Digital Commons Network^™

Emerging Therapeutic Options For Follicular-Derived Thyroid Cancer In The Era Of Immunotherapy, Naimah Turner, Sarah Hamidi, Rim Ouni, Rene Rico, Ying C Henderson, Maria Puche, Sayan Alekseev, Jocelynn G Colunga-Minutti, Mark E Zafereo, Stephen Y Lai, Sang T Kim, Maria E Cabanillas, Roza Nurieva

Faculty, Staff and Student Publications

Although most follicular-derived thyroid cancers are well differentiated and have an overall excellent prognosis following treatment with surgery and radioiodine, management of advanced thyroid cancers, including iodine refractory disease and poorly differentiated/undifferentiated subtypes, is more challenging. Over the past decade, better understanding of the genetic drivers and immune milieu of advanced thyroid cancers has led to significant progress in the management of these patients. Numerous targeted kinase inhibitors are now approved by the U.S Food and Drug administration (FDA) for the treatment of advanced, radioiodine refractory differentiated thyroid cancers (DTC) as well as anaplastic thyroid cancer (ATC). Immunotherapy has also …

ฤทธิ์ของสารสกัดจากมะกรูดต่อภาวะเครียด Oxidative Stress ในหนอน Caenorhabditis Elegans, ณัฐพงศ์ นพโลหะ

Chulalongkorn University Theses and Dissertations (Chula ETD)

ภาวะโรคไม่ติดต่อเรื้อรัง หรือ Non-Communicable Disease (NCDs) เป็นภาวะโรคที่ไม่ได้ติดต่อจากคนสู่คนได้รวมถึงไม่ได้เกิดจากการติดเชื้อโรค โดยสาเหตุหนึ่งของภาวะกลุ่มโรคนี้คือการเกิดภาวะ oxidative stress ที่ทำให้ร่างกายมีปริมาณของสารอนุมูลอิสระไม่สมดุล โดยที่ผ่านมาจำนวนผู้ป่วยในโรคนี้มีจำนวนเพิ่มขึ้นอย่างต่อเนื่อง ซึ่งแนวทางการรักษาส่วนใหญ่มักจะมาจากการรักษาตามอาการ ดังนั้นการแก้ปัญหาโรคนี้ให้ได้ผลมากที่สุดคือการป้องกันการเกิดโรคมากกว่าการรักษา ผู้วิจัยจึงสนใจที่จะนำมะกรูดที่มีสรรพคุณต้านอนุมูลอิสระมาทดสอบ โดยมีวัตถุประสงค์เพื่อศึกษาฤทธิ์ของสารสกัดจากใบมะกรูดและผิวมะกรูด ในการช่วยลดการเกิดภาวะ oxidative stress สำหรับการช่วยยืดอายุของ C. elegans ที่ถูกชักนำให้เกิดภาวะ oxidative stress โดยแบ่งการศึกษาออกเป็น 4 ขั้นตอน ได้แก่ ตอนที่ 1 ศึกษาฤทธิ์ของสารสกัดจากมะกรูดต่อ E.coli OP50 ที่เป็นอาหารของ C. elegans พบว่าสารสกัดจากใบมะกรูดและผิวมะกรูดไม่มีผลในการยับยั้งการเจริญของ E.coli OP50 เมื่อเทียบกับการยับยั้งการเจริญเติบโตของยา Penicillin-Streptomycin ที่ใช้เป็นกลุ่มควบคุม จึงสามารถใช้สารสกัดจากใบมะกรูดและผิวมะกรูดในการทดสอบได้ โดยที่ไม่มีผลต่อ E.coli OP50 ที่ใช้เป็นอาหารของ C. elegans ตอนที่ 2 การศึกษาฤทธิ์ของสารสกัดจากใบมะกรูดและผิวมะกรูดที่มีผลต่อการรอดชีวิตของ C. elegans ที่ถูกชักนำให้เกิดภาวะ oxidative stress พบว่าสารสกัดจากใบมะกรูดและผิวมะกรูดที่ความเข้มข้น 50 , 100 และ 200 ug/ml มีอัตราการรอดชีวิตของ C. elegans เมื่อเทียบกับ C. elegans ที่ไม่ได้ให้สารสกัดจากใบมะกรูดและผิวมะกรูด แตกต่างกันอย่างมีนัยสำคัญทางสถิติ 0.05 และตอนที่ 3 การศึกษาฤทธิ์ของสารสกัดจากใบมะกรูดและผิวมะกรูดต่อการยับยั้งปริมาณ ROS ของ C. elegans ที่ถูกชักนำให้เกิดภาวะ oxidative stress โดยพบว่าใบมะกรูดและผิวมะกรูดที่ความเข้มข้น 50 , 100 และ 200 ug/ml มีค่าปริมาณสาร ROS ของ C. elegans ที่ให้สารสกัดจากใบมะกรูดและผิวมะกรูด เมื่อเทียบกับ C. elegans ที่ไม่ให้สารสกัดจากใบมะกรูดและผิวมะกรูด …

การปรับสมดุลไมโครไบโอมในลำไส้ด้วยเชื้อ Lactobacillus Rhamnosus Gg ช่วยบรรเทาความรุนแรงจากการติดเชื้อในกระแสเลือด ในหนูที่ถูกเหนี่ยวนำให้เกิดความชราโดยน้ำตาล D-Galactose และกระตุ้นภาวะติดเชื้อในกระแสเลือดโดยวิธีการผูกและเจาะลำไส้ใหญ่ส่วนต้น, ชาลิสา พินิจจันทร์

Chulalongkorn University Theses and Dissertations (Chula ETD)

การเสียสมดุลของจุลินทรีย์ในลำไส้อาจทำให้เกิดภาวะลำไส้รั่ว เกิดการติดเชื้อในกระแสเลือดตามมาได้ ซึ่งสภาวะดังกล่าวมักพบมากในผู้สูงอายุ การศึกษาก่อนหน้านี้พบว่าโพรไบโอติกสามารถลดการเสียสมดุลของจุลินทรีย์ในลำไส้ แต่การศึกษาเรื่องผลของการรับประทานเชื้อโพรไบโอติดต่อของการลดความรุนแรงจากการติดเชื้อในกระแสเลือด รวมทั้งภาวะ Sepsis-associated encephalopathy (SAE) ในผู้สูงอายุนั้นยังไม่มีการศึกษาที่ชัดเจน วัตถุประสงค์ของการศึกษา เพื่อทดสอบความสามารถของเชื้อโพรไบโอติกสายพันธุ์ Lacticaseibacillus rhamnosus GG (LGG) ในการช่วยลดความรุนแรงของการติดเชื้อในกระแสเลือดในหนูที่ถูกเหนี่ยวนำให้เกิดสภาวะชราโดยการใช้น้ำตาลกาแลคโตส ผู้วิจัยทำการให้เชื้อ LGG ทางปากกับหนูทดลอง เปรียบเทียบกับกลุ่มควบคุม และทดสอบความแตกต่างของจุลินทรีย์ในลำไส้ในอุจจาระของหนูด้วยวิธี 16S RNA sequencing พร้อมวัดสภาวะความชราของหนูด้วยเทคนิค Histochemistry ในอวัยวะภายใน จากนั้นหนูทั้ง 2 กลุ่มจะถูกกระตุ้นให้เกิดการติดเชื้อในกระแสเลือดโดยวิธีการผูกและเจาะลำไส้ใหญ่ส่วนต้น (CLP) และวัดความรุนแรงของการติดเชื้อในกระแสเลือดโดยการวัดอัตราการตาย ระดับ creatinine (Scr), Alanine transaminase (ALT), cytokines (IL-6 TNF-α IL-10 และ IL-1ß) ในซีรัมโดยเทคนิค Enzyme-linked immunosorbent assay (ELISA) การตรวจวัด Sepsis encephalopathy ผู้วิจัยใช้ค่ามาตรฐาน SHIRPA เพื่อช่วยในการวัด นอกจากนี้เพื่อหาสาเหตุของการลดความรุนแรงจากการติดเชื้อในกระแสเลือดด้วยเชื้อโพรไบโอติก ผู้วิจัยนำ Lactobacillus condition media (LCM) ร่วมกับ Lipopolysaccharide (LPS) มาใช้ในการกระตุ้นเซลล์ RAW 264.7 , เซลล์ BV-2 และเซลล์ HT-22 จากนั้นทำการวัดปริมาณ Inflammatory cytokines ด้วยเทคนิค ELISA และวัดการแสดงออกของยีน IL-6 TNF-α IL-10 IL-1ß Fizz Arg-1 NF-kB TLR-4 และยีน iNOS ด้วยเทคนิค Quantitative real-time PCR (qPCR) จากผลการวิเคราะห์จุลินทรีย์ในอุจจาระ แสดงให้เห็นว่าหนูชรามีการสูญเสียสมดุลของจุลินทรีย์ในลำไส้ และพบการเกิดพังผืดในปอด ไต และตับ ซึ่งเชื้อ …

Optimization Of An Immune Assay To Detect Binding Of Nod2 To Staphylococcus Aureus, Precious Mckenzie

All Student Theses and Dissertations

Staphylococcus aureus, a gram-positive, commensal bacterium, is the cause of a multitude of opportunistic diseases and infections. While S. aureus has evolved ways to escape innate immune responses in the host, the mechanisms are not fully understood. One area of active research involves mechanisms by which S. aureus avoids detection by Pattern Recognition Receptors (PRRs), such as Nuclear Oligomerization Domain 2 (NOD2), present on the surface of and inside innate immune cells. This study aimed to design and optimize an assay that can be utilized to investigate S. aureus components that contribute to the activation of NOD2 receptors. The …

Elucidating Mechanisms Of Enhanced Dsrna-Nanophytoglycogen Innate Immune Responses In Healthy Human Cells, Nicholas Jadaa

Theses and Dissertations (Comprehensive)

Immunostimulatory nucleic acids, such as long double-stranded RNA (ds)RNA, can stimulate innate immune responses in a non-sequence specific manner. These molecules are recognized by pattern-recognition receptors in the cytoplasm, endosome, and on the cell surface. Activation leads to the production of mediators of innate immune pathways, including type I interferon and proinflammatory cytokines. Although these receptors are present in all cells, their role in non-immune cells is often overlooked due to their lower level of responsiveness. Nanocarriers can enhance these nucleic acid-mediated responses, allowing for exploration of innate immune pathways in non-immune cells. Nanoparticles as carriers of nucleic acids can …

Antiangiogenic Therapy Combined With Immune Checkpoint Blockade In Urothelial Cancer: Systematic Review And Meta-Analysis, Mohammad Jad Moussa, Iuliia Kovalenko, Emanuele Crupi, Ekaterina Proskuriakova, Yimin Geng, Giuseppe Fallara, Raed Benkhadra, Daniele Raggi, Matthew T. Campbell, Pavlos Msaouel, Omar Alhalabi

Department of Medicine Faculty Publications

Background: Antiangiogenic therapy had been tested in urothelial cancer (UC) without reaching the clinic.

Objective: We provide a systematic review and meta-analysis of trials to assess efficacy of immune checkpoint inhibitors (ICI) combined with antiangiogenic agents in UC.

Methods: Following PRISMA guidelines, we searched for trials with at least one arm of patients with UC treated with ICI plus antiangiogenics. Data were analyzed with the "meta" package from R using a one-staged frequentist meta-analysis.

Results: After screening 13,708 titles and abstracts, 9 studies were selected for analysis with 14 identified cohorts comprising 621 patients: 448 were ICI-naïve (ICI-N) and 173 …

Factors Associated With Hepatitis C-Related Hospitalizations And Inpatient Mortality In The United States, Pre- And Post-Onset Of The Covid-19 Pandemic, Christina R. Samuel

College of Graduate Studies: Theses & Dissertations

Background: Hepatitis C is a significant public health problem in the United States and imposes a substantial burden on the healthcare system. Previous research shows that the COVID-19 pandemic response efforts have overshadowed hepatitis C testing and treatment measures in health care settings across the country. The purpose of this study was to describe and examine the factors associated with hepatitis C-related hospitalizations and inpatient mortality in the United States, pre- and post-onset of the COVID-19 pandemic. Methods: Data were obtained from the 2019-2020 National Inpatient Sample database. The study population included persons aged ≥18 years with hepatitis C-related inpatient …

Bridging The Gap: Assessing Cmv Dnaemia In Kidney Transplant Recipients With Previous Solid Organ Transplants, Goni Katz-Greenberg, Julie M Steinbrink, Krishna Shah, Jennifer S Byrns

Faculty, Staff and Students Publications

Cytomegalovirus (CMV) infection poses a significant threat to solid organ transplant (SOT) recipients and can lead to various complications and adverse outcomes. In an effort to prevent CMV infection, it is common to utilize prophylactic strategies, including antiviral medications such as valganciclovir, especially for high-risk patients. Risk factors for CMV infection in kidney transplant recipients (KTRs) include CMV mismatch between donor and recipient (i.e., donor positive, recipient negative), and intensity of immunosuppression, such as the use of T-cell depleting agents. However, little attention has been given to KTRs with a history of prior SOTs, despite their prolonged exposure to immunosuppressive …

Case Report: P40phox Deficiency Underlying Pediatric-Onset Systemic Lupus Erythematosus, Alejandro Nieto-Patlán, Natalia S Fernández Dávila, Yuqing Wang, Michelle Zelnick, Eyal Muscal, Martha Curry, James R Lupski, Steven M Holland, Bo Yuan, Douglas B Kuhns, Tiphanie P Vogel, Ivan K Chinn

Faculty, Staff and Students Publications

Introduction

Systemic lupus erythematosus is a multi-faceted autoimmune disorder of complex etiology. Pre-pubertal onset of pediatric systemic lupus erythematosus (pSLE) is uncommon and should raise suspicion for a genetic driver of disease. Autosomal recessive p40^phox deficiency is a rare immunologic disorder characterized by defective but not abolished NADPH oxidase activity with residual production of reactive oxygen species (ROS) by phagocytic cells.

Case presentation

We report the case of a now 18-year-old female with pSLE onset at 7 years of age. She presented with recurrent fever and malar rash. Aspects of her immune dysregulation over time have included typical pSLE …

Translational And Oncologic Significance Of Tertiary Lymphoid Structures In Pancreatic Adenocarcinoma, Zachary Gao, Joseph Azar, Huili Zhu, Sophia Williams-Perez, Sung Wook Kang, Celia Marginean, Mark P Rubinstein, Shalini Makawita, Hyun-Sung Lee, E Ramsay Camp

Faculty, Staff and Students Publications

Pancreatic adenocarcinoma (PDAC) is an aggressive tumor with poor survival and limited treatment options. PDAC resistance to immunotherapeutic strategies is multifactorial, but partially owed to an immunosuppressive tumor immune microenvironment (TiME). However, the PDAC TiME is heterogeneous and harbors favorable tumor-infiltrating lymphocyte (TIL) populations. Tertiary lymphoid structures (TLS) are organized aggregates of immune cells that develop within non-lymphoid tissue under chronic inflammation in multiple contexts, including cancers. Our current understanding of their role within the PDAC TiME remains limited; TLS are complex structures with multiple anatomic features such as location, density, and maturity that may impact clinical outcomes such as …

Structure And Funding Of Clinical Informatics Fellowships: A National Survey Of Program Directors, Tushar N Patel, Aaron J Chaise, John J Hanna, Kunal P Patel, Karl M Kochendorfer, Richard J Medford, Dara E Mize, Edward R Melnick, Jonathan D Hron, Kenneth Youens, Deepti Pandita, Michael G Leu, Gregory A Ator, Feliciano Yu, Nicholas Genes, Carrie K Baker, Douglas S Bell, Joshua M Pevnick, Steven A Conrad, Aarti R Chandawarkar, Kendall M Rogers, David C Kaelber, Ila R Singh, Bruce P Levy, John T Finnell, Joseph Kannry, Natalie M Pageler, Vishnu Mohan, Christoph U Lehmann

Faculty, Staff and Students Publications

BACKGROUND: In 2011, the American Board of Medical Specialties established clinical informatics (CI) as a subspecialty in medicine, jointly administered by the American Board of Pathology and the American Board of Preventive Medicine. Subsequently, many institutions created CI fellowship training programs to meet the growing need for informaticists. Although many programs share similar features, there is considerable variation in program funding and administrative structures.

OBJECTIVES: The aim of our study was to characterize CI fellowship program features, including governance structures, funding sources, and expenses.

METHODS: We created a cross-sectional online REDCap survey with 44 items requesting information on program administration, …

How Individuals’ Opinions Influence Society’S Resistance To Epidemics: An Agent-Based Model Approach, Geonsik Yu, Michael J. Garee, Mario Ventresca, Yuehwern Yih

Faculty Publications

Background: Protecting public health from infectious diseases often relies on the cooperation of citizens, especially when self-care interventions are the only viable tools for disease mitigation. Accordingly, social aspects related to public opinion have been studied in the context of the recent COVID-19 pandemic. However, a comprehensive understanding of the effects of opinion-related factors on disease spread still requires further exploration. Methods: We propose an agent-based simulation framework incorporating opinion dynamics within an epidemic model based on the assumption that mass media channels play a leading role in opinion dynamics. The model simulates how opinions about preventive interventions change over …

Sialylation As A Mechanism For Preferential Ligand Binding In Cfs1r, Eric J. Beaulaurier

EWU Masters Thesis Collection

Macrophages are immune cells that help provide the first line of defense against a wide range of internal and external insults and create the bridge between innate and adaptive immune responses. When macrophage homeostasis is disrupted, disease states occur. Associated disease states include rheumatoid arthritis, Alzheimer’s disease, and multiple sclerosis. The survival and proliferation of macrophages is largely controlled by signaling through colony stimulating factor 1 receptor (CSF1R). Notably, this receptor can be activated by two non-homologous ligands, colony stimulating factor 1 (CSF1) and interleukin- 34 (IL-34). These two ligands are differentially required for macrophage homeostasis across body systems and …

Personalized Molecular Therapies For Advanced Non-Small Cell Lung Cancer: Overcoming Heterogeneity To Optimize Treatment Response And Clinical Outcomes, Zuan-Fu Lim

Graduate Theses, Dissertations, and Problem Reports (ETD)

Lung cancer remains one of the deadliest cancers. Novel, paradigm shifting treatments including immunotherapy and targeted therapies have recently been developed to cull the deadly effects of lung cancer, but many challenges remain. There remains a significant unmet need to accurately predict and optimally select for patients who will respond to immune checkpoint inhibitors (ICI) treatment. In Chapter 2 of this dissertation, we investigated a novel live single cell cytokine profiling lab-on-chip platform, IsoLight, using peripheral CD4+ and CD8+ T-cells for ICI biomarker development. A total of 55,175 single T-lymphocytes were analyzed in this proof-of-concept study. We found that an …

The Identification And Characterization Of Novel And Improved Antigens For Next-Generation Pertussis Vaccines, Gage Michael Pyles

Graduate Theses, Dissertations, and Problem Reports (ETD)

Whooping cough, or pertussis, is a highly infectious respiratory disease caused by infection with the Gram-negative bacterial pathogen Bordetella pertussis. Pertussis affects all age groups and populations; however, it is most severe in infants who are too young to receive vaccinations and remains a global health concern with more than­­­­ 200,000 cases reported globally in 2023. Vaccines against pertussis have been available in the United States since the 1940’s with the development and widespread use of whole cell pertussis vaccines. Following their introduction, the incidence of pertussis was controlled and limited to fewer than 5,000 cases per year. Despite …

Endogenous Glucocorticoid Signaling Is Required For Normal Macrophage Response To H. Pylori Infection, Stuti Khadka

Graduate Theses, Dissertations, and Problem Reports (ETD)

Gastric cancer is the fifth leading cause of cancer-related deaths worldwide, affecting millions of people. H. pylori is the strongest risk factor for gastric cancer, with about 90% of the cases strongly associated with H. pylori infection. Half of the world's population is infected with this bacterium. However, only a small subset of the infected population (1-3 %) go on to develop gastric cancer. Diagnosis of the disease at an early stage is the biggest challenge because of the widespread prevalence of H. pylori infection and a long asymptomatic phase before the advanced stages. Patients are left with limited treatment …

Sars-Cov-2 Immunogenicity Models Inform Novel Strategies That Can Improve Mrna Vaccines, Katherine S. Lee

Graduate Theses, Dissertations, and Problem Reports (ETD)

The onset of the 2020 COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, issued a call to action in the fields of biomedical science and public health to implement strategies to contain and protect against the viral threat. In record times, pharmaceutical companies produced antiviral therapies and novel mRNA vaccines that were approved by the FDA for human use. With time, these vaccines were able to assist in ending the pandemic. However, time also showed the limits of mRNA vaccine induced immunity. Despite antibody responses being initially robust, titers dramatically wane with time and are limited in cross-neutralizing ability. As …

Immune Outcomes Affected By Selection For Parasite Resistance In Katahdin Sheep, Kelsey Lynne Bentley

Graduate Theses, Dissertations, and Problem Reports (ETD)

Our understanding of the complex connection between selection for parasite resistance and the overall health outcomes in livestock is unclear. This study investigates the impact of post-weaning fecal egg count (PFEC) estimated breeding values (EBV) on health outcomes and immune responses in Katahdin sheep. Selection for PFEC, favoring Low-PFEC lambs, not only affects survivability to weaning but also suggests broader implications for immunity beyond parasite resistance. The effect of PFEC EBV on antibody production in response to vaccination against Clostridium perfringens type C&D and tetanus toxoid (CD&T) revealed a stepwise decrease in immunoglobin (IgG) from Low-PFEC to High-PFEC groups upon …

The Sex Chromosome Complement And Gut Microbiome Act Independently And Collaboratively To Impart Sex Dimorphisms In Humoral Immunity, Carly J. Amato-Menker

Graduate Theses, Dissertations, and Problem Reports (ETD)

Sex dimorphisms in immunity are well-documented and have significant clinical implications. While the immunomodulatory effects of sex hormones have been extensively documented, recent recognition of the nuanced contributions of the sex chromosome complement (XX vs. XY) and the gut microbiome to immune sex dimorphisms underscores the need for a more comprehensive understanding. Within this context, the work herein focuses on unraveling the individual and collaborative impacts of the sex chromosome complement and gut microbiota on humoral immune activation. We assessed humoral immune responses to immunization with heat-killed Streptococcus pneumoniae (HKSP) in Four Core Genotype (FCG) mice and found elevated IgM-secreting …

Evaluating The Role Of Glucocorticoids On The Host Response To Helicobacter Pylori Infection, Sara Druffner

Graduate Theses, Dissertations, and Problem Reports (ETD)

Gastric cancer is the fifth most common cancer and the fifth leading cause of cancer deaths worldwide. Helicobacter pylori infection is the number one risk factor for gastric cancer development. Roughly 50% of the world’s population is infected with H. pylori, though only 1-3% of those infected will develop cancer. H. pylori drives chronic inflammation that creates the requisite environment for carcinogenesis, yet it remains unclear why some individuals develop cancer and others do not. Most mechanistic studies are done in mice, however H. pylori is not a natural mouse pathogen. Research is typically done either with mouse-adapted strains of …

Faslpr Gene Dosage Tunes The Extent Of Lymphoproliferation And T Cell Differentiation In Lupus, Ritu Bohat, Xiaofang Liang, Yanping Chen, Chunyu Xu, Ningbo Zheng, Ashley Guerrero, Jiakai Hou, Roshni Jaffery, Nicholas A Egan, Yaxi Li, Yitao Tang, Esra Unsal, Adolfo Robles, Si Chen, Angela M Major, Hadil Elldakli, Sang-Hyuk Chung, Han Liang, M John Hicks, Yong Du, Jamie S Lin, Xiqun Chen, Chandra Mohan, Weiyi Peng

Faculty, Staff and Student Publications

Sle1 and Fas^lpr are two lupus susceptibility loci that lead to manifestations of systemic lupus erythematosus. To evaluate the dosage effects of Fas^lpr in determining cellular and serological phenotypes associated with lupus, we developed a new C57BL/6 (B6) congenic lupus strain, B6.Sle1/Sle1.Fas^lpr/+ (Sle1homo.lprhet) and compared it with B6.Fas^lpr/lpr (lprhomo), B6.Sle1/Sle1 (Sle1homo), and B6.Sle1/Sle1.Fas^lpr/lpr (Sle1homo.lprhomo) strains. Whereas Sle1homo.lprhomo mice exhibited profound lymphoproliferation and early mortality, Sle1homo.lprhet mice had a lifespan comparable to B6 mice, with no evidence of splenomegaly or lymphadenopathy. Compared to B6 monogenic lupus strains, Sle1homo.lprhet mice exhibited significantly …

Childhood And Adolescent Relapsed/Refractory Aggressive B-Cell Lymphomas With T(8;14) And Bcl2 Expression, Burkitt Lymphoma Versus Diffuse Large B-Cell Lymphoma: A Diagnostic Challenge, Fouad El Dana, Sofia Alexandra Garces Narvaez, Nader K El-Mallawany, Jennifer E Agrusa, Zoann E Dreyer, Andrea N Marcogliese, Mohamed Tarek Elghetany, Jyotinder N Punia, Chi Young Ok, Keyur P Patel, Dolores H Lopez-Terrada, Kevin E Fisher, Choladda V Curry

Faculty, Staff and Students Publications

We present 2 diagnostically challenging cases of pediatric/adolescent relapsed/refractory aggressive mature B-cell non-Hodgkin lymphoma (B-NHL) within the spectrum of Burkitt lymphoma and diffuse large B-cell lymphoma and illustrate the different therapeutic regimens that are employed for pediatric and adult cancer centers. Both cases displayed varying-sized lymphoma cells with occasional single prominent nucleoli and heterogeneous BCL2 expression. Cytogenetics revealed complex karyotypes with t(8:14)(q24.2;q32) and IGH::MYC rearrangement by FISH. Next generation sequencing revealed deleterious TP53 and MYC mutations. We concluded that both could be diagnosed as “DLBCL-NOS with MYC rearrangement” using the current pathologic classifications, 2022 International Consensus Classification (ICC) and World …

Genital Tract Infections, The Vaginal Microbiome And Gestational Age At Birth Among Pregnant Women In South Africa: A Cohort Study Protocol, Ranjana M.S. Gigi, Mandisa M. Mdingi, Hyunsul Jung, Shantelle Claassen-Weitz, Lukas Bütikofer, Jeffrey D. Klausner, Christina A. Muzny, Christopher M. Taylor, Janneke H.H.M. Van De Wijgert, Remco P.H. Peters, Nicola Low

School of Medicine Faculty Publications

Introduction Preterm birth complications are the most common cause of death in children under 5 years. The presence of multiple microorganisms and genital tract inflammation could be the common mechanism driving early onset of labour. South Africa has high levels of preterm birth, genital tract infections and HIV infection among pregnant women. We plan to investigate associations between the presence of multiple lower genital tract microorganisms in pregnancy and gestational age at birth. Methods and analysis This cohort study enrols around 600 pregnant women at one public healthcare facility in East London, South Africa. Eligible women are ≥18 years and …

Hepatoprotective Effect Of Berberis Lycium In Αlpha-Naphthylisothiocyanate Induced Cholestatic Mouse Models, Shamaila Bashir, Hassan Hameed, Nida Irshad, Aqsa Ashraf, Muhammad Faizan, Saiyada Fatima Maida Halim, Hafiz M. Mazhar Asjad, Andleeb Batool, Imran Sohail

Journal of Bioresource Management

Cholestasis is characterized by the obstruction of bile flow from hepatocytes to the intestine. It results in accumulation of bile acids in the liver, which cause oxidative stress, inflammation, apoptosis, fibrosis, and cirrhosis. Till now, the treatment options against cholestasis are limited. Therefore, there is an utmost requirement to develop and evaluate the drugs with potential anti-cholestatic effects. In the current study, the drug-induced cholestasis mouse models were generated via oral administration of α-naphthylisothiocyanate (ANIT). The mice were placed into three groups of six animals each. Group I was the control group and was given saline. The cholestasis model Group …

The Potential Of Stem Cell Therapy In Multiple Sclerosis Treatment: A Review, Sorina Amarculesei, Ava O'Meara Cushen, Cathy Brougham

SURE Journal: Science Undergraduate Research Experience Journal

Multiple Sclerosis is an autoimmune and neurodegenerative disease of the central nervous system. There are currently 2.8 million people living with Multiple Sclerosis worldwide, including 9000 people in Ireland, with a prevalence of 193 per 100,000 people. Symptoms of Multiple Sclerosis include sensory loss, fatigue, cognitive dysfunction, spasticity, depression, optic neuritis, gait ataxia, diplopia, and loss of bladder control. Currently, there is no standardised treatment or cure for Multiple Sclerosis with many strategies focusing on symptoms. Stem cells have emerged as promising approaches for Multiple Sclerosis therapeutics. Clinical trials primarily focus on mesenchymal stem cell-based therapies for Multiple Sclerosis. Furthermore, …

Treatment Response Of Gingival Squamous-Cell Carcinoma To Palliative Intent Immunotherapy, Natalia Trehan, Angelina Debbas, Mykaihla Sternick, Jennifer Johnson, James Gates

Department of Medical Oncology Faculty Papers

The use of PD-1 immune checkpoint inhibitor medications has become a common practice in the treatment of recurrent and metastatic head and neck squamous-cell carcinomas. Success in this setting has led to the investigation of their efficacy in locally advanced cases as a part of first-line therapy. In this report, we detail the treatment response to palliative intent immunotherapy of three geriatric patients with mandibular gingival squamous-cell carcinoma who decided against surgical intervention. Patient #1 was treated with pembrolizumab, a PD-1 inhibitor, and displayed complete clinical and radiologic response of the gingival mass after three months of treatment, which is …

Role Of The Anti-Viral Immune Response In Neural Cell Modulation And Neurological Sequelae Of Childhood Viral Infections, Yashika Kamte

Electronic Theses and Dissertations

Viral infections of the central nervous system (CNS) often result in neurological sequelae and are considered a risk factor for the development of neurological disease. Moreover, the outcomes of a viral infection are largely dependent on the age of the host, with younger hosts developing more profound neuropathology. Perhaps the developing brain coupled with an immature immune system contributes to worse outcomes in the very young. Children suffering from brain infections are more prone to develop enduring neurological impairments even after recovery from the infection. Although majority of the brain growth occurs in utero, neurodevelopment continues throughout the juvenile …

The Effect Of Db1976 On The Fibrotic Response In Three-Spined Stickleback (Gasterosteus Aculeatus), Saif Quraishi

Honors Scholar Theses

The study of fibrosis in stickleback has been a growing field in which there have been a few studies conducted. This study examines two experiments involving the inhibition of fibrosis in stickleback. The first experiment used fish from the Kenai River Flats (KRF) in Alaska. The second experiment used fish from Roselle Lake in British Columbia, Canada. To determine the impact the drug had on fibrosis, sticklebacks from the KRF population were treated with DB1976 as well as alum, a pro‐inflammatory vaccine adjuvant that causes fibrosis (Kool et. al 2012). When each DB1976 + alum treatment group was compared with …

Towards A Mode Of Action For The Anti-Schistosomal Aryl Hydantoins, Thomas Schulze

Theses & Dissertations

Schistosomiasis is a significant human disease caused by the helminth parasite Schistosoma mansoni. Praziquantel remains the only clinically used treatment, yet it is rapidly metabolized and only effective against the adult stage worm infection. Ro 13-3978 (AR02) is a potent antischistosomal compound with activity against multiple S. mansoni life stages; however, it manifests anti-androgenic activity. Additionally, the mechanism of action for worm clearance remains unknown. The structure of Ro 13-3979 was used to generate optimized derivatives, including AR102, that show increased potency towards worms, reduced off-target anti-androgen effects, and extended half-life thereby increasing the feasibility for a single-dose curative treatment. …

Understanding The Effect Of Chikungunya Virus Infection On Bone Homeostasis, Enakshi Roy

Theses & Dissertations

Chikungunya virus (CHIKV) is a mosquito-borne virus that causes Chikungunya fever (CHIKF), characterized by high fever, headache, rash, and joint pain. With global travel on the rise, infections caused by CHIKV have emerged in new regions, expanding their geographic range and infecting susceptible hosts. Currently, no approved prophylactic or therapeutic measures exist to prevent or treat these infections, with prevention strategies primarily focused on vector control. However, these measures have proven inadequate due to the emergence of mutations that enhance viral transmission or vector range. Therefore, urgent attention is needed to develop therapies to treat the infection. Although CHIKV has …