An Antimicrobial Polydopamine Surface Coating To Reduce Biofouling On Telemetry Tags Used In Marine Conservation Practices, 2022 Michigan Technological University
An Antimicrobial Polydopamine Surface Coating To Reduce Biofouling On Telemetry Tags Used In Marine Conservation Practices, Ariana Smies
Dissertations, Master's Theses and Master's Reports
Satellite telemetry tags are used to track the migration patterns of large cetaceans. These tags penetrate the dermis and remain embedded in the underlying blubber tissue. As the dermis of cetaceans is host to a diverse microbiome, and it is impossible to clean the skin before implanting the devices, the potential for infection is increased when the tags penetrate through the skin. H2O2 is a potential antimicrobial agent that, in addition to showing broad-spectrum efficacy against gram-negative and gram-positive bacteria, can promote wound healing outcomes by promoting proliferative factors and peptides that protect against oxidative stress. However, …
Management Of Car T-Cell Related Toxicities: What Did The Learning Curve Teach Us So Far?, 2022 Division of Hematology-Oncology and Blood and Marrow Transplantation and Cellular Therapy Programs, Mayo Clinic, Jacksonville, FL, USA
Management Of Car T-Cell Related Toxicities: What Did The Learning Curve Teach Us So Far?, Hemant S. Murthy, Farah Yassine, Madiha Iqbal, Shaikha Alotaibi, Mohamad A. Moustafa, Mohamed A. Kharfan-Dabaja
Hematology/Oncology and Stem Cell Therapy
Chimeric antigen receptor T cell (CAR-T) therapy is an immunotherapy, which represents a therapeutic breakthrough in the treatment of B-cell malignancies and multiple myeloma. Since the first CAR T-cell approval in 2017, there have been five FDA approved CAR-T products, more approved disease indications for CAR-T therapy, and investigational trials launched for other cancers, including solid organ malignancies. CAR-T therapy possesses unique toxicities. Better understanding of these toxicities over time has helped in more efficient diagnosis, management, and treatment strategies. This review will focus on CAR-T-related toxicities including cytokine release syndrome, immune effector cell associated neurotoxicity syndrome (ICANS), cytokine release …
Chimeric Antigen Receptor Structure And Manufacturing Of Clinical Grade Car Engineered Cells Using Different Bioreactors, 2022 Stem Cell & Tissue Re-engineering Program (Dpt)-R., King Faisal Specialist Hospital & Research Centre, Riyadh 11211, Kingdom of Saudi Arabia
Chimeric Antigen Receptor Structure And Manufacturing Of Clinical Grade Car Engineered Cells Using Different Bioreactors, Farhatullah Syed, Riad El Fakih, Ali Debsan Alahmari, Ahmed Syed Osman Ali, Mahmoud Aljurf
Hematology/Oncology and Stem Cell Therapy
Increasing success of adaptive cell therapy (ACT), such as genetically engineered T cells to express chimeric antigen receptors (CARs) proven to be highly significant technological advancements and impressive clinical outcomes in selected haematological malignancies, with promising efficacy. The evolution of CAR designs beyond the conventional structures is necessary to address some of the limitations of conventional CAR therapy and to expand the use of CAR T cells to a wider range of malignancies. There are various obstacles with a wide range of engineering strategies in order to improve the safety, efficacy and applicability of this therapeutic modality. Here we describe …
Lisocabtagene Maraleucel In Relapsed Or Refractory Diffuse Large B Cell Lymphoma: What Is The Evidence?, 2022 Division of Hematology–Oncology and Blood and Marrow Transplantation and Cellular Therapy Programs, Mayo Clinic, Jacksonville, FL, USA
Lisocabtagene Maraleucel In Relapsed Or Refractory Diffuse Large B Cell Lymphoma: What Is The Evidence?, Mohamed A. Kharfan-Dabaja, Farah Yassine, Muhamad Alhaj Moustafa, Madiha Iqbal, Hemant Murthy
Hematology/Oncology and Stem Cell Therapy
Lisocabtagene maraleucel (liso-cel) is an autologous CD19-directed chimeric antigen receptor (CAR) T cell product, with a CD3f activatory domain connected to 4-1BB costimulatory domain. Liso-cel, unlike the other two approved products—axicabtagene ciloleucel and tisagenlecleucel— is manufactured separately from CD4 and CD8 T cells and then administered as a sequential infusion of the two components at equal target doses. The approval of liso-cel was based on the results of Transcend NHL 001, a single-arm, open-label, multicenter, seamless design trial that enrolled 344 patients, of whom 269 received conforming liso-cel. The most common histology was diffuse large B cell lymphoma, not otherwise …
Cytogenetic Influence On Prognosis In Acute Promyelocytic Leukaemia: A Cohort Study In Vietnam, 2022 Hanoi Medical University, Department of Hematology, Hanoi, Viet Nam
Cytogenetic Influence On Prognosis In Acute Promyelocytic Leukaemia: A Cohort Study In Vietnam, Minh Phuong Vu, Cuc Nhung Nguyen, Hoang Vu
Hematology/Oncology and Stem Cell Therapy
Objective/Background: To analyse the influence of chromosomal aberrations in addition to t (15;17)(q22;q21) in acute promyelocytic leukaemia (APL) on clinical characteristics and treatment outcomes. Methods: Fifty-seven patients with new APL diagnoses underwent conventional cytogenetic analysis; fluorescence in situ hybridization for t(15;17)(q22;q21) and reverse transcriptase–p olymerase chain reaction detected PML/RARa in two forms: L (length) and S (short) and accepted treatment with all-trans retinoic acid and chemotherapy. Patients with additional chromosome aberrations were designated as the complex karyotype group and were compared with patients with only t(15;17), who were designated as the simple karyotype group. Results: Additional chromosome aberrations was observed …
Priapism In Lymphoproliferative Disorders: A Systematic Review, 2022 Internal Medicine Department, Hamad Medical Corporation, Doha, Qatar
Priapism In Lymphoproliferative Disorders: A Systematic Review, Elrazi A. Ali, Sundus Sardar, Mohamed A. Yassin
Hematology/Oncology and Stem Cell Therapy
Priapism is defined as a persistent penile erection lasting more than 4 h. We searched the literature for reviews, case reports, and series for patients with lymphoproliferative disorders who developed priapism. The search involved all the lymphoproliferative disorders included in the revised 2016 World Health Organization classification of lymphoid neoplasms including chronic lymphocytic leukemia, multiple myeloma, Waldenstro¨m macroglobulinemia, and lymphomas. A total of 16 articles were found. The search included cases up to 4th January 2021. Priapism was seen most commonly as the first manifestation of lymphoproliferative disorders, rarely seen after treatment or after diagnosis.
Prevalence Of Sleep Aid Medication Use In Patients Receiving A Hematopoietic Cell Transplant On An Inpatient Unit, 2022 Center for International Blood and Marrow Transplant Research (CIBMTR), Medical College of Wisconsin, Milwaukee, WI, USA
Prevalence Of Sleep Aid Medication Use In Patients Receiving A Hematopoietic Cell Transplant On An Inpatient Unit, Rachel Cusatis, Antony Ibrahim, Jennifer M. Knight, Anita D'Souza, Bronwen E. Shaw
Hematology/Oncology and Stem Cell Therapy
Background and objectives: There is a lack of research regarding the use of sleep aids after hematopoietic stem cell transplantation (HCT). We describe the prevalence of sleep aid administration in the HCT unit and identify associations with patient or clinical characteristics. Patients and methods: In this retrospective analysis of sequential inpatient HCTs from July 1 to December 31, 2016 we describe whether and when patients were prescribed sleep aid medications. Chi-square tests determined significant differences between patient characteristics, sleep aid prescription, and time of prescription. Results: Of the 225 patients identified, 193 (86%) were prescribed sleep aids. Significantly more women …
Hematologic Manifestations Of Parvovirus B 19 Infection, 2022 Department of Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
Hematologic Manifestations Of Parvovirus B 19 Infection, Ghada Algwaiz, Abrar Alharbi, Khuloud Alsehaim, Ali Alahmari, Riad El Fakih, Mahmoud Aljurf
Hematology/Oncology and Stem Cell Therapy
Parvovirus B19 virus infection is widespread among humans because of its highly infectious and obstinate nature, with up to 80% of the population testing positive for IgG antibodies against the virus. Pronormoblasts observed in biopsy are the hallmarks of PVB19 infection. In addition, PVB19 affects the skin, heart, brain, joints, and liver and can be diagnosed through antibody detection or DNA detection via PCR. Due to its capsid proteins’ high affinity for bone marrow receptors, its main presentation is the suppression of bone marrow functions. It has been shown to affect patients with hemolytic anemia and patients with hematological malignancies, …
Modulation Of Polyamines To Elucidate Function Within Osteogenesis Of Mesenchymal Stromal Cells, 2022 Cal Poly Humboldt
Modulation Of Polyamines To Elucidate Function Within Osteogenesis Of Mesenchymal Stromal Cells, Amin S. Cressman
Cal Poly Humboldt theses and projects
Snyder-Robinson Syndrome (SRS), an X-linked intellectual disability that arises in children, exhibits debilitating phenotypes like severe osteoporosis. These patients demonstrate an inability to produce mineralized new bone in comparison to the rate at which bone is resorbed, thus leading to weaker skeletal structure and atraumatic fractures. The known cause of SRS is due to loss-of-function mutations within the gene that encodes Spermine Synthase (SMS). Loss of SMS enzymatic activity, which catalyzes the conversion of polyamines spermidine into spermine, demonstrates an increase in the spermidine/spermine ratio in all documented cases of this disorder. The involvement of polyamines in osteogenesis is still …
Determining Haplotype Specific X Chromosome Inactivation State And Related Epigenetic Features In Female X-Linked Genes, 2022 Cal Poly Humboldt
Determining Haplotype Specific X Chromosome Inactivation State And Related Epigenetic Features In Female X-Linked Genes, Ariah Dawn Mackie
Cal Poly Humboldt theses and projects
Females with heterozygous X-linked mutations are prone to pseudo-haploinsufficiency because random X chromosome inactivation (XCI) silences one of their two X chromosomes. A prior study explored the theory that reactivating the silenced healthy allele could be a treatment for pseudo-haploinsufficient females. The next step was to evaluate this approach in a clinically relevant stem cell model of the rare neurological disease CDKL5 Deficiency Disorder (CDD). It was necessary to validate X-inactivation state with respect to CDKL5 allele expression in one of these models. We explored CDKL5 allele expression in two populations of CDD female patient-derived induced pluripotent stem cells (iPSCs) …
Evaluating Novel Combinations Of Polyamine Targeting Therapeutics In Pancreatic Ductal Adenocarcinoma, 2022 University of Central Florida
Evaluating Novel Combinations Of Polyamine Targeting Therapeutics In Pancreatic Ductal Adenocarcinoma, Sai Preethi Nakkina
Electronic Theses and Dissertations, 2020-
Pancreatic cancer overall has a poor five-year survival rate of less than 8%. Well-tolerated regimens and immune cell infiltration to promote anti-cancer treatments are major challenges. Studies described herein leveraged testing different combinations/doses of polyamine targeting inhibitors to further understand the impact of targeting key polyamine pathway mediators in pancreatic ductal adenocarcinoma (PDAC). Placebo controls were compared to groups treated with difluoromethylornithine (DFMO, a polyamine biosynthesis inhibitor of ornithine decarboxylase), different polyamine transport inhibitors, and compound combinations in strategies for polyamine blockage therapy (PBT). Informatic analyses showed that the dysregulation of key polyamine pathway mediators are associated with poor patient …
Targeting The Bcl6 Transcription Factor In Ovarian Cancer, 2022 University of New Hampshire, Durham
Targeting The Bcl6 Transcription Factor In Ovarian Cancer, Harrison H. Parent
Honors Theses and Capstones
Ovarian cancer is one of the most common reproductive malignancies for women in the United States, as well as one of the deadliest. Many deaths attributed to ovarian cancer, as well as cancer generally, are due to metastasis of the original tumor to different tissues throughout the body. The BCL6 transcription factor has been identified to play a key role in the metastasis of these tumors, as well as the invasion of these cancer cells through mesothelial cell layers, which contributes to ovarian cancer’s unique metastatic behavior. In an attempt to target these metastases and prevent mesothelial penetration, drugs were …
Elucidating The Role Of Kmt2d In Her2+ Breast Cancer, 2022 Loyola University Chicago
Elucidating The Role Of Kmt2d In Her2+ Breast Cancer, Emily Ma
Dissertations
Breast cancer is the second leading cause of cancer-related deaths among women in the US. Histone modifications are common epigenetic changes that have been implicated in several breast cancers, including HER2+ breast cancers. Current therapies, such as trastuzumab, block the HER2 receptor to reduce tumor growth. Unfortunately, HER2+ breast cancers have found ways to overcome these therapies, leading to tumor resistance, metastases, and poor survival outcomes. A better understanding of the underlying mechanisms contributing to HER2+ breast cancer resistance may lead to the discovery of novel therapeutic strategies to improve patient outcomes.One prognostic marker for poor survival in women with …
Genetic Underpinnings Of Novel Trait Development In A Euwallacea-Fusarium Mutualism, 2022 West Virginia University
Genetic Underpinnings Of Novel Trait Development In A Euwallacea-Fusarium Mutualism, Elaina J. Spahr
Graduate Theses, Dissertations, and Problem Reports
Evolutionary Developmental Biology seeks to answer fundamental questions about the mechanisms underlying the evolution and innovation towards increasing structural complexity within the body plan. The ambrosia symbiosis, a polyphyletic group of xylem-feeding beetles, provides a wealth of diversity in novel pouch-like structures called mycangia. This diversity could serve as a rich model for understanding how mutualisms may prompt structural innovation and diversification in a host organism. The ambrosia symbiosis has become a fast-growing research subject in entomology and forest pathology but has yet to experience the same attention under the lens of evolutionary developmental genetics.
Development of mycangia was examined …
Characterization Of Two Krab-Containing Zinc Finger Transcription Factors In Bovine Preimplantation Embryonic Development, 2022 West Virginia University
Characterization Of Two Krab-Containing Zinc Finger Transcription Factors In Bovine Preimplantation Embryonic Development, Mingxiang Zhang
Graduate Theses, Dissertations, and Problem Reports
Oocyte developmental competence or oocyte intrinsic quality describes the capability of oocytes to resume meiosis, cleave and develop to blastocyst stage after fertilization, implant and develop to term in a good health. A growing number of evidences indicate that the majority of embryonic mortality occurs during early embryonic development in different species, including human, horse and cattle primarily due to poor oocyte quality. Maternal effect genes are key aspects of oocyte quality, which are transcribed during the process of oogenesis and folliculogenesis. The maternal factors are accumulated in oocytes, orchestrating various early developmental events including fertilization, epigenetic reprogramming and zygotic …
Cell-Engineered Vesicles For Therapeutic Delivery And Immunomodulatory Applications, 2022 University of Kentucky
Cell-Engineered Vesicles For Therapeutic Delivery And Immunomodulatory Applications, Khaga Neupane
Theses and Dissertations--Chemistry
Development of a new kind of drug delivery system (DDS) that could efficiently deliver therapeutics to the cell of interest would allow us to accomplish cell-specific drug delivery while eliminating systemic toxicity. Although nanocarriers including endogenously released extracellular vesicles (EEVs), liposomes, and small molecules seem to be promising drug delivery systems, biological challenges persist for their use in clinical applications. Here, we demonstrate nanovesicles engineered by fragmenting cellular membranes can be exploited as versatile DDSs for therapeutics delivery as well as immunomodulatory functions. Cell-engineered vesicles were produced by cavitating cells using nitrogen gas at high pressure followed by serial centrifugation. …
Identifying Adp-Ribosylation As The Biochemical Signal That Marks Dna-Protein Crosslinks For Sprtn-Dependent Proteolysis, 2022 South Dakota State University
Identifying Adp-Ribosylation As The Biochemical Signal That Marks Dna-Protein Crosslinks For Sprtn-Dependent Proteolysis, Katelyn Hurley
Electronic Theses and Dissertations
DNA-protein crosslinks (DPCs) form when proteins covalently attach to DNA. It is estimated that hundreds of DPCs form in our cells each day. Because these lesions are cytotoxic, mammalian cells have evolved multiple intricate repair systems to remove DPCs and restore genome integrity. One mechanism mammalian cells rely on for DPC repair is direct proteolysis by the metalloprotease, SPRTN. While it is known that SPRTN degrades a heterogenous array of DPCs, including both naturally occurring and chemically induced, how SPRTN selects DPCs amongst chromatin-associated proteins remains unknown. Our main objective is to determine how DPC repair is regulated. In Chapter …
Characterizing The Lir Domain Of Abin1 And Identifying Its Role As A Regulator Of Mitophagy, 2022 South Dakota State University
Characterizing The Lir Domain Of Abin1 And Identifying Its Role As A Regulator Of Mitophagy, Andrew Rhiner
Electronic Theses and Dissertations
A20 Inhibitor of NF-κB (ABIN1/TNIP1) is a known regulator of TNFα signaling induced cell death and inflammation. The regulatory activity has been attributed to ABIN1’s recruitment of the ubiquitin editing enzyme TNF-α-induced protein 3 (TNFAIP3/A20) to Receptor-interacting serine/threonine-protein kinase 1 (RIPK1). The regulation of RIPK1 by ABIN1 and A20 relies on a third player, linear ubiquitin chain assembly complex (LUBAC), which is involved in the recruitment of ABIN1 to RIPK1. Loss of LUBAC or ABIN1 is embryonic lethal, but loss of A20 is not embryonic lethal. The embryonic lethality due to loss of ABIN1, paired with the lack of lethality …
Phip Variants Associated With Chung–Jansen Syndrome Disrupt Replication Fork Stability And Genome Integrity, 2022 University of South Florida
Phip Variants Associated With Chung–Jansen Syndrome Disrupt Replication Fork Stability And Genome Integrity, Neysha Tirado-Class, Caitlin Hathaway, Wendy K. Chung, Huzefa Dungrawala
Molecular Biosciences Faculty Publications
Chung–Jansen syndrome (CJS) is a rare, autosomal dominant disorder characterized by developmental delay, intellectual disability/cognitive impairment, behavioral challenges, obesity, and dysmorphic features. CJS is associated with heterozygous variants in PHIP (Pleckstrin-Homology Interacting Protein), a gene that encodes one of several substrate receptors for Cullin4-RING (CRL4) E3 ubiquitin ligase complex. Full-length PHIP, also called DCAF14, was recently identified to function as a replication stress response protein. Herein, we report the identification of two PHIP missense variants identified by exome sequencing in unrelated individuals with CJS. The variants p.D488V and p.E963G occur in different functional elements of DCAF14-WD40 repeat domain and pleckstrin …
Sequence Properties Of An Intramolecular Interaction That Inhibits P53 Dna Binding, 2022 University of South Florida
Sequence Properties Of An Intramolecular Interaction That Inhibits P53 Dna Binding, Emily Gregory, Gary W. Daughdrill
Molecular Biosciences Faculty Publications
An intramolecular interaction between the p53 transactivation and DNA binding domains inhibits DNA binding. To study this autoinhibition, we used a fragment of p53, referred to as ND WT, containing the N-terminal transactivation domains (TAD1 and TAD2), a proline rich region (PRR), and the DNA binding domain (DBD). We mutated acidic, nonpolar, and aromatic amino acids in TAD2 to disrupt the interaction with DBD and measured the effects on DNA binding affinity at different ionic strengths using fluorescence anisotropy. We observed a large increase in DNA binding affinity for the mutants consistent with reduced autoinhibition. The ΔΔG between DBD and …