Digital Commons Network^™

Microsporidian Spores And The Integrin Binding Loop Of The Madam Protein Are Important For Integrin Signaling And Attachment To Host Cells, Cindy L. Barrett

Electronic Theses and Dissertations

Microsporidia are a distant fungal pathogen that have severe clinical consequences for the immunocompromised. Previous work identified a microsporidian pathogen protein termed Microsporidian ADAM or MADAM. This protein has close sequence homology to other ADAM proteins (A Disintegrin and Metalloproteinase) in two microsporidian species, Encephalitozoon intestinalis and E. cuniculi. ADAM proteins have a wide range of functions, including binding to integrins and host signaling. It is known that many pathogens manipulate integrins to invade host cells, and it is predicted that microsporidia are also exploiting this host target. Previous work with the MADAM protein demonstrated that this protein has a …

Investigating The Distinct Role Of Pd-L2 In Modulating Human T Cells Responses, Anupallavi Srinivasamani

Dissertations and Theses (Open Access)

INVESTIGATING THE DISTINCT ROLE OF PD-L2 IN MODULATING HUMAN T CELL RESPONSES

Anupallavi Srinivasamani, M.S.

Advisory Professor: Michael A. Curran, Ph.D.

Therapeutic blockade of the Programmed cell death-1 (PD-1) receptor and its ligand Programmed death ligand-1 (PD-L1) has revolutionized the treatment of multiple cancers and made durable tumor regression a possibility in the clinic. PD-1 blockade prolonged progression-free survival and overall survival with lesser high-grade toxicity in patients with advanced melanoma when compared to the other FDA-approved checkpoint blockade target, CTLA-4. Unlike CTLA-4, PD-1 is unique in its ability to regulate T cell functions in lymphoid tissues as well as …

Molecular Mechanisms Behind Sars-Cov-2 Induced Host Genome Restructuring, Erin Simpson

Dissertations and Theses (Open Access)

Severe Acute Respiratory Syndrome Coronavirus -2 (SARS-CoV-2) has caused unprecedented morbidity and mortality worldwide. There are two pathophysiological hallmarks associated with severe patient outcomes after SARS-CoV-2 acute infection, namely delayed/weakened interferon production and overactive inflammatory responses. Our previous work has shown that these altered immune responses are due, at least in part, to significant alterations in 3D genome organization and epigenetic landscape following SARS-CoV-2 infection that are distinct from and more severe than changes caused by other viral infections or immune stimulants. While these changes at the chromatin level are important for understanding the immune dysregulation seen in some cases …

Unveiling Immune Checkpoint Therapy Resistance Mechanisms In The Tumor Microenvironment Using High-Dimensional Analyses, Swetha Anandhan

Dissertations and Theses (Open Access)

The advent of immune checkpoint therapy (ICT) has transformed cancer treatment, but its effectiveness is limited in certain cancers like pancreatic ductal adenocarcinoma (PDAC), which exhibit resistance to this therapy. To overcome this challenge, it is crucial to understand the underlying mechanisms that determine tumor response to ICT and develop rational therapeutic combinations. The tumor microenvironment (TME), including suppressive myeloid cells, regulatory T cells (Tregs), and cancer-associated fibroblasts (CAFs), plays a pivotal role in ICT responses. Leveraging single-cell technologies, this study explores the role and function of immune subsets in the TME that induce therapy resistance.

Using single-cell RNA sequencing …

Role Of Il-17/Il-17ra Signaling In The Pancreatic Tumor Microenvironment, Susana Castro Pando, Susana Castro Pando

Dissertations and Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) is projected to become the second leading cause of cancer-related deaths. PDAC is characterized by the early establishment of a highly immunosuppressive fibro-cellular tumor microenvironment (TME). Our research has revealed the important role of IL-17 in the development and progression of pancreatic cancer, yet the specific cellular compartment responsible for IL-17-mediated tumor promotion remains unknown. We generated a transgenic mouse model with pancreatic KrasG12D activation and selective deletion of IL-17RA in the epithelial vs. immune component using either genetic manipulation or bone marrow transplantation. Deletion of IL17RA from the pancreatic epithelial compartment delayed premalignant lesion development …

Investigating The Role Of Il-10 Producing Nkt Cells In Prevention Of Graft Versus Host Disease, Drew Boagni

Dissertations and Theses (Open Access)

The standard curative treatment for hematologic malignancies is allogeneic stem cell transplantation (ASCT), in which the patient’s immune system is replaced with that of a healthy donor. This can lead to cure through the graft versus leukemia (GVL) effect but can also cause graft versus host disease (GVHD), which is characterized by systemic inflammation and organ damage mediated by dysregulated donor T cells. Preclinical studies have shown invariant natural killer T cells (iNKT) cells can prevent GVHD while preserving GVL. iNKT cells are unconventional T cells which recognize glycolipid antigens presented in the context of CD1d. Upon activation, they secrete …

Met Alterations In Glioblastoma: Characterization Of Patient-Derived Xenografts And Therapeutic Strategies, Anna Musket

Electronic Theses and Dissertations

Glioblastoma is the most commonly diagnosed central nervous system primary malignancy and it is considered a terminal diagnosis with few treatment options available. Glioblastoma tumors frequently develop treatment resistance due in part to their highly heterogenic nature. The heterogeneity of glioblastoma is partially attributed to the presence of glioma stem-like cells (GSC), which are highly invasive and resistant to chemotherapy and irradiation treatments. Signaling of the receptor tyrosine kinase MET is a known regulator of GSC. Glioblastoma patients have an increasingly poor prognosis that corresponds with increasing MET expression. Both GSC and MET are known to contribute to treatment resistance …

Nivolumab And Ipilimumab In Combination With Radiotherapy In Patients With High-Risk Locally Advanced Squamous Cell Carcinoma Of The Head And Neck., Jennifer Johnson, Ioannis A. Vathiotis, Larry Harshyne, Ayesha Ali, Voichita Bar-Ad, Rita S. Axelrod, Emily Lorber, Joseph Curry, David Cognetti, Adam J. Luginbuhl, Madalina Tuluc, Scott W Keith, M.G. Mahoney, Athanassios Argiris

Department of Medical Oncology Faculty Papers

BACKGROUND: The combination of nivolumab and ipilimumab has been approved for the treatment of multiple solid tumors. This was a phase I study investigating definitive radioimmunotherapy (RIT) with nivolumab and ipilimumab for the treatment of locally advanced (LA) squamous cell carcinoma of the head and neck (SCCHN).

METHODS: Patients with newly diagnosed, stage IVA-IVB SCCHN eligible for cisplatin-based chemotherapy received nivolumab (3 mg/kg every 2 weeks for a total of 17 doses) and ipilimumab (1 mg/kg every 6 weeks for a total of 6 doses) starting 2 weeks prior to radiotherapy. The primary endpoint was safety of definitive RIT. Secondary …

The Hylefm Gene In Phylefm Of Enterococcus Faecium Is Not Required In Pathogenesis Of Murine Peritonitis, Victoria H Wu, Bryan S Yung, Farhoud Faraji, Robert Saddawi-Konefka, Zhiyong Wang, Alexander T Wenzel, Miranda J Song, Meghana S Pagadala, Lauren M Clubb, Joshua Chiou, Sanju Sinha, Marin Matic, Francesco Raimondi, Thomas S Hoang, Rebecca Berdeaux, Dario A A Vignali, Ramiro Iglesias-Bartolome, Hannah Carter, Eytan Ruppin, Jill P Mesirov, J Silvio Gutkind

Faculty, Staff and Student Publications

Immune checkpoint blockade (ICB) targeting PD-1 and CTLA-4 has revolutionized cancer treatment. However, many cancers do not respond to ICB, prompting the search for additional strategies to achieve durable responses. G-protein-coupled receptors (GPCRs) are the most intensively studied drug targets but are underexplored in immuno-oncology. Here, we cross-integrated large singe-cell RNA-sequencing datasets from CD8+ T cells covering 19 distinct cancer types and identified an enrichment of Gαs-coupled GPCRs on exhausted CD8+ T cells. These include EP2, EP4, A2AR, β1AR and β2AR, all of which promote T cell dysfunction. We also developed transgenic mice expressing a chemogenetic CD8-restricted Gαs–DREADD to activate …

Do Vaccinations Influence The Development Of Alzheimer Disease?, Avram S Bukhbinder, Yaobin Ling, Kristofer Harris, Xiaoqian Jiang, Paul E Schulz

Faculty, Staff and Student Publications

A growing literature supports a protective association between vaccines targeting an array of pathogens (e.g., influenza, pneumococcus, herpes zoster) and the risk of Alzheimer disease (AD). This article discusses the potential underlying mechanisms for this apparent protective effect of immunizations against infectious pathogens on the risk of AD; explores the basic and pharmacoepidemiologic evidence for this association, with particular attention paid to important methodological variations among the epidemiologic studies; and reviews the remaining uncertainties regarding the effects of anti-pathogen vaccines on Alzheimer disease and all-cause dementia, with recommendations for future directions to address those uncertainties.

T-Cell Receptor Beta Variable Gene Polymorphism Predicts Immune-Related Adverse Events During Checkpoint Blockade Immunotherapy, Bettzy Stephen, Joud Hajjar, Shrutii Sarda, Dzifa Yawa Duose, Jeffrey M Conroy, Carl Morrison, Anas Alshawa, Mingxuan Xu, Abdulrazzak Zarifa, Sapna P Patel, Ying Yuan, Evan Kwiatkowski, Linghua Wang, Jordi Rodon Ahnert, Siqing Fu, Funda Meric-Bernstam, Geoffrey M Lowman, Timothy Looney, Aung Naing

Faculty, Staff and Students Publications

BACKGROUND: Immune checkpoint inhibitors have revolutionized cancer treatment. However, they are associated with a unique spectrum of side effects, called immune-related adverse events (irAEs), which can cause significant morbidity and quickly progress to severe or life-threatening events if not treated promptly. Identifying predictive biomarkers for irAEs before immunotherapy initiation is therefore a critical area of research. Polymorphisms within the T-cell receptor beta (TCRB) variable (TRBV) gene have been implicated in autoimmune disease and may be mechanistically linked to irAEs. However, the repetitive nature of the TCRB locus and incomplete genome assembly has hampered the evaluation of TRBV polymorphisms in the …

Comparison Of Random Urine Protein/Creatinine Ratio With 24-Hour Urine Protein In Suspected Pre-Eclampsia, Lily Olayinka, Emily Garnett, Brian Burnett, Sridevi Devaraj

Faculty, Staff and Students Publications

INTRODUCTION: Proteinuria is one of the classical criteria for the diagnosis of pre-eclampsia. The gold standard remains the measurement of 24-h urine protein which is time consuming and prone to preanalytical errors. Random urine protein creatinine ratio (UPCR) is endorsed by clinical practice guidelines as a faster alternative. The aim of this study was to evaluate the correlation between the 24-h urine protein excretion and UPCR in the identification of proteinuria in suspected preeclamptic patients.

METHOD: A total of 51 women with suspected pre-eclampsia from the maternal fetal clinic of our institution were retrospectively studied. The correlation between the UPCR …

Inhibition Of Microsomal Prostaglandin E2 Synthase Reduces Collagen Deposition In Melanoma Tumors And May Improve Immunotherapy Efficacy By Reducing T-Cell Exhaustion, Yasunari Fukuda, Sun-Hee Kim, Matias A Bustos, Sung-Nam Cho, Jason Roszik, Jared K Burks, Hong Kim, Dave S B Hoon, Elizabeth A Grimm, Suhendan Ekmekcioglu

Faculty, Staff and Student Publications

The arachidonic acid pathway participates in immunosuppression in various types of cancer. Our previous observation detailed that microsomal prostaglandin E2 synthase 1 (mPGES-1), an enzyme downstream of cyclooxygenase 2 (COX-2), limited antitumor immunity in melanoma; in addition, genetic depletion of mPGES-1 specifically enhanced immune checkpoint blockade therapy. The current study set out to distinguish the roles of mPGES-1 from those of COX-2 in tumor immunity and determine the potential of mPGES-1 inhibitors for reinforcing immunotherapy in melanoma. Genetic deletion of mPGES-1 showed different profiles of prostaglandin metabolites from that of COX-2 deletion. In our syngeneic mouse model, mPGES-1-deficient cells exhibited …

The Role Of Fas Receptor Methylation In Osteosarcoma Metastasis, Jiayi M Sun, Wing-Yuk Chow, Gufeng Xu, M John Hicks, Manjula Nakka, Jianhe Shen, Patrick Kwok Shing Ng, Aaron M Taylor, Alexander Yu, Jason E Farrar, Donald A Barkauskas, Richard Gorlick, Jaime M Guidry Auvil, Daniela Gerhard, Paul Meltzer, Rudy Guerra, Tsz-Kwong Man, Ching C Lau, On Behalf Of The Target Osteosarcoma Consortium

Faculty, Staff and Students Publications

Osteosarcoma is the most frequent primary malignant bone tumor with an annual incidence of about 400 cases in the United States. Osteosarcoma primarily metastasizes to the lungs, where FAS ligand (FASL) is constitutively expressed. The interaction of FASL and its cell surface receptor, FAS, triggers apoptosis in normal cells; however, this function is altered in cancer cells. DNA methylation has previously been explored as a mechanism for altering FAS expression, but no variability was identified in the CpG island (CGI) overlapping the promoter. Analysis of an expanded region, including CGI shores and shelves, revealed high variability in the methylation of …

Distribution Of The Soft Tick Carios Vespertilionis In Lowlands And Low Mountain Regions Of Germany, Anja Fritzsche, Stefan Zaenker, Jannis Gottwald, Renate Keil, Christian Zaenker, Michael Bröker, Lidia Chitimia-Dobler

Harold W. Manter Laboratory of Parasitology: Library Materials

In Germany, the knowledge about ticks infesting bats is limited, and is restricted only to a few studies, most of them dating back decades. To further improve our knowledge on ticks parasitising bats, healthy and sick bats in central Germany were examined for ticks. In total 519 larvae and one nymph of Carios vespertilionis were collected from nine bat species: Eptesicus nilssonii, Eptesicus serotinus, Myotis daubentonii, Myotis myotis, Nyctalus leisleri, Pipistrellus nathusii, Pipistrellus pygmaeus, Pipistrellus pipistrellus, and Vespertilio murinus. Either the presence of C. vespertilionis was new for some areas or it was confirmed in some federal states in …

A Phase Ii Clinical Trial Of Pembrolizumab Efficacy And Safety In Advanced Renal Medullary Carcinoma, Chijioke Nze, Pavlos Msaouel, Mohamed H Derbala, Bettzy Stephen, Abdulrahman Abonofal, Funda Meric-Bernstam, Nizar M Tannir, Aung Naing

Faculty, Staff and Student Publications

Background: Renal medullary carcinoma (RMC) is one of most aggressive renal cell carcinomas and novel therapeutic strategies are therefore needed. Recent comprehensive molecular and immune profiling of RMC tissues revealed a highly inflamed phenotype, suggesting the potential therapeutic role for immune checkpoint therapies. We present the first prospective evaluation of an immune checkpoint inhibitor in a cohort of patients with RMC.

Methods: A cohort of patients with locally advanced or metastatic RMC was treated with pembrolizumab 200 mg intravenously every 21 days in a phase II basket trial (ClinicalTrials.gov: NCT02721732). Responses were assessed by irRECIST. Tumor tissues were evaluated …

Harnessing Autoimmunity With Dominant Self-Peptide: Modulating The Sustainability Of Tissue-Preferential Antigen-Specific Tregs By Governing The Binding Stability Via Peptide Flanking Residues, Youwei Lin, Shun Sakuraba, Chandirasegaran Massilamany, Jayagopala Reddy, Yoshimasa Tanaka, Sachiko Miyake, Takashi Yamamura

School of Veterinary and Biomedical Sciences: Faculty Publications

Sensitization to self-peptides induces various immunological responses, from autoimmunity to tumor immunity, depending on the peptide sequence; however, the underlying mechanisms remain unclear, and thus, curative therapeutic options considering immunity balance are limited. Herein, two overlapping dominant peptides of myelin proteolipid protein, PLP136-150 and PLP139-151, which induce different forms of experimental autoimmune encephalomyelitis (EAE), monophasic and relapsing EAE, respectively, were investigated. Mice with monophasic EAE exhibited highly resistant to EAE re-induction with any encephalitogenic peptides, whereas mice with relapsing EAE were susceptible, and progressed, to EAE re-induction. This resistance to relapse and reinduction in monophasic EAE mice was associated with …

Preclinical Evaluation Of Anti-Cd38 Therapy In Mature T-Cell Neoplasms, Colleen Isabelle, William Johnson, Kathleen Mcconnell, Ashley Vogel, Jonathan Brammer, Amy Boles, Robyn Keller, Paola Sindaco, Liam Nisenfeld, Guldeep Uppal, Neda Nikbakht, Bruno Calabretta, Patrizia Porazzi, Jerald Gong, Nitin Chakravarti, Pierluigi Porcu, Anjali Mishra

Kimmel Cancer Center Faculty Papers

No abstract provided.

Role Of Short Interspersed Nuclear Elements (Sines) Of Maternally Imprinted Microrna Clusters In Hemochorial Placental Antiviral Immunity, Ishani Wickramage

USF Tampa Graduate Theses and Dissertations

The evolution of hemochorial placentas in which the fetal trophoblast is bathed in maternal blood has vastly improved fetal development and survival in primates and rodents, due to the enhanced efficiency of nutrient, gas and waste exchange between the mother and the fetus. However, the extensive contact between the fetal tissues and maternal blood in these placentas also poses an increased risk of vertical transmission of pathogens such as viruses from the mother to the fetus. In response to this selection pressure, hemochorial placentas have evolved robust defense mechanisms to protect the immunologically naive fetus. Unlike somatic cells that require …

The Knowns And Unknowns Of Cardiac Autoimmunity In Viral Myocarditis, Kiruthiga Mone, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

Myocarditis can result from various infectious and non‐infectious causes that can lead to dilated cardiomyopathy (DCM) and heart failure. Among the infectious causes, viruses are commonly suspected. But the challenge is our inability to demonstrate infectious viral particles during clinical presentations, partly because by that point, the viruses would have damaged the tissues and be cleared by the immune system. Therefore, viral signatures such as viral nucleic acids and virus-reactive antibodies may be the only readouts pointing to viruses as potential primary triggers of DCM. Thus, it becomes hard to explain persistent inflammatory infiltrates that might occur in individuals affected …

Phase Ii Trial Of Medi0457 And Durvalumab For Patients With Recurrent/Metastatic Human Papillomavirus-Associated Cancers, Van K Morris, Amir Jazaeri, Shannon N Westin, Curtis Pettaway, Solly George, Ryan W Huey, Michaela Grinsfelder, Aaron Shafer, Benny Johnson, David Vining, Ming Guo, Bryan Fellman, Michael Frumovitz

Faculty, Staff and Student Publications

BACKGROUND: Human papillomavirus (HPV) types 16/18 drive oncogenesis for most patients with cervical, anal, and penile cancers. MEDI0457, a therapeutic DNA vaccine containing plasmids for E6 and E7 HPV-16/18 viral oncogenes and IL-12 adjuvant, is safe and provokes an immune response against E6/E7. We tested MEDI0457 with the anti-PD-L1 antibody durvalumab for patients with HPV-associated cancers.

METHODS: Patients with recurrent/metastatic, treatment-refractory HPV-16/18 cervical cancer, or rare HPV-associated (anal and penile) cancers were eligible. Prior immune checkpoint inhibition was not permitted. Patients received MEDI0457 7 mg intramuscularly (weeks 1, 3, 7, 12, and every 8 weeks thereafter) and durvalumab 1500 mg …

Naturally Occurring Highly Pathogenic Avian Influenza Virus H5n1 Clade 2.3.4.4b Infection In Three Domestic Cats In North America During 2023, Sarah J. Sillman, Mary Drozd, Duan S. Loy, Seth P. Harris

School of Veterinary and Biomedical Sciences: Faculty Publications

The Eurasian strain of highly pathogenic avian influenza (HPAI) H5N1 is a devastating pathogen for birds that also has the capacity to infect mammals. This report describes the presentation, clinical case findings (including haemogram and serum biochemistry), gross and microscopic lesions and virus detection in three HPAI H5N1-infected domestic cats from the USA in 2023. All three cats presented with neurological abnormalities and were euthanized due to a poor prognosis within 2 days (two cats) or 10 days (one cat) of known clinical disease onset. Necropsy consistently revealed pulmonary congestion and oedema, and cerebrocortical malacia with haemorrhage was also seen …

Sheep Worms – Sustainable Summer-Autumn Worm Control, Department Of Primary Industries And Regional Development, Western Australia

Animal production and livestock factsheets

A summer drenching program for sheep worm control is now recognised as a key cause of drench resistance in Western Australia. However, some small changes can increase the sustainability of pre-emptive control programs. Drenches in summer should always be given to younger, growing sheep (current and previous year’s age groups), whereas adult sheep should be drenched in autumn, or if drenched in summer, some should be left untreated (if drenching at all). Research shows that this reduces the chance of developing drench resistance but still provides effective worm control.

Exploring The Interactions Between Sars-Cov-2 And Host Proteins, Sojan Shrestha

School of Biological Sciences: Dissertations, Theses, and Student Research

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the current pandemic, Coronavirus Disease 2019 (COVID-19). SARS-CoV-2 is considered to be of zoonotic origin; it originated in non-human animals and was transmitted to humans. Since the early stage of the pandemic, however, the evidence of transmissions from humans to animals (reverse zoonoses) has been found in multiple animal species including mink, white-tailed deer, and pet and zoo animals. Furthermore, secondary zoonotic events of SARS-CoV-2, transmissions from animals to humans, have been also reported. It is suggested that non-human hosts can act as SARS-CoV-2 reservoirs where accumulated …

Clonal Hematopoiesis Is Associated With Protection From Alzheimer's Disease, Hind Bouzid, Julia A Belk, Max Jan, Yanyan Qi, Chloé Sarnowski, Sara Wirth, Lisa Ma, Matthew R Chrostek, Herra Ahmad, Daniel Nachun, Winnie Yao, Alexa Beiser, Alexander G Bick, Joshua C Bis, Myriam Fornage, William T Longstreth, Oscar L Lopez, Pradeep Natarajan, Bruce M Psaty, Claudia L Satizabal, Joshua Weinstock, Eric B Larson, Paul K Crane, C Dirk Keene, Sudha Seshadri, Ansuman T Satpathy, Thomas J Montine, Siddhartha Jaiswal

Faculty, Staff and Student Publications

Clonal hematopoiesis of indeterminate potential (CHIP) is a premalignant expansion of mutated hematopoietic stem cells. As CHIP-associated mutations are known to alter the development and function of myeloid cells, we hypothesized that CHIP may also be associated with the risk of Alzheimer's disease (AD), a disease in which brain-resident myeloid cells are thought to have a major role. To perform association tests between CHIP and AD dementia, we analyzed blood DNA sequencing data from 1,362 individuals with AD and 4,368 individuals without AD. Individuals with CHIP had a lower risk of AD dementia (meta-analysis odds ratio (OR) = 0.64, P …

First-In-Human Study Of Oleclumab, A Potent, Selective Anti-Cd73 Monoclonal Antibody, Alone Or In Combination With Durvalumab In Patients With Advanced Solid Tumors, Johanna Bendell, Patricia Lorusso, Michael Overman, Anne M Noonan, Dong-Wan Kim, John H Strickler, Sang-We Kim, Stephen Clarke, Thomas J George, Peter S Grimison, Minal Barve, Manik Amin, Jayesh Desai, Trisha Wise-Draper, Steven Eck, Yu Jiang, Anis A Khan, Yuling Wu, Philip Martin, Zachary A Cooper, Nairouz Elgeioushi, Nancy Mueller, Rakesh Kumar, Sandip Pravin Patel

Faculty, Staff and Student Publications

BACKGROUND: CD73 upregulation in tumors leads to local immunosuppression. This phase I, first-in-human study evaluated oleclumab (MEDI9447), an anti-CD73 human IgG1λ monoclonal antibody, alone or with durvalumab in patients with advanced colorectal cancer (CRC), pancreatic ductal adenocarcinoma (PDAC), or epidermal growth factor receptor-mutant non-small-cell lung cancer (NSCLC).

METHODS: Patients received oleclumab 5-40 mg/kg (dose-escalation) or 40 mg/kg (dose-expansion) intravenously every 2 weeks (Q2W), alone (escalation only) or with durvalumab 10 mg/kg intravenously Q2W.

RESULTS: 192 patients were enrolled, 66 during escalation and 126 (42 CRC, 42 PDAC, 42 NSCLC) during expansion. No dose-limiting toxicities occurred during escalation. In the monotherapy …

Barriers To A Successful Healthcare Transition For Individuals With Urea Cycle Disorders, Farah A Ladha, Cynthia Le Mons, William J Craigen, Pilar L Magoulas, Ronit Marom, Andrea M Lewis

Faculty, Staff and Students Publications

The pediatric to adult healthcare transition (HCT) is a process for individuals with chronic health conditions to gradually shift from a pediatric to an adult-oriented care system. Autonomy and self-management skills required for an individual's HCT readiness can be evaluated through the transition readiness assessment questionnaire (TRAQ). Despite general HCT preparation guidelines, little is known about the HCT experience of individuals with a urea cycle disorder (UCD). This is the first study to report the parent or guardian perception of the HCT process in children with a UCD by investigating the stages of transition readiness and transition outcome. We identify …

Pediatric Vitamin D: Pseudo-Hypervitaminosis, Lily Olayinka, Izmarie Poventud-Fuentes, Emily Garnett, Sridevi Devaraj

Faculty, Staff and Students Publications

BACKGROUND: Vitamin D toxicity is rare in pediatric population. Falsely elevated levels of 25-hydroxyvitamin D have been reported as a major challenge with immunoassay methods for quantifying vitamin D metabolites.

CASE PRESENTATION AND METHOD: Here, we present two pediatric cases of falsely elevated 25-hydroxyvitamin D that resulted in unnecessary further testing. We also report significant same-day variation in the measurement of 25-hydroxyvitamin D using the Abbott i2000SR immunoassay. Samples were spun twice and their values were confirmed with the gold standard liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for confirmation.

CONCLUSION: The addition of a centrifugation step prior to sample testing …

Withaferin A And Immune Checkpoint Blocker Therapy For The Treatment Of Non-Small Cell Lung Cancer, Roukiah Khalil

USF Tampa Graduate Theses and Dissertations

Lung cancer is the first cause of cancer-related deaths in both men and women with an overall five-year survival rate of 28%. Although immune checkpoint blockers (ICBs) are currently FDA-approved for the treatment of non-small cell lung cancer (NSCLC), only 17-20% of patients achieve durable responses by the induction of immunologic memory. The lack of response in most patients can be attributed to the tumor-intrinsic or tumor-extrinsic immune resistance mechanisms. A biomarker of importance is the Programmed Death Ligand-1 (PD-L1), as higher PD-L1 expression is usually associated with a better response to ICBs. Although studies have attempted to combine ICBs …

Acetate-Encapsulated Linolenic Acid Liposomes Reduce Sars-Cov-2 And Rsv Infection, Andrew R. Mcgill

USF Tampa Graduate Theses and Dissertations

Coronavirus disease-19 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), is an ongoing pandemic-endemic. In the United States, it remains the third leading cause of death in 2022. SARS-CoV-2, an RNA virus, has a genome prone to rapid mutation, generating variant species capable of resisting therapies and vaccination efforts. However, it has been estimated that more than 40% of SARS-CoV-2 infections may be asymptomatic, which calls into question any biological differences between the asymptomatic and afflicted groups. Additionally, Respiratory Syncytial Virus (RSV) is the most significant cause of bronchiolitis and asthma in neonates, with an increasing burden on the …