Digital Commons Network^™

The Setd2 L1609p Mutation Found In Leukemia Disrupts Methyltransferase Activity And Reduces Histone H3k36 Trimethylation, Christina Michail, Jérémy Berthelet, Ariel E Mechaly, Linh-Chi Bui, Haopeng Yang, Duo Cai, Amira Al Mahi, Aowei Xie, Valeria Bisio, Valentina Sirri, Jean-Marie Dupret, Fabien Guidez, Ximing Xu, Nicolas Joly, Leslie Regad, Mireille Viguier, Frédérique Deshayes, Nicolas Dulphy, Michael R Green, Ahmed Haouz, Fernando Rodrigues Lima

Faculty, Staff and Student Publications

SETD2 is the primary methyltransferase responsible for generating H3K36me3, an epigenetic mark that is essential for transcriptional regulation and chromatin integrity. SETD2 mutations are frequently observed in various cancers and tend to cluster within its catalytic SET domain. Despite the clinical relevance of SETD2 missense mutations in cancer, their biochemical and structural consequences remain insufficiently characterized. Here, we present the enzymatic and structural characterization of the SETD2 L1609P mutant enzyme identified in leukemia. The L1609 residue is located in the SET domain within a conserved hydrophobic pocket that is involved in substrate H3K36 recognition. Interestingly, site-directed mutagenesis of residues within …

Zingiber Officinale-Mediated Zinc Oxide Nanoparticles: Antimicrobial Activity Against Multidrug-Resistant Bacteria, Maureen Bakor Tabe, Ovgu Isbilen, Jennifer N Walker, Ender Cinar

Faculty, Staff and Student Publications

Background: The fight against infectious diseases has transformed over the past century with the emergence of multidrug-resistant bacteria, where pathogens that exhibit resistance to multiple antibiotic classes leading to significant challenges to modern medicine. Zingiber officinale is well-documented to exhibit diverse biological activities, including strong antioxidant, antimicrobial, and anti-neuroinflammatory effects. Zinc oxide nanoparticles can be synthesized cost-effectively and are widely utilized in biomedical applications, including their use as anticancer agents and drug-delivery systems, as well as for their intrinsic antibacterial and anti-inflammatory properties. In this study, we aimed to take a combinatorial approach to investigate the antimicrobial effects of Z. …

Identification Of A Cytokine Biomarker For Prognostic Modeling Of Breast Cancer-Related Lymphedema, Alison J Wu, Neil Lin, Jie Su, Cherie Lin, Madison-Shira Hossack, Wei Shi, Farnoosh Abbas-Aghababazadeh, Wei Xu, Benjamin Haibe-Kains, Simona F Shaitelman, Melissa B Aldrich, Fei-Fei Liu, Jennifer Y Y Kwan

Faculty, Staff and Student Publications

Lymphedema is a chronic complication of breast cancer treatment, and early intervention is crucial to reduce morbidity. This study evaluated the role of blood-based cytokine biomarkers in the prognostication of breast cancer-related lymphedema (BCRL) to improve risk prediction. A secondary analysis of inflammatory biomarkers for BCRL was performed using a previously published cohort of 147 breast cancer patients who had undergone serum cytokine profiling during their treatment at the Princess Margaret Cancer Centre from 2010-2014. Prognostic cytokine variables for lymphedema were selected by regression analysis and independence from known clinical risk factors. Regression-based modeling was employed to integrate prognostic variables …

Endothelial Oncogenic Kras Mutation Drives The Dynamics Of Microglia And Macrophages In Brain Arteriovenous Malformation, Hyejin Park, Jung-Eun Park, Bridger H Freeman, Bosco Seong Kyu Yang, Shun-Ming Ting, Alexander K Suh, Jude Pj Savarraj, Shuning Huang, Jakob Körbelin, Huimahn Alex Choi, Sean P Marrelli, Jaroslaw Aronowski, Peng Roc Chen, Eunhee Kim, Eun S Park

Faculty, Staff and Student Publications

Mutation of KRAS in endothelial cells (KRAS-EC) leads to intracerebral hemorrhage (ICH) in brain arteriovenous malformations (bAVM), resulting in severe disabilities or even death. However, it is unclear what causes this hemorrhagic conversion of bAVM. Here, using a locally established, clinically-relevant sporadic bAVM mouse model, created by overexpressing mutant KRAS (KRASG12V) in the brain EC, we demonstrate that KRAS-EC act as trigger for microglia (MG) activation and infiltration of macrophages (Mϕ). Using three-dimensional immunostaining approach with cleared human and mouse bAVM tissues, we demonstrate an abundance of MG/Mϕ around the bAVM nidus. The presence of MG/Mϕ are correlated to the …

Effects Of Bungee-Based Training On Physical Performance And Arch Jump Kinematics In Female College Rhythmic Gymnasts, Nasser Abouzeid, Mariola Gepfert, Abdulrahman I. Alaqil, Abdulmalek K. Bursais, Hussein Hashoos, Mohammed S. Alibrahim, Labeeb Z. Moseekh, Amr S. Hamza

Baltic Journal of Health and Physical Activity

Background: The purpose of this study was to examine the effects of an eight-week bungee-based training program on selected physical performance variables and arch jump kinematics in female college rhythmic gymnasts. Material and methods: Eighteen female college students (age: 18.1 ± 0.9 years) were randomly assigned to an experimental group (EG; n = 9) or a control group (CG; n = 9). The EG completed a bungee workout training program three times per week for eight weeks, while the CG followed a traditional rhythmic gymnastics training program. Physical performance variables included vertical jump, leg strength, back strength, standing long jump, …

The Heart’S Hidden Influencer: Epicardial Adipose Tissue In The Pathogenesis Of Heart Failure, Aobo Li, Avilash Mondal, Jianli Zhao, John Zhang, Xin-Liang Ma

Department of Emergency Medicine Faculty Papers

Abstract – Heart failure (HF) is a complex, multifactorial clinical syndrome with diverse etiologies and phenotypic manifestations, affecting millions of people globally. HF is broadly classified into 3 subtypes: HF with reduced ejection fraction, HF with mildly reduced ejection fraction, and HF with preserved ejection fraction. Each subtype exhibits distinct pathophysiological mechanisms, clinical trajectories, and therapeutic responses, posing significant challenges in terms of diagnosis and management. Epicardial adipose tissue (EAT), a metabolically active visceral fat depot situated in close proximity to the myocardium, plays a dual role in physiological and pathological states, offering potential utility as a biomarker and therapeutic …

Ubiquitination Of Oncogenic Mutant P53 Via Attenuation Of Ribosome Biogenesis Machinery Effectively Inhibits Pancreatic Tumor Growth, Mudassier Ahmad, Sahir Sultan Alvi, Haider Ahsan, Carlos Perez, Andrew Massey, Vivek K Kashyap, Neeraj Chauhan, Emmanuel Anning, Manish K Tripathi, Dae J Kim, Nirakar Sahoo, Tamer Oraby, Murali M Yallapu, Mohammad Moshahid Khan, Manu M Sebastian, Subhash C Chauhan, Bilal B Hafeez

Faculty, Staff and Student Publications

Dysregulated ribosome biogenesis and p53 mutations are known to play oncogenic roles in various cancers, including pancreatic cancer. In this study, we demonstrated the therapeutic potential of BMH-21, a pharmacologic inhibitor of RNA polymerase I, against pancreatic cancer by uncovering a novel molecular mechanism involving RPA194-mediated ubiquitination of mutant p53 without affecting the ubiquitination of wild-type p53. Our key findings are that (i) BMH-21 selectively induces apoptosis and cell growth inhibition of pancreatic cancer cells with no effect on normal human pancreatic ductal epithelial cells; (ii) BMH-21 degrades RPA194; (iii) BMH-21 inhibits recruitment of both RPA194 and RPA135 on rDNA …

The Next Layer: Augmenting Foundation Models With Structure-Preserving And Attention-Guided Learning For Local Patches To Global Context Awareness In Computational Pathology, Muhammad Waqas, Rukhmini Bandyopadhyay, Eman Showkatian, Amgad Muneer, Anas Zafar, Frank R Alvarez, Maricel Corredor Marin, Wentao Li, David Jaffray, Cara Haymaker, John V Heymach, Natalie Vokes, Luisa M Solis Soto, Jianjun Zhang, Jia Wu

Faculty, Staff and Student Publications

Foundation models have emerged as powerful feature extractors in computational pathology. However, they typically omit mechanisms for leveraging the global spatial structure of tissues and the local contextual relationships among diagnostically relevant regions-key elements for understanding the tumor microenvironment. Multiple instance learning (MIL) remains an essential next step following the foundation model, designing a framework to aggregate patch-level features into slide-level predictions. We present EAGLE-Net, a structure-preserving, attention-guided MIL architecture designed to augment prediction and interpretability. EAGLE-Net integrates multi-scale absolute spatial encoding to capture global tissue architecture, a top-K neighborhood-aware loss to focus attention on local microenvironments, and background suppression …

Tumor Radiosensitization With Gold Nanoparticles: Evolving Strategies To Improve Tumoral Gold Uptake And Catalyze Future Clinical Translation, Prapannajeet Biswal, Geraldine V Vijay, Gabrielle Krouse, Phuoc Minh Quan Mai, Bhoomika Muruvekere Lakshmisha, Sanaz Keshavarz Shahbaz, Mahdieh Yousefi Taba, Aria Sabbagh, Lydia Wt Cheung, Yuri Mackeyev, Khadijeh Koushki, Sunil Krishnan

Faculty, Staff and Student Publications

Radiation therapy is integral to the treatment regimens of over 50% of cancer patients. However, it is not biologically targeted to just the tumor, leading to adverse effects in peritumoral normal tissue. Selective uptake of gold nanoparticles (AuNPs) by tumors realizes tumor-specific radiosensitization via increased secondary electron release from high atomic number gold atoms. Here, we review AuNP-mediated radiosensitization and outline strategies to optimize tumor-targeted AuNP delivery. Modifying the physicochemical characteristics of AuNPs, including size, shape, charge, and surface chemistry, can increase their ability to evade the reticuloendothelial system (RES) and penetrate the dense tumor stromal architecture, thereby promoting tumor …

Exploring Sex Differences In Stroke Outcomes: A Comprehensive Analysis From The Span 1 Trial, Anjali Chauhan, Eunyoung Angela Lee, Rakesh B Patel, Mariia Kumskova, Enrique C Leira, Anil Chauhan, Yanrong Shi, Suyi Cao, Raymond C Koehler, Krishnan M Dhandapani, Mohammad Badruzzaman Khan, Pradip K Kamat, Ali Arbab, David C Hess, Alison L Herman, Ligia Boisserand, Lauren H Sansing, Andreia Morais, Xuyan Jin, Sanem Aykan, Takahiko Imai, Cenk Ayata, Karisma A Nagarkatti, Jessica Lamb, Márcio A Diniz, Patrick D Lyden, Jaroslaw Aronowski, Louise D Mccullough

Faculty, Staff and Student Publications

Background: Stroke is a sexually dimorphic disease, with different risk factors, incidence, outcomes, and treatment responses in men and women. While sex differences have been documented in preclinical studies, these findings often come from single-site studies with small sample sizes and require validation across diverse research settings.

Methods: We used data from the SPAN (Stroke Preclinical Assessment Network), a randomized, placebo-controlled, blinded, multilaboratory trial, to determine if sex differences in neurological outcomes are present in preclinical stroke models. We analyzed data from 665 stroke animals treated with saline, including young mice, diet-induced obese mice, aging mice, young rats, and spontaneously …

Characterizing The Effects Of Antimuscarinics On Rhoa Signaling, Zuhra Tukhtamisheva, Elizabeth L. Mcduffie, Jordan Lee, Steven S. An, Reynold A. Panettieri Jr., Charles Scott

Alpha Omega Alpha Research Symposium Posters

Purpose: Airway hyperresponsiveness in asthma is driven by acetylcholine-mediated activation of the muscarinic acetylcholine 3 receptor (M3R), promoting bronchoconstriction, mucus hypersecretion, and airway remodeling. Despite directly targeting this pathway, antimuscarinics remain adjunctive rather than first-line therapy, suggesting a disconnect between biological rationale and clinical efficacy. Recent work from the Scott Lab at Thomas Jefferson University demonstrates that M3R in human airway smooth muscle (HASM) cells drives muscle shortening through G_12/13–driven RhoA signaling rather than through G_q/11-dependent calcium flux. We therefore investigated whether clinically prescribed antimuscarinics effectively inhibit G_12/13-dependent RhoA signaling in HASM cells.

Methods: …

Systematic Evaluation Of Batch Effects In The Cancer Genome Atlas Program Underscores The Need For Batch-Controlled Analysis, Zhongxuan Chen, Stepan Nersisyan, Isidore Rigoutsos, Eric Londin

Alpha Omega Alpha Research Symposium Posters

Purpose: To systematically assess the impact of batch effects on differential expression of isomiR, mRNA, and non-coding RNA (sncRNA) across 13 The Cancer Genome Atlas (TCGA) cancer types and develop a standardized, batch-controlled analysis protocol for TCGA datasets.

Methods: Data analysis and visualization were performed using Python v3.12. Plots were generated using matplotlib and seaborn. isomiR, mRNA, and sncRNA sequences across 13 TCGA cancer types were used. Principal Component Analysis (PCA) was performed using scikit-learn for dimensionality reduction. Differential expression was conducted using DESeq2 under the following protocols: 1) primary tumor samples vs matched normal samples processed in the same …

Elucidating The Binding Site Of The Arrestin-Biased Agonist Icl1-20, Kesara Wein, Roger Armen, Jeffrey L. Benovic, Charles P. Scott

Alpha Omega Alpha Research Symposium Posters

Background and Purpose: 6.7 million Americans live with congestive heart failure (CHF). In CHF, catecholamines are released into cardiac tissue, bind β-adrenergic receptors (βARs), and activate G-protein signaling cascades, causing ischemia and apoptosis. Accordingly, β-blockers are used to antagonize catecholamine binding to βARs and suppress apoptotic downstream effects. However, β-blockers have dose-limiting hypotension, bradycardia and fail to stimulate the cardioprotective β-arrestin signaling pathway. These limits create opportunities for the development of drugs that selectively stimulate β-arrestin signaling while suppressing cardiotoxic G protein signaling. We have previously reported a biased agonist of the β-arrestin pathway (ICL1-20) that selectively stimulates β-arrestin recruitment …

Survival Impact Of Intraoperative Co2 Dysregulation In Patients Undergoing Pancreaticoduodenectomy For Pancreatic Ductal Adenocarcinoma, Ashley Wetzel, Andrea Feci, Joseph Gorman, Isabel Lavine, Edoardo Manca, Richard Zheng, Md, Nader Hanna, Md, Harish Lavu, Md, Charles J. Yeo, Md, Avinoam Nevler, Md

Alpha Omega Alpha Research Symposium Posters

Purpose: Pancreatic ductal adenocarcinomas (PDAC) are aggressive malignancies with poor prognoses. Emerging evidence suggests tissue hypercapnia (elevated CO₂) promotes aggressive, treatment resistant tumor biology. End-tidal CO₂ (ETCO₂) offers a composite measure of ventilation, systemic perfusion, and tissue CO₂ production. During curative-intent pancreaticoduodenectomy, we hypothesized that intraoperative ETCO₂ could serve as a marker of tissue CO₂ dyscapnia; both low levels indicating decreased circulatory reserves and high levels indicating tissue hypercapnia may result in worse outcomes.

Methods: We conducted a retrospective review (2017-2023) of 343 patients undergoing pancreaticoduodenectomy for PDAC. Intraoperative ETCO₂ data …

Mom Is Developing Too: Preliminary Evidence For The Reciprocal Effects Of Infant Sensory Reactivity And Maternal Behavior, Emily C. Sweiss, Vincent Berardi, Elysia Poggi Davis, Curt A. Sandman, Laura M. Glynn

Psychology Faculty Articles and Research

Caregiver sensitivity to infant cues is well-established as a predictor of child development. Infants also actively influence their social environment, especially their caregivers, even from their earliest days. Sensory reactivity, characterized as hypo- (under) and hyper- (over) responding to environmental stimuli, is one domain of development that is likely to influence caregiver-infant interaction, due to its role in regulating emotions and responses to both physical and social stimuli. Although sensory reactivity could be an important target for improving caregiver-child interaction, the longitudinal, reciprocal relations between infant sensory reactivity and caregiver behaviors are currently unknown. In the present proof-of-concept study, we …

Cd8+ T Cells In The Tumor Microenvironment Modulate The Response To Endocrine Therapy In Breast Cancer, Fabiana Napolitano, Yunguan Wang, Dhivya R Sudhan, Paula I Gonzalez-Ericsson, Luigi Formisano, Nisha Unni, Shahbano Shakeel, James Z Zhu, Khushi Ahuja, Lei Guo, María Rosario Chica-Parrado, Yuki Matsunaga, Pamela Luna, Chang-Ching A Lin, Yasuaki Uemoto, Kyung-Min Lee, Hongli Ma, Nathaniel J Evans, Alberto Servetto, Saurabh Mendiratta, Spencer D Barnes, Roberto Bianco, Yisheng V Fang, Lin Xu, Jeon Lee, Tao Wang, Justin M Balko, Gordon B Mills, Marilyne Labrie, Ariella B Hanker, Carlos L Arteaga

Faculty, Staff and Student Publications

The role of the tumor immune microenvironment (TIME) in modulating responses to antiestrogen therapy in hormone receptor-positive (HR+) breast cancers remains unclear. We analyzed pre- and on-treatment biopsies from patients with HR+ breast cancer treated with letrozole to induce estrogen deprivation (ED). Stromal tumor-infiltrating lymphocytes, assessed by H&E staining, and immune-related gene sets, including IFN-γ signaling genes, measured by RNA-Seq, were increased in ED-resistant tumors. Cyclic immunofluorescence and spatial transcriptomics revealed an abundance of CD8+ T cells and enhanced antigen processing and immune gene signatures in ED-resistant tumors. In this group, the expression of CXCL9, CXCL10, and CXCL11 - chemokine …

Osimertinib Activates A Tgf-Β2-Dependent Secretory Program That Drives Lung Adenocarcinoma Progression, Madhurima Ghosh, Chao Wu, Abhishek Kumar, Monique Nilsson, John V Heymach, Weina Zhao, Jiang Yu, Xin Liu, Na Ding, Shike Wang, Guan-Yu Xiao, Angelo Chen, Kate Grimley, William K Russell, Chad J Creighton, Xiaochao Tan, Jonathan M Kurie

Faculty, Staff and Student Publications

EGFR-mutant lung adenocarcinomas (LUADs) that are vulnerable to the EGFR antagonist osimertinib (Osi) eventually relapse, owing in part to the emergence of drug-tolerant persister (DTP) cells that arise through epigenetic mechanisms. Intratumoral DTP cells can herald a worse clinical outcome, but the way in which DTP cells influence LUAD progression remains unclear. Osi-resistant (OR) cells exhibit typical DTP cell features, including a propensity to undergo senescence and epithelial-mesenchymal transition (EMT), which can activate heightened secretory states. Therefore, we postulated that OR cells influence LUAD progression through paracrine mechanisms. To test this hypothesis, we utilized congenic pairs of EGFR-mutant LUAD cell …

Dispersion-Enhanced Nitrogen-Centered Photocatalysis Of The Direct Hydrogen Atom Transfer, Jiasong Zhang, Kaitong Zhuang, Ramon Trevino, Babu Raj Dhungana, Huiying Sun, Shuyu Yin, Yuting Li, Jacob A Sanchez, Xiaoyu Xia, Ramy Elerian, Yao Sun, Seth O Fremin, Chao Huang, Min He, Maosheng Cheng, Oleg V Larionov, Shengfei Jin

Faculty, Staff and Student Publications

The development of structurally distinct and modular photocatalysts for direct hydrogen atom transfer (HAT) has emerged as a key frontier in radical-mediated C-H functionalization of strong carbon-hydrogen bonds. Despite the largely untapped potential across the fields of organic synthesis, medicinal chemistry, and materials science, few classes of direct HAT photocatalysts are currently known, and the approaches to enhancing their photocatalytic activity remain underdeveloped. We report herein the development of nitrogen-centered direct HAT photocatalysts based on the acridine framework, which leverage a C9-ortho-biaryl substituent for enhancing the photocatalytic activity through stabilizing dispersion interactions with the substrate as the key steering effect. …

Neuroinflammation And Its Role In Depression– A Review Of Emerging Biomarkers And Therapeutic Targets, Sophia M. Valerino

Advances in Clinical Medical Research and Healthcare Delivery

Major depressive disorder (MDD) is a prevalent and debilitating mental illness that affects millions globally. Traditionally, the pathophysiology of MDD was thought to be due primarily neurotransmitter imbalances. However, emerging research highlights the role of neuroinflammation in MDD pathogenesis. Elevated levels of pro-inflammatory cytokines, microglial activation, and blood-brain barrier dysfunction have been implicated in the etiology of MDD. Additionally, biomarkers such as C-reactive protein and neuroimaging findings further support the neuroinflammatory hypothesis. This growing body of evidence has led to increased interest in novel treatment approaches, including anti-inflammatory medications and lifestyle interventions, as potential therapeutic strategies. While selective serotonin reuptake …

Mycobacterium Shimoidei: A Case Report Of A Rare Nontuberculous Mycobacterial Infection In An American Patient With A Favorable Outcome, Madison Baker, Farah Majdoub, Asad Nasir

Advances in Clinical Medical Research and Healthcare Delivery

Non-tuberculous mycobacteria (NTM) are common environmental pathogens, but they are an uncommon cause of illness. One such mycobacteria, Mycobacterium shimoidei, was discovered in 1968 and found to cause a respiratory illness in 1975. Since then, fewer than 100 cases have been reported worldwide. Symptoms can include cough, fever, weight loss, and hemoptysis This report describes an American patient with no travel history who was found to have significant pulmonary disease caused by this rare non-tuberculous mycobacteria.

Cleavage And Polyadenylation Specificity Factor Subunit 5 Regulates Pulmonary Artery Smooth Muscle Expansion And Hypoxic Response, Scott D Collum, Lisha Zhu, Tingting W Mills, Rene Girard, Jamie Tran, Tinne C J Mertens, Cory Wilson, Nancy Wareing, Erik E Suarez, Howard J Huang, Rahat Hussain, Bindu Akkanti, Wenjin J Zheng, Hari K Yalamanchili, Bela Patel, Eric J Wagner, Sandeep Agarwal, Harry Karmouty-Quintana

Faculty, Staff and Student Publications

Pulmonary hypertension (PH) is a fatal condition that affects individuals with systemic sclerosis (SSc), a multiorgan fibrotic disease with limited treatment options. A central feature of PH is vascular remodeling, defined by the narrowing of the arteriole lumen due to cell proliferation and extracellular matrix deposition. Herein, we identify a central mechanism that can regulate multiple transcripts important for vascular remodeling. The highlight of our study is the demonstration that reduced pulmonary artery smooth muscle (PASMC) Nudt21, which codes for the RNA binding protein Cleavage and Polyadenylation Specificity Factor Subunit 5 (CPSF5) The, known to regulate alternative polyadenylation, results …

The Role Of C-Terminal Crosslinking Telopeptide Of Type Ii Collagen (Ctx-Ii) After Anterior Cruciate Ligament Reconstruction: A Systematic Review., Ali Naderi, S Ali Ghasemi, Andrea Fabregas, Gene Shaffer, James Raphael

Orthopedic Surgery Resident Research

Anterior cruciate ligament (ACL) injuries are known to accelerate cartilage degradation and predispose patients to early-onset osteoarthritis. C-terminal cross-linked telopeptide of type II collagen (CTX-II), a biomarker of cartilage breakdown, can be detected in various body fluids, including urine, offering a non-invasive method for evaluating cartilage degeneration. This systematic review aimed to assess existing evidence on urinary CTX-II (uCTX-II) levels following ACL reconstruction (ACLR). A systematic search of two medical databases was conducted in accordance with PRISMA guidelines. Studies were screened for inclusion based on their assessment of CTX-II in human subjects undergoing ACLR, and methodological quality was evaluated using …

Rectal Adenocarcinoma Presenting As Full-Thickness Prolapse With External Haemorrhoids: Case Report., Samantha Temucin, Sean Singh, Valerie Bauer, Roy Sandau

General Surgery Resident Research

We present a case of a 51-year-old male with a colonic adenocarcinoma that presented as a full-thickness rectal prolapse with external haemorrhoids. This patient had no significant medical or surgical history and presented to the emergency department with a rectal prolapse which had become incarcerated and increasingly painful over the previous 2 weeks. A computed tomography (CT) abdomen and pelvis appeared benign, demonstrating a full-thickness rectal prolapse with no definite rectal mass. A colonoscopy was performed, revealing anterior rectal mucosal edema, fibrosis, and a possible mass. This prompted the patient to be taken to the operating room for a low …

Pregnancy Outcomes Among Women With And Without Hiv Infections Who Underwent Excisional Treatment For High-Grade Cervical Intraepithelial Neoplasia: A Retrospective Cohort Study In Low-Resource Settings, Poli Amubuomombe, Peter Itsura, Philiph Tonui, Elkanah Orang'o, Benjamin Odongo, Patrick Loehrer, Susan Cu-Uvin

Obstetrics and Gynaecology, East Africa

Objective The standard treatment for high-grade squamous intraepithelial lesions is excisional involving the uterine cervix, while surveillance is an acceptable approach for low-grade squamous intraepithelial lesions. There is controversy about excisional treatment on pregnancy outcomes. The objective of this study was to determine pregnancy outcomes in women living with and without HIV who underwent excisional treatment for high-grade cervical intraepithelial lesions.

Design This retrospective cohort study compared the pregnancy outcomes of women with and without HIV who were or were not treated for cervical intraepithelial lesions. A cohort of 488 women with and without HIV infection who did or did …

Ubiquitination Of Oncogenic Mutant P53 Via Attenuation Of Ribosome Biogenesis Machinery Effectively Inhibits Pancreatic Tumor Growth, Mudassier Ahmad, Sahir Sultan Alvi, Haider Ahsan, Carlos Perez, Vivek Kashyap, Neeraj Chauhan, Dae Joon Kim, Nirakar Sahoo, Tamer Oraby, Murali Yallapu, Subhash Chuahan, Bilal Hafeez

School of Medicine Publications

Dysregulated ribosome biogenesis and p53 mutations are known to play oncogenic roles in various cancers, including pancreatic cancer. In this study, we demonstrated the therapeutic potential of BMH-21, a pharmacologic inhibitor of RNA polymerase I, against pancreatic cancer by uncovering a novel molecular mechanism involving RPA194-mediated ubiquitination of mutant p53 without affecting the ubiquitination of wild-type p53. Our key findings are that (i) BMH-21 selectively induces apoptosis and cell growth inhibition of pancreatic cancer cells with no effect on normal human pancreatic ductal epithelial cells; (ii) BMH-21 degrades RPA194; (iii) BMH-21 inhibits recruitment of both RPA194 and RPA135 on rDNA …

Age And Sex Impact The Role Of Thrombospondin-2 And Thrombospondin-5 In Response To Hindlimb Ischemia, Irene Helenowski, Ashley Peters, Melissa Rangel, Corinne Bunn Md, Xuerong Wang, Kristopher Maier, Vivian Gahtan

Biostatistics Collaborative Core: Faculty Publications and Other Works

Peripheral arterial disease progression to critical limb ischemia remains a significant burden in the aged, necessitating revascularization. Therapies to enhance neovascularization, such as angiogenesis or arteriogenesis, may provide an option for patients not suitable for surgery. The thrombospondins (TSPs) are secreted matricellular glycoproteins, with TSP-1, TSP-2, and TSP-5 implicated in neovascularization. Currently, there is little data regarding the effects of TSP-2, TSP-5, sex, and aging on angiogenesis and arteriogenesis. In vitro, the effect of TSP-2 or TSP-5 on early or late passage endothelial cell (EC) tubule formation or disruption was assessed. In vivo, angiogenesis, and arteriogenesis in male and female, …

Ischemic Stroke As The Initial Presentation Of Advanced Pancreatic Adenocarcinoma: A Case Of Marantic Endocarditis., Micah Harris

Ambulatory and Primary Care Articles

Nonbacterial thrombotic endocarditis (NBTE), formerly known as marantic endocarditis, is a rare condition characterized by sterile vegetations on cardiac valves and is often associated with hypercoagulable states such as adenocarcinoma. We describe a patient who presented with multiple embolic cerebrovascular accidents, ultimately found to be secondary to NBTE, which served as the initial manifestation of previously undiagnosed advanced pancreatic adenocarcinoma. This case underscores the importance of considering NBTE in patients with multifocal embolic infarcts, particularly when blood cultures are negative, echocardiography reveals valvular abnormalities without evidence of infection, and clinical suspicion for an underlying malignancy is present.

Does Hormone Replacement Therapy Reduce Bone Resorption In Postmenopausal Women With An Intact Uterus?, Ashley Harding

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not hormone replacement therapy reduces bone resorption in postmenopausal women with an intact uterus.

STUDY DESIGN: A systematic review of three double blind randomized control trials (RCTs) published from 2016 to 2022.

DATA SOURCES: All RCTs were published in peer reviewed journals in English and were found on PubMed and Google Scholar. Articles were chosen based on relevance to the clinical question.

OUTCOME MEASURED: Level of bone resorption was measured via assessment of bone turnover markers at baseline and after use of hormone replacement therapy in all …

Asthma Phenotypes And Control In 22q11.2 Deletion Syndrome: A Single-Center Retrospective Study, Cody Shopper, Katey Campbell, Nikita S. Raje

Posters

Background: Patients with 22q11.2 deletion syndrome have increased rates of atopy and immune dysregulation and may experience a higher burden of asthma; however, real-world data describing asthma control, severity, and treatment patterns in this population are limited. We hypothesized that asthma control and severity patterns in patients with 22q11.2 deletion syndrome differ from those observed in the general asthma population. Objectives/Goal: To characterize asthma control, severity, and treatment patterns among patients with 22q11.2 deletion syndrome and to compare observed patterns with those typically reported in the general asthma population. Methods/Design: We conducted a retrospective observational cohort study of patients with …

Pair-Feeding Study Designs Can Create Biases And Inflate Type I Error Rates: A Simulation Study, Wasiuddin Najam, Daniel E Kpormegbey, Deependra K Thapa, Bret Rust, Lilian Golzarri-Arroyo, Lance H Baumgard, Louis Wai-Tong Fan, Joseph G Ibrahim, Edith J Mayorga, David B Allison

Children’s Nutrition Research Center Staff Publications

Objective: Pair-feeding is a study design element where one group's food intake is provided to another group to assess whether a treatment effect is independent of food intake. Investigators often assume equivalent food intake across experimental conditions and exclude it from the statistical analysis. However, the impact of this practice on type I error (T1Er) rates has not been quantified.

Methods: We conducted a Monte Carlo simulation in which animals were assigned baseline weights and food intakes, then randomized to non-pair-fed or pair-fed groups. Daily food intake for both groups was initially drawn from the baseline food intake distribution. For …