Digital Commons Network^™

Integration Of Electrospun Scaffolds And Biological Polymers For Enhancing The Delivery And Efficacy Of Mesenchymal Stem/Stromal Cell Therapies, Allan John R Barcena, Archana Mishra, Dominic Karl M Bolinas, Benjamin M Martin, Marites P Melancon

Faculty, Staff and Student Publications

Mesenchymal stem/stromal cells (MSCs) have emerged as a promising therapeutic approach for a variety of diseases due to their immunomodulatory and tissue regeneration capabilities. Despite their potential, the clinical application of MSC therapies is hindered by limited cell retention and engraftment at the target sites. Electrospun scaffolds, with their high surface area-to-volume ratio and tunable physicochemical properties, can be used as platforms for MSC delivery. However, synthetic polymers often lack the bioactive cues necessary for optimal cell-scaffold interactions. Integrating electrospun scaffolds and biological polymers, such as polysaccharides, proteins, and composites, combines the mechanical integrity of synthetic materials with the bioactivity …

What Questions Do Patients Ask About Biologic Therapies For Chronic Sinusitis With Nasal Polyps?, Samuel E Razmi, Lexi Goehring, Aatin K Dhanda, Jason Shenoi, Faizaan Khan, Keyvon Rashidi, Daniel Gorelik, Kenneth R Sims, Meha G Fox, Masayoshi Takashima, Omar G Ahmed

Faculty, Staff and Students Publications

Objective: The objective of this study is to explore the questions commonly asked online about biologic therapies for use in treatment of chronic sinusitis with nasal polyps (CRSwNP) and the quality of the available content.

Methods: Most common search terms were identified via Google Trends. People Also Ask (PAA) questions were identified and extracted with their associated website using an online data-scraping program [Search Engine Optimization (SEO) Minion, Keywords Everywhere]. Sources were evaluated using Flesch Kincaid Grade Level (FKGL) and Flesch Reading Ease (FRE, higher number = better) score for readability; Journal of American Medical Association (JAMA) Benchmark …

Black Holes In Time: The Effect Of Grid Radiation On The Tumor Immune Microenvironment, Rebecca A. Bekker

USF Tampa Graduate Theses and Dissertations

Tumor-immune interactions shape a developing tumor and its tumor immune microenvironment (TIME) resulting in either well-infiltrated, immunologically inflamed ‘hot’ tumor beds, or ‘cold’ immune deserts with low levels of infiltration. The pre-treatment immune state of the TIME is associated with treatment outcome; immunologically hot tumors generally exhibit better responses to radio- and immunotherapy than cold tumors. However, radiotherapy is known to induce opposing immunological consequences, resulting in both immunostimulatory and inhibitory responses. In fact, it is thought that the radiation induced tumoricidal immune response is curtailed by subsequent applications of radiation. Thus, I hypothesize that spatially fractionated radiotherapy (SFRT), administered …

Agenda (Pdf), Department Of Orthopaedic Surgery

Dept. of Orthopaedics: Robert D. D’Ambrosia Lectureship & Research Day

No abstract provided.

Event Booklet (Pdf), Department Of Orthopaedic Surgery

Dept. of Orthopaedics: Robert D. D’Ambrosia Lectureship & Research Day

No abstract provided.

Methphaser: Methylation-Based Long-Read Haplotype Phasing Of Human Genomes, Yilei Fu, Sergey Aganezov, Medhat Mahmoud, John Beaulaurier, Sissel Juul, Todd J Treangen, Fritz J Sedlazeck

Faculty, Staff and Students Publications

The assignment of variants across haplotypes, phasing, is crucial for predicting the consequences, interaction, and inheritance of mutations and is a key step in improving our understanding of phenotype and disease. However, phasing is limited by read length and stretches of homozygosity along the genome. To overcome this limitation, we designed MethPhaser, a method that utilizes methylation signals from Oxford Nanopore Technologies to extend Single Nucleotide Variation (SNV)-based phasing. We demonstrate that haplotype-specific methylations extensively exist in Human genomes and the advent of long-read technologies enabled direct report of methylation signals. For ONT R9 and R10 cell line data, we …

The Effect Of Early Postnatal Auditory Stimulation On Outcomes In Preterm Infants, Juliann M. Di Fiore, Gloria Liu, Kenneth A. Loparo, Cynthia F. Bearer

Faculty Scholarship

Abstract: Preterm infants are deprived of in utero sensory stimulation during the third trimester, an important period of central nervous system development. As a result, maturational trajectories are often reduced in infants born preterm. One such system affected is the brain including the auditory and respiratory control pathways. During normal pregnancy the intrauterine environment attenuates external auditory stimuli while exposing the fetus to filtered maternal voice, intra-abdominal sounds, and external stimuli. In contrast, during the third trimester of development, preterm infants are exposed to a vastly different soundscape including non-attenuated auditory sounds and a lack of womb related stimuli, both …

Aso Author Reflections: Isolated Margin Positivity In Localized Pancreatic Ductal Adenocarcinoma And Operative Margin Revision, Lee M. Ocuin

Faculty Scholarship

No abstract provided.

Multiple Omics Levels Of Chronic Lymphocytic Leukemia, Aleksander Turk, Eva Čeh, George A Calin, Tanja Kunej

Faculty, Staff and Student Publications

Chronic lymphocytic leukemia (CLL) is a lymphoproliferative malignancy characterized by the proliferation of functionally mature but incompetent B cells. It is the most prevalent type of leukemia in Western populations, accounting for approximately 25% of new leukemia cases. While recent advances, such as ibrutinib and venetoclax treatment have improved patient outlook, aggressive forms of CLL such as Richter transformation still pose a significant challenge. This discrepancy may be due to the heterogeneity of factors contributing to CLL development at multiple -omics levels. However, information on the omics of CLL is fragmented, hindering multi-omics-based research into potential treatment options. To address …

Elucidating Immune-Related Gene Transcriptional Programs Via Factorization Of Large-Scale Rna-Profiles, Shan He, Matthew M Gubin, Hind Rafei, Rafet Basar, Merve Dede, Xianli Jiang, Qingnan Liang, Yukun Tan, Kunhee Kim, Maura L Gillison, Katayoun Rezvani, Weiyi Peng, Cara Haymaker, Sharia Hernandez, Luisa M Solis, Vakul Mohanty, Ken Chen

Faculty, Staff and Student Publications

Recent developments in immunotherapy, including immune checkpoint blockade (ICB) and adoptive cell therapy (ACT), have encountered challenges such as immune-related adverse events and resistance, especially in solid tumors. To advance the field, a deeper understanding of the molecular mechanisms behind treatment responses and resistance is essential. However, the lack of functionally characterized immune-related gene sets has limited data-driven immunological research. To address this gap, we adopted non-negative matrix factorization on 83 human bulk RNA sequencing (RNA-seq) datasets and constructed 28 immune-specific gene sets. After rigorous immunologist-led manual annotations and orthogonal validations across immunological contexts and functional omics data, we demonstrated …

Alzheimer's Disease Risk Gene Cd2ap Is A Dose-Sensitive Determinant Of Synaptic Structure And Plasticity, Taeyong Ahn, Gabrielle E Largoza, Julia Younis, Mary E Dickinson, Chih-Wei Hsu, Joshua D Wythe

Faculty, Staff and Students Publications

Tissue clearing is an essential prerequisite for 3D volumetric imaging of larger tissues or organs. Here, we present a detailed protocol for optical, aqueous-based clearing of adult murine tissues using EZ Clear. We describe steps to ensure successful perfusion and fixation of organs from the adult mouse and supply guidelines for optimal lipid removal, refractive index matching, and tissue clearing. Finally, we provide imaging parameters for visualizing both exogenous perfused fluorescent dyes and endogenous fluorescence reporters in the adult mouse. For complete details on the use and execution of this protocol, please refer to Hsu et al.

Protocol For Preclinical Evaluation Of Locoregionally Delivered Car T Cells In Patient-Derived Xenograft Models Of Brain Tumors, Benjamin Draper, Chantelle Bowers, Eleni Vassalou, Ailsa Greppi, John Anderson, Nabil Ahmed, Michael D Taylor, Laura K Donovan

Faculty, Staff and Students Publications

Here, we present a protocol for preclinical evaluation of locoregionally delivered CAR T cells in patient-derived xenograft models of primary, metastatic, and recurrent brain tumors. We provide instructions for isolating peripheral blood mononuclear cells (PBMCs), producing CAR T cells in conjunction with locoregional delivery, and preclinical trial design and analysis involving CAR T cells. Additionally, we describe comprehensive preclinical readouts and guidelines for critical endpoint sample collections. In line with clinical trial procedures, our protocol broadens available treatment modalities for direct clinical translation. For complete details on the use and execution of this protocol, please refer to Donovan et al …

Analyzing Efficiency Of A Lentiviral Shrna Knockdown System In Human Enteroids Using Western Blot And Flow Cytometry, Adam P Wilson, Karni S Moshal, Addison P Franca, Sasirekha Ramani, Randle Gallucci, Hala Chaaban, Kathryn Y Burge

Faculty, Staff and Students Publications

Enteroids are in vitro models to study gastrointestinal pathologies and test personalized therapeutics; however, the inherent complexity of enteroids often renders standard gene editing approaches ineffective. Here, we introduce a refined lentiviral transfection protocol, ensuring sufficient lentiviral engagement with enteroids while considering spatiotemporal growth variability throughout the extracellular matrix. Additionally, we highlight a selection process for transduced cells, introduce a protocol to accurately measure transduction efficiency, and explore methodologies to gauge effects of gene knockdown on biological processes.

Esr1 And P53 Interactome Alteration Defines Mechanisms Of Tamoxifen Response In Luminal Breast Cancer, Chetan C Oturkar, Spencer R Rosario, Alan D Hutson, Adrianne Groman, Stephen B Edge, Carl D Morrison, Wendy M Swetzig, Jianmin Wang, Jun Hyoung Park, Benny Abraham Kaipparettu, Prashant K Singh, Shicha Kumar, Helen H Cappuccino, Manish Ranjan, Araba Adjei, Mohammad Ghasemi, Andrew K L Goey, Swati Kulkarni, Gokul M Das

Faculty, Staff and Students Publications

The canonical mechanism behind tamoxifen's therapeutic effect on estrogen receptor α/ESR1+ breast cancers is inhibition of ESR1-dependent estrogen signaling. Although ESR1+ tumors expressing wild-type p53 were reported to be more responsive to tamoxifen (Tam) therapy, p53 has not been factored into choice of this therapy and the mechanism underlying the role of p53 in Tam response remains unclear. In a window-of-opportunity trial on patients with newly diagnosed stage I-III ESR1+/HER2/wild-type p53 breast cancer who were randomized to arms with or without Tam prior to surgery, we reveal that the ESR1-p53 interaction in tumors was inhibited by Tam. This resulted in …

Comprehensive Single-Cell Atlas Of The Mouse Retina, Jin Li, Jongsu Choi, Xuesen Cheng, Justin Ma, Shahil Pema, Joshua R Sanes, Graeme Mardon, Benjamin J Frankfort, Nicholas M Tran, Yumei Li, Rui Chen

Faculty, Staff and Students Publications

Single-cell RNA sequencing (scRNA-seq) has advanced our understanding of cellular heterogeneity by characterizing cell types across tissues and species. While several mouse retinal scRNA-seq datasets exist, each dataset is either limited in cell numbers or focused on specific cell classes, thereby hindering comprehensive gene expression analysis across all retina types. To fill the gap, we generated the largest retinal scRNA-seq dataset to date, comprising approximately 190,000 single cells from C57BL/6J mouse retinas, enriched for rare population cells via antibody-based magnetic cell sorting. Integrating this dataset with public datasets, we constructed the Mouse Retina Cell Atlas (MRCA) for wild-type mice, encompassing …

Protocol For Optical, Aqueous-Based Clearing Of Murine Tissues Using Ez Clear, Taeyong Ahn, Gabrielle E Largoza, Julia Younis, Mary E Dickinson, Chih-Wei Hsu, Joshua D Wythe

Faculty, Staff and Students Publications

Tissue clearing is an essential prerequisite for 3D volumetric imaging of larger tissues or organs. Here, we present a detailed protocol for optical, aqueous-based clearing of adult murine tissues using EZ Clear. We describe steps to ensure successful perfusion and fixation of organs from the adult mouse and supply guidelines for optimal lipid removal, refractive index matching, and tissue clearing. Finally, we provide imaging parameters for visualizing both exogenous perfused fluorescent dyes and endogenous fluorescence reporters in the adult mouse. For complete details on the use and execution of this protocol, please refer to Hsu et al.

Identifying Interventions To Improve Diagnostic Safety In Emergency Departments: Protocol For A Participatory Design Study, Woosuk Seo, Sun Young Park, Zhan Zhang, Hardeep Singh, Kalyan Pasupathy, Prashant Mahajan

Faculty, Staff and Students Publications

Background: Emergency departments (EDs) are complex and fast-paced clinical settings where a diagnosis is made in a time-, information-, and resource-constrained context. Thus, it is predisposed to suboptimal diagnostic outcomes, leading to errors and subsequent patient harm. Arriving at a timely and accurate diagnosis is an activity that occurs after an effective collaboration between the patient or caregiver and the clinical team within the ED. Interventions such as novel sociotechnical solutions are needed to mitigate errors and risks.

Objective: This study aims to identify challenges that frontline ED health care providers and patients face in the ED diagnostic process and …

Sensory Asic3 Channel Exacerbates Psoriatic Inflammation Via A Neurogenic Pathway In Female Mice, Chen Huang, Pei-Yi Sun, Yiming Jiang, Yuandong Liu, Zhichao Liu, Shao-Ling Han, Bao-Shan Wang, Yong-Xin Huang, An-Ran Ren, Jian-Fei Lu, Qin Jiang, Ying Li, Michael X Zhu, Zhirong Yao, Yang Tian, Xin Qi, Wei-Guang Li, Tian-Le Xu

Faculty, Staff and Student Publications

Psoriasis is an immune-mediated skin disease associated with neurogenic inflammation, but the underlying molecular mechanism remains unclear. We demonstrate here that acid-sensing ion channel 3 (ASIC3) exacerbates psoriatic inflammation through a sensory neurogenic pathway. Global or nociceptor-specific Asic3 knockout (KO) in female mice alleviates imiquimod-induced psoriatic acanthosis and type 17 inflammation to the same extent as nociceptor ablation. However, ASIC3 is dispensable for IL-23-induced psoriatic inflammation that bypasses the need for nociceptors. Mechanistically, ASIC3 activation induces the activity-dependent release of calcitonin gene-related peptide (CGRP) from sensory neurons to promote neurogenic inflammation. Botulinum neurotoxin A and CGRP antagonists prevent sensory neuron-mediated …

Changes In Plasma Concentrations Of Per- And Polyfluoroalkyl Substances After Bariatric Surgery In Adolescents From The Teen-Longitudinal Assessment Of Bariatric Surgery (Teen-Labs) Study, Brittney O Baumert, Sandrah P Eckel, Jesse A Goodrich, Zhenjiang Li, Nikos Stratakis, Douglas I Walker, Yinqi Zhao, Fabian Christoph Fischer, Scott Bartell, Damaskini Valvi, Xiangping Lin, Zoe Coates Fuentes, Thomas Inge, Justin Ryder, Todd Jenkins, Rohit Kohli, Stephanie Sisley, Stavra Xanthakos, Sarah Rock, Michele A La Merrill, Rob Mcconnell, David V Conti, Lida Chatzi

Faculty, Staff and Students Publications

Exposure to per- and poly-fluoroalkyl substances (PFAS) is ubiquitous due to their persistence in the environment and in humans. Extreme weight loss has been shown to influence concentrations of circulating persistent organic pollutants (POPs). Using data from the multi-center perspective Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) cohort, we investigated changes in plasma-PFAS in adolescents after bariatric surgery. Adolescents (Mean age = 17.1 years, SD = 1.5 years) undergoing bariatric surgery were enrolled in the Teen-LABS study. Plasma-PFAS were measured at the time of surgery and then 6-, 12-, and 36 months post-surgery. Linear mixed effect models were used to evaluate …

Troponin: Think Before Testing, Shakirat Ganiyu, Fatimah Bello, Danielle Stone, Gregory Ruhnke, James Stone

School of Medicine Publications

This is a high-value care-based quality improvement project that was carried out to decrease inappropriate troponin testing in the emergency department (ED) of a tertiary health institution in the United States with the goal of promoting evidence-based practices, minimizing waste, and enhancing the quality of care.

Editorial For "Parallel Cnn-Deep Learning Clinical-Imaging Signature For Assessing Pathologic Grade And Prognosis Of Soft Tissue Sarcoma Patients", Pegah Khosravi

Publications and Research

No abstract provided.

Neuroecological Links Of The Exposome And One Health, Agustin Ibanez, Lucia Melloni, Paweł Świeboda, William Hynes, Burcin Ikiz, Rym Ayadi, Massamba Thioye, Consuelo Walss-Bass, Bahar Güntekin, Jyoti Mishra, Mohamed Salama, Sarah Dunlop, Claudia Duran-Aniotz, Harris A Eyre

Faculty, Staff and Student Publications

This NeuroView assesses the interplay among exposome, One Health, and brain capital in health and disease. Physical and social exposomes affect brain health, and green brain skills are required for environmental health strategies. Ibanez et al. address current gaps and strategies needed in research, policy, and technology, offering a road map for stakeholders.

Challenges And Opportunities In Cancer Immunotherapy: A Society For Immunotherapy Of Cancer (Sitc) Strategic Vision, Leisha A Emens, Pedro J Romero, Ana Carrizosa Anderson, Tullia C Bruno, Christian M Capitini, Deborah Collyar, James L Gulley, Patrick Hwu, Avery D Posey, Ann W Silk, Jennifer A Wargo

Faculty, Staff and Student Publications

Cancer immunotherapy has flourished over the last 10-15 years, transforming the practice of oncology and providing long-term clinical benefit to some patients. During this time, three distinct classes of immune checkpoint inhibitors, chimeric antigen receptor-T cell therapies specific for two targets, and two distinct classes of bispecific T cell engagers, a vaccine, and an oncolytic virus have joined cytokines as a standard of cancer care. At the same time, scientific progress has delivered vast amounts of new knowledge. For example, advances in technologies such as single-cell sequencing and spatial transcriptomics have provided deep insights into the immunobiology of the tumor …

Mediterranean Diet Information On Tiktok And Implications For Digital Health Promotion Research: Social Media Content Analysis, Margaret Raber, Haley Allen, Sophia Huang, Maria Vazquez, Echo Warner, Debbe Thompson

Children’s Nutrition Research Center Staff Publications

Background: The Mediterranean diet has been linked to reduced risk for several cardiometabolic diseases. The lack of a clear definition of the Mediterranean diet in the scientific literature and the documented proliferation of nutrition misinformation on the internet suggest the potential for confusion among consumers seeking web-based Mediterranean diet information.

Objective: We conducted a social media content analysis of information about the Mediterranean diet on the influential social media platform, TikTok, to examine public discourse about the diet and identify potential areas of misinformation. We then analyzed these findings in the context of health promotion to identify potential challenges and …

Case Report: Dementia Sensitivity To Altitude Changes And Effective Treatment With Hyperbaric Air And Glutathione Precursors, Edward F. Fogarty, Paul G. Harch

School of Medicine Faculty Publications

A 78-year-old man with dementia experienced waxing and waning of symptoms with changes in altitude as he traveled from his home in the Rocky Mountains to lower elevations and back. To replicate the improvement in his symptoms with travel to lower elevations (higher pressure), the patient was treated with a near-identical repressurization in a hyperbaric chamber using compressed air. With four 1-h treatments at 1.3 Atmospheres Absolute (ATA) and concurrent administration of low-dose oral glutathione amino acid precursors, he recovered speech and showed improvement in activities of daily living. Regional broadcast media had documented his novel recovery. Nosocomial COVID-19 and …

Keep Fingers On The Cpg Islands, Xing Zhang, Robert M Blumenthal, Xiaodong Cheng

Faculty, Staff and Student Publications

The post-genomic era has ushered in the extensive application of epigenetic editing tools, allowing for precise alterations of gene expression. The use of reprogrammable editors that carry transcriptional corepressors has significant potential for long-term epigenetic silencing for the treatment of human diseases. The ideal scenario involves precise targeting of a specific genomic location by a DNA-binding domain, ensuring there are no off-target effects and that the process yields no genetic remnants aside from specific epigenetic modifications (i.e., DNA methylation). A notable example is a recent study on the mouse

Microglial P2y6 Calcium Signaling Promotes Phagocytosis And Shapes Neuroimmune Responses In Epileptogenesis, Anthony D Umpierre, Bohan Li, Katayoun Ayasoufi, Whitney L Simon, Shunyi Zhao, Manling Xie, Grace Thyen, Benjamin Hur, Jiaying Zheng, Yue Liang, Dale B Bosco, Mark A Maynes, Zhaofa Wu, Xinzhu Yu, Jaeyun Sung, Aaron J Johnson, Yulong Li, Long-Jun Wu

Faculty, Staff and Student Publications

Microglial calcium signaling is rare in a baseline state but strongly engaged during early epilepsy development. The mechanism(s) governing microglial calcium signaling are not known. By developing an in vivo uridine diphosphate (UDP) fluorescent sensor, GRABUDP1.0, we discovered that UDP release is a conserved response to seizures and excitotoxicity across brain regions. UDP can signal through the microglial-enriched P2Y6 receptor to increase calcium activity during epileptogenesis. P2Y6 calcium activity is associated with lysosome biogenesis and enhanced production of NF-κB-related cytokines. In the hippocampus, knockout of the P2Y6 receptor prevents microglia from fully engulfing neurons. Attenuating microglial calcium signaling through calcium …

To Revise Or Not Revise? Isolated Margin Positivity In Localized Pancreatic Ductal Adenocarcinoma, Victoria S. Wu, Henry J. Stitzel, John B. Ammori, Jeffrey Hardacre, Lee M. Ocuin

Faculty Scholarship

Background: The study determined the proportion of patients with pancreatic adenocarcinoma (PDAC) who had margin-positive disease and no other adverse pathologic findings (APF) using institutional and administrative datasets. Methods: Patients with clinical stage I or II PDAC in the National Cancer Database (NCDB 2010–2020) and those who underwent pancreatectomy at the authors’ institution (2010–2021) were identified. Isolated margin positivity (IMP) was defined as a positive surgical margin with no APF (negative nodes, no lymphovascular/perineural invasion). Results: The study included 225 patients from the authors’ institution and 23,598 patients from the NCDB. The margin-positive rates were 21.8% and 20.3%, and the …

Leveraging Integrated Rna Sequencing To Decipher Adrenomedullin's Protective Mechanisms In Experimental Bronchopulmonary Dysplasia, Subarna Palit, Amrit Kumar Shrestha, Shyam Thapa, Sandra L Grimm, Cristian Coarfa, Fabian Theis, Lukas M Simon, Binoy Shivanna

Faculty, Staff and Students Publications

Bronchopulmonary dysplasia (BPD) is a chronic lung disease commonly affecting premature infants, with limited therapeutic options and increased long-term consequences. Adrenomedullin (Adm), a proangiogenic peptide hormone, has been found to protect rodents against experimental BPD. This study aims to elucidate the molecular and cellular mechanisms through which Adm influences BPD pathogenesis using a lipopolysaccharide (LPS)-induced model of experimental BPD in mice. Bulk RNA sequencing of Adm-sufficient (wild-type or Adm+/+) and Adm-haplodeficient (Adm+/−) mice lungs, integrated with single-cell RNA sequencing data, revealed distinct gene expression patterns and cell type alterations associated with Adm deficiency …

A Single Cell Rna Sequence Atlas Of The Early Drosophila Larval Eye, Komal Kumar Bollepogu Raja, Kelvin Yeung, Yumei Li, Rui Chen, Graeme Mardon

Faculty, Staff and Students Publications

The Drosophila eye has been an important model to understand principles of differentiation, proliferation, apoptosis and tissue morphogenesis. However, a single cell RNA sequence resource that captures gene expression dynamics from the initiation of differentiation to the specification of different cell types in the larval eye disc is lacking. Here, we report transcriptomic data from 13,000 cells that cover six developmental stages of the larval eye. Our data show cell clusters that correspond to all major cell types present in the eye disc ranging from the initiation of the morphogenetic furrow to the differentiation of each photoreceptor cell type as …