNAs conferring resistance to androgen deprivation therapy (ADT) and promoting immune evasion. Mechanistically, MITF represses through direct promoter binding eIF3B, which in turn regulates the translation of specific mRNAs. Genome-wide eIF3B enhanced cross-linking immunoprecipitation sequencing (eCLIP-seq) showed specialized binding to a UC-rich motif present in subsets of 5' untranslated regions. Indeed, translation of the androgen receptor and major histocompatibility complex I (MHC-I) through this motif …

Xtx101, A Tumor-Activated, Fc-Enhanced Anti-Ctla-4 Monoclonal Antibody, Demonstrates Tumor-Growth Inhibition And Tumor-Selective Pharmacodynamics In Mouse Models Of Cancer, Kurt A. Jenkins, Miso Park, Magali Pederzoli-Ribeil, Ugur Eskiocak, Parker Johnson, Wilson Guzman, Megan Mclaughlin, Deborah Moore-Lai, Caitlin O'Toole, Zhen Liu, Benjamin Nicholson, Veronica Flesch, Huawei Qiu, Tim Clackson, Ronan C. O'Hagan, Ulrich Rodeck, Margaret Karow, Jennifer O'Neil, John C. Williams

Department of Dermatology and Cutaneous Biology Faculty Papers

INTRODUCTION: The clinical benefit of the anti-CTLA-4 monoclonal antibody (mAb) ipilimumab has been well established but limited by immune-related adverse events, especially when ipilimumab is used in combination with anti-PD-(L)1 mAb therapy. To overcome these limitations, we have developed XTX101, a tumor-activated, Fc-enhanced anti-CTLA-4 mAb.

METHODS: XTX101 consists of an anti-human CTLA-4 mAb covalently linked to masking peptides that block the complementarity-determining regions, thereby minimizing the mAb binding to CTLA-4. The masking peptides are designed to be released by proteases that are typically dysregulated within the tumor microenvironment (TME), resulting in activation of XTX101 intratumorally. Mutations within the Fc region …

The Importance Of Triple Panel Testing For Hepatitis B And The Burden Of Isolated Anti-Hepatitis B Core Antibodies Within A Community Sample, Catherine Freeland, Vivek Sreepathi, Richard Hass, Jonathan Fenkel, Jessie Torgersen, Kenneth Rothstein, Chari Cohen, Robert Gish

College of Population Health Faculty Papers

Within the United States (US), 2.4 million individuals are living with chronic hepatitis B, but less than 20% are diagnosed. Isolated anti-hepatitis B core (iAHBc) antibodies indicate serology in an individual that is positive for anti-HBc antibodies, while negative for surface antigen (HBsAg) and surface antibodies (anti-HBs). A result of iAHBc could indicate a chronic occult bloodstream infection, necessitating further testing. This study assesses the prevalence and risk factors associated with anti-HBc and iAHBc within community high-risk screening in Greater Philadelphia. Participants (n = 177) were screened for HBsAg, anti-HBs, and anti-HBc during community screening events in 2022. Chi-square tables …

Interleukin 31 Receptor Α Promotes Smooth Muscle Cell Contraction And Airway Hyperresponsiveness In Asthma, Santhoshi Akkenepally, Dan Yombo, Sanjana Yerubandi, Geereddy Bhanuprakash Reddy, Deepak Deshpande, Francis Mccormack, Satish Madala

Center for Translational Medicine Faculty Papers

Asthma is a chronic inflammatory airway disease characterized by airway hyperresponsiveness (AHR), inflammation, and goblet cell hyperplasia. Multiple cytokines, including IFNγ, IL-4, and IL-13 are associated with asthma; however, the mechanisms underlying the effects of these cytokines remain unclear. Here, we report a significant increase in the expression of IL-31RA, but not its cognate ligand IL-31, in mouse models of allergic asthma. In support of this, IFNγ, IL-4, and IL-13 upregulated IL-31RA but not IL-31 in both human and mice primary airway smooth muscle cells (ASMC) isolated from the airways of murine and human lungs. Importantly, the loss of IL-31RA …

Microstructural Alterations Of Major Thalamic Nuclei In The Chronic Pediatric Spinal Cord Injured Population, K. Kang, K. Fleming, A. Sathe, J. Muller, J. Harrop, D. Middleton, J. Heller, A. Sharan, F. Mohamed, L. Krisa, M. Alizadeh

Department of Radiology Faculty Papers

BACKGROUND: The brain undergoes reorganization following spinal cord injury (SCI), but little is known about how the thalamus is affected in pediatric SCIs.

PURPOSE: To characterize microstructural alterations in the thalamus after SCI with diffusion tensor imaging (DTI) metrics.

METHODS: 18 pediatric participants with chronic SCI (8-20 years) were stratified using the American Spinal Injury Association Impairment Scale (AIS) into groups: A, B, and C/D. DTI of the brain used a 3 T Siemens Verio MRI using the parameters: 20 directions, number of averages = 3, b = 1000 s/mm

DATA ANALYSIS: DTI metrics were acquired by superimposing the AAL3 …

Sirtuin 6 Activation Rescues The Age-Related Decline In Dna Damage Repair In Primary Human Chondrocytes, Michaela E. Copp, Jacqueline Shine, Hannon L. Brown, Kirti R. Nimmala, Oliver B. Hansen, Susan Chubinskaya, John A. Collins, Richard F. Loeser, Brian O. Diekman

Department of Orthopaedic Surgery Faculty Papers

While advanced age is widely recognized as the greatest risk factor for osteoarthritis (OA), the biological mechanisms behind this connection remain unclear. Previous work has demonstrated that chondrocytes from older cadaveric donors have elevated levels of DNA damage as compared to chondrocytes from younger donors. The purpose of this study was to determine whether a decline in DNA repair efficiency is one explanation for the accumulation of DNA damage with age, and to quantify the improvement in repair with activation of Sirtuin 6 (SIRT6). After acute damage with irradiation, DNA repair was shown to be more efficient in chondrocytes from …

Diet And Nutrition In Inflammatory Bowel Disease: A Review Of The Literature, Scott Manski, Nicholas Noverati, Tatiana Policarpo, Emily Rubin, Raina Shivashankar

Division of Gastroenterology and Hepatology Faculty Papers

Diet is thought to contribute to the development of inflammatory bowel disease (IBD) and may act as a mediator of inflammation in patients with IBD. Patients commonly associate their diet with symptoms and inquire about dietary modifications to manage their IBD. Without clinical guidelines and well-established nutritional data, healthcare providers managing patients with IBD may find it difficult to provide recommendations. Strong evidence for enteral nutrition, particularly in the pediatric population, has been established in Crohn's disease (CD) as a therapeutic option. Enteral nutrition may also serve as an adjunct to an exclusion diet. Recent studies such as the randomized …

Identification Of Ct-Based Non-Invasive Radiomic Biomarkers For Overall Survival Prediction In Oral Cavity Squamous Cell Carcinoma, Xiao Ling, Gregory S. Alexander, Jason Molitoris, Jinhyuk Choi, Lisa Schumaker, Ranee Mehra, Daria A. Gaykalova, Lei Ren

Department of Radiation Oncology Faculty Papers

This study addresses the limited non-invasive tools for Oral Cavity Squamous Cell Carcinoma (OSCC) survival prediction by identifying Computed Tomography (CT)-based biomarkers to improve prognosis prediction. A retrospective analysis was conducted on data from 149 OSCC patients, including CT radiomics and clinical information. An ensemble approach involving correlation analysis, score screening, and the Sparse-L1 algorithm was used to select functional features, which were then used to build Cox Proportional Hazards models (CPH). Our CPH achieved a 0.70 concordance index in testing. The model identified two CT-based radiomics features, Gradient-Neighboring-Gray-Tone-Difference-Matrix-Strength (GNS) and normalized-Wavelet-LLL-Gray-Level-Dependence-Matrix-Large-Dependence-High-Gray-Level-Emphasis (HLE), as well as stage and alcohol usage, …

A Phenotypically Robust Model Of Spinal And Bulbar Muscular Atrophy In Drosophila, Kristin Richardson, Medha Sengupta, Alyson Sujkowski, Kozeta Libohova, Autumn C. Harris, Robert Wessells, Diane E. Merry, Sokol V. Todi

Department of Biochemistry and Molecular Biology Faculty Papers

Spinal and bulbar muscular atrophy (SBMA) is an X-linked disorder that affects males who inherit the androgen receptor (AR) gene with an abnormal CAG triplet repeat expansion. The resulting protein contains an elongated polyglutamine (polyQ) tract and causes motor neuron degeneration in an androgen-dependent manner. The precise molecular sequelae of SBMA are unclear. To assist with its investigation and the identification of therapeutic options, we report here a new model of SBMA in Drosophila melanogaster. We generated transgenic flies that express the full-length, human AR with a wild-type or pathogenic polyQ repeat. Each transgene is inserted into the same safe …

Novel Urine Cell-Free Dna Methylation Markers For Hepatocellular Carcinoma, Selena Lin, Wei Xia, Amy Kim, Dion Chen, Shelby Schleyer, Lin Choi, Zhili Wang, James Hamilton, Harry Luu, Hie-Won Hann, Ting-Tsung Chang, Chi-Tan Hu, Abashai Woodard, Terence Gade, Ying-Hsiu Su

Division of Gastroenterology and Hepatology Faculty Papers

An optimized hepatocellular carcinoma (HCC)-targeted methylation next generation sequencing assay was developed to discover HCC-associated methylation markers directly from urine for HCC screening. Urine cell-free DNA (ucfDNA) isolated from a discovery cohort of 31 non-HCC and 30 HCC was used for biomarker discovery, identifying 29 genes with differentially methylated regions (DMRs). Methylation-specific qPCR (MSqPCR) assays were developed to verify the selected DMRs corresponding to 8 genes (GRASP, CCND2, HOXA9, BMP4, VIM, EMX1, SFRP1, and ECE). Using archived ucfDNA, methylation of GRASP, HOXA9, BMP4, and ECE1, were found to be significantly different (p < 0.05) between HCC and non-HCC patients. The four markers together with previously reported GSTP1 and RASSF1A markers were assessed as a 6-marker panel in an independent training cohort of 87 non-HCC and 78 HCC using logistic regression modeling. AUROC of 0.908 (95% CI, 0.8656-0.9252) was identified for the 6-marker panel with AFP, which was significantly higher than AFP-alone (AUROC 0.841 (95% CI, 0.778-0.904), p = 0.0026). Applying backward selection method, a 4-marker panel was found to exhibit similar performance to the 6-marker panel with AFP having 80% sensitivity compared to 29.5% by AFP-alone at a specificity of 85%. This study supports the potential use of methylated transrenal ucfDNA for HCC screening.

Fluorescent Peptide For Detecting Factor Xiiia Activity And Fibrin In Whole Blood Clots Forming Under Flow, Yue Liu, Jennifer Crossen, Timothy J. Stalker, Scott L. Diamond

Cardeza Foundation for Hematologic Research

Background

During clotting, thrombin generates fibrin monomers and activates plasma-derived transglutaminase factor (F) XIIIa; collagen and thrombin-activated platelets offer thrombin-independent cellular FXIIIa (cFXIIIa) for clotting. Detecting fibrin on collagen and tissue factor surfaces in whole blood clotting typically uses complex reagents like fluorescent fibrinogen or antifibrin antibody.

Objectives

We want to test whether the peptide using the α2- antiplasmin crosslinking mechanism by FXIIIa is a useful tool in both monitoring FXIIIa activity, and visualize and monitor fibrin formation, deposition, and extent of crosslinking within fibrin structures in whole blood clots formed under flow.

Methods

We tested a fluorescent peptide derived …

Negative Pressure Wound Therapy For Complex Oral Wounds, Mykaihla Sternick, James Gates, Allen Champion, Andrew Yampolsky

Department of Oral and Maxillofacial Surgery Faculty Papers

Negative pressure wound therapy provides a nonsurgical treatment option for many types of complex wounds. This therapy utilizes the vacuum-assisted closure device, which decreases air pressure, removes fluid that accumulates within the wound, and aids to facilitate changes that promote healing. Despite the increased use of negative pressure wound therapy in the head and neck region, there is substantially less data available on the management of transoral vacuum-assisted wound closure. Herein, we present a case of a novel approach for the creation and use of a transoral wound vac for a patient with a refractory orocutaneous wound in the setting …

Simultaneous Detection Of Methylation And Genetic Variations Of Bcr-Abl1 Gene By Nanopore Cas9-Targeted Sequencing, Shuilian Xie, Ying Yang, Junjie Zhang, Menglin Zhu, Wang Li, Mengting Li, Yijian Chen, Hailiang Li, Weidan Lun, Weelic Chong, Shaogui Wan

Department of Medicine Faculty Papers

No abstract provided.