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2024

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Full-Text Articles in Diseases

Protective Immunity Of The Pore-Forming Domains Of Actinobacillus Pleuropneumoniae Apx Toxins In A Mouse Model, Kamonpun Chuekwon, Li-Ting Cheng, Chun-Yen Chu Aug 2024

Protective Immunity Of The Pore-Forming Domains Of Actinobacillus Pleuropneumoniae Apx Toxins In A Mouse Model, Kamonpun Chuekwon, Li-Ting Cheng, Chun-Yen Chu

The Thai Journal of Veterinary Medicine

The hemolytic/leukolytic toxins ApxI, II, and III play a central role in the pathogenicity of Actinobacillus pleuropneumoniae and may serve as effective vaccine antigens. However, since these toxins are large in size, we aimed to determine whether only the pore-forming domain of the toxins may be sufficient for protective immunity. Mice were vaccinated with the pore-forming domains for immune response analysis and challenge test. Significant antibody response was observed for the ApxI and II vaccine groups. For cellular immune response, CD4+ and CD8+ T cell expansion was observed for ApxI. Pro-inflammatory cytokine (IL-1b, IL-6) and TH2-type …


Discovery Of Chicken Proventricular Necrosis Virus From Transmissible Viral Proventriculitis Outbreak In Broilers, Thailand, ์Nantaporn Wandee, Preeda Lertwatchrasarakul, Thaweesak Songserm Aug 2024

Discovery Of Chicken Proventricular Necrosis Virus From Transmissible Viral Proventriculitis Outbreak In Broilers, Thailand, ์Nantaporn Wandee, Preeda Lertwatchrasarakul, Thaweesak Songserm

The Thai Journal of Veterinary Medicine

Transmissible viral proventriculitis (TVP) is an infectious disease-causing retarded growth in chickens. In Thailand, many stunted chickens have been found on commercial broiler farms since 2017. Significant post-mortem lesions are found only in the proventriculus. This study aims to investigate the causative agents of TVP outbreaks focusing on chicken proventricular necrosis virus (CPNV), the possible significant cause of TVP. CPNV was reproduced in specific pathogen-free (SPF) chickens. Affected chickens that have undergone proventriculitis are CPNV-positive by RT-PCR and nucleotide sequencing followed by phylogenetic analysis. The result showed that proventriculitis could be experimentally reproduced by inoculation of proventricular homogenate obtained from …


Hyperpolarized Magnetic Resonance Imaging, Nuclear Magnetic Resonance Metabolomics, And Artificial Intelligence To Interrogate The Metabolic Evolution Of Glioblastoma, Kang Lin Hsieh, Qing Chen, Travis C Salzillo, Jian Zhang, Xiaoqian Jiang, Pratip K Bhattacharya, Shyan Shams Aug 2024

Hyperpolarized Magnetic Resonance Imaging, Nuclear Magnetic Resonance Metabolomics, And Artificial Intelligence To Interrogate The Metabolic Evolution Of Glioblastoma, Kang Lin Hsieh, Qing Chen, Travis C Salzillo, Jian Zhang, Xiaoqian Jiang, Pratip K Bhattacharya, Shyan Shams

Faculty, Staff and Student Publications

Glioblastoma (GBM) is a malignant Grade VI cancer type with a median survival duration of only 8-16 months. Earlier detection of GBM could enable more effective treatment. Hyperpolarized magnetic resonance spectroscopy (HPMRS) could detect GBM earlier than conventional anatomical MRI in glioblastoma murine models. We further investigated whether artificial intelligence (A.I.) could detect GBM earlier than HPMRS. We developed a deep learning model that combines multiple modalities of cancer data to predict tumor progression, assess treatment effects, and to reconstruct in vivo metabolomic information from ex vivo data. Our model can detect GBM progression two weeks earlier than conventional MRIs …


Recurrent Inflammatory Myofibroblastic Tumor Of Larynx Harboring A Novel Thbs1::Alk Fusion, Namra Ajmal, Stacey Gargano, Ujwala Gosavi, Madalina Tuluc Aug 2024

Recurrent Inflammatory Myofibroblastic Tumor Of Larynx Harboring A Novel Thbs1::Alk Fusion, Namra Ajmal, Stacey Gargano, Ujwala Gosavi, Madalina Tuluc

Computational Medicine Center Faculty Papers

Inflammatory myofibroblastic tumor (IMT) is a rare soft tissue tumor primarily occurring in the abdominopelvic region of young patients, and it is characterized by spindle-shaped myofibroblasts, or fibroblasts surrounded by inflammatory infiltrate. Herein, we report a case of a 24-year-old male with a firm submucosal mass in the anterior right vocal fold diagnosed as an IMT that recurred 14 months later. The tumor demonstrated a novel THBS1::ALK fusion containing Exons 1-7 of the thrombospondin 1 (THBS1) gene fused to Exon 19 of the anaplastic lymphoma kinase (ALK) gene via next-generation sequencing with the NextSeq sequencer. The fusion of THBS1 to …


Infant And Adult Human Intestinal Enteroids Are Morphologically And Functionally Distinct, Grace O Adeniyi-Ipadeola, Julia D Hankins, Amal Kambal, Xi-Lei Zeng, Ketki Patil, Victoria Poplaski, Carolyn Bomidi, Hoa Nguyen-Phuc, Sandra L Grimm, Cristian Coarfa, Fabio Stossi, Sue E Crawford, Sarah E Blutt, Allison L Speer, Mary K Estes, Sasirekha Ramani Aug 2024

Infant And Adult Human Intestinal Enteroids Are Morphologically And Functionally Distinct, Grace O Adeniyi-Ipadeola, Julia D Hankins, Amal Kambal, Xi-Lei Zeng, Ketki Patil, Victoria Poplaski, Carolyn Bomidi, Hoa Nguyen-Phuc, Sandra L Grimm, Cristian Coarfa, Fabio Stossi, Sue E Crawford, Sarah E Blutt, Allison L Speer, Mary K Estes, Sasirekha Ramani

Faculty, Staff and Students Publications

UNLABELLED: Human intestinal enteroids (HIEs) are gaining recognition as physiologically relevant models of the intestinal epithelium. While HIEs from adults are used extensively in biomedical research, few studies have used HIEs from infants. Considering the dramatic developmental changes that occur during infancy, it is important to establish models that represent infant intestinal characteristics and physiological responses. We established jejunal HIEs from infant surgical samples and performed comparisons to jejunal HIEs from adults using RNA sequencing (RNA-Seq) and morphologic analyses. We then validated differences in key pathways through functional studies and determined whether these cultures recapitulate known features of the infant …


A Review Of The Literature On The Utilization Of Stem Cells In Knee Osteoarthritis, Katrina Krist Aug 2024

A Review Of The Literature On The Utilization Of Stem Cells In Knee Osteoarthritis, Katrina Krist

Theses and Graduate Projects

Background: This literature review evaluates the utilization of various types of stem cells in the treatment of osteoarthritis.

Purpose: To assess the different types of stem cell therapy available in an attempt to determine its effectiveness and viability as a long term therapy option.

Methods: Articles were found by searching Augsburg Library Services, Google Scholar, and PubMed for recent, original studies using both allogeneic or autologous stem cells from a variety of cell lines including bone marrow and adipose tissue.

Conclusions: The utilization of stem cells as a viable treatment option for osteoarthritis shows improvement in pain management and return …


Efficacy Of Probiotics In Decreasing Rates Of Necrotizing Enterocolitis And Sepsis In Preterm Neonates, Valisa K. Teekadharry Aug 2024

Efficacy Of Probiotics In Decreasing Rates Of Necrotizing Enterocolitis And Sepsis In Preterm Neonates, Valisa K. Teekadharry

Theses and Graduate Projects

Background: The incidence of preterm infants developing serious infections is a common finding in many neonatal intensive care units. Probiotics have been a supplement that has been used by numerous people to improve the microbiota of the intestine for prevention of infection.

Purpose: The purpose of this literature review is to explore the efficacy of using probiotics in preterm infants for prevention of serious infections such as necrotizing enterocolitis (NEC) and sepsis.

Methods: A comprehensive literature review was conducted using Lindell Library, Pub Med, Science Direct and Google Scholar. Using the search terms probiotics, probiotics in premature infants, probiotics and …


Molecular Detection Of Pathogenic Bacteria In American Dog Ticks (Dermacentor Variabilis) In Brown County, Nebraska, Nicole Messbarger, Darby Carlson, Keith Geluso, Julie Shaffer Aug 2024

Molecular Detection Of Pathogenic Bacteria In American Dog Ticks (Dermacentor Variabilis) In Brown County, Nebraska, Nicole Messbarger, Darby Carlson, Keith Geluso, Julie Shaffer

Transactions of the Nebraska Academy of Sciences and Affiliated Societies

Ticks carry and transmit disease pathogens that cause many human illnesses. Many of these diseases in humans are accompanied by a wide variety of symptoms making tick-borne illnesses often difficult to diagnose. The rate of reported tick-borne illnesses in humans has increased during the past decades in the United States, alongside a rise in concern for public health and safety. In northern Nebraska, the American dog tick (Dermacentor variabilis) is the primary tick encountered by humans and domestic animals in the region. This species is a known vector for spotted fever group (SFG) rickettsioses and tularemia (Francisella …


Recruiting Transgender Men In The Southeastern United States For Genital Microbiome Research: Lessons Learned, Olivia Van Gerwen, Z. Alex Sherman, Emma Sophia Kay, Jay Wall, Joy Lewis, Isaac Eastlund, Keonte J. Graves, Saralyn Richter, Angela Pontius, Kristal J. Aaron, Krishmita Siwakoti, Ben Rogers, Evelyn Toh, Jacob H. Elnaggar, Christopher M. Taylor, Nicholas J. Van Wagoner, Christina A. Muzny Aug 2024

Recruiting Transgender Men In The Southeastern United States For Genital Microbiome Research: Lessons Learned, Olivia Van Gerwen, Z. Alex Sherman, Emma Sophia Kay, Jay Wall, Joy Lewis, Isaac Eastlund, Keonte J. Graves, Saralyn Richter, Angela Pontius, Kristal J. Aaron, Krishmita Siwakoti, Ben Rogers, Evelyn Toh, Jacob H. Elnaggar, Christopher M. Taylor, Nicholas J. Van Wagoner, Christina A. Muzny

School of Medicine Faculty Publications

Background Transgender men (TGM) are underrepresented in genital microbiome research. Our prospective study in Birmingham, AL investigated genital microbiota changes over time in TGM initiating testosterone, including the development of incident bacterial vaginosis (iBV). Here, we present lessons learned from recruitment challenges encountered during the conduct of this study. Methods Inclusion criteria were assigned female sex at birth, TGM or non-binary identity, age ≥18 years, interested in injectable testosterone but willing to wait 7 days after enrollment before starting, and engaged with a testosterone-prescribing provider. Exclusion criteria were recent antibiotic use, HIV/STI infection, current vaginal infection, pregnancy, or past 6 …


Stargardt’S: Trends In Treatment Modalities, Dallas Myers Aug 2024

Stargardt’S: Trends In Treatment Modalities, Dallas Myers

Theses and Graduate Projects

Background: This review is aimed at furthering understanding of Stargardt’s, including disease pathophysiology, treatment methods, and the future of vision restoration.

Purpose: Stargardt’s (STGD) was initially discovered in 1909, but it was not fully understood until 1997. It is the most common form of inherited macular degeneration. There are few resources for patients and providers regarding treatment options and lifestyle recommendations.

Methods: A comprehensive literature review was conducted using NIH, UpToDate, and Google Scholar. Specific terms are further detailed in the review. Inclusion criteria were studies focused on STGD patients. Exclusion criteria for were those that only …


An Evidence-Based Bundle To Decrease Pressure Injuries (Pis) In Homecare, Esther Owookade Aug 2024

An Evidence-Based Bundle To Decrease Pressure Injuries (Pis) In Homecare, Esther Owookade

Student Scholarly Projects

Practice Problem: Pressure injuries are a significant problem in healthcare settings. The older adult patients in this home health agency have experienced an increased in incidences of pressure injuries which necessitates intervention.

PICOT: The PICOT question that guided this project was" In older adults 65years and above with pressure injuries in the home healthcare setting(P), does a pressure injury care bundle(I), compared to the current practices of standard care of repositioning alone( C),reduce the incidence of pressure injuries( O ) in 10 weeks (T)?"

Evidence: The evidence used to guide this evidence-based change project was from relevant health …


Personalized Neoantigen Vaccines As Early Intervention In Untreated Patients With Lymphoplasmacytic Lymphoma: A Non-Randomized Phase 1 Trial, Szymon J Szymura, Lin Wang, Tiantian Zhang, Soung-Chul Cha, Joo Song, Zhenyuan Dong, Aaron Anderson, Elizabeth Oh, Vincent Lee, Zhe Wang, Sapna Parshottam, Sheetal Rao, Jasper B Olsem, Brandon N Crumpton, Hans C Lee, Elisabet E Manasanch, Sattva Neelapu, Larry W Kwak, Sheeba K Thomas Aug 2024

Personalized Neoantigen Vaccines As Early Intervention In Untreated Patients With Lymphoplasmacytic Lymphoma: A Non-Randomized Phase 1 Trial, Szymon J Szymura, Lin Wang, Tiantian Zhang, Soung-Chul Cha, Joo Song, Zhenyuan Dong, Aaron Anderson, Elizabeth Oh, Vincent Lee, Zhe Wang, Sapna Parshottam, Sheetal Rao, Jasper B Olsem, Brandon N Crumpton, Hans C Lee, Elisabet E Manasanch, Sattva Neelapu, Larry W Kwak, Sheeba K Thomas

Faculty, Staff and Student Publications

Lymphoplasmacytic lymphoma (LPL) is an incurable low-grade lymphoma with no standard therapy. Nine asymptomatic patients treated with a first-in-human, neoantigen DNA vaccine experienced no dose limiting toxicities (primary endpoint, NCT01209871). All patients achieve stable disease or better, with one minor response, and median time to progression of 72+ months. Post-vaccine single-cell transcriptomics reveal dichotomous antitumor responses, with reduced tumor B-cells (tracked by unique B cell receptor) and their survival pathways, but no change in clonal plasma cells. Downregulation of human leukocyte antigen (HLA) class II molecules and paradoxical upregulation of insulin-like growth factor (IGF) by the latter suggest resistance mechanisms. …


Antibiotic Resistance In Livestock: A Literature Review Of Its Consequences And International Effort On Human Antimicrobial Agents Resistant Crisis, Ha Nguyen Aug 2024

Antibiotic Resistance In Livestock: A Literature Review Of Its Consequences And International Effort On Human Antimicrobial Agents Resistant Crisis, Ha Nguyen

Theses and Graduate Projects

Background: Despite their benefits, the overuse of antibiotics in livestock has resulted in negative consequences to human health and the augmenting of an antibiotic-resistant crisis. Countries worldwide have conducted analyses and confirmed the growth of bacterial strains immune to most antibiotics. The widespread use of antibiotics is shown in various sectors, including human medicine and agriculture, leading to the emergence of antibiotic-resistant bacterial strains.

Purpose: This comprehensive literature review focuses on finding the connection between the usage of antibiotics in livestock, the transfer of antibiotic resistance to humans through consumption and exposure, and international efforts to find solutions to antimicrobial …


Absence Of Motor Impairments Or Pathological Changes In Tmem230 Knockout Rats, Wenjuan Zhang, Hao Peng, Daihe Yang, Guohua Song, Juan He, Yun Zhou, Cao Huang, Bo Huang Aug 2024

Absence Of Motor Impairments Or Pathological Changes In Tmem230 Knockout Rats, Wenjuan Zhang, Hao Peng, Daihe Yang, Guohua Song, Juan He, Yun Zhou, Cao Huang, Bo Huang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Parkinson's disease (PD), which is the second most common neurodegenerative disorder, is characterized by progressive movement impairment and loss of midbrain dopaminergic neurons in the substantia nigra. Although mutations in TMEM230 are linked to familial PD, the pathogenic mechanism underlying TMEM230-associated PD remains to be elucidated. To explore the effect of TMEM230 depletion in vivo, we created TMEM230 knockout rats using CRISPR-Cas9 technology. TMEM230 knockout rats did not exhibit any core features of PD, including impaired motor function, loss of dopaminergic neurons in the substantia nigra, or altered expression of proteins related to autophagy, the Rab family, or vesicular trafficking. …


Association Between Agrichemical Mixtures And Pediatric Health Outcomes: Evidence From A Nebraska Population-Based Surveillance, Jabeen Taiba Aug 2024

Association Between Agrichemical Mixtures And Pediatric Health Outcomes: Evidence From A Nebraska Population-Based Surveillance, Jabeen Taiba

Theses & Dissertations

Human exposure to environmental contaminants is associated with various pediatric health outcomes. Agrichemicals are a significant environmental risk factor for childhood cancers and congenital anomalies, and reduced exposure could improve pediatric health outcomes. Previous studies in Nebraska have explored the association between single pollutants and pediatric cancers and birth defects. However, it is important to estimate the overall effect of the agrichemical mixture on these pediatric health outcomes. In addition to environmental risk factors, several social vulnerability factors also contribute to increased agrichemical exposure and show disparities in pediatric cancers and birth defects. The objectives of this dissertation are to …


Improving Firefighter Health Through Education In Sleep Science, Elisabeth J. Filiss Aug 2024

Improving Firefighter Health Through Education In Sleep Science, Elisabeth J. Filiss

Master's Projects and Capstones

Sleep impacts all aspects of life, from mental health to physical well-being to job performance. Nowhere is this more important than in the fire service, where extreme working conditions are the norm. One of 44 stations in a large fire department (XFD), Firehouse X, has 21 full-time members, six on duty per shift. A microsystem assessment of Firehouse X revealed poor sleep habits and environmental factors that are not conducive to quality sleep. The role of sleep in the fire service has recently been examined, and interventions aimed at improving firefighters’ sleep have been recommended.

This quality improvement project implemented …


Understanding The Role Of Mastl In Colon Homeostasis And Colitis-Associated Cancer Development, Kristina Pravoverov Aug 2024

Understanding The Role Of Mastl In Colon Homeostasis And Colitis-Associated Cancer Development, Kristina Pravoverov

Theses & Dissertations

Colitis-associated cancer (CAC) is the most devastating complication of longstanding inflammatory bowel disease (IBD). Understanding the mechanisms underlying the switch from damage-repair to dysplasia in IBD is critical for identifying novel therapies to facilitate mucosal healing while mitigating CAC risk. Microtubule-associated serine-threonine kinase-like (MASTL), though crucial in cell growth and repair, is upregulated in sporadic colorectal cancer and CAC. This study sought to delineate the role of MASTL in colitis and CAC development.

First, we examined whether MASTL is associated with colitis and recovery. Review of publicly available data found significant elevation of MASTL and interleukin (IL)-22 in biopsies from …


A Third Generation Long-Acting Dimeric Dolutegravir Prodrug Nanoformulation, Bhoomika Suresh Gowda Aug 2024

A Third Generation Long-Acting Dimeric Dolutegravir Prodrug Nanoformulation, Bhoomika Suresh Gowda

Theses & Dissertations

Dolutegravir (DTG) is an integrase strand transfer inhibitor (INSTI) widely used as a part of first-line combination antiretroviral therapy. DTG has a high barrier to resistance However, one therapeutic challenge centers on its life-long daily use. Sub-optimal adherence to daily oral pills underscore the need for long-acting formulations. To these ends, our research activities have focused on the development and translation of ultra-long-acting ART. Monomeric ester prodrugs provided initial success in extending the apparent half-life of DTG and other INSTIs. One is the DTG prodrug formulation called NM2DTG. NM2DTG’s significantly extended the parent drug’s apparent half-life [Nature Communications, 3226 (2022)]. …


The Impact Of Bariatric Surgery On Glutathione Synthesis In Individuals With Severe Obesity, Hong Chang Tan, Jean W Hsu, E Shyong Tai, Shaji Chacko, Jean-Paul Kovalik, Farook Jahoor Aug 2024

The Impact Of Bariatric Surgery On Glutathione Synthesis In Individuals With Severe Obesity, Hong Chang Tan, Jean W Hsu, E Shyong Tai, Shaji Chacko, Jean-Paul Kovalik, Farook Jahoor

Faculty, Staff and Students Publications

Glycine is deficient in individuals with obesity but improves following bariatric surgery. Glycine deficiency could impair glutathione (GSH) synthesis and worsen oxidative stress. We examined the impact of obesity-associated glycine deficiency and bariatric surgery on GSH synthesis. Twenty-one participants with severe obesity and twenty-one healthy weight controls were recruited. [1,2-13C2] glycine was infused to measure the erythrocyte (RBC) GSH synthesis rate. Participants with obesity underwent bariatric surgery, and 19 were restudied six months post-surgery. Compared to healthy weight controls, individuals with obesity had significantly lower concentrations of RBC GSH (2.43 ± 0.23 vs. 2.63 ± 0.26 mmol/L, p < 0.01). However, there were no differences in GSH fractional synthesis rate [78.0 (51.4–123.7) vs. 76.9 (49.3–110.1) % pool/day, p = …


Enpp1 Enzyme Replacement Therapy Improves Ectopic Calcification But Does Not Rescue Skeletal Phenotype In A Mouse Model For Craniometaphyseal Dysplasia, Ernst Reichenberger, Kevin O'Brien, Ayano Hatori, Thomas Carpenter, Koen Van De Wetering, Lisa Flaman, Jennifer Howe, Daniel Ortiz, Yves Sabbagh, I-Ping Chen Aug 2024

Enpp1 Enzyme Replacement Therapy Improves Ectopic Calcification But Does Not Rescue Skeletal Phenotype In A Mouse Model For Craniometaphyseal Dysplasia, Ernst Reichenberger, Kevin O'Brien, Ayano Hatori, Thomas Carpenter, Koen Van De Wetering, Lisa Flaman, Jennifer Howe, Daniel Ortiz, Yves Sabbagh, I-Ping Chen

Jefferson Institute of Molecular Medicine Papers and Presentations

Craniometaphyseal dysplasia (CMD) is a rare genetic bone disorder, characterized by progressive thickening of craniofacial bones and flared metaphyses of long bones. Craniofacial hyperostosis leads to the obstruction of neural foramina and neurological symptoms such as facial palsy, blindness, deafness, or severe headache. Mutations in ANKH (mouse ortholog ANK), a transporter of small molecules such as citrate and ATP, are responsible for autosomal dominant CMD. Knock-in (KI) mice carrying an ANKF377del mutation (AnkKI/KI) replicate many features of human CMD. Pyrophosphate (PPi) levels in plasma are significantly reduced in AnkKI/KI mice. PPi is a potent inhibitor of …


Sedation For Gi Endoscopy In The Morbidly Obese: Challenges And Possible Solutions, Lalitha Sundararaman, Basavana Goudra Aug 2024

Sedation For Gi Endoscopy In The Morbidly Obese: Challenges And Possible Solutions, Lalitha Sundararaman, Basavana Goudra

Department of Anesthesiology Faculty Papers

With the increasing prevalence of obesity and morbid obesity, this subgroup's contribution to patients presenting for elective procedures requiring sedation is significant. Gastrointestinal (GI) procedures clearly form the largest group of such procedures. These procedures may be intended to treat obesity such as the insertion of an intragastric balloon or one or more unrelated procedures such as a screening colonoscopy and (or) diagnostic/therapeutic endoscopy. Regardless of the procedure, these patients pose significant challenges in terms of choice of sedatives, dosing, airway management, ventilation, and oxygenation. An understanding of dissimilarity in the handling of different groups of medications used by an …


Syphilitic Gumma Presenting As Squamous Cell Carcinoma Of Vulva: A Case Report, R.M. Nuss, A.J. Lazenby, Holly C. Provost, Tara Castellano Aug 2024

Syphilitic Gumma Presenting As Squamous Cell Carcinoma Of Vulva: A Case Report, R.M. Nuss, A.J. Lazenby, Holly C. Provost, Tara Castellano

School of Medicine Faculty Publications

Introduction: Tertiary syphilis, a late form of the disease with neurologic, cutaneous, and cardiovascular manifestations, is rarely seen in the United States in modern times. Also called the “great imitator,” syphilis tends to mimic other disease processes, which can lead to a delay in proper diagnosis and treatment. Case: We present the case of a 59-year-old woman who presented for evaluation of possible squamous cell carcinoma of the vulva. After multiple inconclusive biopsies and extensive workup with multiple providers, she was instead found to have cutaneous and neurologic tertiary syphilis. A correct diagnosis was delayed in this patient due to …


Antibody Therapies For Alzheimer's Disease, Alexandra Zerr Aug 2024

Antibody Therapies For Alzheimer's Disease, Alexandra Zerr

University Honors Theses

Alzheimer's Disease (AD) is the leading cause of dementia worldwide. Patients with this condition first experience mild cognitive impairment, followed by the loss of memory, cognitive skills, identity, and the ability to perform daily tasks unassisted, eventually culminating in death.

The dominant hypothesis for the mechanism of Alzheimer's, the amyloid cascade hypothesis, based on early-onset AD, suggests that amyloid plaques formed by Aβ peptides cause a cascading effect involving an increase in toxic tau protein, which is correlated with the disease progression of Alzheimer's patients. While the mechanism of late sporadic AD is not fully understood, this has been used …


The Dna Methylome Of Pediatric Brain Tumors Appears Shaped By Structural Variation And Predicts Survival, Fengju Chen, Yiqun Zhang, Lanlan Shen, Chad J Creighton Aug 2024

The Dna Methylome Of Pediatric Brain Tumors Appears Shaped By Structural Variation And Predicts Survival, Fengju Chen, Yiqun Zhang, Lanlan Shen, Chad J Creighton

Faculty, Staff and Students Publications

Structural variation heavily influences the molecular landscape of cancer, in part by impacting DNA methylation-mediated transcriptional regulation. Here, using multi-omic datasets involving >2400 pediatric brain and central nervous system tumors of diverse histologies from the Children's Brain Tumor Network, we report hundreds of genes and associated CpG islands (CGIs) for which the nearby presence of somatic structural variant (SV) breakpoints is recurrently associated with altered expression or DNA methylation, respectively, including tumor suppressor genes ATRX and CDKN2A. Altered DNA methylation near enhancers associates with nearby somatic SV breakpoints, including MYC and MYCN. A subset of genes with SV-CGI methylation associations …


Clinical Implementation Of Tissue-Sparing Posterior Cervical Fusion: Addressing Market Access Challenges, Morgan Lorio, Pierce Nunley, Joshua Heller, Bruce Mccormack, Kai-Uwe Lewandrowski, Jon Block Aug 2024

Clinical Implementation Of Tissue-Sparing Posterior Cervical Fusion: Addressing Market Access Challenges, Morgan Lorio, Pierce Nunley, Joshua Heller, Bruce Mccormack, Kai-Uwe Lewandrowski, Jon Block

Department of Neurosurgery Faculty Papers

Background: The traditional open midline posterior cervical spine fusion procedure has several shortcomings. It can cause soft tissue damage, muscle atrophy, compromise of the lateral masses and painful prominent posterior cervical instrumentation or spinous process if there is dehiscence of the fascia. Additionally, patients frequently experience the rapid development of adjacent segment disease, which can result in the reemergence of debilitating pain and functional impairment. Clinical relevance: Tissue-sparing posterior cervical fusion is an alternative method for treating patients with symptomatic cervical degenerative disc disease. However, widespread clinical adoption has been challenged by ambiguity, misunderstandings and misinterpretations regarding appropriate procedural reimbursement …


A Machine Learning Model For Risk Stratification Of Postdiagnosis Diabetic Ketoacidosis Hospitalization In Pediatric Type 1 Diabetes: Retrospective Study, Devika Subramanian, Rona Sonabend, Ila Singh Aug 2024

A Machine Learning Model For Risk Stratification Of Postdiagnosis Diabetic Ketoacidosis Hospitalization In Pediatric Type 1 Diabetes: Retrospective Study, Devika Subramanian, Rona Sonabend, Ila Singh

Faculty, Staff and Students Publications

BACKGROUND: Diabetic ketoacidosis (DKA) is the leading cause of morbidity and mortality in pediatric type 1 diabetes (T1D), occurring in approximately 20% of patients, with an economic cost of $5.1 billion/year in the United States. Despite multiple risk factors for postdiagnosis DKA, there is still a need for explainable, clinic-ready models that accurately predict DKA hospitalization in established patients with pediatric T1D.

OBJECTIVE: We aimed to develop an interpretable machine learning model to predict the risk of postdiagnosis DKA hospitalization in children with T1D using routinely collected time-series of electronic health record (EHR) data.

METHODS: We conducted a retrospective case-control …


Comparative Plan Analysis: Helical Tomotherapy Vs. Linac Vmat For Lower Extremity Sarcomas, Marie E. Dibona Aug 2024

Comparative Plan Analysis: Helical Tomotherapy Vs. Linac Vmat For Lower Extremity Sarcomas, Marie E. Dibona

Masters Projects

Abstract

Introduction

Soft tissue sarcomas (STS) affect about 13,500 people annually in the United States, and those in the lower extremities present unique challenges in radiation therapy due to the wide variability in tumor sizes, sometimes exceeding 30cm. Traditional treatment involves C-Arm linear accelerators using Volumetric Modulated Radiation Therapy (VMAT), which provides precise targeting while sparing nearby organs. Helical Tomotherapy (HT) is another option, delivering radiation in a helical pattern with a binary MLC for a uniform dose distribution. However, no studies have compared VMAT and HT for lower extremity sarcomas of different sizes. This study aims to compare these …


Stress Granule Formation Helps To Mitigate Neurodegeneration, M. Rebecca Glineburg, Evrim Yildirim, Nicolas Gomez, Genesis Rodriguez, Jaclyn Pak, Xingli Li, Christopher Altheim, Jacob Waksmacki, Gerald M. Mcinerney, Sami J. Barmada, Peter K. Todd Aug 2024

Stress Granule Formation Helps To Mitigate Neurodegeneration, M. Rebecca Glineburg, Evrim Yildirim, Nicolas Gomez, Genesis Rodriguez, Jaclyn Pak, Xingli Li, Christopher Altheim, Jacob Waksmacki, Gerald M. Mcinerney, Sami J. Barmada, Peter K. Todd

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Cellular stress pathways that inhibit translation initiation lead to transient formation of cytoplasmic RNA/protein complexes known as stress granules. Many of the proteins found within stress granules and the dynamics of stress granule formation and dissolution are implicated in neurodegenerative disease. Whether stress granule formation is protective or harmful in neurodegenerative conditions is not known. To address this, we took advantage of the alphavirus protein nsP3, which selectively binds dimers of the central stress granule nucleator protein G3BP and markedly reduces stress granule formation without directly impacting the protein translational inhibitory pathways that trigger stress granule formation. In Drosophila and …


Effects Of E-Cigarettes On The Lung And Systemic Metabolome In People With Hiv, Aline Zaparte, Courtney J. Christopher, Connie Arnold, Lauren Richey, Adairre Castille, Kyle Mistretta, Christopher M. Taylor, Huiyi Lin, Steve Nelson, John P. Kirwan, John W. Apolzan, Shawn R. Campagna, David A. Welsh Aug 2024

Effects Of E-Cigarettes On The Lung And Systemic Metabolome In People With Hiv, Aline Zaparte, Courtney J. Christopher, Connie Arnold, Lauren Richey, Adairre Castille, Kyle Mistretta, Christopher M. Taylor, Huiyi Lin, Steve Nelson, John P. Kirwan, John W. Apolzan, Shawn R. Campagna, David A. Welsh

School of Medicine Faculty Publications

The popularity of e-cigarettes (vaping) has soared, creating a public health crisis among teens and young adults. Chronic vaping can induce gut inflammation and reduce intestinal barrier function through the production of the proinflammatory molecule hydrogen sulfide (H2S). This is particularly concerning for people with HIV (PWH) as they already face impaired immune function and are at a higher risk for metabolic dysregulation, diabetes, and chronic liver disease. Furthermore, PWH experience unhealthy behaviors, making it crucial to understand the systemic metabolic dysregulation and pathophysiological mechanisms associated with vaping in this population. Here, we employed liquid chromatography–mass spectrometry (LC-MS)-based metabolomics to …


Stanniocalcin 2 Governs Cancer Cell Adaptation To Nutrient Insufficiency Through Alleviation Of Oxidative Stress, Shuo Qie, Haijuan Xiong, Yaqi Liu, Chenhui Yan, Yalei Wang, Lifeng Tian, Chenguang Wang, Nianli Sang Aug 2024

Stanniocalcin 2 Governs Cancer Cell Adaptation To Nutrient Insufficiency Through Alleviation Of Oxidative Stress, Shuo Qie, Haijuan Xiong, Yaqi Liu, Chenhui Yan, Yalei Wang, Lifeng Tian, Chenguang Wang, Nianli Sang

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Solid tumours often endure nutrient insufficiency during progression. How tumour cells adapt to temporal and spatial nutrient insufficiency remains unclear. We previously identified STC2 as one of the most upregulated genes in cells exposed to nutrient insufficiency by transcriptome screening, indicating the potential of STC2 in cellular adaptation to nutrient insufficiency. However, the molecular mechanisms underlying STC2 induction by nutrient insufficiency and subsequent adaptation remain elusive. Here, we report that STC2 protein is dramatically increased and secreted into the culture media by Gln-/Glc- deprivation. STC2 promoter contains cis-elements that are activated by ATF4 and p65/RelA, two transcription factors activated by …