Digital Commons Network^™

Analyzing Early Medieval Perspectives Of Fetal Development, Nivedha Srinivasan

Honors Undergraduate Theses

This thesis examines early medieval perspectives of fetal development by analyzing two manuscripts: British Library, Cotton Tiberius A III and Leiden University, Vossianus lat. Q69. This study will investigate how knowledge of pregnancy was shared throughout England before the establishment of universities. Interest in medieval reproductive language has piqued in importance in recent years, especially due to modern legal debates surrounding reproductive rights. By examining descriptions of the nine months of fetal development in these two manuscripts, as well as in widely known earlier medical texts like Pliny’s Natural History and Vindicianus’ Gynaecia, this research explores how monastic writers in …

Post-Metabolites Of Two Commensal Bacteria Suppress Dna Damage In An Experimental Model Of Acid Reflux Disease, Maanya Pradeep

Honors Undergraduate Theses

Chronic heartburn or gastroesophageal reflux disease (GERD) affects approximately 25% of the US population [1]. Repeated bile acid exposure from the regurgitation of stomach contents leads to the production of reactive oxygen species (ROS), which can cause oxidative DNA damage and promote genomic instability [2]. Barrett’s esophagus (BE), which can develop as a response to chronic bile acid exposure, increases the risk of esophageal adenocarcinoma (EAC) by 30% to 125% [1].

There are more than 18,000 new cases of esophageal cancer in the United States each year, and while its incidence is relatively low compared to other cancers, its mortality …

The Role Of P2y1 And P2y2 Receptors In Human Neural Stem Cell Proliferation, Daria Sokolova

Honors Undergraduate Theses

Endogenous neural stem cells (NSCs) are located in specialized niches of the adult brain and play a vital role in both neurogenesis and neuronal repair. However, declines in NSC proliferation and metabolism associated with age and pathology make these cells less efficient at responding to neurodegenerative disease. Understanding signaling pathways that regulate NSC function is therefore essential for the understanding and development of treatments for these conditions. P2Y receptors are G-protein-coupled purinergic receptors that are activated by extracellular nucleotides and regulate cellular metabolism and proliferation. Among the eight known P2Y subtypes, P2Y1 and P2Y2 have been linked to neuronal signaling …

Exploring Anticholinergic Neurotoxicity: Diphenhydramine's Impact On Neuro-2a Cell Morphology, Expression, And Viability, Jordan B. Mcintyre

Honors Undergraduate Theses

Anticholinergic medications, such as diphenhydramine (commonly known as Benadryl), are increasingly recognized for their association with cognitive impairment and neurodegenerative disease. These medications, which inhibit the action of acetylcholine, a neurotransmitter essential for the formation and utilization of the central and peripheral nervous system, have been implicated in conditions such as dementia and may impact fundamental cellular processes like neurogenesis and cell proliferation. This study investigates the effects of diphenhydramine on neurogenesis when introduced to Neuro-2a cells during differentiation. For all studies cells were plated on coverslips or in 6-well plates with differentiation media containing 0 ng/mL, 50 ng/mL, …

The Effects Of Attending Prediabetes Prevention Workshops On Improving Students' Awareness, Knowledge, And Interest, Madelene Hamann

DNP Research Projects

Abstract

Objective:This DNP project evaluated the effectiveness of a five-week educational intervention on adolescents’ knowledge of prediabetes, awareness, and intentions to adopt healthy lifestyle behaviors. Method and Intervention:Youth aged 13 to 18 years participated in five 40-minute school-based workshops. Outcomes were measured using the Adolescent Diabetes Awareness Test (ADAT), Health Belief Model (HBM), and Centers for Disease Control and Prevention (CDC) workshop evaluation. Effect sizes and 95% confidence intervals (CIs) were used to determine clinical relevance. Results:The intervention had a large, clinically relevant effect on prediabetes knowledge and awareness measured by the ADAT (Hedges’ g = 1.10) …

Microarray Analysis Of Human Abdominal Aortic Aneurysm With Emphasis On Cardiovascular Genes Revealed Differentially Expressed Genes, Song Lu, Li Ping Li, John V. White, Xiaoying Zhang, Ifeyinwa Nwaneshiudu, Adaobi Nwaneshiudu, Nectaria Ntaoula, John Gaughan, Dimitri S. Monos, Wan-Lu Lin, Charalambos C. Solomides, Emilia L. Oleszak, Chris D. Platsoucas

Biological Sciences Faculty Publications

Background/Aim: We examined gene expression profiles in abdominal aortic aneurysm (AAA) lesions vs. normal aortas by cDNA microarray and real-time quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR).

Materials and Methods: Phosphorus (32P)-labeled cDNA from AAA specimens (mean AAA size 6.65 cm) and normal aortas were hybridized with a 588-gene microarray primarily of the cardiovascular system. The results were validated by qRT-PCR.

Results: A total of 35 out of the 588 genes were differentially expressed, with either log2 ratio of AAAs/controls ≥1 (upregulated; 20 genes) or ≤−1 (downregulated; 15 genes) in AAA lesions vs. normal aorta, and 25 of these were significantly …

Examining Widely Held Propositions On Human Dietary Protein Needs And Benefits: A Critical Review Of The Science That Shapes Both The Data And Our Understanding Of An Essential Macronutrient, Mitchell M Kanter, Sally Aaron, Steven N Austad, Andrew W Brown, Nicholas A Burd, Wayne W Campbell, Mark Cope, Teresa A Davis, John W Erdman, Miguel Freitas, Kristen Hicks-Roof, Samuel Klein, Wantanee Kriengsinyos, Dudley W Lamming, Donald K Layman, Heather J Leidy, Kevin C Maki, Richard D Mattes, Shalene Mcneill, Daniel R Moore, Stefan M Pasiakos, Stuart M Phillips, David Raubenheimer, Wendy Reinhardt, Nancy R Rodriguez, Stephen Simpson, Hans H Stein, Luc J C Van Loon, Connie M Weaver, David B Allison

Children’s Nutrition Research Center Staff Publications

The essentiality of protein in the human diet is unequivocal. Yet researchers, clinicians, and lay people often believe numerous propositions about dietary protein despite insufficient supporting or refuting data in some instances. To address this disconnect, and to "pressure-test" current beliefs about dietary protein, the Indiana University School of Public Health-Bloomington convened a workshop in February 2025 titled "Human Dietary Protein Needs and Benefits: A Critical Assessment of Postulated Propositions." More than 20 international experts discussed (1) methodologic issues affecting data acquisition and interpretation; (2) "optimal" dietary protein intakes and effects on muscle protein synthesis rates, muscle protein accretion, …

Bop2-Comb: Bayesian Optimal Phase Ii Design For Optimizing Doses And Assessing Contribution Of Components In Drug Combinations, Xiaohan Chi, Ying Yuan, Ruitao Lin

Faculty, Staff and Student Publications

Background: Personalized cancer treatment using combination therapies offers substantial therapeutic benefits over single-agent treatments in most cancers. However, unmet clinical needs and increasing market competition pressure drug developers to quickly optimize combination doses and clearly demonstrate the contribution of each component when developing and evaluating new combination treatments.

Methods: We propose a Bayesian optimal phase II drug-combination (BOP2-Comb) design that optimizes the combination dose and evaluates the proof-of-concept as well as the contribution of each component in two seamless stages. Our optimal calibration scheme minimizes the total trial sample size while controlling incorrect decision rates at nominal levels. This calibration …

Freeze-Dried, Not Frozen: Lyophilized Mesenchymal Stromal Cell-Derived Extracellular Vesicles And Therapeutic Function In Neuroinflammatory Models, Janet R Ashley, Aidan M Collier, Scott D Olson, Charles S Cox

Faculty, Staff and Student Publications

Background: Mesenchymal stromal cell (MSC)-derived extracellular vesicles (EVs) offer a promising acellular therapy for immune modulation, but clinical translation is hindered by variability and storage constraints. Lyophilization (freeze-drying) could enable shelf-stable EV therapeutics, although its effects on biological activity remain incompletely defined.

Study design: We compared the immunomodulatory effects of frozen and lyophilized EVs from bone marrow (BM), adipose tissue (AD), and umbilical cord (UC) MSCs using lipopolysaccharide-stimulated rodent splenocytes and microglial models and human peripheral blood mononuclear cells (PBMCs). Variables included batch scale (small vs large), cytokine priming, and MSC source. Tumor necrosis factor alpha (TNF-α) secretion was measured …

Digital Communication Strategies For Culinary Medicine In Cancer Prevention And Survivorship: Information-Seeking Habits And Content Preferences Of Online Cooking Media Among Adults Participating In Four Cancer Prevention And Control Cohort Studies, Margaret Raber, Sara Fares, Maria Vazquez, Larkin Strong, Carrie Daniel-Macdougall, Lorna Mcneill, Karen Basen-Engquist

Faculty, Staff and Student Publications

Introduction

Poor diet and excess weight have been linked to increased risk for at least 13 types of cancer. Culinary medicine utilizes experiential cooking skill development to improve individuals’ capacity for healthy eating. Digital communication strategies offer pathways for scalable culinary medicine interventions, but little research has explored how online cooking tools could be leveraged for cancer prevention messaging. We conducted a cross-sectional survey study exploring online cooking information-seeking habits and content preferences among participants in four cancer prevention and control cohorts to inform future digital culinary medicine interventions.

Methods

A cross-sectional survey study was conducted with a convenience sample …

T Cells Modulate The Development And Maintenance Of Painful Paclitaxel-Induced Peripheral Neuropathy In Rnu Rats, Ahmed Olalekan Bakare, Gerard Limerick, Vasudha Goel, Ratan K Banik, Lei Zheng, Andrew J Shepherd, Kristine Glunde, Qin Zheng, Eellan Sivanesan

Faculty, Staff and Student Publications

The role of T cells in chemotherapy-induced peripheral neuropathy (CIPN) is complex and shaped by biological and experimental factors, including sex, hormonal status, genetic background, and cancer model. This complexity has contributed to inconsistent findings among studies, limiting therapeutic progress. In this study, we investigate how T cells contribute to painful paclitaxel (PTX)-induced peripheral neuropathy (PIPN). Adult male T cell-competent (RNU+/−) and T cell-deficient (RNU−/−) rats were subcutaneously inoculated with tumor cells and subsequently treated with intraperitoneal PTX (8 mg/kg total dose). Reflexive (mechanical, heat, cold) and non-reflexive (burrowing, gait) pain behaviors were assessed from baseline through week 6. Immunohistochemistry …

The Lysine Demethylase Kdm4c Is An Oncogenic Driver And Regulates Erk Activity In Kras-Mutant Pancreatic Ductal Adenocarcinoma, Menna-T-Allah Shaheen, Sarah Dhebat, Kimal I Rajapakshe, Bidyut Ghosh, Benson Chellakkan Selvanesan, Shariq S Ansari, Cara L Haymaker, Dorsay Sadeghian, Huamin Wang, Ching-Fei Li, Haoqiang Ying, Anirban Maitra

Faculty, Staff and Student Publications

Deregulation of proteins involved in chromatin regulation is common in pancreatic ductal adenocarcinoma (PDAC). Lysine demethylase 4C (KDM4C) is one of the chromatin-modifying proteins frequently overexpressed across multiple solid cancers and is linked to chromatin instability, increased cell proliferation, and enhanced stem cell–like behavior. We observed upregulation of KDM4C protein in a panel of human PDAC cell lines and patient samples compared with nonneoplastic controls. CRISPR/Cas9-mediated deletion of KDM4C in human and murine PDAC cells reduced proliferation, clonogenicity, and increased survival of orthotopically implanted murine PDAC allografts. Transcriptomic and proteomic analyses revealed that loss of KDM4C in both human and …

Prickle4 Drives Microenvironmental Remodeling And Resistance To Parp Inhibition In Idh-Mutant Glioma, Ju Yang, Hua Yang, Yifan Yuan, Chenyang Zhang, Ziwei Fu, Yanyan Chen, Yinghong Xiong, Shuyu Chen, Kexin Ling, Ying Liu, Jason T Huse, Bo Chen, Timothy A Chan, Zengxin Qi, Zhao Zhang, Xiuping Liu, Yuxiang Wang

Faculty, Staff and Student Publications

Mutations in isocitrate dehydrogenase (IDH) genes sensitize gliomas to PARP inhibition (PARPi) by inducing epigenetic reprogramming of DNA damage repair circuits. However, tumors treated with PARPi eventually relapse despite initial responsiveness. In this study, it is demonstrated that the anti-angiogenic agent lenvatinib synergizes effectively with PARPi, resulting in substantial tumor regression and significantly extended survival. Genomic analysis of tumors reveals that PARPi induces widespread transcriptomic changes that are predominantly pro-inflammatory, thereby promoting tumor angiogenesis. Prickle4, a planar cell polarity protein, is identified as a critical mediator of PARPi-induced neovascularization. Targeting Prickle4 effectively overcomes PARPi resistance in these tumors. Collectively, these …

Hyperglycemia In Combination With Excess Fat Intake Promotes Renal Pyroptosis And Fibrosis Through Gα12-Dependent Endoplasmic Reticulum Stress, Muhammad Sohaib Khan, Boram Kim, Yerim Jeon, Jihoon Tak, Yun Seok Kim, Sang Gil Lee, Eun Byul Lee, Chang-Hoon Lee, Cheol Bin Eom, Hyun Sook Lee, Hyeon-Ki Jang, Nakyeom Lee, Jeong Hae Kie, Jee Myung Yang, Yoon Mee Yang, Sang Geon Kim

Faculty, Staff and Student Publications

Background: Chronic exposure to free fatty acids (FFAs) and glucose may disrupt metabolic homeostasis and initiate pathological processes. This study investigated the effects of hyperglycemia and fat overload on renal endoplasmic reticulum (ER) stress, pyroptosis and fibrogenesis in mice and the underlying basis. We hypothesized that the combined insult would more severely induce Gα12-dependent ER stress and renal complications.

Methods: Mice were subjected to either high fat diet (HFD)+streptozotocin (STZ), or STZ treatment, and AZ2 was used as an anti-diabetic agent. Blood sera were used for blood biochemistry, and tissues were employed for RNA sequencing, immunoblottings, TEM, histology and immunohistochemistry. …

Congenital Syphilis: From Near-Elimination To Crisis, Chad J Abresch, Irene A Stafford, Regan M Johnson, Kayode Olabanji, Ashleigh M Sutphen, Helen E Cejtin, Ashley Hoover

Faculty, Staff and Student Publications

This analytic essay examines the transformation of congenital syphilis (CS) in the United States from near-elimination to crisis. Drawing from the January 2025 Congenital Syphilis Summit in Atlanta, Georgia-convening public health leaders, Tribal health departments, the National Coalition of STD Directors, and Centers for Disease Control and Prevention experts-we contrast prevention systems during near-elimination (1998-2005) with the current crisis (2018-2025). Evidence revealed how dismantling public health infrastructure produced dramatically different outcomes, with CS cases increasing 937% over the past decade and racial/ethnic disparities worsening. American Indian/Alaska Native communities face rates up to 100 times higher than White populations in some …

“Do Everything” Versus Realistic Surgical Interventions: Navigating The Road To Shared Decision-Making In Trauma Surgery, Victoria E Wagner, Ashna S Karpe, Martin L Blakely, Lillian S Kao, Thaddeus J Puzio

Faculty, Staff and Student Publications

"DO EVERYTHING!!" How many times have you heard that phrase from a distressed family member? We routinely receive this desperate plea, and our knee-jerk reaction is to press on, push harder, be more aggressive. We, as acute care surgeons, have spent our lives learning a craft geared towards "doing everything" to heal patients so this response comes naturally. However, how do we respond to "do everything" when the probability of a meaningful recovery is extremely low or non-existent? These situations create moral tension for surgeons who must reconcile the desire to preserve life with the obligation to avoid harm, respect …

Ornithine Metabolism In Retinal Pigment Epithelium And Retina And Implications In Gyrate Atrophy, Artjola Puja

Graduate Theses, Dissertations, and Problem Reports (ETD)

Ornithine aminotransferase (OAT) is a mitochondrial enzyme that regulates ornithine metabolism by converting ornithine to pyrroline-5-carboxylate, a precursor for proline and glutamate synthesis. Deficiency of OAT causes systemic ornithine accumulation and leads to gyrate atrophy (GA) of the choroid and retina, a hereditary disorder characterized by progressive chorioretinal degeneration and irreversible vision loss. Chorioretinal atrophy typically starts at the mid-peripheral retina and progresses toward the macula. Although elevated ornithine is considered toxic to the eye, how ornithine is metabolized in ocular tissues and why OAT deficiency causes selective, region-specific vulnerability remain unclear. We combined ex vivo and in vivo stable …

Stim1-Dependent Treg Dysfunction Promotes Cardiometabolic Hfpef: Insights From Patients And Animal Studies, Balaji Srinivas, Alluri Kiran, Hongmei Peng, Jiang Xu, Paula Fortuno, Jennifer May, Ismail El Moudden, Nour-Eddine Rhaleb, John M. Herre, Raymond L. Benza, Khalid Matrougui

Department of Biomedical and Translational Sciences Faculty Publications

Background

Heart failure with preserved ejection fraction (HFpEF) arises from chronic cardiometabolic and vascular stress and is increasingly recognized as an inflammatory syndrome with immune dysregulation. Regulatory T cells (Tregs) are critical modulators of cardiovascular inflammation, yet the mechanisms driving Treg dysfunction in HFpEF remain poorly defined. stromal interaction molecule 1 (STIM1)-dependent calcium signaling is a key stress-responsive pathway in immune cells; however, its role in Treg maladaptation during HFpEF remains unknown.

Methods

Circulating Tregs from patients with and without HFpEF were analyzed for abundance, STIM1 expression, and stress-associated signaling pathways. To establish causality, mice with Treg-specific deletion of STIM1 …

Blood Flow Regulates Metabolism In Hematopoietic Development, Pamela L Wenzel

Faculty, Staff and Student Publications

Blood flow modifies oxygen availability and biomechanical forces within the vasculature of the embryo as the hematopoietic system develops. The aorta-gonad-mesonephros (AGM) envelops the largest artery in the body and is a critical site for the emergence of hematopoietic stem cells (HSCs). Herein, I discuss the role of hypoxia-inducible factors (HIFs) and force as determinants of metabolism and fate determination. To address the effects of blood flow on hematopoietic development, I employ mouse embryo models and biomimetic culture. Real-time cell metabolic analyses show that oxygen consumption rates (OCR) and extracellular acidification rates (ECAR) are altered by flow in cultures of …

Engineering Mutation Clones In Mammalian Cells With Crispr/Cas9, Zijun Huo, Jian Tu, Rachel Shoemaker, Dung-Fang Lee, Ruiying Zhao

Faculty, Staff and Student Publications

CRISPR, Clustered Regularly Interspaced Short Palindromic Repeat, as a powerful genome engineering system, has been widely accepted and employed in gene editing of a vast range of cell types. Compared to zinc finger nucleases (ZFNs) or transcription activator-like effector nucleases (TALENs), CRISPR shows a less complicated process and higher efficiency. With the development of different CRISPR systems, it can be used not only to knock out a gene but also to make precise modifications, activate or repress target genes with epigenetic modifications, and even for genome wide screening. Here we will describe the procedure of generating a stable cell line …

Fgf19 As A Colorectal Cancer Serum Biomarker And Fgfr4 As A Mediator Of Anti-Her2 Resistance In Breast Cancer, Jordan Beardsley

Graduate Studies Theses and Dissertations 2026

The fibroblast growth factor 19 (FGF19)-fibroblast growth factor receptor 4 (FGFR4) signaling pathway regulates hepatic metabolism, bile acid (BA) synthesis, and hepatocyte proliferation. This signaling axis also is implicated in promoting tumor progression, therapeutic resistance, and metastasis in certain cancers.

In colorectal cancer (CRC) there is a critical need for non-invasive biomarkers for disease detection and monitoring. We identified FGF19 as a candidate CRC serum marker through meta-transcriptomics and found FGF19 to be expressed and secreted by CRC cell lines. Tumor-derived FGF19 was detectable in mouse serum at levels correlating with tumor volume in a subcutaneous xenograft model. RNA sequencing …

Pioglitazone Uncouples Macrophage Inflammatory Signaling From Epithelial Oxidative Stress During Map Infection Mimicking Crohn’S Disease Treatment, Sabera Akter Bushra

Graduate Studies Theses and Dissertations 2026

Crohn’s disease (CD) is a chronic inflammatory bowel disease characterized by intestinal inflammation, epithelial barrier dysfunction, and abnormal immune signaling. CD pathophysiology is increasingly linked to Mycobacterium avium subspecies paratuberculosis (MAP) infection, which increases chronic macrophage activation and the production of inflammatory mediators that lead to epithelial damage. Among these mediators, CXCL10, TNF-α, and IL-6 contribute in inflammation, while NOX-1 and SERPINE-1 indicate epithelial oxidative stress and damage. Despite the role of macrophage-epithelial interaction in CD, selective pharmaceutical regulation of this axis remains unclear. Pioglitazone, an FDA-approved PPARγ agonist used for type 2 diabetes, is an appealing repurposing candidate, given …

Combating Antibiotic Resistance With Plasmid-Dependent Phages, Rhiannon T. Mariano

Electronic Theses & Dissertations (2024 - present)

The alarming rise of carbapenem-resistant bacteria poses an urgent global health threat, driven in large part by the horizontal spread of carbapenemase-encoding plasmids (Ma et al., 2023). These plasmids are often highly mobile and transmissible, enabling rapid dissemination of resistance genes across diverse bacterial populations. Their mobility is largely mediated by conjugation, a process dependent on the formation of pili, which serve as physical bridges for plasmid transfer between cells (Murray et al. 2022; San Millan and MacLean 2017; Virolle et al. 2020). Beyond their role in gene exchange, these pili also act as entry points for a unique class …

Organ Chips And Translational Research: Identifying And Examining New Ethical Issues, Melanie Jeske

Center for Medical Ethics and Health Policy Staff Publications

Organ chips, also known as organ-on-a-chip devices, tissue chips, or microphysiological systems, have emerged over the last decade as a promising translational technology amidst growing concern about the translational crisis between laboratory research and patient bedside. Pointing to high rates of failure between nonhuman animal models and safety and efficacy in humans, organ chips and similar new approach methods have attracted substantial public and private investment. As human-cell-based alternatives to animal models, organ chips promise more predictive, efficient, and ethical platforms for pharmaceutical and toxicity testing. Engineered cultivation systems that enable cells to assemble into tissue-like structures (e.g. kidney, brain, …

Anything But Endo: Diagnostic Buck-Passing In Endometriosis Diagnosis, Rita Dexter, Megan Kitts, Heather Welty, Melanie Jeske

Center for Medical Ethics and Health Policy Staff Publications

People living with endometriosis, a disease in which tissue similar to the lining of the uterus grows elsewhere in the body, often experience prolonged diagnostic journeys because of symptom variability, normalisation of period pain and other symptoms, and lack of awareness of the condition. In this article, we analyse the endometriosis diagnostic journey through the lens of epistemic injustice. Drawing on in-depth interviews with 52 people living with endometriosis in the United States, we introduce the concept of diagnostic buck-passing to characterise the phenomenon wherein individuals who seek treatment for their symptoms end up stuck in a cycle of seeing …

Access To Digital Health Technologies: Personalized Framework And Global Perspectives, Sanjiv M Narayan, Mina K Chung, Demilade Adedinsewo, Luisa C C Brant, Leslie L Davis, David Duncker, Jennifer L Hall, Janet K Han, Carolyn S P Lam, Eldrin Lewis, Joseph Loscalzo, Manlio F Márquez, Vasiliki Rahimzadeh, Fatima Rodriguez, Prashanthan Sanders, Emma Svennberg, Kenneth Stein, Mintu Turakhia, Clyde Yancy, Antonis A Armoundas

Center for Medical Ethics and Health Policy Staff Publications

The emergence and rapid adoption of digital health technologies (DHT) present unprecedented opportunities to democratize and reduce disparities in health care by monitoring health and disease at the point of care in all patients. However, limited access to DHT is becoming a major obstacle to realizing these goals. Access to DHT is influenced not only by well-recognized social determinants of health, but also by digital determinants of health, such as digital literacy and the need for broad access to digital infrastructure, as well as commercial and economic factors. Addressing these challenges and designing unbiased systems of care are essential to …

Tau In Alzheimer’S Disease: Shaping The Future Patient Journey, Catherine J Mummery, Christopher Chen Li-Hsian, Cristian A Lasagna-Reeves, Rik Ossenkoppele, Christopher C Rowe, Douglas W Scharre, Huali Wang, Simon Kyaga, Jeffrey L Cummings

Faculty, Staff and Students Publications

Alzheimer's disease is a complex and multifactorial disease characterized by two key pathological hallmarks: amyloid-beta plaques and tau neurofibrillary tangles. Recent progress has led to the development and approval of disease-targeted therapies for Alzheimer's disease in the form of anti-amyloid-beta monoclonal antibodies. However, findings suggest that amelioration of multiple pathological drivers may be required to maximize clinical effect. An increasing body of evidence suggests that tau is a critical player in Alzheimer's disease pathophysiology, contributing significantly to neurodegeneration and cognitive decline. There are now several tau-targeting drugs in clinical development. In this review, we build on research and advancements in …

Senolytic-Resistant Senescent Cells Have A Distinct Sasp Profile And Functional Impact: The Path To Developing Senosensitizers, Utkarsh Tripathi, Masayoshi Suda, Vagisha Kulshreshtha, Bryan T Piatkowski, Allyson K Palmer, Nino Giorgadze, Christina Inman, Nathan Gasek, Ming Xu, Kurt O Johnson, Tamar Pirtskhalava, Selim Chaib, Larissa P G Langhi Prata, Yi Zhu, Renuka Kandhaya-Pillai, Stefan G Tullius, Saranya P Wyles, Rambabu Majji, Hari Krishna Yalamanchili, David B Allison, Tamar Tchkonia, James L Kirkland

Faculty, Staff and Students Publications

The senescent cell (SC) fate is linked to aging, multiple disorders and diseases, and physical dysfunction. Senolytics, agents that selectively eliminate 30%-70% of SCs, act by transiently disabling the senescent cell antiapoptotic pathways (SCAPs), which defend those SCs that are proapoptotic and pro-inflammatory from their own senescence-associated secretory phenotype (SASP). Consistent with this, a JAK/STAT inhibitor, Ruxolitinib, which attenuates the pro-inflammatory SASP of senescent human preadipocytes, caused them to become "senolytic-resistant". Administering senolytics to obese mice selectively decreased the abundance of the subset of SCs that is pro-inflammatory. In cell cultures, the 30%-70% of human senescent preadipocytes or human umbilical …

Challenges In The Diagnosis Of Concurrent T-Lymphoblastic Leukemia/Lymphoma And Thymic Neuroendocrine Carcinoma: A Case Report, Kristen Oliveira, Mary Doan, Ying Pei, Marwan Yared, Songlin Zhang

Faculty, Staff and Students Publications

The co-occurrence of T-lymphoblastic leukemia/lymphoma and thymic neoplasia is a rare event that can present a diagnostic challenge. In this case report, we describe a 31-year-old man who was found to have thymic neuroendocrine carcinoma and T-lymphoblastic leukemia/lymphoma 2 years after initial treatment for T-lymphoblastic leukemia/lymphoma. The thymic neuroendocrine carcinoma was initially detected in a malignant pleural effusion, and a retrospective review of a preceding lung biopsy suggested the involvement of both tumors within one tissue sample. Immunohistochemical analysis was imperative in highlighting these two elements because despite their unique cytomorphological characteristics, a limited amount of each component was seen …

Integrating A Project-Based Learning Methodology Into A Department-Wide Quality Improvement Curriculum: A Nine-Year Experience In Pediatric Subspecialty Training, Venessa Lynn Pinto, Danny Castro, Constance M Wiemann, Liza Bonin, Cagri Yildirim-Toruner, Nicholas A Ettinger, Sharada Hiranya Gowda, Joyee Vachani, Mehmet Fatih Okcu

Faculty, Staff and Students Publications

Background: Quality improvement (QI) training of subspecialty fellows is an essential component of graduate medical education, yet often delivered in silos within departments through a variety of instructional methodologies.

Objective: We applied project-based learning (PjBL) as a guiding methodology for a QI curriculum for pediatric subspecialty fellows and describe our curriculum development, instructional design, and its implementation.

Methods: We integrated the Institute for Healthcare Improvement (IHI) Model for Improvement with the 6 key features of PjBL: a driving question, defined learning goals, active participation in educational tasks, collaboration among learners, scaffolding with learning technology, and production of tangible artifacts. The …