Digital Commons Network^™

Development Of A Structurally Distinct Topbp1 Inhibitor That Enhances Parp Blockade And Reverses Osimertinib Resistance, Fang-Tsyr Lin, Shwu-Jiuan Lin, Kang Liu, Yang Xiao, Lidija A Wilhelms Garan, Helena Folly-Kossi, Weei-Chin Lin

Faculty, Staff and Students Publications

Therapeutic resistance remains a major challenge in cancer treatment, driven by compensatory signaling and stress response pathways that sustain tumor survival. Topoisomerase IIβ-binding protein 1 (TopBP1), a multifunctional scaffold protein with nine BRCT domains, integrates replication stress signaling with oncogenic networks and is frequently overexpressed in aggressive cancers. Its BRCT7/8 domains mediate critical interactions with E2F1, mutant p53, MIZ1, PLK1, and CIP2A, making TopBP1-BRCT7/8 an attractive therapeutic target. Using docking-guided screening and structure-activity relationship–driven optimization, we developed CS18 as a potent and selective BRCT7/8 inhibitor that disrupts oncogenic TopBP1 complexes without interfering with DNA replication. CS18 suppresses MYC transcriptional programs, …

Interpreting Continuous Glucose Monitoring Through Metabolic Physiology: A Framework For Precision Nutrition In Type 2 Diabetes, Jitendra D. Belani

College of Pharmacy Faculty Papers

Background: Type 2 diabetes is characterized by substantial interindividual variability in postprandial glucose responses, yet continuous glucose monitoring (CGM)-derived glucose patterns are commonly described using quantitative metrics without sufficient consideration of the physiological mechanisms that generate them. Objective: To develop a physiology-based framework for interpreting CGM-derived glycemic phenotypes in relation to dietary exposures and individual metabolic characteristics, thereby supporting precision nutrition in adults with type 2 diabetes. Methods: A structured narrative review of the literature was conducted using PubMed to identify studies examining CGM, postprandial glucose regulation, dietary exposures, metabolic physiology, and precision nutrition. Evidence was synthesized within a predefined …

Influence Of Lumpectomy Cavity Depth On Plan Quality In 3d Arc-Based Simultaneous Integrated Boost For Whole-Breast Radiotherapy, Emmett Dwyer

Masters Projects

Abstract

Purpose: Dynamic conformal arc (DCA) is a three-dimensional (3D) radiation therapy technique that can be used to deliver a simultaneous integrated boost (SIB) during whole-breast irradiation (WBI). This study investigated whether the depth of the lumpectomy cavity affects the feasibility of creating a successful DCA SIB treatment plan for breast radiotherapy.

Methods and Materials: 30 patients who previously received WBI followed by a 3D sequential boost (SeqB) were selected for this retrospective study. A DCA plan was created for each patient and combined with the original whole-breast tangent fields to create a SIB plan. Each plan was required to …

Hematopoietic Stem And Progenitor Cell Reprogramming During Breast Cancer Progression Promotes Myeloid-Biased Hematopoiesis, Emily Maria Eul

Arts & Sciences Graduate Student Theses and Dissertations

Breast cancer progression is associated with systemic immune dysregulation characterized by the expansion of immunosuppressive myeloid populations that promote tumor progression, metastasis, and resistance to therapy. However, the mechanisms that sustain pathological myeloid expansion remain incompletely understood. In particular, it remains unknown whether solid tumors functionally reprogram hematopoietic stem and progenitor cells (HSPCs) to drive enhanced myeloid output and if bone-derived signals can regulate tumor-associated hematopoietic remodeling. In murine models of primary and metastatic breast cancer, tumor progression induced the remodeling of the hematopoietic compartment, characterized by the expansion of HSPCs, enhanced myeloid differentiation, and systemic accumulation of myeloid populations. …

Automated Flim-Fret Segmentation Within Rnp Condensates, Noah D Powell, Joshua M Marcus, Leyla E Fahim, Jason E Lee

Faculty, Staff and Students Publications

Ribonucleoprotein (RNP) condensates are membraneless organelles that exist alongside many RNA-driven processes, such as transcription and splicing. Despite their ubiquity, the biological necessity of forming a condensed phase remains unclear, particularly because the same RNP components exist both within these organelles and in the surrounding dilute phase. Most current methods for studying biochemical interaction dynamics within condensates rely on in vitro reconstitution of minimal factors or low-throughput single-molecule studies. However, RNP condensates are complex organelles containing tens to hundreds of proteins and hundreds to thousands of different RNAs. Here, we describe a scalable, high-throughput fluorescence microscopy–based approach to analyze protein–protein …

Childhood Cancer Predisposition Study: A Prospective Registry And Biorepository Protocol, Melissa R Perrino, Suzanne P Macfarland, Luke Maese, Jennie Vagher, Junne Kamihara, Surya Rednam, Philip J Lupo, Garrett M Brodeur, Joshua Schiffman, Lisa Diller, Lauren Desrosiers-Battu, Sharon E Plon, Kim E Nichols, Samuel L Volchenboum, David Malkin, Anita Villani, Christopher C Porter

Faculty, Staff and Students Publications

Introduction: Cancer is the most common cause of disease-related mortality in children, highlighting the urgent need for improved care in this population. It is estimated that >15% of children diagnosed with cancer harbour a germline pathogenic variant in a cancer predisposition gene which confers an increased risk to develop cancer. There are over 100 genes associated with cancer predisposition syndromes (CPSs) and greater availability and acceptability of genetic testing in the last decade has facilitated their recognition in childhood. However, individually, each of these CPSs is rare, impeding robust research and advancement of clinical care. Once a specific CPS is …

Clinical Utility Of An Fda-Authorized Artificial Intelligence Imaging Platform In Interstitial Lung Disease Diagnosis, Arjun Prakash Tambe, Ryan Boente, Gautam George, Fayez Kheir, Omid Tahamtani Omran, Kavitha Selvan

Division of Pulmonary, Allergy, and Critical Care Medicine Faculty Papers

Background/Objectives: The diagnosis of interstitial lung disease (ILD) is challenging and frequently delayed. Clinically accessible and minimally invasive diagnostic tools are needed to expedite the diagnosis of ILD while minimizing risk to patients. Fibresolve is an imaging artificial intelligence (AI) tool recently approved by the Food and Drug Administration (FDA) for use in ILD diagnosis and made available to clinicians. The objective of this study was to describe its utility in clinical practice. Methods: We conducted a prospective, observational study of patients across the United States (US) in whom Fibresolve was utilized during routine clinical practice between July 2024 and …

Effect Of Hydrogel Rectal Spacers On Bladder Wall And Regional Substructure Dose In Prostate Cancer Patients Undergoing Volumetric Modulated Arc Therapy With Simultaneous Integrated Boost: A Retrospective Planning Study, Geronimo Sosa

Masters Projects

Purpose: Hydrogel rectal spacers reduce rectal dose during prostate radiotherapy, but their effect on bladder wall dose is not well characterized, particularly with volumetric modulated arc therapy with simultaneous integrated boost (VMAT-SIB). This study evaluated the effect of spacer placement on whole and regional bladder wall dose.

Methods: Twenty-nine patients treated with VMAT-SIB (70 Gy in 28 fractions) were analyzed retrospectively: 9 with and 20 without a spacer. The bladder wall was defined as the whole bladder minus a 3-mm inner margin. Primary endpoints were D0.03 cc and D1 cc; secondary endpoints included D2 cc, D3 cc, D10 cc, volume-based …

A Topology-Aware Extension Of Guttae Area Ratio In Fuchs Endothelial Corneal Dystrophy, Molly Orlick, Henry Bair

Wills Eye Hospital Papers

No abstract provided.

An Assessment Of The Multidisciplinary Approach To Fetal Echocardiography Education, Riley Allen

Masters Projects

With congenital heart disease (CHD) being the most common birth defect, there is a growing demand for utilization of fetal echocardiography (FE). In clinical practice FE requires an interdisciplinary approach to performance and patient care, and integration of techniques from both the obstetric and pediatric cardiac areas of medicine. While practitioners align on the need for an interdisciplinary approach to practice and the specific methods of performance, there is little consensus on how to comprehensively educate the sonography workforce. Literature has identified gaps in both the obstetric and pediatric cardiac sonographer education bases, predominantly focusing on the lack of specific …

Rates Of, Reasons For, And Reactions To Discontinuation Of Glp-1 Receptor Agonists: A Narrative Review, Henry D Heisey, L Parker Gregg, Christopher D Verrico, Dennis T Villareal, Terri L Fletcher

Faculty, Staff and Students Publications

GLP-1RAs are increasingly used for their glucose-lowering and weight-management effects, but many patients discontinue them. In this narrative review we aim to review real-world, quantitative and qualitative GLP-1RA discontinuation, adherence, and persistence evidence as it aligns with an established conceptual framework for understanding medication adherence in noncommunicable chronic disease. Many inconsistencies exist in how discontinuation, adherence, and persistence are studied in this literature. Few qualitative studies have focused on discontinuation of GLP-1RAs. Quantitative approaches often focus on medication-related factors and more superficial aspects of socioeconomic and condition-related factors. Very few studies encompass all 5 dimensions of the medication adherence conceptual …

Early-Onset Colorectal Cancer With Liver-Only Metastases: A Retrospective Cohort Study Integrating Prospectively Collected Real-World Clinical And Molecular Data From An Australian National Database (2009–2024) To Guide Treatment Planning, Savio G. Barreto, Christos S. Karapetis, Shahid Ullah, Matthew Burge, Susan Caird, Angus Campbell, Azim Jalali, Ross Jennens, Muhammad A. Khattak, Belinda Lee, Stephanie H. Lim, Shehara Mendis, Louise Nott, Timothy J. Price, Jeremy D. Shapiro, Jeanne Tie, Javier Torres, Colin Williams, Rachel Wong, Vanessa Wong, Peter Gibbs

Research outputs 2022 to 2026

Objective: To leverage the Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) registry (an Australian cancer database) to explore the ideal timing and sequence of therapies and the factors influencing these decisions in colorectal cancer (CRC) patients with liver-only metastases to inform contemporary decision-making and future trials.

Study Type: Retrospective registry-based cohort study using the TRACC registry.

Setting and Participants: Consecutive patients with liver-only metastatic CRC enrolled in the TRACC registry.

Main Outcome Measures: To explore cancer biology, intended treatment at presentation, actual treatment received and the resultant outcomes for early-onset CRC (EOCRC) (≤ 50 years) and late-onset CRC (LOCRC) …

An Update On The Role Of Multimodal Analgesia In Perioperative Pain Management, Whitney N. Kuwamoto, Grace C. Eddy, Edward R. Mariano, Eric S. Schwenk

Department of Anesthesiology Faculty Papers

Multimodal analgesia has become a foundational principle of acute perioperative pain management and enhanced recovery and involves the application of nonpharmacologic, pharmacologic, and/or interventional techniques. The overall goal of this approach is to apply a combination of different modalities that target discrete points along the pain pathway and thereby avoid the overreliance on opioids and associated side effects. Since our review in 2018, there have been significant developments that have prompted an updated review of multimodal analgesia. In this article, we identify and summarize important trends that influence the current approach to acute perioperative pain management as well as provide …

All-Cause And Cause-Specific Mortality In Gambling Disorder: Evidence From A Nation-Wide Matched And Sibling Cohort Study In Taiwan, Yang-Chieh Brian Chen, Chih-Wei Hsu, Liang-Jen Wang, Mu-Hong Chen, Yao-Hsu Yang, Chih-Sung Liang, Edward Chia-Cheng Lai

Children’s Nutrition Research Center Staff Publications

Background and aims: Gambling disorder (GD) has been linked to suicidal ideation and suicide deaths; however, evidence on all-cause and cause-specific mortality-particularly in Asian populations-remains limited. Using a retrospective cohort study based on nationwide matched and sibling cohort, we investigated all-cause and cause-specific mortality risk in patients with GD.

Design, setting and participants: A retrospective cohort study was conducted using 2000-2022 data from Taiwan's National Health Insurance Research Database. A cohort of 961 individuals diagnosed with GD was identified. An age- and sex-matched control cohort (n = 3,844) and an unaffected sibling cohort (n = 675) were constructed. Cumulative survival …

Assessing The Feasibility Of A Self-Management Intervention For Individuals With Advanced Prostate Cancer And Comorbid Type Ii Diabetes Mellitus, Amy L. Shaver, Christina Steinbock-Malfer, William Tester, Patrick Mille, William K. Kelly, Kevin K. Zarrabi, Costas D. Lallas, Mihir M. Shah, Rose Dimarco, Emily Brand, Shawntel Brown, Swapnil Sharma, Nikita Nikita, Cindy Cogen, Scott W. Keith, Grace Lu-Yao

Kimmel Cancer Center Faculty Papers

BACKGROUND: Many older adults with cancer have at least one comorbidity. Type II diabetes mellitus (T2DM) is a common comorbidity among patients with prostate cancer (PC) and represents an important consideration in this population. Comorbid T2DM can negatively impact cancer-specific outcomes for patients, suggesting the need for better glycemic management, especially for patients on active cancer treatment. The goal of this modified Diabetes Self-Management Education Services (mDSMES) pilot study was to provide patients with the opportunity to learn methods of diabetes self-management, including how to manage their glucose levels, improve their understanding and utilization of medication to promote improvements in …

Myocarditis, Children's Mercy Kansas City

Clinical Pathways

No abstract provided.

Small But Mighty: How Can Pediatric Psychologists Harness The Power Of Digital Single-Session Interventions?, Christina Amaro, Alexandra Monzon, Melissa Alderfer, Kimberly Canter, Michael Amylon, Stephanie Fooks-Parker, Jessica Schleider, Susana Patton, Katie Devine

Department of Pediatrics Faculty Papers

OBJECTIVE: Single-session interventions (SSIs) are an innovative, scalable approach for addressing the unmet behavioral and mental health needs of pediatric patients and their families. Specifically, digital SSIs, which are self-guided and delivered online, offer a low-cost and accessible approach but are currently underutilized in pediatric psychology.

METHODS: This topical review aims to describe SSIs broadly and the specific need for digital SSIs, explore potential applications within pediatric psychology, outline future directions and considerations, and present two examples of community-engaged digital SSI design.

RESULTS: SSIs evidence small to medium effects across a range of mental health concerns, including distress, anxiety, and …

Dnp Final Report: Improving Diabetes Self-Efficacy Through Nutrition Education: A Quality Improvement Project, Lakimberely S. Wooten

DNP Final Reports

Diabetes affects 12.7% of residents in Northeast Texas and is the 7th leading cause of death. Internal evidence indicates low health literacy and a heavy disease burden in the service area, underscoring the need for a standardized, low-cost, and feasible approach to nutrition education. This quality improvement project evaluated the feasibility of implementing an instructor-led nutrition education session. Guided by the Johns Hopkins Evidence-Based Practice Framework and the ADKAR behavioral change model, adult participants with Type 2 diabetes received instruction on the Plate Method. Participants enrolled in a 4-week, instructor-led diabetes education class completed a 1-hour, nutrition education session using …

Computational And Ai Tools For Understanding Telomere-Associated Cancer Mechanisms, Eleni Adam

Computer Science Theses & Dissertations

Telomeres are the protective caps of the human chromosomes and are critical for genome stability. Dysfunctional telomeres caused by their erosion with age and cell proliferation as well as by defects in their maintenance is a major early event leading to genome changes and cancer. Subtelomeres possess the critical role of regulating adjacent telomeres. Due to their complex repeat structure and high variance from one person to another, these areas have not been analyzed in detail. We present a set of computational and machine learning tools to aid in the understanding of subtelomere structure and its rearrangements in cancer.

Initially, …

Increased Risk Of Sarcomas In Children With Congenital Anomalies: Findings From The Genetic Overlap Between Anomalies And Cancer In Kids (Goback) Registry Linkage Study, Russ Wolters, Ji Yun Tark, Tiffany M Chambers, Tania A Desrosiers, Michael E Scheurer, Charles Shumate, Wendy N Nembhard, Mahsa M Yazdy, Eirini Nestoridi, Amanda E Janitz, Jean Paul Tanner, Russell S Kirby, Jason L Salemi, Yao Yu, Chad D Huff, Sharon E Plon, Philip J Lupo, Jeremy M Schraw

Faculty, Staff and Students Publications

Background: Pediatric sarcomas are a heterogeneous group of tumors that contribute disproportionately to cancer mortality in children. Although congenital anomalies are among the strongest known risk factors for childhood cancer, the risk of specific sarcoma subtypes among affected individuals has not yet been thoroughly evaluated.

Procedure: We obtained data on maternal and perinatal characteristics, congenital anomalies, and pediatric sarcoma diagnoses for all live births in nine states. We used Cox proportional hazards regression to estimate the hazard ratio (HR) and 95% confidence interval (CI) of sarcoma (overall and by subtype) among children with non-syndromic congenital anomalies. We considered all non-syndromic …

De Novo Complex Genomic Rearrangement Spanning 2q31.1 In A Proband With Congenital Malformations: Genotype-Phenotype Correlation And Development Of A Cgr Detection Pipeline, Katherine Helle, Jesse D Bengtsson, Mira Gandhi, Christopher M Grochowski, Ming Yin Lun, Neha Sudhir, Shalini N Jhangiani, Fritz J Sedlazeck, Seema R Lalani, Neil A Hanchard, Claudia M B Carvalho

Faculty, Staff and Students Publications

The 2q31 region is commonly associated with pathogenic alleles of the HOXD cluster leading to various clinical phenotypes related to skeletal development. We present a proband with tetralogy of Fallot and multiple congenital anomalies. Genomic variant screening including an in-house CGR detection pipeline pairing genome sequencing (GS) structural variant calls with read-depth data revealed a de novo complex genomic rearrangement (CGR) spanning 2.7 Mb across 2q31 characterized by a series of duplications and triplications including the HOXD gene cluster. The genomic structure was assembled by applying combined methodologies including short-read and long-read GS, and optical genome mapping (OGM). This in-house …

Quantitative Imaging Of Pyruvate Metabolism In A Patient With Anaplastic Thyroid Cancer, James A Bankson, Joshua S Niedzielski, Collin J Harlan, Yunyun Chen, Christopher M Walker, Philip L Lorenzi, Lin Tan, Vikas Kundra, Matthew E Merritt, Mukundan Ragavan, Dawid Schellingerhout, Renjie He, Yao Ding, Sahana Datar, Qing Wang, Christine B Peterson, Clifton D Fuller, Vlad C Sandulache, Stephen Y Lai

Faculty, Staff and Students Publications

Purpose: Magnetic resonance imaging using hyperpolarized (HP) [1-13C]-pyruvate enables assessment of pyruvate metabolism in vivo and offers new insight into metabolic changes in response to cancer therapy. Widely used semi-quantitative metrics of pyruvate metabolism can be affected by physiological factors that are extrinsic to intracellular metabolism. A validated pharmacokinetic (PK) model for analysis of intracellular pyruvate metabolism is needed to enhance the accuracy of quantitative metrics and clinical translation of metabolic MRI using HP pyruvate.

Methods: A PK model with two physical compartments and two chemical pools was developed to analyze the conversion of labeled pyruvate into lactate in vitro. …

Trauma: Cervical Spine Clearance, Children's Mercy Kansas City

Clinical Pathways

No abstract provided.

Ai-Driven Segmentation And Volumetric Response Modeling Of Liver Regions To Radiotherapy, Aashish Chandra Gupta

Dissertations and Theses (Open Access)

In liver-directed radiotherapy (RT), liver regions receiving higher doses typically undergo atrophy while contralateral/adjacent lower-dose regions may exhibit compensatory hypertrophy through regeneration of healthy tissue. Optimizing the RT plan to promote regional hypertrophy while minimizing the risk of developing atrophy has the potential to enhance post-RT liver function and long-term survivorship. However, current clinical practice largely relies on global liver dose-volume metrics during RT-planning, which may obscure favorable dose-response correlation and limit actionable guidance for clinicians. Therefore, we hypothesized that post-RT regional liver response is governed by a combination of region-specific dose-volume and patient clinical features, and that these responses …

“We’Re Just Always There For Each Other”: Examining Social Support For African American Caregivers Of Oncology Patients, Madeleine Lee, Keisha White Makinde

Posters

No abstract provided.

Operationalizing Frailty: A Comparison Of Measurement Frameworks, Audrey P. Doege, Madeline Donnelli, Daniel Forsha, Thomas Cochran, William R. Black, David A. White

Posters

No abstract provided.

Emergency Medical Services Mental Health: Causes Of Providers Leaving The Industry, Brian C. Selke

Graduate Theses and Dissertations (2019 - present)

Employee resilience and mental health have become critical concerns in Emergency Medical Services (EMS) as workforce shortages increasingly threaten staffing stability and patient care. National Registry of Emergency Medical Technicians (NREMT) data indicates that more than 30% of eligible EMS providers did not recertify between 2020 and 2023, raising concerns about workforce sustainability. This study examines EMS providers’ intentions to leave the profession and identifies workplace factors associated with turnover. A statewide survey of more than 1,200 licensed EMS providers in Alabama was analyzed using regression techniques to evaluate the relationship between workplace conditions and turnover intentions. Results demonstrate that …

"I Can See Where This Is Taking Me": Medical Students' Perceptions Of Humanities Courses At Aga Khan University, Kenya, Catherine Gathu, Marthaclaire Zammit, Urvi Saboo, Robert Opoka

Family Medicine, East Africa

Background Humanities courses in medical training are increasingly recognized as essential for developing empathetic, reflective and socially responsive physicians. Although well-established globally, their integration into medical education in African contexts remains limited. In Kenya, humanities are often peripheral within curricula dominated by biomedical sciences and clinical medicine. Aga Khan University (AKU), Nairobi, has introduced a novel medical curriculum that embeds seven core humanities courses as central components of the initial phase of its MBChB program. This study explored students’ perceptions and lived experiences of these humanities courses.

Methods A retrospective descriptive study using an embedded mixed-methods design was conducted among …

Demographic And Clinical Characteristics Of Participants In The Neuropsychiatric Genetics Of African Populations-Psychosis (Neurogap-Psychosis) Study: A Descriptive Analysis, Rocky Stroud, Kimberly Hook, Melkam Alemayehu, Lukoye Atwoli, Mark Baker, Lori Chibnik, Bizu Gelaye, Stella Gichuru, Symon Kariuki, Rehema Mwema

Internal Medicine, East Africa

Background Approximately 1.3 million individuals in sub-Saharan Africa, as well as millions of others worldwide, live with psychotic disorders. However, there is limited mental health research based on these populations and even less of a focus on neuropsychiatric genetics research within these settings.

Methods To address this gap, the Neuropsychiatric Genetics of African Populations-Psychosis (NeuroGAP-Psychosis), a case-control study, collected data identifying genetic and environmental risk factors associated with psychotic disorders in Ethiopia, Kenya, South Africa, and Uganda. This paper describes baseline demographic and clinical characteristics of the 42,953 participants recruited between 2018–2023 and compares these characteristics by country and case …

Surgeon Health And Well-Being Initiative: A Survey Of General And Orthopedic Surgery Residents' Reports Of Musculoskeletal Pain., Maryam Mohamed, Grace J Kim, Kristen Conrad-Schnetz, Zhan Yang, Mary Carneval

Ambulatory and Primary Care Articles

Background Musculoskeletal (MSK) pain is a well-known risk among surgeons, resulting from the multifactorial physical demands of the occupation. Because of the demands faced by resident surgeons, many individuals find themselves with sometimes debilitating MSK pain. Although these risks are well documented and there have been proposed solutions, there is little discussion on the role that osteopathic manipulative treatment (OMT) can play in relief of MSK pain over time in this population. Objective The purpose of this study is to determine the prevalence and distribution of MSK pain among general and orthopedic surgery residents at Cleveland Clinic Foundation (CCF). Based …