Digital Commons Network^™

Comparative Analysis Of Ctdna Monitoring Strategies In Advanced Nsclc With Met Exon 14 Skipping Mutations Treated With Ensartinib, Mo Zhou, Yin Zhu, Xuqi Sun, Ying Han, Rui Jin, Panwen Tian, Jun Zhao, Yang Jin, Zhiyuan Guo, Yongchang Zhang, Yiran Meng, Fei Liu, Wen Li, Xiuning Le, Haifeng Shen, Yang Xia

Faculty, Staff and Student Publications

Mesenchymal-epithelial transition exon 14 skipping mutations (METex14) define a targetable molecular subset of non-small cell lung cancer (NSCLC), but optimal circulating tumor DNA (ctDNA) biomarkers to guide MET tyrosine kinase inhibitor therapy remain undefined. Within the EMBRACE trial of ensartinib, we conducted a prospective biomarker analysis with plasma collected at baseline (V0) and 4 weeks after treatment initiation (V1). ctDNA was profiled using a hybrid-capture next-generation sequencing panel covering 229 cancer-related genes, and mutations were classified into three monitoring paradigms: MET-specific alterations, canonical alterations (tier I/II), and pan-alterations (any variant in any gene on the panel). Baseline ctDNA positivity rates …

Pain Prevalence And Pain Management At The End Of Life: Regional And Urban-Rural Differences From A National-Representative Survey Of Chinese Older Adults, Yaolin Pei, Xiang Qi, Zexi Zhou, Yifan Lou, Jing Wang, Yang Li, Bei Wu

Faculty, Staff and Student Publications

Background: Effective pain management is essential for improving quality of life at the end of life. However, challenges persist globally, particularly in China, where palliative care remains underdeveloped. This study investigates pain prevalence and the associations between pain severity, place of death, and the quality of pain management among older adults in China, with a focus on regional and urban-rural disparities.

Methods: We used data from the 2014, 2016, 2018, and 2020 waves of the China Longitudinal Aging Social Survey. The final sample included 1,525 older adults who died during the study period. We conducted OLS regression analyses to examine …

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 …

Staff Education To Use Mindfulness Strategies To Prevent Burnout In Psychiatric Health Settings, Rebecca Ikeoluwa Gabriel

Walden Dissertations and Doctoral Studies

There was a significant gap in practice at an outpatient psychiatric mental health clinic regarding organized, evidence-based training on mindfulness techniques to reduce stress and emotional exhaustion among psychiatric mental health staff. This project’s practice-focused question was “Does educating psychiatric mental health staff on mindfulness strategies for burnout improve their knowledge, as evidenced by pre- and post-surveys?” This educational intervention was developed, implemented, and evaluated using the Johns Hopkins Evidence-Based Practice paradigm and the ADDIE instructional design model. A literature search was conducted using CINAHL Complete, MEDLINE/PubMed, ProQuest, and the Cochrane Library, with assistance from the librarians at Walden University. …

Staff Education To Improve Tirzepatide Education And Lifestyle Counseling, Daisy Asemota

Walden Dissertations and Doctoral Studies

This Doctor of Nursing Practice (DNP) project was a practice-focused staff education initiative designed to improve clinical staff knowledge, confidence, and readiness to educate adult patients enrolled in a Tirzepatide weight-management program. Tirzepatide has demonstrated superior weight-loss outcomes compared to other glucagon-like peptide-1 (GLP-1) receptor agonists; however, inconsistent staff education practices related to medication administration, adverse-event management, and lifestyle counseling present a gap in practice. Variability in staff knowledge and teaching approaches may reduce confidence, contribute to inconsistent patient education, and limit the effectiveness of evidence-based care delivery. The purpose of this DNP project was to address this practice gap …

Targeting Tau In Alzheimer's Disease: Rationale, Approach And Challenges, Aram Aslanyan, Martha S Foiani, Tatiana A Giovannucci, Eric Mcdade, Karen E Duff, Catherine J Mummery, Michael Schöll, Kristin R Wildsmith, Ross W Paterson

2020-Current year OA Pubs

Alzheimer’s Disease (AD) is the most common neurodegenerative disorder and the leading cause of dementia characterised by the accumulation of beta amyloid (Aβ) plaques and neurofibrillary tangles (NFT). Several monoclonal antibodies against amyloid in early AD have shown the utility of reducing brain amyloid in large phase 3 studies, resulting in modest clinical benefit. To further slow, or even halt disease progression, targeting additional pathobiological pathways is likely to be necessary. In this review, we aim to appraise the scientific rationale for targeting tau in AD. The burden of tau pathology is correlated with disease severity and its role in …

Körperliche Und Psychische Aspekte Der Menstruation, Sarah Grossman

COD in Lingua

This text provides an overview of menstruation, its physiological processes, and its physical and psychological effects. It explains the menstrual cycle, including the follicular and luteal phases, hormone regulation, and ovulation. Common symptoms such as cramps, fatigue, mood swings, and breast tenderness are discussed, as well as the importance of understanding hormonal changes. The text also highlights social issues, including unequal access to menstrual products, and emphasizes the significance of education and awareness for managing menstruation and promoting health.

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, …

Predicting The Prognosis Of Primary And Substance-Associated Psychoses Using Urine Drug Screens: A 5-Year Retrospective Longitudinal Study Using Medical Records, Erich J. Aschenbrenner, Andrew C. Voluse

Psychiatry Publications

Substance use is frequently implicated in psychosis. However, the prognostic assumptions guiding differential treatment decisions between substance-induced and primary/affective psychoses have received inconsistent support. Substance-induced psychosis research has often been limited by aggregating substances or using diagnosis as both a grouping variable and an outcome (i.e., diagnostic conversion). The current study examined medical records for 1379 patients for 5 years following their first presentation with psychosis after January 2013 to a regional medical center. Clinically relevant outcomes were compared across groups defined by the substances detected in patients' urine at their initial presentation. Initial drug screen results predicted the initial …

Infectious Causes Of Acute Febrile Illness In Belize, 2020-2022, Adrianna Maliga, Shannon E Ronca, Russell Manzanero, Roberto Melendez, Sarah M Gunter, Allison Lino, Joy Mackey, Andres Espinosa-Bode, Beatriz Lopez, Rafael Chacon-Fuentes, Freedom M Green, Oluwadara Okeremi, Sarah Strobel, Daniel P Rehm, Flor M Muñoz, Loren Cadena, Melissa Diaz-Musa, Francis Morey, Emily Zielinski-Gutierrez, Gerhaldine Morazan, Kristy O Murray

Faculty, Staff and Students Publications

Acute febrile illness (AFI) surveillance networks can play a key role in identifying emerging pathogens and promoting global health security, especially for vulnerable populations in low- and middle-income countries. In January 2020, the Belize AFI Surveillance network was formed, and 5,643 participants were enrolled over the first 3-year period across 11 participating public hospitals. Using real-time polymerase chain reaction testing for vector-borne pathogen detection and BioFire® diagnostic testing for respiratory and gastrointestinal pathogens, the causes of illness were examined in relation to 54 pathogens in these participants. In response to the coronavirus disease 2019 pandemic, surveillance was expanded to detect …

Assessing Social Determinants Of Health Training In Graduate Medical Education: A Narrative Review Using Kirkpatrick’S Model, Surya Namboodiri, Bharathi Gadad, Juan Lopez-Alvarenga, Chelsea Chang

School of Medicine Publications

Social determinants of health (SDOH) training is a critical component of medical education, equipping physicians to address factors such as economic stability, education, and health care access. Despite its importance, the evaluation of SDOH training often focuses on lower-level outcomes, such as learner satisfaction and knowledge assessment, with limited emphasis on behavioral change and patient outcomes. Kirkpatrick’s model offers a validated framework for addressing this gap by categorizing training outcomes into four levels: Reaction, Learning, Behavior, and Results.

By applying Kirkpatrick’s model in combination with Grading of Recommendations Assessment, Development and Evaluation (GRADE) quality assessment and bibliometric network analysis, this …

Mutations Altering The Dna Binding Domains Of The Human Rad52 Protein Exert Distinct Effects On Homologous Recombination Repair In Saccharomyces Cerevisiae, Glenn M. Manthey, Elise W. Wolf, Jason Xu, M. Cristina Negritto, Renee A. Bouley, Ruben C. Petreaca, Adam M. Bailis

College of Health Professions Faculty Papers

RAD52 is a conserved member of the homologous recombination repair (HRR) apparatus from yeast to humans. Mutating conserved amino acids in the internal and external DNA binding domains of the human RAD52 protein (HsRAD52) has discrete effects in vitro. Previous studies have shown that HsRAD52 supports multiple mechanisms of HRR in budding yeast, suggesting the utility of this model system for exploring the correspondence between losses of HsRAD52 function in vitro and their impact in vivo. We report that disrupting the internal and external DNA binding domains of HsRAD52 produced distinct effects on the repair of genomic DNA double-strand breaks …

A Case Of Dislocation And Successful Reduction Of A Right Anterior Shoulder Inside A Space Suit: Considerations For Future Protocols, Samuel Beger, Curtis Lowery, Nicolas Heft, Amran Asadi, Brandon Trapp, Jaime Mateus, Alejandro Garbino

Faculty, Staff and Student Publications

Shoulder dislocations are prevalent on Earth and pose unique challenges in spaceflight and spaceflight training, particularly during extravehicular activities (EVAs). This case report describes a 50-year-old male who experienced an anterior shoulder dislocation while performing an emergency egress exercise in a SpaceX EVA suit. The report describes the medical thought process, the operational constraints, and the reduction techniques employed to achieve a successful shoulder reduction without fully removing or damaging the suit. NASA estimates a high likelihood of shoulder injuries during long-duration lunar missions, emphasizing the importance of suit designs and rescue protocols. Quick and effective medical intervention is crucial, …

Multimodal Education To Improve Metabolic Monitoring Knowledge Among Psychiatric Nurse Practitioners, Tania Alfonso

Walden Dissertations and Doctoral Studies

This Doctor of Nursing Practice (DNP) staff education project was a multimodal educational intervention to improve outpatient psychiatric nurse practitioner (PNP) knowledge of metabolic monitoring guidelines for patients prescribed second-generation antipsychotics (SGAs). The project addressed low adherence to national monitoring standards that contribute to increased cardiometabolic risks associated with SGAs. The project question was: Does staff education regarding metabolic monitoring guidelines improve nursing knowledge as compared pre- to posteducation? The purpose was to enhance PNP knowledge of metabolic monitoring guidelines. Guided by the Johns Hopkins evidence-based practice (JHEBP) model, I conducted a focused literature search and identified 28 peer-reviewed articles …

Staff Education Project To Improve Hypertension Medication Adherence In An Underserved Clinic, Margaret Mboe Etukeni

Walden Dissertations and Doctoral Studies

Hypertension is one of the most common chronic conditions managed in primary care. The identified practice problem for this staff education project was the lack of structured staff training and inconsistent provider knowledge regarding evidence-based strategies to improve medication adherence among patients with hypertension. Poor medication contributes to preventable complications such as stroke, heart failure, and kidney disease. The purpose was to evaluate if an educational intervention could improve provider knowledge related to medication adherence strategies in an underserved clinical setting. The practice question guiding the project was: In clinical staff working in an underserved clinic, does a staff education …

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 …

Proned But Not Pressured: Saving Skin One Turn At A Time, Sophie Despres, Brandon Evans, Hannah Keetch, Destiny Lane

2025

No abstract provided.

Multiparent Recombinant Inbred Lines Crossed To A Tester Provide Novel Insights Into Sources Of Cis And Trans Regulation Of Gene Expression, Fabio Marroni, Alison M Morse, Adalena V Nanni, Nadja Nolte, Patricka Williams-Simon, Luis G León-Novelo, Rita M Graze, Paul Schmidt, Elizabeth King, Lauren M Mcintyre

Faculty, Staff and Student Publications

To understand the relative importance of cis and trans effects on regulation, we crossed multi-parent recombinant-inbred lines (RILs) to a common tester and measured allele-specific gene expression in the offspring. Testing the difference of allelic imbalance between two RIL × Tester crosses is a test of cis or trans, depending on the RIL alleles compared. The study design also enables to separation of two sources of trans variation, genetic and environmental, detected via interactions with cis effects. We demonstrate the effectiveness of this approach in a long-read RNA-seq experiment in female abdominal tissue at two time points in Drosophila melanogaster. …

Staff Education On Standardized Appointment Reminder & Follow-Up Protocol, Sambila V. Zangre Congo

Walden Dissertations and Doctoral Studies

Inconsistent staff performance in making appointment reminders and follow-up calls contributed to workflow variability and reduced patient engagement in outpatient primary care settings. This DNP Quality Improvement Project intended to enhance staff knowledge, confidence, and consistency in implementing standardized reminder and follow-up call protocols using an evidence-based educational intervention. A quantitative pre/posttest design was used to evaluate changes in staff competency, supported by descriptive and comparative analyses of test scores, percentage changes, and qualitative feedback. Seven clinic staff members attended the PowerPoint education session, and pretest and posttest data were used to address a practice-focused question about standardized communication workflows. …

Staff Education On Implementing Exercise For The Management Of Depression In Adults In A Comprehensive Mental Health Facility, Afolasade Jarrett

Walden Dissertations and Doctoral Studies

In a comprehensive mental health facility, patients diagnosed with major depression continue to experience depressive symptoms despite treatment. Despite using standard treatment with antidepressants and psychotherapy, facility data showed that 40% of these patients are still experiencing depression symptoms that negatively impact their overall functioning and quality of life. There is evidence supporting exercise as an effective strategy for depression treatment. Therefore, a staff education project was proposed to educate staff about exercise for depression management in adults. A thorough literature search in four databases yielded 12 articles with high quality evidence supporting educating staff to use exercise for depression …

Early Postnatal Polymerase Chain Reaction Testing In The Identification Of Perinatal Transmission Of Hepatitis C Virus, Mona Prasad, Grecio J Sandoval, George R Saade, Brenna L Hughes, Rebecca G Clifton, Uma M Reddy, Anna Bartholomew, Ashley Salazar, Edward K Chien, Alan T N Tita, John M Thorp, Torri D Metz, Ronald J Wapner, Vishakha Sabharwal, Hyagriv N Simhan, Geeta K Swamy, Kent D Heyborne, Baha M Sibai, William A Grobman, Yasser Y El-Sayed, Brian M Casey, Samuel Parry, George A Macones

Faculty, Staff and Student Publications

In this study, a single hepatitis C virus (HCV) RNA at 2-6 months was sensitive and specific (86.7% and 95% confidence interval [CI], 62.1%-96.3% and 100% and 95% CI, 98.8%-100%, respectively) in identifying perinatal transmission of HCV. No cases of perinatal infection requiring treatment were missed.

Gain Of Function Notch4 Variants Disrupt Angiogenesis In Systemic Sclerosis, Urvashi Kaundal, Pei-Suen Tsou, Mousumi Sahu, Mengqi Huang, Steven E Boyden, Curtis M Woodford, Daniel Shriner, Emilee Stenson, Sarah Ayla Safran, Yuechen Zhou, Taylor A Talley, Kaavya Gudapati, Xuetao Zhang, Yosuke Kunishita, Janet Wang, Ami A Shah, Maureen D Mayes, Ayo P Doumatey, Amy R Bentley, Robyn Domsic, Thomas A Medsger, Paula S Ramos, Richard M Silver, Virginia Steen, John Varga, Vivien Hsu, Lesley Ann Saketkoo, Elena Schiopu, Jessica K Gordon, Lindsey A Criswell, Heather Gladue, Chris Derk, Elana J Bernstein, S Louis Bridges, Victoria Shanmugam, Lorinda Chung, Suzanne Kafaja, Reem Jan, Marcin Trojanowski, Avram Goldberg, Benjamin D Korman, James Mullikin, James W Thomas, Stefania Dell'orso, Davide Randazzo, Adebowale Adeyemo, Elaine F Remmers, Pamela L Schwartzberg, Ivona Aksentijevich, Charles Rotimi, Fredrick M Wigley, Rong A Wang, Francesco Boin, Dinesh Khanna, Robert Lafyatis, Daniel L Kastner, Pravitt Gourh

Faculty, Staff and Student Publications

Objectives: Vasculopathy and fibrosis are central to the pathogenesis of systemic sclerosis (SSc) and their genetic underpinnings are largely unknown. Here, we sought to examine the aetiology of severe vascular phenotypes and poorer outcomes in African American (AA) patients with SSc.

Methods: The study focuses on AA patients with SSc who have more severe vascular phenotypes and poorer outcomes and combines genetics, single-cell RNA sequencing, functional assays, and a mouse model to explore the role of NOTCH4 in SSc vasculopathy and the potential for NOTCH4-directed therapies.

Results: Gene-based testing identified NOTCH4 association at an exome-wide significance with SSc (P = …

Heterogeneity In The Association Of Genetic Risk For Ra And Resultant Ra Phenotypes, Thomas R Riley, Iris Lee, Et Al.

2020-Current year OA Pubs

OBJECTIVES: The impact of the genetic risk for RA on resultant disease phenotype in RA is incompletely understood. Using individual genetic variants associated with RA and a polygenic score (PGS), we hypothesized that those with higher genetic risk for RA would demonstrate a more severe disease course.

METHODS: We genotyped participants from the Veterans Affairs RA registry (VARA), a prospective cohort of RA. We evaluated associations between PTPN22 R620W genotype, HLA-DRB1 shared epitope (SE; 0, 1, or 2 copies of a high-risk HLA allele), and a non-HLA PGS with RA disease activity scores and disease characteristics using linear and logistic …

Protocol For Personalised Prediction Of Persistent Postsurgical Pain, Katherine J Holzer, Harutyun Alaverdyan, Ziqi Xu, Madelyn R Frumkin, Karen A Frey, Stephen H Gregory, Thomas L Rodebaugh, Chenyang Lu, Christopher R King, Denise Head, Thomas Kannampallil, Simon Haroutounian

2020-Current year OA Pubs

INTRODUCTION: Persistent postsurgical pain (PPSP) affects up to 15% of patients after major surgery, impairing physical function, quality of life and increasing risk for long-term opioid use. Current PPSP prediction models rely on static or retrospective data and fail to incorporate dynamic perioperative factors. The Personalised Prediction of Persistent Postsurgical Pain (P5) study aims to develop individualised, multimodal prediction models by integrating preoperative behavioural, psychophysical and neurocognitive assessments and high-frequency symptom monitoring.

METHODS AND ANALYSIS: P5 is a prospective, single-centre cohort study enrolling 2500 adults aged 18-75 undergoing major surgery at a tertiary academic hospital. Participants complete baseline surveys, cognitive …

Staff Education On Vital Sign Assessment And Electronic Health Record Documentation For Acute And Critical Care Nurses And Patient Care Technicians, Natalie Brock

Walden Dissertations and Doctoral Studies

A staff educational quality improvement initiative aimed at enhancing the knowledge and accuracy of acute care nurses and patient care technicians (PCTs) in vital sign documentation was the focus of the doctoral project. Gaps in vital sign obtainment and electronic health record (EHR) documentation were identified through organizational serious safety event reviews, highlighting risks to patient safety and clinical decision-making. The project addressed the question of whether, in the inpatient hospital setting, a staff educational training program for acute and critical care nurses improves their knowledge of accurate vital sign documentation in the EHR. I analyzed pre- and posttest assessments …

Education To Nursing Staff On Evidence-Based Lifestyle Interventions For Hypertension, Meagan Deese

Walden Dissertations and Doctoral Studies

This Doctor of Nursing Practice (DNP) project was a staff education project that addressed a practice gap in a primary care setting related to limited nursing knowledge of evidence-based lifestyle interventions for hypertension management. Hypertension is a prevalent chronic condition and a major contributor to cardiovascular morbidity and mortality. Although clinical guidelines recommend lifestyle modification as first-line management, nurses may receive limited formal training in nonpharmacologic interventions. The practice-focused question was, in a primary care setting, does a nursing education program on evidence-based lifestyle interventions for hypertension improve nursing knowledge as measured pre- to post education? The purpose of the …

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 …

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 …

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 …