Digital Commons Network^™

Novel Human Recombinant N-Acetylgalactosamine-6-Sulfate Sulfatase Produced In A Glyco-Engineered Escherichia Coli Strain, Luisa N. Pimentel-Vera, Alexander Rodríguez-López, Angela J. Espejo-Mojica, Aura María Ramírez, Carolina Cardona, Luis H. Reyes, Shunji Tomatsu, Thapakorn Jaroentomeechai, Matthew P. Delisa, Oscar F. Sánchez, Carlos J. Alméciga-Díaz

Department of Pediatrics Faculty Papers

Mucopolysaccharidosis IVA (MPS IVA) is a lysosomal storage disease caused by mutations in the gene encoding the lysosomal enzyme N-acetylgalactosamine-6-sulfate sulfatase (GALNS), resulting in the accumulation of keratan sulfate (KS) and chondroitin-6-sulfate (C6S). Previously, it was reported the production of an active human recombinant GALNS (rGALNS) in E. coli BL21(DE3). However, this recombinant enzyme was not taken up by HEK293 cells or MPS IVA skin fibroblasts. Here, we leveraged a glyco-engineered E. coli strain to produce a recombinant human GALNS bearing the eukaryotic trimannosyl core N-glycan, Man3GlcNAc2 (rGALNSoptGly). The N-glycosylated GALNS was produced at 100 …

Ethical, Legal, And Policy Challenges In Field-Based Neuroimaging Research Using Emerging Portable Mri Technologies: Guidance For Investigators And For Oversight, Francis X. Shen, Susan M. Wolf, Frances P. Lawrenz, Donnella S. Comeau, Kafui Dzirasa, Barbara J. Evans, Damien A. Fair, Martha J. Farah, Duke Han, Judy Illes, Jonathan D. Jackson, Eran Klein, Karen S. Rommelfanger, Matthew S. Rosen, Efraín Torres, Paul Tuite, J. Thomas Vaughan, Michael Garwood

UF Law Faculty Publications

Researchers are rapidly developing and deploying highly portable MRI technology to conduct field-based research. The new technology will widen access to include new investigators in remote and unconventional settings and will facilitate greater inclusion of rural, economically disadvantaged, and historically underrepresented populations. To address the ethical, legal, and societal issues raised by highly accessible and portable MRI, an interdisciplinary Working Group (WG) engaged in a multi-year structured process of analysis and consensus building, informed by empirical research on the perspectives of experts and the general public. This article presents the WG’s consensus recommendations. These recommendations address technology quality control, design …

Social Determinants Of Health And Other Predictors In Initiation Of Treatment With Cdk4/6 Inhibitors For Hr+/Her2- Metastatic Breast Cancer, Ravi K Goyal, Sean D Candrilli, Susan Abughosh, Hua Chen, Holly M Holmes, Michael L Johnson

Faculty, Staff and Student Publications

In hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer (MBC), cyclin-dependent kinase 4/6 inhibitors (CDK4/6is) have replaced endocrine therapy alone as the standard of care; however, several barriers to treatment initiation still exist. We assessed social determinants of health (SDOH) and other factors associated with the initiation of CDK4/6i for HR+/HER2- MBC in the Medicare population. Using a retrospective cohort design, patients aged ≥65 years and diagnosed during 2015-2017 were selected from the SEER-Medicare database. Time from MBC diagnosis to first CDK4/6i initiation was the study outcome. The effect of SDOH measures and other predictors on the …

Defining The Kras- And Erk-Dependent Transcriptome In Kras-Mutant Cancers, Jeffrey A Klomp, Jennifer E Klomp, Clint A Stalnecker, Kirsten L Bryant, A Cole Edwards, Kristina Drizyte-Miller, Priya S Hibshman, J Nathaniel Diehl, Ye S Lee, Alexis J Morales, Khalilah E Taylor, Sen Peng, Nhan L Tran, Laura E Herring, Alex W Prevatte, Natalie K Barker, Laura D Hover, Jill Hallin, Alexey Sorokin, Preeti Marie Kanikarla, Saikat Chowdhury, Oluwadara Coker, Hey Min Lee, Craig M Goodwin, Prson Gautam, Peter Olson, James G Christensen, John P Shen, Scott Kopetz, Lee M Graves, Kian-Huat Lim, Andrea Wang-Gillam, Krister Wennerberg, Adrienne D Cox, Channing J Der

Faculty, Staff and Student Publications

How the KRAS oncogene drives cancer growth remains poorly understood. Therefore, we established a systemwide portrait of KRAS- and ERK-dependent gene transcription in KRAS-mutant cancer to delineate the molecular mechanisms of growth and of inhibitor resistance. Unexpectedly, our KRAS-dependent gene signature diverges significantly from the frequently cited Hallmark KRAS signaling gene signature, is driven predominantly through the ERK mitogen-activated protein kinase (MAPK) cascade, and accurately reflects KRAS- and ERK-regulated gene transcription in KRAS-mutant cancer patients. Integration with our ERK-regulated phospho- and total proteome highlights ERK deregulation of the anaphase promoting complex/cyclosome and other components of the cell cycle machinery as …

Placental Co-Transcriptional Activator Vestigial-Like 1 (Vgll1) Drives Tumorigenesis Via Increasing Transcription Of Proliferation And Invasion Genes, Heather M Sonnemann, Barbara Pazdrak, Barbara Nassif, Yimo Sun, Lama Elzohary, Amjad H Talukder, Arjun S Katailiha, Krishna Bhat, Gregory Lizée

Faculty, Staff and Student Publications

INTRODUCTION: Vestigial-like 1 (VGLL1) is a co-transcriptional activator that binds to TEA domain-containing transcription factors (TEADs). Its expression is upregulated in a variety of aggressive cancer types, including pancreatic and basal-like breast cancer, and increased transcription of VGLL1 is strongly correlated with poor prognosis and decreased overall patient survival. In normal tissues, VGLL1 is most highly expressed within placental trophoblast cells, which share the common attributes of rapid cellular proliferation and invasion with tumor cells. The impact of VGLL1 in cancer has not been fully elucidated and no VGLL1-targeted therapy currently exists.

METHODS: The aim of this study was to …

Vertebral Hu Value And The Pectoral Muscle Index Based On Chest Ct Can Be Used To Opportunistically Screen For Osteoporosis, Xiong-Yi Wang, Sheng Pan, Wei-Feng Liu, Yi-Ke Wang, Si-Min Yun, You-Jia Xu

Faculty, Staff and Student Publications

BACKGROUND: Existing studies have shown that computed tomography (CT) attenuation and skeletal muscle tissue are strongly associated with osteoporosis; however, few studies have examined whether vertebral HU values and the pectoral muscle index (PMI) measured at the level of the 4th thoracic vertebra (T4) are strongly associated with bone mineral density (BMD). In this study, we demonstrate that vertebral HU values and the PMI based on chest CT can be used to opportunistically screen for osteoporosis and reduce fracture risk through prompt treatment.

METHODS: We retrospectively evaluated 1000 patients who underwent chest CT and DXA scans from August 2020-2022. The …

Hnrnpm Protects Against The Dsrna-Mediated Interferon Response By Repressing Line-Associated Cryptic Splicing, Rong Zheng, Mikayla Dunlap, Georg O M Bobkov, Carlos Gonzalez-Figueroa, Khushali J Patel, Jingyi Lyu, Samuel E Harvey, Tracey W Chan, Giovanni Quinones-Valdez, Mudra Choudhury, Charlotte A Le Roux, Mason D Bartels, Amy Vuong, Ryan A Flynn, Howard Y Chang, Eric L Van Nostrand, Xinshu Xiao, Chonghui Cheng

Faculty, Staff and Students Publications

RNA splicing is pivotal in post-transcriptional gene regulation, yet the exponential expansion of intron length in humans poses a challenge for accurate splicing. Here, we identify hnRNPM as an essential RNA-binding protein that suppresses cryptic splicing through binding to deep introns, maintaining human transcriptome integrity. Long interspersed nuclear elements (LINEs) in introns harbor numerous pseudo splice sites. hnRNPM preferentially binds at intronic LINEs to repress pseudo splice site usage for cryptic splicing. Remarkably, cryptic exons can generate long dsRNAs through base-pairing of inverted ALU transposable elements interspersed among LINEs and consequently trigger an interferon response, a well-known antiviral defense mechanism. …

Metabolic Regulator Errγ Governs Gastric Stem Cell Differentiation Into Acid-Secreting Parietal Cells, Mahliyah Adkins-Threats, Sumimasa Arimura, Yang-Zhe Huang, Margarita Divenko, Sarah To, Heather Mao, Yongji Zeng, Jenie Y Hwang, Joseph R Burclaff, Shilpa Jain, Jason C Mills

Faculty, Staff and Students Publications

Parietal cells (PCs) produce gastric acid to kill pathogens and aid digestion. Dysregulated PC census is common in disease, yet how PCs differentiate is unclear. Here, we identify the PC progenitors arising from isthmal stem cells, using mouse models and human gastric cells, and show they preferentially express cell-metabolism regulator and orphan nuclear receptor Estrogen-related receptor gamma (Esrrg, encoding ERRγ). Esrrg expression facilitated the tracking of stepwise molecular, cellular, and ultrastructural stages of PC differentiation. Esrrg^P2ACreERT2 lineage tracing revealed Esrrg expression commits progenitors to differentiate into mature PCs. scRNA-seq indicated the earliest Esrrg+ PC progenitors preferentially …

Quantitative Proteomic Analysis Reveals Unique Hsp90 Cycle-Dependent Client Interactions, Erick I Rios, Davi Gonçalves, Kevin A Morano, Jill L Johnson

Faculty, Staff and Student Publications

Hsp90 is an abundant and essential molecular chaperone that mediates the folding and activation of client proteins in a nucleotide-dependent cycle. Hsp90 inhibition directly or indirectly impacts the function of 10-15% of all proteins due to degradation of client proteins or indirect downstream effects. Due to its role in chaperoning oncogenic proteins, Hsp90 is an important drug target. However, compounds that occupy the ATP-binding pocket and broadly inhibit function have not achieved widespread use due to negative effects. More selective inhibitors are needed; however, it is unclear how to achieve selective inhibition. We conducted a quantitative proteomic analysis of soluble …

Clinical Practice Guidelines For The Care Of Girls And Women With Turner Syndrome, Claus H Gravholt, Niels H Andersen, Sophie Christin-Maitre, Shanlee M Davis, Anthonie Duijnhouwer, Aneta Gawlik, Andrea T Maciel-Guerra, Iris Gutmark-Little, Kathrin Fleischer, David Hong, Karen O Klein, Siddharth K Prakash, Roopa Kanakatti Shankar, David E Sandberg, Theo C J Sas, Anne Skakkebæk, Kirstine Stochholm, Janielle A Van Der Velden, International Turner Syndrome Consensus Group, Philippe F Backeljauw

Faculty, Staff and Student Publications

Turner syndrome (TS) affects 50 per 100 000 females. TS affects multiple organs through all stages of life, necessitating multidisciplinary care. This guideline extends previous ones and includes important new advances, within diagnostics and genetics, estrogen treatment, fertility, co-morbidities, and neurocognition and neuropsychology. Exploratory meetings were held in 2021 in Europe and United States culminating with a consensus meeting in Aarhus, Denmark in June 2023. Prior to this, eight groups addressed important areas in TS care: (1) diagnosis and genetics, (2) growth, (3) puberty and estrogen treatment, (4) cardiovascular health, (5) transition, (6) fertility assessment, monitoring, and counselling, (7) health …

Medmicromaps, A Novel Decision-Tree Guide For Infectious Diseases Differential Diagnoses, And Evaluation Of Pre- And Post-Pandemic User Engagement By Preclinical Medical Students, Jason Ceballos, Tavsimran Luthra, Lucia Garces-Torres, Valerie Lentz, Jack Nelson, Claudia Carceles-Roman, Ian Holyoak, Jane Harrington

International Journal of Emerging and Disruptive Innovation in Education : VISIONARIUM

Background: Medical education has undergone major changes in the past 5 years to adapt to the digital-centered student population with diverse learning preferences. To address the challenges of shifting delivery modalities, multimedia resources were created to provide interactive e-learning material on infectious diseases for year 2 medical students.

Methods: Medical students at a USA-accredited Caribbean medical school were provided with supplemental e-learning materials including animations, illustrations, diagnostic algorithms aka MedMicroMaps, and Case-Based tutorials. Participants were classified by semester and lecture delivery: In-person: Cohort 1 (n=526); Virtual: Cohort 2 (n=651); and Hybrid: Cohort 3 ( …

Developing An Ethics And Policy Framework For Psychedelic Clinical Care: A Consensus Statement, Amy L Mcguire, I Glenn Cohen, Dominic Sisti, Matthew Baggott, Yuria Celidwen, Nese Devenot, Sabrina Gracias, Charles Grob, Ifetayo Harvey, Brent Kious, Mason Marks, Michael Mithoefer, Elizabeth Nielson, Dost Öngür, Alexandra Pallas, Andrew Peterson, Eduardo E Schenberg, Paul Summergrad, Brett Waters, Monnica T Williams, David B Yaden

Center for Medical Ethics and Health Policy Staff Publications

Importance: As government agencies around the globe contemplate approval of the first psychedelic medicines, many questions remain about their ethical integration into mainstream medical practice.

Objective: To identify key ethics and policy issues related to the eventual integration of psychedelic therapies into clinical practice.

Evidence review: From June 9 to 12, 2023, 27 individuals representing the perspectives of clinicians, researchers, Indigenous groups, industry, philanthropy, veterans, retreat facilitators, training programs, and bioethicists convened at the Banbury Center at Cold Spring Harbor Laboratory. Prior to the meeting, attendees submitted key ethics and policy issues for psychedelic medicine. Responses were categorized into 6 …

Phosphatidylserine Regulates Plasma Membrane Repair Through Tetraspanin-Enriched Macrodomains, Yang E Li, Dougall M Norris, Fanqian N Xiao, Elvis Pandzic, Renee M Whan, Sandra Fok, Ming Zhou, Guangwei Du, Yang Liu, Ximing Du, Hongyuan Yang

Faculty, Staff and Student Publications

The integrity of the plasma membrane is critical to cell function and survival. Cells have developed multiple mechanisms to repair damaged plasma membranes. A key process during plasma membrane repair is to limit the size of the damage, which is facilitated by the presence of tetraspanin-enriched rings surrounding damage sites. Here, we identify phosphatidylserine-enriched rings surrounding damaged sites of the plasma membrane, resembling tetraspanin-enriched rings. Importantly, the formation of both the phosphatidylserine- and tetraspanin-enriched rings requires phosphatidylserine and its transfer proteins ORP5 and ORP9. Interestingly, ORP9, but not ORP5, is recruited to the damage sites, suggesting cells acquire phosphatidylserine from …

Irx4204 Induces Senescence And Cell Death In Her2-Positive Breast Cancer And Synergizes With Anti-Her2 Therapy, Cassandra L Moyer, Amanda Lanier, Jing Qian, Darian Coleman, Jamal Hill, Vidyasagar Vuligonda, Martin E Sanders, Abhijit Mazumdar, Powel H Brown

Faculty, Staff and Student Publications

PURPOSE: Rexinoids, agonists of nuclear retinoid X receptor (RXR), have been used for the treatment of cancers and are well tolerated in both animals and humans. However, the usefulness of rexinoids in treatment of breast cancer remains unknown. This study examines the efficacy of IRX4204, a highly specific rexinoid, in breast cancer cell lines and preclinical models to identify a biomarker for response and potential mechanism of action.

EXPERIMENTAL DESIGN: IRX4204 effects on breast cancer cell growth and viability were determined using cell lines, syngeneic mouse models, and primary patient-derived xenograft (PDX) tumors. In vitro assays of cell cycle, apoptosis, …

Identifying Targetable Vulnerabilities To Circumvent Or Overcome Venetoclax Resistance In Diffuse Large B-Cell Lymphoma, Clare M. Adams, Amanda Mcbride, Peter Michener, Irina Shkundina, Ramkrishna Mitra, Hyun Hwan An, Pierluigi Porcu, Christine M. Eischen

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Clinical trials with single-agent venetoclax/ABT-199 (anti-apoptotic BCL2 inhibitor) revealed that diffuse large B-cell lymphoma (DLBCL) is not solely dependent on BCL2 for survival. Gaining insight into pathways/proteins that increase venetoclax sensitivity or unique vulnerabilities in venetoclax-resistant DLBCL would provide new potential treatment avenues. Therefore, we generated acquired venetoclax-resistant DLBCL cells and evaluated these together with intrinsically venetoclax-resistant and -sensitive DLBCL lines. We identified resistance mechanisms, including alterations in BCL2 family members that differed between intrinsic and acquired venetoclax resistance and increased dependencies on specific pathways. Although combination treatments with BCL2 family member inhibitors may overcome venetoclax resistance, RNA-sequencing and drug/compound …

Individuals With Jak1 Variants Are Affected By Syndromic Features Encompassing Autoimmunity, Atopy, Colitis, And Dermatitis, Michael E Horesh, Marta Martin-Fernandez, Conor Gruber, Sofija Buta, Tom Le Voyer, Eve Puzenat, Harry Lesmana, Yiming Wu, Ashley Richardson, David Stein, Stephanie Hodeib, Mariam Youssef, Jacob A Kurowski, Elizabeth Feuille, Luis A Pedroza, Ramsay L Fuleihan, Alexandria Haseley, Alain Hovnanian, Pierre Quartier, Jérémie Rosain, Georgina Davis, Daniel Mullan, O'Jay Stewart, Roosheel Patel, Angelica E Lee, Rebecca Rubinstein, Leyla Ewald, Nikhil Maheshwari, Virginia Rahming, Ivan K Chinn, James R Lupski, Jordan S Orange, Vanessa Sancho-Shimizu, Jean-Laurent Casanova, Noura S Abul-Husn, Yuval Itan, Joshua D Milner, Jacinta Bustamante, Dusan Bogunovic

Faculty, Staff and Students Publications

Inborn errors of immunity lead to autoimmunity, inflammation, allergy, infection, and/or malignancy. Disease-causing JAK1 gain-of-function (GoF) mutations are considered exceedingly rare and have been identified in only four families. Here, we use forward and reverse genetics to identify 59 individuals harboring one of four heterozygous JAK1 variants. In vitro and ex vivo analysis of these variants revealed hyperactive baseline and cytokine-induced STAT phosphorylation and interferon-stimulated gene (ISG) levels compared with wild-type JAK1. A systematic review of electronic health records from the BioME Biobank revealed increased likelihood of clinical presentation with autoimmunity, atopy, colitis, and/or dermatitis in JAK1 variant-positive individuals. Finally, …

Klrg1 Cell Depletion As A Novel Therapeutic Strategy In Patients With Mature T-Cell Lymphoma Subtypes, Bimarzhan Assatova, Robert Willim, Christopher Trevisani, Garrett Haskett, Khyati Maulik Kariya, Kusha Chopra, Sung Rye Park, Michael Yevgeniy Tolstorukov, Sean M Mccabe, Jessica Duffy, Abner Louissaint, Jani Huuhtanen, Dipabarna Bhattacharya, Satu Mustjoki, Min Jung Koh, Foster Powers, Elizabeth A Morgan, Lei Yang, Brandy Pinckney, Matthew J Cotton, Andrew Crabbe, Jessica Beth Ziemba, Ian Brain, Tayla B Heavican-Foral, Javeed Iqbal, Ronald Nemec, Anna Baird Rider, Josie Germain Ford, Min Ji Koh, Nora Scanlan, David J Feith, Thomas P Loughran, Won Seog Kim, Jaehyuk Choi, Juliette Roels, Lena Boehme, Tom Putteman, Tom Taghon, Jeffrey A Barnes, P Connor Johnson, Eric D Jacobsen, Steven A Greenberg, David M Weinstock, Salvia Jain

Faculty, Staff and Student Publications

Purpose: Develop a novel therapeutic strategy for patients with subtypes of mature T-cell and NK-cell neoplasms.

Experimental design: Primary specimens, cell lines, patient-derived xenograft models, commercially available, and proprietary anti-KLRG1 antibodies were used for screening, target, and functional validation.

Results: Here we demonstrate that surface KLRG1 is highly expressed on tumor cells in subsets of patients with extranodal NK/T-cell lymphoma (ENKTCL), T-prolymphocytic leukemia (T-PLL), and gamma/delta T-cell lymphoma (G/D TCL). The majority of the CD8+/CD57+ or CD3-/CD56+ leukemic cells derived from patients with T- and NK-large granular lymphocytic leukemia (T-LGLL and NK-LGLL), respectively, expressed surface KLRG1. The humanized afucosylated anti-KLRG1 …

Maintenance Pembrolizumab Therapy In Patients With Metastatic Her2-Negative Breast Cancer With Prior Response To Chemotherapy, Toshiaki Iwase, Evan N Cohen, Hui Gao, Angela Alexander, Megumi Kai, Vivian Chiv, Xiaoping Wang, Savitri Krishnamurthy, Diane Liu, Yu Shen, Kumiko Kida, Alexandre Reuben, Rachel M Layman, David L Ramirez, Debasish Tripathy, Stacy L Moulder, Clinton Yam, Vicente Valero, Bora Lim, James M Reuben, Naoto T Ueno

Faculty, Staff and Student Publications

Purpose: Accumulating toxicities hinder indefinite chemotherapy for many patients with metastatic/recurrent HER2-negative breast cancer. We conducted a phase II trial of pembrolizumab monotherapy following induction chemotherapy to determine the efficacy of maintenance immunotherapy in patients with metastatic HER2-negative inflammatory breast cancer (IBC) and non-IBC triple-negative breast cancer (TNBC) and a biomarker study.

Patients and methods: Patients with a complete response, partial response, or stable disease (SD) after at least three cycles of chemotherapy for HER2-negative breast cancer received pembrolizumab, regardless of programmed death-ligand 1 expression. Pembrolizumab (200 mg) was administered every 3 weeks until disease progression, intolerable toxicity, or 2 …

Telomere Dysfunction Alters Intestinal Stem Cell Dynamics To Promote Cancer, Kyle A Labella, Wen-Hao Hsu, Jiexi Li, Yutao Qi, Yonghong Liu, Jingjing Liu, Chia-Chin Wu, Yang Liu, Zingzhi Song, Yiyun Lin, Jonathan M Blecher, Shan Jiang, Xiaoying Shang, Jincheng Han, Denise J Spring, Jianhua Zhang, Yan Xia, Ronald A Depinho

Faculty, Staff and Student Publications

Telomere dynamics are linked to aging hallmarks, and age-associated telomere loss fuels the development of epithelial cancers. In Apc-mutant mice, the onset of DNA damage associated with telomere dysfunction has been shown to accelerate adenoma initiation via unknown mechanisms. Here, we observed that Apc-mutant mice engineered to experience telomere dysfunction show accelerated adenoma formation resulting from augmented cell competition and clonal expansion. Mechanistically, telomere dysfunction induces the repression of EZH2, resulting in the derepression of Wnt antagonists, which causes the differentiation of adjacent stem cells and a relative growth advantage to Apc-deficient telomere dysfunctional cells. Correspondingly, in this mouse model, …

Assessment Of Brain-Derived Extracellular Vesicle Enrichment For Blood Biomarker Analysis In Age-Related Neurodegenerative Diseases: An International Overview, Amanpreet Badhwar, Yael Hirschberg, Natalia Valle-Tamayo, Florencia Iulita, Chinedu Momoh, Anna Matton, Rawan Tarawneh, Robert Rissman, Aurélie Ledreux, Charisse Winston

Brain and Mind Institute

INTRODUCTION Brain-derived extracellular vesicles (BEVs) in blood allows for minimally-invasive investigations of central nervous system (CNS) -specific markers of age-related neurodegenerative diseases (NDDs). Polymer-based EV- and immunoprecipitation (IP)-based BEV-enrichment protocols from blood have gained popularity. We systematically investigated protocol consistency across studies, and determined CNS-specificity of proteins associated with these protocols.

METHODS NDD articles investigating BEVs in blood using polymer-based and/or IP-based BEV enrichment protocols were systematically identified, and protocols compared. Proteins used for BEV-enrichment and/or post-enrichment were assessed for CNS- and brain-cell-type-specificity, extracellular domains (ECD+), and presence in EV-databases.

RESULTS A total of 82.1% of studies used polymer-based (ExoQuick) …

An Indocyanine Green-Based Liquid Biopsy Test For Circulating Tumor Cells For Pediatric Liver Cancer, Andres F Espinoza, Pavan Kureti, Roma H Patel, Susan L Do, Saiabhiroop R Govindu, Bryan W Armbruster, Martin Urbicain, Kalyani R Patel, Dolores Lopez-Terrada, Sanjeev A Vasudevan, Sarah E Woodfield

Faculty, Staff and Students Publications

Background: Hepatoblastoma and HCC are the most common malignant hepatocellular tumors seen in children. The aim of this study was to develop a liquid biopsy test for circulating tumor cells (CTCs) for these tumors that would be less invasive and provide real-time information about tumor response to therapy.

Methods: For this test, we utilized indocyanine green (ICG), a far-red fluorescent dye used clinically to identify malignant liver cells during surgery. We assessed ICG accumulation in cell lines using fluorescence microscopy and flow cytometry. For our CTC test, we developed a panel of liver tumor-specific markers, including ICG, Glypican-3, and DAPI, …

Challenges And Implications For Substance Use And Mental Healthcare Among Under-Resourced Women In The Covid-19 Era, Maria C Mejia, Alicia Kowalchuk, Sandra J Gonzalez, Muktha Nair, Lisa Webb, Nadine Scamp

Faculty, Staff and Students Publications

BACKGROUND: The COVID-19 pandemic exacerbated disparities in mental healthcare and substance use disorder (SUD) treatment access, especially in under-resourced communities. This study aimed to comprehend the experiences of under-resourced women with SUD during the pandemic, their knowledge and attitudes toward it, and its impact on substance use and treatment access.

METHODS: A cross-sectional study included 66 under-resourced women receiving medically managed withdrawal treatment at a community residential SUD center. Data collection occurred between November 2021 and August 2022, utilizing a 75-item instrument covering COVID-19 exposure and its impact on health, substance use, treatment access, vaccination status, beliefs, and knowledge. Descriptive …

Kcnk1 Promotes Proliferation And Metastasis Of Breast Cancer Cells By Activating Lactate Dehydrogenase A (Ldha) And Up-Regulating H3k18 Lactylation, Xiangchan Hou, Jiawei Ouyang, Le Tang, Pan Wu, Xiangying Deng, Qijia Yan, Lei Shi, Songqing Fan, Chunmei Fan, Can Guo, Qianjin Liao, Yong Li, Wei Xiong, Guiyuan Li, Zhaoyang Zeng, Fuyan Wang

Faculty, Staff and Students Publications

Breast cancer is the most prevalent malignancy and the most significant contributor to mortality in female oncology patients. Potassium Two Pore Domain Channel Subfamily K Member 1 (KCNK1) is differentially expressed in a variety of tumors, but the mechanism of its function in breast cancer is unknown. In this study, we found for the first time that KCNK1 was significantly up-regulated in human breast cancer and was correlated with poor prognosis in breast cancer patients. KCNK1 promoted breast cancer proliferation, invasion, and metastasis in vitro and vivo. Further studies unexpectedly revealed that KCNK1 increased the glycolysis and lactate production in …

An Indocyanine Green-Based Liquid Biopsy Test For Circulating Tumor Cells For Pediatric Liver Cancer, Andres F Espinoza, Pavan Kureti, Roma H Patel, Susan L Do, Saiabhiroop R Govindu, Bryan W Armbruster, Martin Urbicain, Kalyani R Patel, Dolores Lopez-Terrada, Sanjeev A Vasudevan, Sarah E Woodfield

Faculty, Staff and Students Publications

Background: Hepatoblastoma and HCC are the most common malignant hepatocellular tumors seen in children. The aim of this study was to develop a liquid biopsy test for circulating tumor cells (CTCs) for these tumors that would be less invasive and provide real-time information about tumor response to therapy.

Methods: For this test, we utilized indocyanine green (ICG), a far-red fluorescent dye used clinically to identify malignant liver cells during surgery. We assessed ICG accumulation in cell lines using fluorescence microscopy and flow cytometry. For our CTC test, we developed a panel of liver tumor-specific markers, including ICG, Glypican-3, and DAPI, …

Why Does The Cost Of Employer-Sponsored Coverage Keep Rising?, Salpy Kanimian, Vivian Ho

Center for Medical Ethics and Health Policy Staff Publications

Over the past 25 years, the gap between the increase in health insurance costs and workers' wages has significantly expanded. This trend has led to significant concerns about healthcare affordability, with surveys revealing conflicting opinions regarding whether hospitals or health insurance companies bear the blame for escalating costs. To better understand these dynamics, we examined consumer price indices for health insurance, hospital services, and professional services from 2006 to 2023 using Bureau of Labor Statistics data. Our analysis shows that the hospital price index rose steadily between 2006 and 2023, faster than insurance premiums or professional services. To examine whether …

Persistent ∆Fosb Expression Limits Recurrent Seizure Activity And Provides Neuroprotection In The Dentate Gyrus Of App Mice, Gabriel S Stephens, Jin Park, Andrew Eagle, Jason You, Manuel Silva-Pérez, Chia-Hsuan Fu, Sumin Choi, Corey P St Romain, Chiho Sugimoto, Shelly A Buffington, Yi Zheng, Mauro Costa-Mattioli, Yin Liu, A J Robison, Jeannie Chin

Faculty, Staff and Student Publications

Recurrent seizures lead to accumulation of the activity-dependent transcription factor ∆FosB in hippocampal dentate granule cells in both mouse models of epilepsy and mouse models of Alzheimer's disease (AD), which is also associated with increased incidence of seizures. In patients with AD and related mouse models, the degree of ∆FosB accumulation corresponds with increasing severity of cognitive deficits. We previously found that ∆FosB impairs spatial memory in mice by epigenetically regulating expression of target genes such as calbindin that are involved in synaptic plasticity. However, the suppression of calbindin in conditions of neuronal hyperexcitability has been demonstrated to provide neuroprotection …

Purkinje Cell Dysfunction Causes Disrupted Sleep In Ataxic Mice, Luis E Salazar Leon, Amanda M Brown, Heet Kaku, Roy V Sillitoe

Duncan NRI Faculty and Staff Publications

Purkinje cell dysfunction disrupts movement and causes disorders such as ataxia. Recent evidence suggests that Purkinje cell dysfunction may also alter sleep regulation. Here, we used an ataxic mouse model generated by silencing Purkinje cell neurotransmission (L7Cre;Vgatfx/fx) to better understand how cerebellar dysfunction impacts sleep physiology. We focused our analysis on sleep architecture and electrocorticography (ECoG) patterns based on their relevance to extracting physiological measurements during sleep. We found that circadian activity was unaltered in the mutant mice, although their sleep parameters and ECoG patterns were modified. The L7Cre;Vgatfx/fx mutant mice had decreased wakefulness and rapid eye movement (REM) sleep, …

Development Of An Antioxidant-Rich Sugar-Free Plantain Candy And Assessment Of Its Shelf Life In A Flexible Laminate, Poulami Sarkar, Paramita Bhattacharjee, Bidhan Das

Faculty, Staff and Student Publications

RESEARCH BACKGROUND: Candy is a popular confection worldwide, and it would be beneficial to society if it were converted into a source of antioxidant molecules to eliminate its adverse health effects. The amount of antioxidants available even in fruit candies is questionable due to the high thermal processing losses they undergo and the presence of various food additives. Plantains (

EXPERIMENTAL APPROACH: To accomplish the first objective, lyophilized plantain powder, sorbitol and mannitol were used as base materials with minimal additives under minimal processing conditions to reduce processing loss. Sensory, proximate, physicochemical and phytochemical properties, including the antioxidant synergy among …

Trends In Shortages Of Lead Chelators From 2001 To 2022, James D Whitledge, Pelayia Soto, Kieran M Glowacki, Diane P Calello, Erin R Fox, Maryann Mazer-Amirshahi

Faculty, Staff and Student Publications

OBJECTIVE: The study aims to describe drug shortages affecting lead chelators in the United States from 2001 through 2022.

METHODS: Drug shortage data were retrieved from the University of Utah Drug Information Service from January 1, 2001, through December 31, 2022. Shortages of first- and second-line lead chelators were analyzed. Drug class, formulation, administration route, shortage reason, shortage duration, generic status, single-source status, and presence of temporally overlapping shortages were examined. Total shortage months, percentages of study period on shortage, and median shortage durations were calculated.

RESULTS: Thirteen lead chelator shortages were reported during the study period. Median duration was …

Social Connectedness And Adolescent Suicide Risk, Alejandra Arango, David Brent, Jacqueline Grupp-Phelan, Bradley J Barney, Anthony Spirito, Megan M Mroczkowski, Rohit Shenoi, Melinda Mahabee-Gittens, T Charles Casper, Cheryl King

Faculty, Staff and Students Publications

Background: Despite evidence of the importance of interpersonal connectedness to our understanding of suicide risk, relatively little research has examined the protective and buffering effects of connectedness among adolescents. The aims of this study were to determine: (a) whether overall connectedness (composite of family, peer, and school) and specific domains of connectedness were related to a lower likelihood of suicide attempts, and (b) whether these factors buffer the prospective risk of suicide attempt for high-risk subgroups (i.e., recent suicidal ideation and/or lifetime history of suicide attempt, peer victimization, or sexual and gender minority status).

Methods: Participants were 2,897 adolescents (64.7% …