Digital Commons Network^™

Utility Of Clinical Next Generation Sequencing Tests In Kit/Pdgfra/Sdh Wild-Type Gastrointestinal Stromal Tumors, Ryan A Denu, Cissimol P Joseph, Elizabeth S Urquiola, Precious S Byrd, Richard K Yang, Ravin Ratan, Maria Alejandra Zarzour, Anthony P Conley, Dejka M Araujo, Vinod Ravi, Elise F Nassif Haddad, Michael S Nakazawa, Shreyaskumar Patel, Wei-Lien Wang, Alexander J Lazar, Neeta Somaiah

Faculty, Staff and Student Publications

Objective: The vast majority of gastrointestinal stromal tumors (GISTs) are driven by activating mutations in KIT, PDGFRA, or components of the succinate dehydrogenase (SDH) complex (SDHA, SDHB, SDHC, and SDHD genes). A small fraction of GISTs lack alterations in KIT, PDGFRA, and SDH. We aimed to further characterize the clinical and genomic characteristics of these so-called "triple-negative" GISTs.

Methods: We extracted clinical and genomic data from patients seen at MD Anderson Cancer Center with a diagnosis of GIST and available clinical next generation sequencing data to identify "triple-negative" patients.

Results: Of …

Examining The Effect Of Genes On Depression As Mediated By Smoking And Modified By Sex, Kirsten Voorhies, Julian Hecker, Sanghun Lee, Georg Hahn, Dmitry Prokopenko, Merry-Lynn Mcdonald, Alexander C Wu, Ann Wu, John E Hokanson, Michael H Cho, Christoph Lange, Karin F Hoth, Sharon M Lutz

Faculty, Staff and Student Publications

Depression is heritable, differs by sex, and has environmental risk factors such as cigarette smoking. However, the effect of single nucleotide polymorphisms (SNPs) on depression through cigarette smoking and the role of sex is unclear. In order to examine the association of SNPs with depression and smoking in the UK Biobank with replication in the COPDGene study, we used counterfactual-based mediation analysis to test the indirect or mediated effect of SNPs on broad depression through the log of pack-years of cigarette smoking, adjusting for age, sex, current smoking status, and genetic ancestry (via principal components). In secondary analyses, we adjusted …

Histone Proteoform Analysis Reveals Epigenetic Changes In Adult Mouse Brown Adipose Tissue In Response To Cold Stress, Bethany C Taylor, Loic H Steinthal, Michelle Dias, Hari Krishna Yalamanchili, Scott A Ochsner, Gladys E Zapata, Nitesh R Mehta, Neil J Mckenna, Nicolas L Young, Alli M Nuotio-Antar

Faculty, Staff and Students Publications

BACKGROUND: Regulation of the thermogenic response by brown adipose tissue (BAT) is an important component of energy homeostasis with implications for the treatment of obesity and diabetes. Our preliminary analyses of RNA-Seq data uncovered many nodes representing epigenetic modifiers that are altered in BAT in response to chronic thermogenic activation. Thus, we hypothesized that chronic thermogenic activation broadly alters epigenetic modifications of DNA and histones in BAT.

RESULTS: Motivated to understand how BAT function is regulated epigenetically, we developed a novel method for the first-ever unbiased top-down proteomic quantitation of histone modifications in BAT and validated our results with a …

New Insights Into Macrophage Polarization And Its Prognostic Role In Patients With Colorectal Cancer Liver Metastasis, Isha Khanduri, Harufumi Maki, Anuj Verma, Riham Katkhuda, Gayathri Anandappa, Renganayaki Pandurengan, Shanyu Zhang, Alicia Mejia, Zhimin Tong, Luisa M Solis Soto, Akshaya Jadhav, Ignacio I Wistuba, David Menter, Scott Kopetz, Edwin R Parra, Jean-Nicolas Vauthey, Dipen M Maru

Faculty, Staff and Student Publications

Background: As liver metastasis is the most common cause of mortality in patients with colorectal cancer, studying colorectal cancer liver metastasis (CLM) microenvironment is essential for improved understanding of tumor biology and to identify novel therapeutic targets.

Methods: We used a multiplex immunofluorescence platform to study tumor associated macrophage (TAM) polarization and adaptive T cell subtypes in tumor samples from 105 CLM patients (49 without and 56 with preoperative chemotherapy).

Results: CLM exhibited M2 macrophage polarization, and helper T cells were the prevalent adaptive T cell subtype. The density of total, M2 and TGFβ-expressing macrophages, and regulatory T cells was …

Simulation And Self-Efficacy In The Student Registered Nurse Anesthetist: A Quantitative, Causal-Comparative Study, Joseph Craig Kiesznowski

Doctoral Dissertations and Projects

The purpose of this quantitative, causal-comparative study was to determine if simulation training causes a significant increase in clinical self-efficacy in Student Registered Nurse Anesthetists. Simulation training in healthcare has been found to improve patient safety and has become a major tenet of nurse anesthetist education. Self-efficacy has been shown to correlate with improved clinical performance. This study builds on the research involving simulation training and clinical self-efficacy in the SRNA population. A convenience sample of SRNAs was taken from 49 different graduate nurse anesthesia programs across 13 different states. The Schwarzer and Jerusalem General Self-efficacy scale was used to …

Vegetation Dieback In The Mississippi River Delta Triggered By Acute Drought And Chronic Relative Sea-Level Rise, Tracy Elsey-Quirk, Austin Lynn, Michael Derek Jacobs, Rodrigo Diaz, James T Cronin, Lixia Wang, Haosheng Huang, Dubravko Justic

Faculty, Staff and Student Publications

Vegetation dieback and recovery may be dependent on the interplay between infrequent acute disturbances and underlying chronic stresses. Coastal wetlands are vulnerable to the chronic stress of sea-level rise, which may affect their susceptibility to acute disturbance events. Here, we show that a large-scale vegetation dieback in the Mississippi River Delta was precipitated by salt-water incursion during an extreme drought in the summer of 2012 and was most severe in areas exposed to greater flooding. Using 16 years of data (2007-2022) from a coastwide network of monitoring stations, we show that the impacts of the dieback lasted five years and …

Reproductive Justice In Mississippi: A Call For Reform And Acknowledgement, Andie Udziela

Honors Theses

In this thesis, I apply the values of the Reproductive Justice Movement to reproductive healthcare resources in Mississippi to advocate for reproductive policy reform. I begin by navigating the historic racial discrimination in gynecology and how it manifested in Mississippi. Dr Sim’s abusive experimentation on Anarcha, Betsy, and Lucy depict how Anti-Black racism took root in gynecology and obstetrics and was later expanded on by the eugenic goals of white supremacy and the feminist movement through Margaret Sanger and the Mississippi Appendectomy. Then I discuss the current availability of reproductive care in Mississippi to low-income individuals to emphasize socioeconomic and …

Chromosomal 3q Amplicon Encodes Essential Regulators Of Secretory Vesicles That Drive Secretory Addiction In Cancer, Xiaochao Tan, Shike Wang, Guan-Yu Xiao, Chao Wu, Xin Liu, Biyao Zhou, Jiang Yu, Dzifa Yawa Duose, Yuanxin Xi, Jing Wang, Kunika Gupta, Apar Pataer, Jack A Roth, Michael P Kim, Fengju Chen, Chad J Creighton, William K Russell, Jonathan M Kurie

Faculty, Staff and Student Publications

Cancer cells exhibit heightened secretory states that drive tumor progression. Here, we identify a chromosome 3q amplicon that serves as a platform for secretory regulation in cancer. The 3q amplicon encodes multiple Golgi-resident proteins, including the scaffold Golgi integral membrane protein 4 (GOLIM4) and the ion channel ATPase Secretory Pathway Ca2+ Transporting 1 (ATP2C1). We show that GOLIM4 recruits ATP2C1 and Golgi phosphoprotein 3 (GOLPH3) to coordinate calcium-dependent cargo loading and Golgi membrane bending and vesicle scission. GOLIM4 depletion disrupts the protein complex, resulting in a secretory blockade that inhibits the progression of 3q-amplified malignancies. In addition to its role …

Role Of Ectopic Olfactory Receptors In The Regulation Of The Cardiovascular-Kidney-Metabolic Axis, Mitchell R Beito, Sadia Ashraf, Dorcas Odogwu, Romain Harmancey

Faculty, Staff and Student Publications

Olfactory receptors (ORs) represent one of the largest yet least investigated families of G protein-coupled receptors in mammals. While initially believed to be functionally restricted to the detection and integration of odors at the olfactory epithelium, accumulating evidence points to a critical role for ectopically expressed ORs in the regulation of cellular homeostasis in extranasal tissues. This review aims to summarize the current state of knowledge on the expression and physiological functions of ectopic ORs in the cardiovascular system, kidneys, and primary metabolic organs and emphasizes how altered ectopic OR signaling in those tissues may impact cardiovascular-kidney-metabolic health.

Full Issue: Volume 2, Issue 1 - April 2024

Bone Bulletin

i - Editors’ Note by Ari Clements & Amit Syal

ii - Foreword by Dr. Alan Hilibrand

7 - Exploring Approaches to Treatment of Musculoskeletal Injuries by Catherine Alvaro

9 - A Spotlight on the Various Subspecialties of Orthopedic Surgery by Ryan Garemani

14 - Exploring the Importance of Implant Selection in Total Hip Arthroplasty by John Czarnecki

16 - Revolutionizing Orthopaedics: Exploring the Therapeutic Potential of Stem Cells by Harrison Fellheimer

18 - Shoulder Arthroplasty in Patients with Inflammatory Arthritis: Preoperative and Perioperative Management of Disease Modifying Anti-Rheumatic Drug Therapy by Daniel Kwak

22 - The Role of Psychological …

The Role Of Psychological Readiness In Recovery From Acl Injury In Female Athletes, Samantha Meacock

Bone Bulletin

The Anterior Cruciate Ligament (ACL) injury is common in sports, with female athletes facing a disproportionately higher risk in comparison to male athletes.¹ This susceptibility is the result of a complex relationship between various factors including anatomical, biomechanical, hormonal, neuromuscular, and environmental influences.² In addition, the unique challenges that females face with respect to sports, violence, body image, and family planning create additional stressors that may further contribute to an increased risk for injury.^3,4 Following ACL Reconstruction (ACLR) surgery, these gender discrepancies carry over into recovery as female athletes exhibit decreased rates of return to sport (RTS) …

Shoulder Arthroplasty In Patients With Inflammatory Arthritis: Preoperative And Perioperative Management Of Disease Modifying Anti-Rheumatic Drug Therapy, Daniel Kwak

Bone Bulletin

Introduction

Inflammatory arthritis is a debilitating systemic autoimmune and inflammatory disease that leads to joint damage, resulting in significant pain and disability. Rheumatoid arthritis (RA) is the most common inflammatory arthritis typically associated with advanced arthritic changes of the glenohumeral joint as well as with rotator cuff tears.²⁰ Since the introduction of disease modifying anti-rheumatic drug (DMARD) therapy, patients diagnosed with inflammatory rheumatic diseases have observed improvements in pain management and functional outcomes, alongside a reduction in the occurrence of upper limb arthroplasties.¹⁶ Nonetheless, total joint arthroplasty still remains common in the treatment of RA.^8,14

One recognized …

The Swi/Snf Atp-Dependent Chromatin Remodeling Complex In Cell Lineage Priming And Early Development, Dhurjhoti Saha, Srinivas Animireddy, Blaine Bartholomew

Faculty, Staff and Student Publications

ATP dependent chromatin remodelers have pivotal roles in transcription, DNA replication and repair, and maintaining genome integrity. SWI/SNF remodelers were first discovered in yeast genetic screens for factors involved in mating type switching or for using alternative energy sources therefore termed SWI/SNF complex (short for SWItch/Sucrose NonFermentable). The SWI/SNF complexes utilize energy from ATP hydrolysis to disrupt histone-DNA interactions and shift, eject, or reposition nucleosomes making the underlying DNA more accessible to specific transcription factors and other regulatory proteins. In development, SWI/SNF orchestrates the precise activation and repression of genes at different stages, safe guards the formation of specific cell …

N-Glycoproteomic Analyses Of Human Intestinal Enteroids, Varying In Histo-Blood Group Geno- And Phenotypes, Reveal A Wide Repertoire Of Fucosylated Glycoproteins, Jonas Nilsson, Inga Rimkute, Carina Sihlbom, Victoria R Tenge, Shih-Ching Lin, Robert L Atmar, Mary K Estes, Göran Larson

Faculty, Staff and Students Publications

Human noroviruses, globally the main cause of viral gastroenteritis, show strain specific affinity for histo-blood group antigens (HBGA) and can successfully be propagated ex vivo in human intestinal enteroids (HIEs). HIEs established from jejunal stem cells of individuals with different ABO, Lewis and secretor geno- and phenotypes, show varying susceptibility to such infections. Using bottom-up glycoproteomic approaches we have defined and compared the N-linked glycans of glycoproteins of seven jejunal HIEs. Membrane proteins were extracted, trypsin digested, and glycopeptides enriched by hydrophilic interaction liquid chromatography and analyzed by nanoLC-MS/MS. The Byonic software was used for glycopeptide identification followed by hands-on …

Immunophenotypic Predictors Of Influenza Vaccine Immunogenicity In Pediatric Hematopoietic Cell Transplant Recipients., Justin Z. Amarin, Daniel E. Dulek, Joshua Simmons, Haya Hayek, James D. Chappell, Cindy Hager Nochowicz, Carrie L. Kitko, Jennifer E. Schuster, Flor M. Muñoz, Claire E. Bocchini, Elizabeth A. Moulton, Susan E. Coffin, Jason L. Freedman, Monica I. Ardura, Rachel L. Wattier, Gabriela Maron, Michael Grimley, Grant Paulsen, Lara Danziger-Isakov, Paul A. Carpenter, Janet A. Englund, Natasha B. Halasa, Andrew J. Spieker, Spyros A. Kalams

Manuscripts, Articles, Book Chapters and Other Papers

Pediatric hematopoietic cell transplant (HCT) recipients exhibit poor serologic responses to influenza vaccination early after transplant. To facilitate the optimization of influenza vaccination timing, we sought to identify B- and T-cell subpopulations associated with influenza vaccine immunogenicity in this population. We used mass cytometry to phenotype peripheral blood mononuclear cells collected from pediatric HCT recipients enrolled in a multicenter influenza vaccine trial comparing high- and standard-dose formulations over 3 influenza seasons (2016-2019). We fit linear regression models to estimate relationships between immune cell subpopulation numbers before vaccination and prevaccination to postvaccination geometric mean fold rises in antigen-specific (A/H3N2, A/H1N1, and …

Structural Variants Involving Mllt10 Fusion Are Associated With Adverse Outcomes In Pediatric Acute Myeloid Leukemia., Oussama Abla, Rhonda E. Ries, Tim Triche, Robert B. Gerbing, Betsy Hirsch, Susana Raimondi, Todd Cooper, Jason E. Farrar, Nathaniel Buteyn, Lauren M. Harmon, Hong Wen, Aniruddha J. Deshpande, E Anders Kolb, Alan S. Gamis, Richard Aplenc, Todd Alonzo, Soheil Meshinchi

Manuscripts, Articles, Book Chapters and Other Papers

MLLT10 gene rearrangements with KMT2A occur in pediatric acute myeloid leukemia (AML) and confer poor prognosis, but the prognostic impact of MLLT10 in partnership with other genes is unknown. We conducted a retrospective study with 2080 children and young adults with AML registered on the Children's Oncology Group AAML0531 (NCT00372593) and AAML1031 trials (NCT01371981). Transcriptome profiling and/or karyotyping were performed to identify leukemia-associated fusions associated with prognosis. Collectively, 127 patients (6.1%) were identified with MLLT10 fusions: 104 (81.9%) with KMT2A::MLLT10, 13 (10.2%) with PICALM::MLLT10, and 10 (7.9%) X::MLLT10: (2 each of DDX3X and TEC), with 6 partners (DDX3Y, CEP164, SCN2B, …

Xpo1 Blockade With Kpt-330 Promotes Apoptosis In Cutaneous T-Cell Lymphoma By Activating The P53-P21 And P27 Pathways, Nitin Chakravarti, Amy Boles, Rachel Burzinski, Paola Sindaco, Colleen Isabelle, Kathleen Mcconnell, Anjali Mishra, Pierluigi Porcu

Kimmel Cancer Center Faculty Papers

Dysregulated nuclear-cytoplasmic trafficking has been shown to play a role in oncogenesis in several types of solid tumors and hematological malignancies. Exportin 1 (XPO1) is responsible for the nuclear export of several proteins and RNA species, mainly tumor suppressors. KPT-330, a small molecule inhibitor of XPO1, is approved for treating relapsed multiple myeloma and diffuse large B-cell lymphoma. Cutaneous T-cell lymphoma (CTCL) is an extranodal non-Hodgkin lymphoma with an adverse prognosis and limited treatment options in advanced stages. The effect of therapeutically targeting XPO1 with KPT-330 in CTCL has not been established. We report that XPO1 expression is upregulated in …

Six-Year Follow-Up And Subgroup Analyses Of A Phase 2 Trial Of Venetoclax For Del(17p) Chronic Lymphocytic Leukemia, Stephan Stilgenbauer, Eugen Tausch, Andrew W Roberts, Matthew S Davids, Barbara Eichhorst, Michael Hallek, Peter Hillmen, Christof Schneider, Johannes Schetelig, Sebastian Böttcher, Arnon P Kater, Yanwen Jiang, Michelle Boyer, Relja Popovic, Majd T Ghanim, Michael Moran, Wendy J Sinai, Xifeng Wang, Nabanita Mukherjee, Brenda Chyla, William G Wierda, John F Seymour

Faculty, Staff and Student Publications

Chromosome 17p deletion (del[17p]) is associated with poor prognosis in patients with chronic lymphocytic leukemia (CLL). Venetoclax is approved for treatment of previously untreated and relapsed/refractory (R/R) CLL, including patients with del(17p), based on the open-label, multicenter, phase 2 M13-982 trial (NCT01889186). Here, we detail the 6-year follow-up analysis for M13-982. A total of 158 patients with previously untreated (n = 5) or R/R (n = 153) del(17p) CLL received 400 mg venetoclax daily after initial ramp-up until progressive disease. After a median follow-up of 70 months, the best objective response rate (ORR) was 77% (21% complete remission …

Associations Between Stress, Health Behaviors, And Quality Of Life In Young Couples During The Transition To Survivorship: Protocol For A Measurement Burst Study, Dalnim Cho, Michael Roth, Susan K Peterson, Kristofer Jennings, Seokhun Kim, Shiao-Pei Weathers, Sairah Ahmed, J Andrew Livingston, Carlos Barcenas, Y Nancy You, Kathrin Milbury

Faculty, Staff and Student Publications

BACKGROUND: Cancer is a life-threatening, stressful event, particularly for young adults due to delays and disruptions in their developmental transitions. Cancer treatment can also cause adverse long-term effects, chronic conditions, psychological issues, and decreased quality of life (QoL) among young adults. Despite numerous health benefits of health behaviors (eg, physical activity, healthy eating, no smoking, no alcohol use, and quality sleep), young adult cancer survivors report poor health behavior profiles. Determining the associations of stress (either cancer-specific or day-to-day stress), health behaviors, and QoL as young adult survivors transition to survivorship is key to understanding and enhancing these survivors' health. …

Endocarditis: A Review Of Recent Literature, Scott Dale, Zaid Tayyem, Steven Maceyko

Jefferson Hospital Staff Papers and Presentations

Purpose of Review

Endocarditis remains a challenging diagnosis, with significant implications for early identification and initiation of therapy. In this review, we examine the evolution in the epidemiology and presentation of infectious endocarditis (IE), the role of new diagnostic tools, and the approach to therapy.

Recent Findings

Staphylococcus and Streptococcus species remain the most common causative organisms, but the prevalence of IE caused by enterococcus and non-HACEK organisms is increasing. While newer antibiotics such as dalbavancin have shown promise, treatment must still be tailored on an individual basis. Evidence suggests that antibiotic prophylaxis to prevent IE be limited to high-risk …

Targeting Genomic Receptors In Voided Urine For Confirmation Of Benign Prostatic Hyperplasia, Mathew Thakur, Vivek S. Tomar, Emma Dale, Leonard G. Gomella, Charalambos Solomides, Oleksandr Kolesnikov, Scott W. Keith, Hector T. Navarro, Olivia Dahlgren, Michael Chaga, Edouard J. Trabulsi

Department of Radiology Faculty Papers

Objectives

The objective of this study is to validate a hypothesis that a non-invasive optical imaging assay targeting genomic VPAC receptors on malignant cells shed in voided urine will represent either benign prostatic hyperplasia (BPH) or prostatic cancer (PCa). Risk for BPH in men 50–70 years old is 50–70% and PCa is 17%. BPH and PCa can coexist in 20% of men with BPH. Most commonly practiced methods to diagnose BPH do not distinguish BPH from PCa.

Patients (or Materials) and Methods

Males with BPH (N = 97, 60.8 ± 6.3 years, prostate-specific antigen 0.7 ± 0.4 ng/mL) and …

Predictive And Prognostic Biomarkers And Tumor Antigens For Targeted Therapy In Urothelial Carcinoma, Aditya Eturi, Amman Bhasin, Kevin Zarrabi, William Tester

Department of Medical Oncology Faculty Papers

Urothelial carcinoma (UC) is the fourth most prevalent cancer amongst males worldwide. While patients with non-muscle-invasive disease have a favorable prognosis, 25% of UC patients present with locally advanced disease which is associated with a 10-15% 5-year survival rate and poor overall prognosis. Muscle-invasive bladder cancer (MIBC) is associated with about 50% 5 year survival when treated by radical cystectomy or trimodality therapy; stage IV disease is associated with 10-15% 5 year survival. Current therapeutic modalities for MIBC include neoadjuvant chemotherapy, surgery and/or chemoradiation, although patients with relapsed or refractory disease have a poor prognosis. However, the rapid success of …

An Ultra Energy-Efficient Hardware Platform For Neuromorphic Computing Enabled By 2d-Tmd Tunnel-Fets, Arnab Pal, Zichun Chai, Junkai Jiang, Wei Cao, Mike Davies, Vivek De, Kaustav Banerjee

Faculty, Staff and Student Publications

Brain-like energy-efficient computing has remained elusive for neuromorphic (NM) circuits and hardware platform implementations despite decades of research. In this work we reveal the opportunity to significantly improve the energy efficiency of digital neuromorphic hardware by introducing NM circuits employing two-dimensional (2D) transition metal dichalcogenide (TMD) layered channel material-based tunnel-field-effect transistors (TFETs). Our novel leaky-integrate-fire (LIF) based digital NM circuit along with its Hebbian learning circuitry operates at a wide range of supply voltages, frequencies, and activity factors, enabling two orders of magnitude higher energy-efficient computing that is difficult to achieve with conventional material and/or device platforms, specifically the silicon-based …

The Mental Health Impact Of Aortic Dissection, Elaine Symanski, Kristina W Whitworth, Hector Mendez-Figueroa, Kjersti M Aagaard, Iman Moussa, Juan Alvarez, Adrien Chardon Fabian, Kurunthachalam Kannan, Cheryl L Walker, Cristian Coarfa, Melissa A Suter, Hamisu M Salihu

Faculty, Staff and Student Publications

INTRODUCTION: The Maternal and Infant Environmental Health Riskscape (MIEHR) Center was established to address the interplay among chemical and non-chemical stressors in the biological, physical, social, and built environments that disproportionately impact perinatal health among Black pregnant people in a large and diverse urban area with documented disparities in the U.S.

METHODS: The MIEHR cohort is recruiting non-Hispanic Black and non-Hispanic white pregnant people who deliver their infants at major obstetric hospitals in Houston, Texas. At enrollment, all participants are asked to provide urine samples for chemical [metals, cotinine, and polycyclic aromatic hydrocarbons (PAHs)] analyses and blood samples. A subset …

Cellular Host Response Sepsis Test For Risk Stratification Of Patients In The Emergency Department: A Pooled Analysis, Hollis R. O'Neal, Roya Sheybani, Chadd K. Kraus, Wesley H. Self, Ajay M. Shah, Christopher B. Thomas, Henry T.K. Tse, Robert Scoggins

School of Medicine Faculty Publications

Objectives: Sepsis is one of the most common, costly, and misdiagnosed conditions in U.S. emergency departments (EDs). ED providers often treat on nonspecific signs, subjective suspicion, or presumption of infection, resulting in over- and undertreatment. An increased understanding of host response has opened a new direction for sepsis diagnostics. The IntelliSep test is a U.S. Food and Drug Administration–cleared cellular host response diagnostic that could help distinguish sepsis in ED settings. Our objective was to evaluate the potential of the cellular host response test to expedite appropriate care for patients who present with signs of infection. Methods: We performed a …

Stimulator Of Interferon Genes Pathway Activation Through The Controlled Release Of Stingel Mediates Analgesia And Anti-Cancer Effects In Oral Squamous Cell Carcinoma, Minh Phuong Dong, Neeraja Dharmaraj, Estela Kaminagakura, Jianfei Xue, David G Leach, Jeffrey D Hartgerink, Michael Zhang, Hana-Joy Hanks, Yi Ye, Bradley E Aouizerat, Kyle Vining, Carissa M Thomas, Sinisa Dovat, Simon Young, Chi T Viet

Faculty, Staff and Student Publications

Oral squamous cell carcinoma (OSCC) presents significant treatment challenges due to its poor survival and intense pain at the primary cancer site. Cancer pain is debilitating, contributes to diminished quality of life, and causes opioid tolerance. The stimulator of interferon genes (STING) agonism has been investigated as an anti-cancer strategy. We have developed STINGel, an extended-release formulation that prolongs the availability of STING agonists, which has demonstrated an enhanced anti-tumor effect in OSCC compared to STING agonist injection. This study investigates the impact of intra-tumoral STINGel on OSCC-induced pain using two separate OSCC models and nociceptive behavioral assays. Intra-tumoral STINGel …

Th2 Cells Are Associated With Tumor Recurrence Following Radiation, Mohamed K Abdelhakiem, Riyue Bao, Phillip M Pifer, David Molkentine, Jessica Molkentine, Andrew Hefner, Beth Beadle, John V Heymach, Jason J Luke, Robert L Ferris, Curtis R Pickering, Jing H Wang, Ravi B Patel, Heath D Skinner

Faculty, Staff and Student Publications

The curative treatment of multiple solid tumors, including head and neck squamous cell carcinoma (HNSCC), utilizes radiation. The outcomes for HPV/p16-negative HNSCC are significantly worse than HPV/p16-positive tumors, with increased radiation resistance leading to worse locoregional recurrence (LRR) and ultimately death. This study analyzed the relationship between immune function and outcomes following radiation in HPV/p16-negative tumors to identify mechanisms of radiation resistance and prognostic immune biomarkers. A discovery cohort of 94 patients with HNSCC treated uniformly with surgery and adjuvant radiation and a validation cohort of 97 similarly treated patients were utilized. Tumor immune infiltrates were derived from RNAseq gene …

Diffuse Hemispheric Glioma With H3 P.K28m (K27m) Mutation: Unusual Non-Midline Presentation Of Diffuse Midline Glioma, H3 K27m-Altered?, Kliment Donev, Vanitha Sundararajan, Derek Johnson, Jagadheshwar Balan, Meagan Chambers, Vera A Paulson, Kathryn P Scherpelz, Zied Abdullaev, Martha Quezado, Patrick J Cimino, Drew Pratt, Ediel Valerio, João Vıctor Alves De Castro, Dirce Maria Carraro, Giovana Tardin Torrezan, Beatriz Martins Wolff, Leslie Domenici Kulikowski, Felipe D'Almeida Costa, Kenneth Aldape, Cristiane M Ida

Neuroscience Articles

Diffuse midline glioma, H3 K27-altered (DMG-H3 K27) is an aggressive group of diffuse gliomas that predominantly occurs in pediatric patients, involves midline structures, and displays loss of H3 p.K28me3 (K27me3) expression by immunohistochemistry and characteristic genetic/epigenetic profile. Rare examples of a diffuse glioma with an H3 p.K28M (K27M) mutation and without involvement of the midline structures, so-called "diffuse hemispheric glioma with H3 p.K28M (K27M) mutation" (DHG-H3 K27), have been reported. Herein, we describe 2 additional cases of radiologically confirmed DHG-H3 K27 and summarize previously reported cases. We performed histological, immunohistochemical, molecular, and DNA methylation analysis and provided clinical follow-up in …

Glycemia And Gluconeogenesis With Metformin And Liraglutide: A Randomized Trial In Youth-Onset Type 2 Diabetes, Katrina B Dietsche, Sheela N Magge, Sydney A Dixon, Faith S Davis, Andrea Krenek, Aruba Chowdhury, Lilian Mabundo, Michael Stagliano, Amber B Courville, Shanna Yang, Sara Turner, Hongyi Cai, Kannan Kasturi, Arthur S Sherman, Joon Ha, Eileen Shouppe, Mary Walter, Peter J Walter, Kong Y Chen, Robert J Brychta, Cody Peer, Yi Zeng, William Figg, Fran Cogen, D Elizabeth Estrada, Shaji Chacko, Stephanie T Chung

Children’s Nutrition Research Center Staff Publications

OBJECTIVE: Elevated rates of gluconeogenesis are an early pathogenic feature of youth-onset type 2 diabetes (Y-T2D), but targeted first-line therapies are suboptimal, especially in African American (AA) youth. We evaluated glucose-lowering mechanisms of metformin and liraglutide by measuring rates of gluconeogenesis and β-cell function after therapy in AA Y-T2D.

METHODS: In this parallel randomized clinical trial, 22 youth with Y-T2D-age 15.3 ± 2.1 years (mean ± SD), 68% female, body mass index (BMI) 40.1 ± 7.9 kg/m2, duration of diagnosis 1.8 ± 1.3 years-were randomized to metformin alone (Met) or metformin + liraglutide (Lira) (Met + Lira) and evaluated before …

Bone Marrow Donor Recruitment Drive And Registry, Elizabeth R. Dovich

Honors Theses

Bone marrow transplants are vital for those with blood cancers and disorders, but not every ethnic group has an equal chance of finding a match. Some of the human leukocyte antigen (HLA) cell markers used to match donors and recipients are unique to certain ethnic groups, making it harder for members of those groups to find a match. This project worked to address this inequality by organizing a bone marrow registry recruitment drive on the campus of Andrews University in partnership with the NMDP registry. It encompassed the planning, promotion, and execution of the drive which took place March 5-7, …