Medicine and Health Sciences Commons^™

Racial Discrimination, Knowledge, And Health Outcomes: The Mediating Role Of Hepatitis B-Related Stigma Among Patients With Chronic Hepatitis B, Julia G. Katcher, Ann C. Klassen, Hie-Won Hann, Mimi Chang, Hee-Soon Juon

Department of Medical Oncology Faculty Papers

It is well described in current literature that Hepatitis B virus (HBV) affects Asian Americans more than any other racial group in the United States and that there is a stigma attached to this condition. The effects of stigma can be lasting, penetrating physiologically and psychologically, yet few studies have focused on the consequences of this phenomenon. The purpose of this study was to examine the mediating role of stigma in the effect of racial discrimination and knowledge (of HBV sequelae) on health status of Korean Americans with chronic hepatitis B (CHB). Three hundred sixty-five CHB patients were recruited and …

Fully Automated Deep Learning Based Auto-Contouring Of Liver Segments And Spleen On Contrast-Enhanced Ct Images, Aashish C Gupta, Guillaume Cazoulat, Mais Al Taie, Sireesha Yedururi, Bastien Rigaud, Austin Castelo, John Wood, Cenji Yu, Caleb O'Connor, Usama Salem, Jessica Albuquerque Marques Silva, Aaron Kyle Jones, Molly Mcculloch, Bruno C Odisio, Eugene J Koay, Kristy K Brock

Faculty, Staff and Student Publications

Manual delineation of liver segments on computed tomography (CT) images for primary/secondary liver cancer (LC) patients is time-intensive and prone to inter/intra-observer variability. Therefore, we developed a deep-learning-based model to auto-contour liver segments and spleen on contrast-enhanced CT (CECT) images. We trained two models using 3d patch-based attention U-Net ([Formula: see text] and 3d full resolution of nnU-Net ([Formula: see text] to determine the best architecture ([Formula: see text]. BA was used with vessels ([Formula: see text] and spleen ([Formula: see text] to assess the impact on segment contouring. Models were trained, validated, and tested on 160 ([Formula: see text]), …

Polyaminer-Bulk Is A Deep Learning-Based Algorithm That Decodes Alternative Polyadenylation Dynamics From Bulk Rna-Seq Data, Venkata Soumith Jonnakuti, Eric J Wagner, Mirjana Maletić-Savatić, Zhandong Liu, Hari Krishna Yalamanchili

Faculty, Staff and Students Publications

Alternative polyadenylation (APA) is a key post-transcriptional regulatory mechanism; yet, its regulation and impact on human diseases remain understudied. Existing bulk RNA sequencing (RNA-seq)-based APA methods predominantly rely on predefined annotations, severely impacting their ability to decode novel tissue- and disease-specific APA changes. Furthermore, they only account for the most proximal and distal cleavage and polyadenylation sites (C/PASs). Deconvoluting overlapping C/PASs and the inherent noisy 3' UTR coverage in bulk RNA-seq data pose additional challenges. To overcome these limitations, we introduce PolyAMiner-Bulk, an attention-based deep learning algorithm that accurately recapitulates C/PAS sequence grammar, resolves overlapping C/PASs, captures non-proximal-to-distal APA changes, …

Juvenile Eosinophilic Fasciitis: A Single Center Case Series, Leigh A Stubbs, Oluwaseun Ogunbona, Emily Beil, Vibha Szafron, Adekunle Adesina, Sara Anvari, Jamie Lai, Andrea Ramirez, Matthew G Ditzler, Marietta Deguzman

Faculty, Staff and Students Publications

BACKGROUND: Eosinophilic fasciitis (EF) is a rare disease characterized by skin induration and musculoskeletal abnormalities. Diagnostic criteria for EF are based on adult populations. There is a need to expand the literature on EF in children due to limited reported cases and potential differences compared to adults.

METHODS: We conducted a retrospective review of medical records for six pediatric patients diagnosed with EF at our institution between November 2011 and April 2023. Inclusion criteria required patients to be under 18 years of age at the time of diagnosis and to have confirmed diagnosis through clinical history, imaging, and histology.

RESULTS: …

Impaired Bone Morphogenetic Protein (Bmp) Signaling Pathways Disrupt Decidualization In Endometriosis, Zian Liao, Suni Tang, Peixin Jiang, Ting Geng, Dominique I Cope, Timothy N Dunn, Joie Guner, Linda Alpuing Radilla, Xiaoming Guan, Diana Monsivais

Faculty, Staff and Students Publications

Endometriosis is linked to increased infertility and pregnancy complications due to defective endometrial decidualization. We hypothesized that identification of altered signaling pathways during decidualization could identify the underlying cause of infertility and pregnancy complications. Our study reveals that transforming growth factor β (TGFβ) pathways are impaired in the endometrium of individuals with endometriosis, leading to defective decidualization. Through detailed transcriptomic analyses, we discovered abnormalities in TGFβ signaling pathways and key regulators, such as SMAD4, in the endometrium of affected individuals. We also observed compromised activity of bone morphogenetic proteins (BMP), a subset of the TGFβ family, that control endometrial receptivity. …

Cros Or Hearing Aid? Selecting The Ideal Solution For Unilateral Ci Patients With Limited Aidable Hearing In The Contralateral Ear, Sarah Lively, Smita Agrawal, Matthew Stewart, Robert Dwyer, Laura Strobel, Paula Marcinkevich, Chris Hetlinger, Julia Croce

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

A hearing aid or a contralateral routing of signal device are options for unilateral cochlear implant listeners with limited hearing in the unimplanted ear; however, it is uncertain which device provides greater benefit beyond unilateral listening alone. Eighteen unilateral cochlear implant listeners participated in this prospective, within-participants, repeated measures study. Participants were tested with the cochlear implant alone, cochlear implant + hearing aid, and cochlear implant + contralateral routing of signal device configurations with a one-month take-home period between each in-person visit. Audiograms, speech perception in noise, and lateralization were evaluated. Subjective feedback was obtained via questionnaires. Marked improvement in …

Pleomorphic Adenoma With A Novel Gene Rearrangement-Linc01606::Plag1, Udit Naik, Sara E Amin, Mahmoud Elsayad, Karan Saluja

Faculty, Staff and Student Publications

Background: Pleomorphic adenoma is a well-known benign salivary gland neoplasm characterized by the presence of varying proportions of three different components, including bi-layered ducts, myoepithelial cells, and admixed within a chondromyxoid/fibrous stroma.

Method: We report an interesting case of an adult male who presented with bleeding from an extensively degenerated parotid gland mass, concerning for a vascular neoplasm versus primary malignant tumor. Microscopically, majority of the viable tumor exhibited diffuse proliferation of spindle to epithelioid cells, with focal areas depicting cribriform glands, ducts, and scant chondromyxoid stroma.

Result: Next-generation sequencing (NGS) RNA-based fusion panel analysis identified a gene rearrangement involving …

Further Recommendations Of The International Paediatric Brain Injury Society (Ipbis) For The Post-Acute Rehabilitation Of Children With Acquired Brain Injury, Mark A Linden, Audrey Mckinlay, Carol Hawley, Catherine Aaro-Jonsson, Ingela Kristiansen, Andreas Meyer-Heim, Linda Ewing-Cobbs, Beth Wicks, Miriam H Beauchamp, Rajendra Prasad, Board Of Directors Of The Ipbis Affiliations

Faculty, Staff and Student Publications

Background: Paediatric acquired brain injury is a life-long condition which impacts on all facets of the individual's lived experience. The existing evidence base continues to expand and new fields of enquiry are established as clinicians and researchers uncover the extent of these impacts.

Primary objective: To add to recommendations described in the International Paediatric Brain Injury Society's 2016 paper on post-acute care for children with acquired brain injury and highlight new areas of enquiry.

Review of information: Recommendations were made based on the opinions of a group of experienced international clinicians and researchers who are current or past members of …

Inhibiting Centrosome Clustering Reduces Cystogenesis And Improves Kidney Function In Autosomal Dominant Polycystic Kidney Disease, Tao Cheng, Aruljothi Mariappan, Ewa Langner, Kyuhwan Shim, Jay Gopalakrishnan, Moe R. Mahjoub

2020-Current year OA Pubs

Autosomal dominant polycystic kidney disease (ADPKD) is a monogenic disorder accounting for approximately 5% of patients with renal failure, yet therapeutics for the treatment of ADPKD remain limited. ADPKD tissues display abnormalities in the biogenesis of the centrosome, a defect that can cause genome instability, aberrant ciliary signaling, and secretion of pro-inflammatory factors. Cystic cells form excess centrosomes via a process termed centrosome amplification (CA), which causes abnormal multipolar spindle configurations, mitotic catastrophe, and reduced cell viability. However, cells with CA can suppress multipolarity via "centrosome clustering," a key mechanism by which cells circumvent apoptosis. Here, we demonstrate that inhibiting …

Notes From The Field: Reemergence Of Mycoplasma Pneumoniae Infections In Children And Adolescents After The Covid-19 Pandemic, United States, 2018-2024., Chris Edens, Benjamin R. Clopper, Jourdan Devies, Alvaro Benitez, Erin R. Mckeever, Dylan Johns, Bernard Wolff, Rangaraj Selvarangan, Jennifer E. Schuster, Geoffrey A. Weinberg, Peter G. Szilagyi, Fatimah S. Dawood, Lakshmi Radhakrishnan, Christina Quigley, Leila C. Sahni, Natasha Halasa, Laura S. Stewart, Meredith L. Mcmorrow, Brett Whitaker, Danielle M. Zerr, Vasanthi Avadhanula, John V. Williams, Marian G. Michaels, Aaron Kite-Powell, Janet A. Englund, Mary Allen Staat, Kathleen Hartnett, Heidi L. Moline, Adam L. Cohen, Maureen Diaz

Manuscripts, Articles, Book Chapters and Other Papers

No abstract provided.

Immunotherapy Resistance In Solid Tumors: Mechanisms And Potential Solutions, Daniel Lefler, Steven Manobianco, Babar Bashir

Kimmel Cancer Center Faculty Papers

While the emergence of immunotherapies has fundamentally altered the management of solid tumors, cancers exploit many complex biological mechanisms that result in resistance to these agents. These encompass a broad range of cellular activities - from modification of traditional paradigms of immunity via antigen presentation and immunoregulation to metabolic modifications and manipulation of the tumor microenvironment. Intervening on these intricate processes may provide clinical benefit in patients with solid tumors by overcoming resistance to immunotherapies, which is why it has become an area of tremendous research interest with practice-changing implications. This review details the major ways cancers avoid both natural …

Estrogen Receptor Mutations As Novel Targets For Immunotherapy In Metastatic Estrogen Receptor-Positive Breast Cancer, Jonathan Goldberg, Na Qiao, Jennifer L Guerriero, Brett Gross, Yagiz Meneksedag, Yoshimi F Lu, Anne V Philips, Tasnim Rahman, Funda Meric-Bernstam, Jason Roszik, Ken Chen, Rinath Jeselsohn, Sara M Tolaney, George E Peoples, Gheath Alatrash, Elizabeth A Mittendorf

Faculty, Staff and Student Publications

UNLABELLED: Estrogen receptor-positive (ER+) breast cancer is not considered immunogenic and, to date, has been proven resistant to immunotherapy. Endocrine therapy remains the cornerstone of treatment for ER+ breast cancers. However, constitutively activating mutations in the estrogen receptor alpha (ESR1) gene can emerge during treatment, rendering tumors resistant to endocrine therapy. Although these mutations represent a pathway of resistance, they also represent a potential source of neoepitopes that can be targeted by immunotherapy. In this study, we investigated ESR1 mutations as novel targets for breast cancer immunotherapy. Using machine learning algorithms, we identified ESR1-derived peptides predicted to form stable complexes …

Comparative Genomics Incorporating Translocation Renal Cell Carcinoma Mouse Model Reveals Molecular Mechanisms Of Tumorigenesis, Gopinath Prakasam, Akhilesh Mishra, Alana Christie, Jeffrey Miyata, Deyssy Carrillo, Vanina T Tcheuyap, Hui Ye, Quyen N Do, Yunguan Wang, Oscar Reig Torras, Ramesh Butti, Hua Zhong, Jeffrey Gagan, Kevin B Jones, Thomas J Carroll, Zora Modrusan, Steffen Durinck, Mai-Carmen Requena-Komuro, Noelle S Williams, Ivan Pedrosa, Tao Wang, Dinesh Rakheja, Payal Kapur, James Brugarolas

Faculty, Staff and Student Publications

Translocation renal cell carcinoma (tRCC) most commonly involves an ASPSCR1-TFE3 fusion, but molecular mechanisms remain elusive and animal models are lacking. Here, we show that human ASPSCR1-TFE3 driven by Pax8-Cre (a credentialed clear cell RCC driver) disrupted nephrogenesis and glomerular development, causing neonatal death, while the clear cell RCC failed driver, Sglt2-Cre, induced aggressive tRCC (as well as alveolar soft part sarcoma) with complete penetrance and short latency. However, in both contexts, ASPSCR1-TFE3 led to characteristic morphological cellular changes, loss of epithelial markers, and an epithelial-mesenchymal transition. Electron microscopy of tRCC tumors showed lysosome expansion, and functional studies revealed simultaneous …

Somatostatin Receptor Subtype-2 Targeting System For Specific Delivery Of Temozolomide, Solmaz Aghaamiri, Sukhen C Ghosh, Servando Hernandez Vargas, Daniel M Halperin, Ali Azhdarinia

Faculty, Staff and Student Publications

Temozolomide (TMZ) is a DNA alkylating agent that produces objective responses in patients with neuroendocrine tumors (NETs) when the DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) is inactivated. At high doses, TMZ therapy exhausts MGMT activity but also produces dose-limiting toxicities. To reduce off-target effects, we converted the clinically approved radiotracer 68Ga-DOTA-TOC into a peptide-drug conjugate (PDC) for targeted delivery of TMZ to somatostatin receptor subtype-2 (SSTR2)-positive tumor cells. We used an integrated radiolabeling strategy for direct quantitative assessment of receptor binding, pharmacokinetics, and tissue biodistribution. In vitro studies revealed selective binding to SSTR2-positive cells with high affinity (5.98 ± 0.96 …

Cagi, The Critical Assessment Of Genome Interpretation, Establishes Progress And Prospects For Computational Genetic Variant Interpretation Methods, Critical Assessment Of Genome Interpretation Consortium

Faculty, Staff and Student Publications

BACKGROUND: The Critical Assessment of Genome Interpretation (CAGI) aims to advance the state-of-the-art for computational prediction of genetic variant impact, particularly where relevant to disease. The five complete editions of the CAGI community experiment comprised 50 challenges, in which participants made blind predictions of phenotypes from genetic data, and these were evaluated by independent assessors.

RESULTS: Performance was particularly strong for clinical pathogenic variants, including some difficult-to-diagnose cases, and extends to interpretation of cancer-related variants. Missense variant interpretation methods were able to estimate biochemical effects with increasing accuracy. Assessment of methods for regulatory variants and complex trait disease risk was …

Deep Phenotyping Of Post-Infectious Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, Brian Walitt, Komudi Singh, Samuel R. Lamunion, Mark Hallett, Steve Jacobson, Kong Chen, Yoshimi Enose-Akahata, Richard Apps, Jennifer J. Barb, Patrick Bedard, Robert J. Brychta, Ashura Williams Buckley, Peter D. Burbelo, Brice Calco, Brianna Cathay, Li Chen, Snigdha Chigurupati, Jinguo Chen, Foo Cheung, Lisa M.K. Chin, Benjamin W. Coleman, Amber B. Courville, Madeleine S. Deming, Bart Drinkard, Li Rebekah Feng, Luigi Ferrucci, Scott A. Gabel, Angelique Gavin, David S. Goldstein, Shahin Hassanzadeh, Sean C. Horan, Silvina G. Horovitz, Kory R. Johnson, Anita Jones Govan, Kristine M. Knutson, Joy D. Kreskow, Mark Levin, Jonathan J. Lyons, Nicholas Madian, Nasir Malik, Andrew L. Mammen, John A. Mcculloch, Patrick M. Mcgurrin, Joshua D. Milner, Ruin Moaddel, Geoffrey A. Mueller, Amrita Mukherjee, Sandra Muñoz-Braceras, Gina Norato, Katherine Pak, Iago Pinal-Fernandez, Traian Popa, Lauren B. Reoma, Michael N. Sack, Farinaz Safavi, Leorey N. Saligan, Brian A. Sellers, Stephen Sinclair, Bryan Smith, Joseph Snow, Stacey Solin, Barbara J. Stussman, Giorgio Trinchieri, Sara A. Turner, C. Stephenie Vetter, Felipe Vial, Carlotta Vizioli, Ashley Williams, Shanna B. Yang, Avindra Nath

Student Papers, Posters & Projects

Post-infectious myalgic encephalomyelitis/chronic fatigue syndrome (PI-ME/CFS) is a disabling disorder, yet the clinical phenotype is poorly defined, the pathophysiology is unknown, and no disease-modifying treatments are available. We used rigorous criteria to recruit PI-ME/CFS participants with matched controls to conduct deep phenotyping. Among the many physical and cognitive complaints, one defining feature of PI-ME/CFS was an alteration of effort preference, rather than physical or central fatigue, due to dysfunction of integrative brain regions potentially associated with central catechol pathway dysregulation, with consequences on autonomic functioning and physical conditioning. Immune profiling suggested chronic antigenic stimulation with increase in naïve and decrease …

A Stool Based Qpcr For The Diagnosis Of Tb In Children And People Living With Hiv In Uganda, Eswatini And Mozambique (Stool4tb): A Protocol For A Multicenter Diagnostic Evaluation, Lucia Carratala-Castro, Willy Ssengooba, Alex Kay, Sozinho Acácio, Joanna Ehrlich, Andrew R Dinardo, Nosisa Shiba, Joachim K Nsubuga, Shilzia Munguambe, Belén Saavedra-Cervera, Patricia Manjate, Durbbin Mulengwa, Busizwe Sibandze, Mangaliso Ziyane, George Kasule, Edson Mambuque, Moorine Penninah Sekadde, Eric Wobudeya, Moses L Joloba, Jan Heyckendorf, Christoph Lange, Sabine Hermans, Anna Mandalakas, Alberto L García-Basteiro, Elisa Lopez-Varela, Stool4tb Global Partnership

Faculty, Staff and Students Publications

BACKGROUND: Tuberculosis (TB) is a major cause of mortality worldwide. Children and people living with HIV (PLHIV) have an increased risk of mortality, particularly in the absence of rapid diagnosis. The main challenges of diagnosing TB in these populations are due to the unspecific and paucibacillary disease presentation and the difficulty of obtaining respiratory samples. Thus, novel diagnostic strategies, based on non-respiratory specimens could improve clinical decision making and TB outcomes in high burden TB settings. We propose a multi-country, prospective diagnostic evaluation study with a nested longitudinal cohort evaluation to assess the performance of a new stool-based qPCR, developed …

Leveraging Artificial Intelligence To Advance Implementation Science: Potential Opportunities And Cautions, Katy E Trinkley, Ruopeng An, Anna M Maw, Russell E Glasgow, Ross C Brownson

2020-Current year OA Pubs

BACKGROUND: The field of implementation science was developed to address the significant time delay between establishing an evidence-based practice and its widespread use. Although implementation science has contributed much toward bridging this gap, the evidence-to-practice chasm remains a challenge. There are some key aspects of implementation science in which advances are needed, including speed and assessing causality and mechanisms. The increasing availability of artificial intelligence applications offers opportunities to help address specific issues faced by the field of implementation science and expand its methods.

MAIN TEXT: This paper discusses the many ways artificial intelligence can address key challenges in applying …

Pro-Inflammatory Cerebrospinal Fluid Profile Of Neonates With Intraventricular Hemorrhage: Clinical Relevance And Contrast With Cns Infection, Maria Garcia-Bonilla, Alexander T Yahanda, Albert M Isaacs, Brandon Baksh, S Hassan A Akbari, Haley Botteron, Diego M Morales, Rowland H Han, James P Mcallister Ii, Amit M Mathur, Jennifer M Strahle, Christopher D Smyser, David D Limbrick

2020-Current year OA Pubs

BACKGROUND: Interpretation of cerebrospinal fluid (CSF) studies can be challenging in preterm infants. We hypothesized that intraventricular hemorrhage (IVH), post-hemorrhagic hydrocephalus (PHH), and infection (meningitis) promote pro-inflammatory CSF conditions reflected in CSF parameters.

METHODS: Biochemical and cytological profiles of lumbar CSF and peripheral blood samples were analyzed for 81 control, 29 IVH grade 1/2 (IVH

RESULTS: PHH infants had higher (p < 0.02) CSF total cell and red blood cell (RBC) counts compared to control, IVH

CONCLUSIONS: Similarities in CSF parameters may reflect common pathological processes in the inflammatory response and show the complexity associated with interpreting CSF profiles, especially in PHH and meningitis/ventriculitis.

Nrf2 Activation In Trp53;P16-Deficient Mice Drives Oral Squamous Cell Carcinoma, Samera H Hamad, Rani S Sellers, Nathan Wamsley, Paul Zolkind, Travis P Schrank, Michael B Major, Bernard E Weissman

2020-Current year OA Pubs

UNLABELLED: Aberrant activation of the NRF2/NFE2L2 transcription factor commonly occurs in head and neck squamous cell carcinomas (HNSCC). Mouse model studies have shown that NRF2 activation alone does not result in cancer. When combined with classic oncogenes and at the right dose, NRF2 activation promotes tumor initiation and progression. Here we deleted the tumor suppressor genes p16INK4A and p53 (referred to as CP mice), which are commonly lost in human HNSCC, in the presence of a constitutively active NRF2E79Q mutant (CPN mice). NRF2E79Q expression in CPN mice resulted in squamous cell hyperplasia or dysplasia with hyperkeratosis in the esophagus, oropharynx, …

Multi-Molecular Hyperspectral Prm-Srs Microscopy, Wenxu Zhang, Yajuan Li, Anthony A Fung, Zhi Li, Hongje Jang, Honghao Zha, Xiaoping Chen, Fangyuan Gao, Jane Y Wu, Huaxin Sheng, Junjie Yao, Dorota Skowronska-Krawczyk, Sanjay Jain, Lingyan Shi

2020-Current year OA Pubs

Lipids play crucial roles in many biological processes. Mapping spatial distributions and examining the metabolic dynamics of different lipid subtypes in cells and tissues are critical to better understanding their roles in aging and diseases. Commonly used imaging methods (such as mass spectrometry-based, fluorescence labeling, conventional optical imaging) can disrupt the native environment of cells/tissues, have limited spatial or spectral resolution, or cannot distinguish different lipid subtypes. Here we present a hyperspectral imaging platform that integrates a Penalized Reference Matching algorithm with Stimulated Raman Scattering (PRM-SRS) microscopy. Using this platform, we visualize and identify high density lipoprotein particles in human …

Orbital And Periocular Complications In Patients With Sinonasal Tumours With Orbital Invasion, Jiawei Zhao, Xinyang Jiang, Ehab Hanna, Shirley Y Su, Amy Moreno, Brandon Gunn, Steven Jay Frank, Renata Ferrarotto, Jing Ning, Bita Esmaeli

Faculty, Staff and Student Publications

Aims: The purpose of this study was to determine the frequency and associated risk factors of orbital/periocular complications in patients with sinonasal tumour with orbital invasion managed with eye-sparing treatments.

Methods: A retrospective case series of patients with primary sinonasal tumour with orbital invasion from January 2008 to December 2018. Patient factors were compared between the following groups: (1)patients with orbital/periocular complications versus those who did not and (2) patients who needed secondary oculoplastic surgical procedures versus those who did not.

Results: Out of 80 patients, 48 had eye-sparing surgery, 8 had orbital exenteration and 24 were managed non-surgically. The …

Collagen Type Xii Is Undetectable In Keratoconus Bowman’S Layer, Mohammed Rigi, Hyeck-Soo Son, Loren Moon, Mario Matthaei, Divya Srikumaran, Albert S Jun, Charles G Eberhart, Uri S Soiberman

Faculty, Staff and Student Publications

PURPOSE: Corneal biomechanical failure is the hallmark of keratoconus (KC); however, the cause of this failure remains elusive. Collagen type XII (

METHODS: TaqMan quantitative PCR was performed on 31 corneal epithelium samples of progressive KC and myopic control eyes. Tissue microarrays were constructed using full-thickness corneas from 61 KC cases during keratoplasty and 18 non-KC autopsy eyes and stained with an antibody specific to COL12A1. Additionally,

RESULTS: COL12A1 expression was reduced at transcript levels in KC epithelium compared to controls (ratio: 0.58, p<0.03). Immunohistochemical studies demonstrated that COL12A1 protein expression in BL was undetectable, with reduced expression in KC epithelium, basement membrane, and stroma.

CONCLUSIONS: The apparent absence of COL12A1 in KC BL, together with the functional importance that

Impact Of Immunopathy And Coagulopathy On Multi-Organ Failure And Mortality In A Lethal Porcine Model Of Controlled And Uncontrolled Hemorrhage, Milomir O Simovic, James Bynum, Bin Liu, Jurandir J Dalle Lucca, Yansong Li

Faculty, Staff and Student Publications

Uncontrolled hemorrhage is a major preventable cause of death in patients with trauma. However, the majority of large animal models of hemorrhage have utilized controlled hemorrhage rather than uncontrolled hemorrhage to investigate the impact of immunopathy and coagulopathy on multi-organ failure (MOF) and mortality. This study evaluates these alterations in a severe porcine controlled and uncontrolled hemorrhagic shock (HS) model. Anesthetized female swine underwent controlled hemorrhage and uncontrolled hemorrhage by partial splenic resection followed with or without lactated Ringer solution (LR) or Voluven® resuscitation. Swine were surveyed 6 h after completion of splenic hemorrhage or until death. Blood chemistry, physiologic …

Treatment Strategies For Anti-Vegf Resistance In Neovascular Age-Related Macular Degeneration By Targeting Arteriolar Choroidal Neovascularization, Yingbin Fu, Zhao Zhang, Keith A Webster, Yannis M Paulus

Faculty, Staff and Students Publications

Despite extensive use of intravitreal anti-vascular endothelial growth factor (anti-VEGF) biologics for over a decade, neovascular age-related macular degeneration (nAMD) or choroidal neovascularization (CNV) continues to be a major cause of irreversible vision loss in developed countries. Many nAMD patients demonstrate persistent disease activity or experience declining responses over time despite anti-VEGF treatment. The underlying mechanisms of anti-VEGF resistance are poorly understood, and no effective treatment strategies are available to date. Here we review evidence from animal models and clinical studies that supports the roles of neovascular remodeling and arteriolar CNV formation in anti-VEGF resistance. Cholesterol dysregulation, inflammation, and ensuing …

Progestin-Associated Meningiomatosis With Unusual Schwannoma-Like Morphology, Katherine A Krause, Jared K Woods, Alexandra J Golby, Eudocia Q Lee, Shyam Tanguturi, Zachary Spigelman, Azra H Ligon, Umberto De Girolami, Matthew Torre

Duncan NRI Faculty and Staff Publications

No abstract provided.

The Pathogenicity Of Vancomycin-Resistant Enterococcus Faecalis To Colon Cancer Cells, Li Zhang, Mingxia Deng, Jing Liu, Jiajie Zhang, Fangyu Wang, Wei Yu

Faculty, Staff and Student Publications

BACKGROUND: The aim of this study was to investigate the pathogenicity of vancomycin-resistant Enterococcus faecalis (VREs) to human colon cells in vitro.

METHODS: Three E. faecalis isolates (2 VREs and E. faecalis ATCC 29212) were cocultured with NCM460, HT-29 and HCT116 cells. Changes in cell morphology and bacterial adhesion were assessed at different time points. Interleukin-8 (IL-8) and vascular endothelial growth factor A (VEGFA) expression were measured via RT-qPCR and enzyme-linked immunosorbent assay (ELISA), respectively. Cell migration and human umbilical vein endothelial cells (HUVECs) tube formation assays were used for angiogenesis studies. The activity of PI3K/AKT/mTOR signaling pathway was measured …

Inhibition Of Csf1r And Kit With Pexidartinib Reduces Inflammatory Signaling And Cell Viability In Endometriosis, Timothy N Dunn, Dominique I Cope, Suni Tang, Tirupataiah Sirupangi, Sydney E Parks, Zian Liao, Fei Yuan, Chad J Creighton, Ramya P Masand, Linda Alpuing Radilla, Xiaoming Guan, Laura Detti, Diana Monsivais, Martin M Matzuk

Faculty, Staff and Students Publications

Endometriosis is a common and debilitating disease, affecting ∼170 million women worldwide. Affected patients have limited therapeutic options such as hormonal suppression or surgical excision of the lesions, though therapies are often not completely curative. Targeting receptor tyrosine kinases (RTKs) could provide a nonhormonal treatment option for endometriosis. We determined that 2 RTKs, macrophage-colony stimulating factor 1 receptor (CSF1R) and mast/stem cell growth factor receptor KIT (KIT), are overexpressed in endometriotic lesions and could be novel nonhormonal therapeutic targets for endometriosis. The kinase activity of CSF1R and KIT is suppressed by pexidartinib, a small molecule inhibitor that was recently approved …

Multimodal Neuro-Nanotechnology: Challenging The Existing Paradigm In Glioblastoma Therapy, Sergej Kudruk, Connor M Forsyth, Michelle Z Dion, Jenny K Hedlund Orbeck, Jingqin Luo, Robyn S Klein, Albert H Kim, Amy B Heimberger, Chad A Mirkin, Alexander H Stegh, Natalie Artzi

2020-Current year OA Pubs

Integrating multimodal neuro- and nanotechnology-enabled precision immunotherapies with extant systemic immunotherapies may finally provide a significant breakthrough for combatting glioblastoma (GBM). The potency of this approach lies in its ability to train the immune system to efficiently identify and eradicate cancer cells, thereby creating anti-tumor immune memory while minimizing multi-mechanistic immune suppression. A critical aspect of these therapies is the controlled, spatiotemporal delivery of structurally defined nanotherapeutics into the GBM tumor microenvironment (TME). Architectures such as spherical nucleic acids or poly(beta-amino ester)/dendrimer-based nanoparticles have shown promising results in preclinical models due to their multivalency and abilities to activate antigen-presenting cells …

Current Strategies For Increasing Knock-In Efficiency In Crispr/Cas9-Based Approaches, Andrés Felipe Leal, Angelica María Herreno-Pachón, Eliana Benincore-Flórez, Amali Karunathilaka, Shunji Tomatsu

Department of Pediatrics Faculty Papers

Since its discovery in 2012, the clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein 9 (Cas9) system has supposed a promising panorama for developing novel and highly precise genome editing-based gene therapy (GT) alternatives, leading to overcoming the challenges associated with classical GT. Classical GT aims to deliver transgenes to the cells via their random integration in the genome or episomal persistence into the nucleus through lentivirus (LV) or adeno-associated virus (AAV), respectively. Although high transgene expression efficiency is achieved by using either LV or AAV, their nature can result in severe side effects in humans. For instance, …