Medicine and Health Sciences Commons^™

Egfr Inhibitor-Resistant Lung Cancers Exhibit Collateral Sensitivity To A Covalent, Cysteine-Independent Keap1 Oligomerizing Molecular Bridge, Christopher F Bassil, Kerry Dillon, Gray R Anderson, Benjamin Mayro, Kayleigh N Askin, Peter S Winter, Stefan Harry, Samuel Gruber, Tierney M Hall, Jacob P Hoj, Christian Cerda-Smith, Haley M Hutchinson, Shane T Killarney, Ava Heffernan, Caroline Teddy, Katherine R Singleton, Li Qin, Kévin Jubien-Girard, Cécile Favreau, Guillaume Robert, Barr Tivon, Ella Livnah, Nir London, Rachid Benhida, Patrick Auberger, Ann Marie Pendergast, Liron Bar-Peled, David M Lonard, Anthony R Martin, Alexandre Puissant, Kris C Wood

Faculty, Staff and Students Publications

Targeted therapies have revolutionized cancer care. Unfortunately, most patients develop refractory, multifocal resistance to these therapies within a matter of months. Here, we demonstrate that the evolution of resistance to EGFR inhibitors in EGFR-mutant non-small cell lung cancer endows cells with hypersensitivity to a PAINS-like small molecule, MCB-613. Systematic proteomic, functional genomic, and biochemical studies revealed that MCB-613 binds KEAP1 in a covalent, cysteine-independent fashion, acting as a divalent molecular bridge that relies upon lysine residues in the KEAP1 dimerization domain to join monomers of KEAP1 together. Oligomerization of KEAP1 by MCB-613 sets into motion a fatal cascade of KEAP1 …

Ophiobolin A Impacts Mitochondrial Redox Biology In An Epithelial-Mesenchymal Transition (Emt)-Specific Manner, Haleigh N Parker, Yongfeng Tao, Jenna Tobin, Kayla L Haberman, Samantha Davis, Emily York, Alysia Martinez, Nobuyuki Matsumoto, Jaquelin Aroujo, Jun Hyoung Park, Bernd Zechmann, Benny Abraham Kaipparettu, Angela Boari, Christie M Sayes, Antonio Evidente, Alexander Kornienko, Benjamin Cravatt, Daniel Romo, Joseph H Taube

Faculty, Staff and Students Publications

Breast cancer progression is facilitated by the epithelial to mesenchymal transition (EMT), generating cancer cells with enhanced metastatic capacity and resistance to chemotherapeutics. The fungus-derived sesterterpenoid natural produce compound, ophiobolin A (OpA), possesses nanomolar cytotoxic activity and a high therapeutic index, although its molecular targets and mechanism of action are not well characterized. Herein, we utilized a model of mammary epithelial cells and breast cancer cell lines with and without EMT features to characterize the mechanism of selectivity towards EMT(+) cells by OpA. Proteins interacting with OpA in EMT(+) cells, including mitochondrial glutathione transporter SLC25A40, were identified through via mass …

Progress And Challenges In Profiling Protein-Rna And Protein-Associated Rna-Rna Interactions, Zhuoyi Song, Eric L Van Nostrand

Faculty, Staff and Students Publications

RNA binding proteins (RBPs) play essential roles in post-transcriptional gene regulation by interacting with a wide range of RNA targets. In addition to regulating RNA processing via individual RBP-RNA interactions, there is a growing appreciation of the regulatory impact of protein-associated RNA-RNA interactions that include both well-studied examples of small regulatory RNAs (e.g. microRNAs, snRNAs, snoRNAs, piRNAs) guiding ribonucleoprotein complexes to their targets as well as structured RNA elements defining the interaction landscape for an RBP. To elucidate the full scope of RBP-RNA interactions, CLIP ( crosslinking and immunoprecipitation)-based methods have emerged as powerful tools. Even with the wide application …

Protocol For The Development Of The Who Gestational Weight Gain Charts, Thais Rangel Bousquet Carrilho, Olufemi Taiwo Oladapo, Jennifer A. Hutcheon, Giovanna Gatica-Domínquez, Kathleen M. Rasmussen, Monica C. Flores-Urrutia, Richard Kumapley, Ӧzge Tunçalp, Dang Bahya-Batinda, Amel A. Fayed, Annick Bogaerts, Aris T. Papageorghiou, Cinthya Muñoz-Manrique, Dayana Rodrigues Farias, Eric Ohuma, Harshpal Sachdev, Hayfaa A. Wahabi, Helena J. Teede, Molin Wang, Nandita Perumal Phd

Faculty Publications

Introduction Gestational weight gain (GWG) is an important indicator of maternal nutrition to be monitored during pregnancy. However, there is no evidence-based tool that can be used to monitor it across all geographic locations and pre-pregnancy body mass index (BMI) categories. The WHO is undertaking a project to develop GWG charts by pre-pregnancy BMI category, and to identify GWG ranges associated with the lowest risks of adverse maternal and infant outcomes. This protocol describes all the steps that will be used to accomplish the development of these GWG charts.

Methods and analysis This project will involve the analysis of individual …

Neuroradiological Features Across Major Psychiatric Disorders And Behavioral Variant Of Alzheimer’S Disease: A Concise Multimodal Synthesis, Sina Dindarian, Joga Chaganti, Nazanin Rafiei, Scott H. Faro

Department of Radiology Faculty Papers

Psychiatric disorders are complex, disabling conditions that continue to rely on subjective diagnostic criteria due to the absence of objective biological markers. Neuroradiology has become a critical discipline for examining the structural, functional, and biochemical underpinnings of these disorders through advanced brain imaging. This review synthesizes findings from five major psychiatric conditions including major depressive disorder, schizophrenia, autism spectrum disorder, obsessive-compulsive disorder, and generalized anxiety disorder, and briefly discusses the behavioral variant of Alzheimer's disease, a variant with neuropsychological overlay, across multiple imaging modalities, including structural magnetic resonance imaging (MRI), diffusion tensor imaging, functional MRI, magnetic resonance spectroscopy, functional near-infrared …

Volumetric Wear Analysis Of Polyethylene Orthopedic Liners Using Point Clouds, Gabriel Landi

Dartmouth College Master’s Theses

In vivo wear of ultra-high molecular weight polyethylene (UHMWPE) orthopedic bearings represents a major problem in shoulder and knee arthroplasty, with significant amounts of devices failing due to the complication itself, and even more due to associated reasons for retrieval, including aseptic loosening. However, quantification of UHMWPE wear has largely been limited to linear and in vitro volumetric analyses, obscuring the understanding of the amount of clinically relevant material loss. This study proposes new methods to measure articular, rim, and backside surfaces of retrieved shoulder and knee UHMWPE liners, centered around the coordinate measuring machine (CMM)-based collection of high density …

Resolution Of A Human Chromosomal Mystery: Evolutionary Complexity Revealed, Jeffrey Rogers

Faculty, Staff and Students Publications

The human complement of chromosomes differs from our closest primate relatives by virtue of a unique chromosome fusion event. In this issue of Cell Genomics, Yang et al. provide the first detailed analysis of the site of chromosome fusion and reconstruct the complex evolutionary relationships among the genomic elements within the human fusion site and their related sequences in our great ape relatives.

Understanding The Compatibility Of Fluoride-Based Radiopharmaceutical Reaction Solutions And Pdms, Mark Mc Veigh, Charles Frech, Mai Lin, Robert Ta, H Charles Manning, Leon M Bellan

Faculty, Staff and Student Publications

Microfluidic devices offer unique and exciting benefits when applied to radiopharmaceutical manufacturing, and these platforms are now starting to be integrated into commercial products. The field has strayed away from the use of polydimethylsiloxane (PDMS), the most common microfluidic device material, due to its suspected incompatibility with 18F, the most commonly used radionuclide. However, existing literature provides conflicting conclusions as to the existence and extent of this incompatibility. In this study, we use several analytical instruments to uncover the underlying interaction between fluoride and PDMS. SEM imaging and profilometry confirm the reactive relationship between the two materials and suggest that …

Autograft Enlargement After The Ross Procedure In Pediatric Patients: Somatic Growth Or Pathologic Dilatation?, Ioannis Zoupas, Alexander C Mills, Scott D Olson, Damien J Lapar

Faculty, Staff and Student Publications

Purpose of ReviewPulmonary autograft autotransplantation represents a popular surgical approach for pediatric patients requiring aortic valve replacement due to the potential for autograft enlargement to accommodate somatic growth. Nevertheless, autograft dilatation and the subsequent need for reintervention are quite common. Published data suggest that autograft enlargement may result from pathological passive remodeling rather than active somatic growth and vice versa. The present review serves to comprehensively evaluate available evidence related to the fate of the pulmonary autograft after the Ross procedure as it relates to the etiology, risk factors and patterns of autograft failure.ResultsStudies present conflicting results supporting both pathological …

Prevalence And Outcomes Of Her2-Low Versus Her2-0 Status In Patients With Metastatic Breast Cancer, Akshara Singareeka Raghavendra, Diane D Liu, Senthil Damodaran, Sarah Pasyar, Yu Shen, Jason A Mouabbi, Carlos H Barcenas, Kelly K Hunt, Debu Tripathy

Faculty, Staff and Student Publications

Background: HER2-low breast cancer (HER2 immunohistochemical [IHC] score 1+, or IHC 2+ without HER2 gene amplification) is distinct from HER2-positive and HER2-0 breast cancer (IHC 0), with a differing prognosis and specific therapeutic options. The DESTINY-Breast04 trial demonstrated notable efficacy of the HER2 antibody-drug conjugate trastuzumab deruxtecan over standard chemotherapy in patients with metastatic breast cancer (MBC) defined as HER2-low. More recently, the DESTINY-Breast06 trial confirmed this benefit in hormone receptor-positive and HER2-ultralow (less than 1+, but with ≤10% of infiltrating cancer cells showing incomplete and faint/weak membrane staining) cases, prompting re-evaluation of HER2 diagnostic thresholds and treatment strategies.

Methods …

Diet-Responsive Genetic Determinants Of Intestinal Colonization In The Yeast Candida Albicans, Musfirat Shubaita, Mazen Oneissi, Elena Lindemann-Pérez, Cecilia Fadhel Alvarez, Anne-Marie Krachler, Diana M Proctor, J Christian Pérez

Faculty, Staff and Student Publications

Dietary components influence microbial composition in the digestive tract. Although often viewed as energy sources, dietary components are likely to shape microbial determinants of intestinal colonization beyond metabolism. Here, we report that a dietary long-chain fatty acid enhances the yeast Candida albicans colonization of the murine gut partly by eliciting modifications to the fungal cell surface. Mice fed an oleic acid-rich diet were readily colonized by C. albicans and exhibited higher fungal load in feces compared with rodents fed an isocaloric control diet. Surprisingly, β-oxidation, a catabolic process to break down fatty acids for energy production, was dispensable for C. …

Real-World Multicenter Assessment Of Sustained Clinical Outcomes After Digital Deep Brain Stimulation, Alireza Gharabaghi, Sergiu Groppa, Elena Casas, Alfons Schnitzler, Laura Muñoz-Delgado, Vicky L. Marshall, Jessica Karl, Lin Zhang, Ramiro Alvarez, Mary S. Feldman, Michael J. Soileau, Lan Luo, Benjamin L. Walter, Chengyuan Wu, Hong Lei, Damian M. Herz, Devyani Nanduri, Claudia A. Salazar, Corneliu Luca, Daniel Weiss

Department of Neurosurgery Faculty Papers

Remote, internet-based deep brain stimulation programming for Parkinson's disease accelerates clinical benefits postoperatively by improving access to therapy adjustments compared to in-clinic optimization. After completion of the initial digital programming phase, we show that clinical outcomes, quality of life, and safety remain sustained over at least twelve months under routine care conditions. Embedding a randomized trial within a larger cohort study enables long-term, real-world evaluation, offering a scalable and pragmatic model for assessing complex digital interventions in routine clinical care. (NCT05269862 registered on 2022-03-08 and NCT04071847 registered on 2019-08-28).

The Relationship Between The Health Science Reasoning Test And Successful Completion Of An Associate Degree Nursing Program: A Retrospective Predictive Study, Joyce A.Ajkuce Kucerovy

Doctoral Dissertations and Projects

The purpose of this study was to retrospectively identify whether the addition of an entrance exam such as the Health Science Reasoning Test (HSRT) to the current admission criteria of an associate degree nursing (ADN) education program would aid in selecting students with the highest chance of successfully completing the program and entering the workforce. A nonexperimental, retrospective, quantitative, predictive correlational study design was used. A retrospective convenience sample of 320 first-year nursing students in an ADN education program was obtained. The G* power analysis showed a minimum sample size of 107 students was needed. Statistical analysis involved a multiple …

Unseen But Felt: Exploring The Emotional And Developmental Impacts Of Father Absence On The Lives Of African American Daughters, Michelle Laniece Mayberry

Doctoral Dissertations and Projects

This phenomenological study explored the lived experiences of African American daughters who grew up with absent fathers, examining how this experience influenced development, relationships, identity formation, and resilience. Through in-depth interviews and thematic analysis, six central themes emerged: (1) father-daughter relationship, (2) emotional and psychological impact, (3) identity and development, (4) social and relational outcomes, (5) decision-making and achievement, and (6) resilience and adaptation. Each theme was interpreted through the lens of attachment and social learning theories with a biblical worldview. The findings revealed that father absence often left emotional and developmental wounds in the lives of the participants. The …

Evaluation Of Handgrip Strength As A Surrogate Measure For Athletic Performance Metrics And Lower-Body Strength In High School Boys Basketball Players, Joseph R. Northcutt

Doctoral Dissertations and Projects

This quantitative correlational study examined relationships between bilateral handgrip strength (HGS) and athletic performance metrics, including vertical jump height, barbell squat one-repetition maximum (1RM), sprint speed, agility, and upper-body muscular endurance (push-up repetitions), in adolescent male basketball players. The study also evaluated whether inter-limb strength asymmetry was associated with the athletic performance outcomes.

29 male athletes aged 14-18 years participated in the research that included handgrip strength, vertical jump, lane agility drill, shuttle run, ¾-court sprint, push-up repetitions, and 1RM barbell squat. Statistical analyses were conducted using Jeffreys’s Amazing Statistics Program (JASP) and included Pearson product-moment correlations, Shapiro-Wilk assumption testing, …

Factors Influencing Sugary Drink Consumption Among Residential Students At Liberty University, Chinonso Felistas Eziechi

Masters Theses

Introduction/Background: Sugary drink consumption among college students remains a public health concern due to its association with obesity, diabetes, and cardiovascular disease. Despite high awareness of health risks, consumption among emerging adults remains elevated. Guided by the Social Cognitive Theory, this study examined the psychosocial, behavioral, and environmental determinants of sugary drink consumption among residential students at Liberty University. Objective: To identify key predictors of sugary drink consumption and evaluate how expectations, self-regulation, and environmental factors shape beverage behaviors. Design, Setting, Participants: This cross-sectional study used an anonymous Qualtrics survey distributed on campus. Of approximately 745 eligible residential students, 473 …

The Impact Of Awareness Of Campus Health Services On Utilization Of Medical Care Among Residential Students At Liberty University, Catherine Pandagade

Masters Theses

College students represent the most prominent group of individuals when considering their lifestyles throughout aging. Therefore, this age group serves as a good opportunity for health education that could build positive health behaviors for life. Existing literature have said that the 18-25 year olds tend to have fewer resources and be often uninsured and have the highest rates of preventable diseases.2 Objective: The aim of this research is to investigate the impact of awareness and its subsequent effect on utilization of available health resources on campus among the student population of Liberty University. Additionally, the purpose of the research through …

Mapping The Transcriptional Regulatory Network Of A Fungal Pathogen By Exploiting Transcription Factor Perturbation, Dhoha Abid, Holly Brown, Chase Mateusiak, Tamara L Doering, Michael R Brent

2020-Current year OA Pubs

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Africa's Digital Health Revolution: The Digital Fit-Viability Model To Move From Innovation To Scaled Implementation, Afra Jiwa, Antony Ngatia, Karim Benali, Niclas Boehmer, Sangu Delle, Patrick Emedom-Nnamdi, Chris Opoku Fofie, Christine M O'Brien, Tobi Olatunji, Kate Obayabgona, Milind Tambe, Richard Ribon Fletcher, Adeline Adwoa Boatin, Bethany Hedt-Gauthier

2020-Current year OA Pubs

Digital innovations hold immense potential to transform health care delivery, particularly in sub-Saharan Africa, where financial, geographical, and infrastructural constraints continue to hinder progress toward universal health care delivery. Although a growing health tech sector offers creative solutions, few digital health interventions reach scaled implementation. In this paper, we present the digital fit/viability model-an adapted determinant framework to describe facilitators and barriers to moving from digital tools to integrated digital health implementation. We then use this model to describe the specific challenges and recommended solutions when developing digital health tools for health systems in sub-Saharan Africa.

Non-Negative Matrix Factorization And Deconvolution As A Dual Simplex Problem, Denis Kleverov, Ekaterina Aladyeva, Alexey Serdyukov, Maxim N Artyomov

2020-Current year OA Pubs

BACKGROUND: Non-negative matrix factorization is a powerful linear algebra tool used in multiple areas of data analysis, including computational biology. Despite numerous optimization methods devised for non-negative matrix factorization, our understanding of the inherent topological structure within factorizable matrices remains limited.

RESULTS: This study reveals the topological properties of linear mixture data, leading to a remarkable reduction of the non-negative matrix factorization optimization problem to a search for K(K-1) variables, where K represents the number of pure components, regardless of the initial matrix size. This is achieved by revealing complementary simplex structures existing in both feature and sample spaces and …

Chiari Network Identified By Ct Imaging: An Uncommon Modality For A Common Incidental Finding, Kyle Admire, Denis Yusupov, Xian Qiao

Eastern Virginia Medical Journal

Chiari networks are anatomical variants that result from incomplete resorption of embryologic tissues and are often discovered incidentally on echocardiography. We describe the case of a large Chiari network we discovered after independent review of the patient’s computed tomography scan showed an unexpected filling defect within the right atrium, prompting further investigation. We also conducted a review of the literature for this anatomic variant of unclear clinical significance.

Bridging Theory And Self-Development In Human Services And Counselor Education, Kristy Carlisle

Journal of Human Services Scholarship and Interprofessional Collaboration

Counselor and human services education increasingly recognize self-awareness as a core component of professional competence and ethical practice. This conceptual manuscript presents a pedagogical framework that integrates major helping theories as tools for structured self-reflection and self-development among students and practitioners. Drawing from experiential learning theory, reflective practice, and models of counselor identity formation, the approach encourages learners to view themselves through theoretical lenses such as person-centered, cognitive-behavioral, and existential frameworks, paralleling the very lenses through which they will view their clients in practice. By engaging in guided reflective activities, students examine personal beliefs, emotions, and behaviors to enhance self-understanding, …

Cognitive Function And Hypertension, Natalia Motzko Noto, Betsi Reinosa Corrada, Lisa S. Robison, Robert Charles Speth

Faculty Proceedings, Presentations, Posters, Speeches, Lectures, etc.

Given the brain’s high energy demands, the blood supply to the brain is critical for its function. Hence the importance of an intact brain vascular system to adequately perfuse the brain to sustain cognitive function. Given the damage to the vascular system that ensues from hypertension, it is a foregone conclusion that chronic hypertension will lead to cognitive impairments that can ultimately lead to dementia. Despite this logical connection, it was not until the 1990’s that the association between hypertension and dementia began to be made. And, it was not until 2000 that the first definitive connection between hypertension and …

Automating Academia: Implications Of Genai Use In Doctoral Research And Online Mentoring, Cheryl Burleigh, Andrea M. Wilson

Journal of Online Mentoring

This study critically examines the use of generative artificial intelligence (GenAI), specifically ChatGPT, in the development of doctoral dissertation proposals, highlighting both its potential and its ethical implications. Through a content analysis of a dissertation proposal created using ChatGPT, the study investigates how GenAI supports structural organization, academic writing, and citation formatting while exposing significant concerns related to fabricated references, methodological misalignment, and diminished scholarly rigor. Although GenAI accelerates the proposal-writing process, its outputs often lack the depth, coherence, and originality expected at the doctoral level, thereby threatening the integrity of academic research. Findings reveal that GenAI-generated content may deceive …

The Role Of Isotocin In Female Zebrafish (Danio Rerio) Reproductive Behavior And Its Implication For Intranasal Oxytocin Therapy In Humans, Katelynn M. Benge

Masters Theses

In the past several decades, oxytocin has been colloquially termed the “cuddle hormone,” due to its role in pair-bonding and monogamy (Carter et al., 1992). In addition to being used experimentally for psychological disorder, it has also been used in couple’s counseling settings (Anagnostou et al., 2014; Domes et al., 2016). The outcomes of this research reveal mixed results, creating a need for further research in the topic to understand the exact mechanisms by which oxytocin works in the brain to induce this prosocial response. This study sought to address this deficit through the zebrafish animal model. The zebrafish serves …

Disease Burden Of Asthma Patients Utilizing Short-Acting Beta-2 Agonist-Only Inhalers As Rescue In The United States, Njira Lugogo, Rena C. Moon, Yen Chung, Joy David, Omar Motawakel, Ning A. Rosenthal, Neil Skolnik

Department of Family & Community Medicine Faculty Papers

Purpose: We aimed to describe the disease burden of asthma and examine relationships between short-acting beta-2 agonist (SABA) use and asthma exacerbations. Patients and Methods: This retrospective cohort study used geographically diverse Premier Healthcare Database (PHD) and linked insurance claims (10/01/2021-09/30/2022) for US patients aged ≥18 years with a SABA-only prescription and a history of asthma exacerbation within 12 months before index date (the earliest SABA prescription date). Three asthma control groups were defined based on SABA usage: well controlled-low (0–1 prescriptions), not well controlled-medium (2–3 prescriptions), very poorly controlled-high (≥4 prescriptions). Four asthma severity groups were defined using asthma …

Deliver Us From Evil., Ethan Schimmoeller

Ambulatory and Primary Care Articles

No abstract provided.

Respiratory Health And Environmental Risks Among California Children: The Role Of Socioeconomic Status, Wen Chieh Chia

Walden Dissertations and Doctoral Studies

Abstract Air pollution has been cited as a factor in the development of respiratory illness in children. Socioeconomic differences can intensify the effects of air pollution exposure on low-income children compared to higher-income children. This correlational study examined the relationship between air pollution exposure and respiratory health outcomes among California children, as well as the moderating role of socioeconomic status. The study was guided by the environmental health disparities framework and used secondary data from the California Environmental Health Tracking Program, analyzing data from 49 California counties (n = 49). Independent variables were PM2.5 concentrations and the number of ozone …

New Comorbidity Index Associated With Survival After Chimeric Antigen Receptor T-Cell Therapy For Large B-Cell Lymphoma, Uri Greenbaum, Amanda Cashen, Et Al.

2020-Current year OA Pubs

No abstract provided.

Identifying Priority Research Questions For Decentralized Wastewater, Bryan W Brooks, Timothy Callahan, Jacob K Stanley, Jamie Holodak, Kevin M Stroski, Alissa H Cox, Thomas W Groves, Anish Jantrania, Jeff C Moeller, Kris Neset, Christopher Walker, Harry Zhang, Amal Bakchan, Kelly D Alley, Jim Bell, Allison Blodig, Eric Casey, Donna Cosper, Victor D'Amato, Mark A Elliott, Greg Graves, Roxanne Groover, Robert Himschoot, Mary G Lusk, Jillian Maxcy-Brown, David Meints, Rojelio Mejia, Matt Pace, Benjamin J Ryan, Brian Scheffe, Tom Schimelfenig, June E Wolfe, Sara F Heger

Faculty, Staff and Students Publications

Decentralized wastewater treatment and reuse represent critical infrastructure across the rural-periurban-urban continuum around the world. Effective, efficient, resilient, and equitable implementation of on-premise technologies and management systems is part of a One Water approach and necessary to protect public health and the environment, yet inconsistent delivery of essential public health services persists in many regions, including across states, tribes, and territories of the United States. We initiated a groundbreaking effort to understand challenges and to identify research opportunities related to the science and practice of decentralized wastewater. A horizon scanning exercise using a bottom up and transparent key questions approach …