Digital Commons Network^™

Medulloblastoma Stem Cell Programs: Molecular Roadmaps Of Disease Progression, Jamie Zagozewski, Parthiv Haldipur, Kathleen J Millen, Tamra E Werbowetski-Ogilvie

Faculty, Staff and Students Publications

Over the last decade, an unprecedented number of sequencing studies have characterized the molecular landscape of pediatric brain cancers, including the highly heterogeneous tumor medulloblastoma (MB). Extensive MB profiling has enabled a much deeper understanding of the primitive neurodevelopmental programs that are hijacked during tumor progression. However, we have yet to successfully target and fully eradicate the putative stem and early progenitor cells that drive MB tumorigenesis. This goal will require better human models that faithfully recapitulate oncogenic events, a deeper understanding of the mechanisms governing cell fate decisions in the primary and metastatic compartments, and comprehensive validation studies of …

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 …

A Chemogenetic Approach For Temporal And Cell-Specific Activation Of Endogenous Gpcrs In Vivo, Gwendolyn Shingles, Qianqian Pang, Jian Weng, Ryan Singer, Waleed Babar, Jiaqi Shen, Luis Vazquez-Rivera, Yao Chen, Peng Li, Wenjing Wang

2020-Current year OA Pubs

Cell-specific regulation of endogenous G protein-coupled receptors (GPCRs) is crucial for understanding their roles in physiological processes. We present chemogenetic tools using shield-1-dependent irreversible protein switches to regulate peptide agonist activity. To demonstrate this platform, we engineered chemogenetically regulated pituitary adenylate cyclase activating polypeptide (cPACAP), which exhibited >15-fold chemical-dependent regulation of endogenous receptor activity. In vivo application of cPACAP allowed neuronal activation via the endogenous receptor for PACAP, engaging neural circuits that control respiratory and feeding behaviors. By integrating cPACAP with transgenic mice, we selectively activated endogenous PACAP receptor signaling in hypocretin-expressing neurons of the lateral hypothalamic area (LHA), revealing …

Defining Rna Oligonucleotides That Reverse Deleterious Phase Transitions Of Rna-Binding Proteins With Prion-Like Domains., Lin Guo, Jacob Mann, Jocelyn Mauna, Katie Copley, Hejia Wang, Jack Rubien, Cristian Bergmann, Jenny Carey, Jessica Merjane, Marilyn Ngo, Jiazhen Xu, Hana Odeh, Jiabei Lin, Bo Lim Lee, Laura Ganser, Emma Robinson, Kevin Kim, Anastasia Murthy, Tapas Paul, Bede Portz, Amanda Gleixner, Zamia Diaz, Ashleigh Smirnov, George Padilla, Ellen Lavorando, Carolann Espy, Yulei Shang, Eric Huang, Alessandra Chesi, Nicolas Fawzi, Sua Myong, Christopher Donnelly, James Shorter

Department of Biochemistry and Molecular Biology Faculty Papers

RNA-binding proteins (RBPs) with prion-like domains (PrLDs), such as FUS and TDP-43, condense into functional liquids, which can transform into pathological fibrils that underpin fatal neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD). Here, we define short RNAs that prevent FUS fibrillization by promoting liquid phases and distinct short RNAs that prevent and reverse FUS condensation and fibrillization. These activities require interactions with multiple RNA-binding domains of FUS and are encoded by RNA sequence, length, and structure. We define a short RNA that dissolves cytoplasmic FUS aggregates, restores nuclear FUS, and mitigates FUS toxicity in optogenetic models and ALS …

The Virtual Kitchen Challenge-Version 2: Validation Of A Digital Assessment Of Everyday Function In Older Adults, Marina Kaplan, Moira Mckniff, Stephanie M. Simone, Molly B. Tassoni, Katherine Hackett, Sophia Holmqvist, Rachel E. Mis, Kimberly Halberstadter, Riya Chaturvedi, Melissa Rosahl, Giuliana Vallecorsa, Mijail Serruya, Deborah A. G. Drabick, Takehiko Yamaguchi, Tania Giovannetti

Department of Medicine Faculty Papers

BACKGROUND: Conventional methods of functional assessment include subjective self- or informant report, which may be biased by personal characteristics, cognitive abilities, and lack of standardization (eg, influence of idiosyncratic task demands). Traditional performance-based assessments offer some advantages over self- or informant reports but are time-consuming to administer and score.

OBJECTIVE: This study aims to evaluate the validity and reliability of the Virtual Kitchen Challenge-Version 2 (VKC-2), an objective, standardized, and highly efficient alternative to current functional assessments for older adults across the spectrum of cognitive aging, from preclinical to mild dementia.

METHODS: A total of 236 community-dwelling, diverse older adults …

Loss Of Kdm6a-Mediated Genomic Instability And Metabolic Reprogramming Regulates Response To Therapeutic Perturbations In Bladder Cancer, Pratishtha Singh, Ranit D'Rozario, Bidisha Chakraborty, Swadhin Meher, Deblina Raychaudhuri, Aminah J Tannir, Yang Li, Anurag Majumdar, Jessalyn Hawkins, Yun Xiong, Philip Lorenzi, Padmanee Sharma, Kadir Akdemir, Patrick Pilie, Abhinav K Jain, Byron Hing Lung Lee, Sangeeta Goswami

Faculty, Staff and Student Publications

Mutations in epigenetic regulators are common in bladder cancer, yet their impact on therapeutic responses remains unclear. Here, we identify that loss-of-function mutations in KDM6A, a histone demethylase altered in about 26% of advanced bladder cancers, are associated with poor survival after cisplatin chemotherapy, whereas they correlate with improved outcomes with anti-PD-1 therapy. Using CRISPR-Cas9-engineered murine and human bladder cancer models, we show that KDM6A deficiency increases formation of extrachromosomal circular DNA carrying chemoresistance loci, promoting cisplatin resistance. In parallel, KDM6A loss impairs DNA repair and rewires tumor metabolism, reducing glycolysis and lactate output. This metabolic shift diminishes histone lactylation …

Pathways, Outputs And Impact Of Nih-Supported Bioinformatics And Genomics Graduate Trainees In Africa, Daudi Jjingo, Andrew Walakira, Suhaila Hashim, Cisse Cheickna, Ronald Galiwango, Caleb Kibet, Florence N Kivunike, Gerald Mboowa, Fredrick Elishama Kakembo, Babajide Ayodele, Jean-Baka Domelevo Entfellner, Santie De Villiers, Karen Wambui, Segun Fatumo, Tinashe Chikowore, John Mukisa, Alfred Ssekagiri, Nicholas Bbosa, Julius Mulindwa, Samuel Kyobe, Mike Nsubuga, Grace Kebirungi, Eric Katagirya, Savannah Mwesigwa, Ibra Lujumba, Rogers Kamulegeya, Samuel Kirimunda, Stephen Kanyerezi, Shahiid Kiyaga, Ivan Sserwadda, Davis Kiberu, Bernard S Bagaya, Julius Okwir, Patricia Nabisubi, Grace Nabakooza, Mugume Twinamatsiko Atwine, Ricard Sserunjogi, Rolanda Julius, Mariam Quiñones, Meghan Mccarthy, Phillip Cruz, Karlynn Noble, Christopher J Whalen, Darrell Hurt, Maria Y Giovanni, Michael Tartakovsky, Deogratius Ssemwanga, John M Kitayimbwa, Steven J Reynolds, Christopher C Whalen, Andrew Kambugu, Neil A Hanchard, Li Jian, Peter Amoako-Yirenkyi, Graeme Mardon, I King Jordan, Samson Pandam Salifu, Mamadou Wele, Ezekiel Adebiyi, Jeffrey G Shaffer, Seydou Doumbia, David Patrick Kateete, Michelle Skelton, Nicola Mulder, Jonathan K Kayondo, Daniel Masiga, H3africa Consortium

Faculty, Staff and Students Publications

Global biomedical and health research is increasingly relying on genomic and computational approaches, largely driven by the increasing volumes of nucleic acid sequencing. Concurrently, epidemiological studies and clinical records are generating enormous amounts of data amenable to disease modeling, machine learning, and artificial intelligence techniques. Bioinformatics and data science expertise is therefore essential for improved population health. Accordingly, in 2012, the US National Institutes of Health (NIH) in partnership with the Wellcome Trust, and with support from the African Society for Human Genetics, initiated the H3Africa (Human Heredity and Health in Africa) consortium. One of its key goals was to …

Postoperative Lymph Is A Proximal Source Of Ctdna For Detection Of Recurrence In Hpv-Independent Head And Neck Cancer, Seka Lazare, Noah Earland, Peter Harris, Ricardo Ramirez, Benjamin Wahle, Sid Puram, Doug Adkins, Wade Thorstad, Rebecca Chernock, Aadel A Chaudhuri, Et Al.

2020-Current year OA Pubs

PURPOSE: Relapse is a major cause of failure in human papillomavirus-independent head and neck squamous cell carcinoma. Clinicopathologic criteria for adjuvant treatment remain imprecise and have not changed for decades. We investigated whether ctDNA in lymphatic exudate collected via surgical drains ("lymph") 24 hours after surgery identified molecular residual disease (MRD) and compared its performance with time-matched plasma.

EXPERIMENTAL DESIGN: Using an ultra-sensitive tumor-informed sequencing approach, tumor variants were called in lymph and plasma to classify patients as ctDNA positive or ctDNA negative, trained in an initial cohort of 36 patients, and replicated in an independent cohort of 37 patients. …

Modality-Agnostic, Patient-Specific Digital Twins Modeling Temporally Varying Digestive Motion, Jorge Tapias Gomez, Nishant Nadkarni, Lando S Bosma, Jue Jiang, Ergys D Subashi, William P Segars, James M Balter, Mert R Sabuncu, Neelam Tyagi, Harini Veeraraghavan

Faculty, Staff and Student Publications

No abstract provided.

A Phase 1, First-In-Human, Dose Escalation Study Of Jnj-80038114, A Psmaxcd3 Bispecific Antibody, In Participants With Metastatic Castration-Resistant Prostate Cancer, Andrew Hudson, Anuradha Jayaram, Benjamin Garmezy, Nicholas Zorko, Kevin Zarrabi, Ligi Mathews, Brent Rupnow, Mengjie Li, Debopriya Ghosh, Karen Urtishak, Peter Francis, Sherry Wang, Edward Attiyeh, Johann De Bono

Department of Medical Oncology Faculty Papers

PURPOSE: Prostate-specific membrane antigen (PSMA) has been identified as a therapeutic target for metastatic castration-resistant prostate cancer (mCRPC). The recent success of radioligands targeting PSMA spurred development of new PSMA-targeting agents including immunotherapy. JNJ-80038114 is a bispecific antibody that binds PSMA on tumor cells and CD3 on T cells to induce anti-tumor activity.

METHODS: This was a phase 1, open-label, multicenter study of JNJ-80038114 in participants with mCRPC and ≥ 1 prior systemic therapy. JNJ-80038114 was administered subcutaneously every 3 weeks (Q3W), starting at 0.1 mg. The primary endpoint was safety. Secondary endpoints included pharmacokinetics (PK), immunogenicity, and prostate-specific antigen …

Predicting Sepsis In Heart Failure Patients Supported By Left Ventricular Assist Devices: The Role Of Ve-Cadherin And Adam10, Shiyi Li, Iván Murrieta-Álvarez, Ismael Garcia, Katherine V Nordick, Rishav Bhattacharya, Shreyo Ghosh, Ronald A Shaju, Adel M Hassan, Carl P Walther, Camila Hochman-Mendez, Alexis E Shafii, Kenneth K Liao, Nandan K Mondal

Faculty, Staff and Students Publications

Vascular endothelial cadherin (VE-Cadherin) is a major endothelial adhesion molecule and can be cleaved explicitly by metalloproteinase domain-containing protein 10 (ADAM10). Vascular hyperpermeability may contribute to a greater susceptibility to sepsis in left ventricular assist device (LVAD) support patients. We aim to evaluate the efficacy of VE-Cadherin and ADAM10 for predicting sepsis in LVAD patients. We prospectively recruited 50 patients with advanced heart failure receiving LVAD therapy. Baseline and weekly postoperative blood samples (weeks 1-4) were collected, and plasma VE-cadherin and ADAM10 levels were measured. Sepsis occurred in 9 of 50 patients (18.0%). Across all sampling points, plasma VE-cadherin and …

Trends In The Implementation Of The Cyberchondria Severity Scale: Bibliometric Analysis, Adam C Powell, Cayetana Calderon-Smith

College of Population Health Faculty Papers

BACKGROUND: Cyberchondria, a combination of the words "cyber" and "hypochondriasis," is a condition that is receiving increasing attention from clinicians and researchers globally. Researchers are currently using multiple instruments to quantify it. Furthermore, the instruments have been translated into multiple languages.

OBJECTIVE: This study aimed to examine the extent to which researchers are measuring cyberchondria using the 33-item Cyberchondria Severity Scale (CSS) and its 12-item abbreviated version, the CSS-12. It also examined the relative use of cyberchondria instruments in different languages.

METHODS: PubMed and PsycInfo were searched for articles published between May 1, 2019, and December 31, 2024, featuring the …

Stakeholder Perspectives On Humanistic Implementation Of Computer Perception In Health Care: Qualitative Study, Kristin M Kostick-Quenet, Meghan E Hurley, Syed Ayaz, John D Herrington, Casey J Zampella, Julia Parish-Morris, Birkan Tunç, Gabriel Lázaro-Muñoz, Jennifer Blumenthal-Barby, Eric A Storch

Center for Medical Ethics and Health Policy Staff Publications

Background: Computer perception (CP) technologies-including digital phenotyping, affective computing, and related passive sensing approaches-offer unprecedented opportunities to personalize health care, especially mental health care, yet they also provoke concerns about privacy, bias, and the erosion of empathic, relationship-centered practice. At present, it remains elusive what stakeholders who design, deploy, and experience these tools in real-world settings perceive as the risks and benefits of CP technologies.

Objective: This study aims to explore key stakeholder perspectives on the potential benefits, risks, and concerns associated with integrating CP technologies into patient care. A better understanding of these concerns is crucial for responding to …

Celltra: Aligning Cell Names With Gene Expression Via A Pathway-Informed Transformer, Zhao Li, Zaiyi Zheng, Rongbin Li, Wenbo Chen, Yuntao Yang, Meer A Ali, Jundong Li, W Jim Zheng

Faculty, Staff and Student Publications

Motivation: Single-cell RNA sequencing (scRNA-Seq) technology enables detailed exploration of gene expression at the individual cell level, crucial for annotating cell types and understanding cellular diversity. Traditional methods for cell type annotation often rely on marker genes and manual labeling, posing challenges due to low data quality and incomplete reference datasets.

Results: We developed CeLLTra, a novel contrastive learning framework that leverages a Transformer-based model integrating biological pathway information to group genes into super tokens, effectively capturing comprehensive gene expression from scRNA-Seq data. By combining this pathway-informed Transformer with a pretrained domain-specific language model, CeLLTra accurately aligns cell-type annotations with …

Cholesterol Efflux Protein, Abca1, Supports Anticancer Functions Of Myeloid Immune Cells, Shruti V Bendre, Yu Wang, Basel Hajyousif, Rajendra K C, Shounak G Bhogale, Dhanya Pradeep, Natalia Krawczynska, Claire P Schane, Erin Weisser, Avni Singh, Simon Han, Hannah Kim, Lara Kockaya, Anasuya Das Gupta, Adam T Nelczyk, Hashni Epa Vidana Gamage, Yifan Fei, Desirée Rodríguez-Casiano, Xingyu Guo, Haoyun Li, Ryan J Deaton, Fei Mo, Maria Sverdlov, Peter H Gann, Saurabh Sinha, Sahil Sahni, Kun Wang, Kevin Van Bortle, Emad Tajkorshid, Wendy A Woodward, Wonhwa Cho, Erik R Nelson

Faculty, Staff and Student Publications

Breast and other solid tumors respond poorly to immune therapy. Myeloid cells (MCs) such as macrophages contribute to resistance. Established clinical evidence links cholesterol to cancer outcomes, with MC function being regulated by cholesterol metabolism. We screened MC-expressed regulators of cholesterol homeostasis linked to survival and identified the cholesterol efflux protein ABCA1. ABCA1 activity increases anticancer functions of macrophages: enhancing tumor infiltration, decreasing angiogenic potential, reducing efferocytosis, and improving support of CD8+ T cell activity. Mechanistically, different AKT isoforms are involved, through both PI3K-dependent and PI3K-independent mechanisms. Highlighting the clinical relevance of our findings are correlations between ABCA1 in macrophages …

Nf2 Loss Malignantly Transforms Human Pancreatic Acinar Cells And Enhances Cell Fitness Under Environmental Stress, Yi Xu, Michael H Nipper, Angel A Dominguez, Chenhui He, Francis E Sharkey, Sajid Khan, Han Xu, Daohong Zhou, Lei Zheng, Yu Luan, Jun Liu, Pei Wang

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) occurs as a complex, multifaceted event driven by the interplay of tumor-permissive genetic mutations, the nature of the cellular origin, and microenvironmental stress. In this study, using primary human pancreatic acinar 3D organoids, we performed a CRISPR-KO screen targeting 199 potential tumor suppressors curated from clinical PDAC samples. Our data revealed significant enrichment of a list of candidate genes, with neurofibromatosis type 2 associated gene (NF2) emerging as the top target. Functional validation confirmed that loss of NF2 promoted the transition of PDAC to an invasive state, potentially through extracellular matrix modulation. NF2 inactivation …

Crossing The Theory Threshold: The Pedagogical Potential Of Generative Artificial Intelligence In Educational Research, Amanda Burbage, Jennifer L. Styron

EVMS School of Health Professions Faculty Publications

Purpose

This paper presents findings from an educational research graduate course in which generative artificial intelligence (AI) was incorporated to strengthen learners' understanding of threshold concepts related to theoretical frameworks. Medical and health professionals often struggle with the transition from a clinical role into the educational research role.

Methods

The study posits that the use of generative AI will help learners understand and apply theoretical frameworks beyond a superficial level, furthering their understanding, constructing new knowledge, and strengthening their ability to develop sound educational research studies. Journal and AI transcripts were analyzed for 37 participants.

Results

Open-ended codes were grouped …

Rewiring The Immune Response In Lung Cancer: Current Progress In Bispecific Antibodies, Car-T Therapy, And The Rise Of In Vivo Car-T Platforms, Lei He, Yi Sun, Bowen Ma, Guojun Lang, Jianguo Wen, George R Blumenschein, Hong Ma

Faculty, Staff and Student Publications

Lung cancer remains the leading cause of cancer mortality worldwide and continues to impose a major clinical burden, particularly in advanced non-small cell lung cancer (NSCLC) and small-cell lung cancer (SCLC). Although targeted therapies, antiangiogenic agents, immune checkpoint inhibitors, and antibody-drug conjugates have improved outcomes in selected patients, durable responses remain limited by primary and acquired resistance. Here, we comprehensively review recent progress in immunologically oriented therapeutic strategies for lung cancer, focusing on bispecific antibodies, chimeric antigen receptor (CAR) T-cell therapy, and emerging in vivo CAR-engineering modalities. We further elaborate on the clinical rationale, latest translational and early clinical evidence, …

A Hybrid Vit-L/32-Maxvit-L Architecture With Adaptive Gated Fusion For Multiclass Gastrointestinal Disease Detection And Multi-Method Post-Hoc Explainability, Shahid Mohammad Ganie, Pijush Kanti Dutta Pramanik, Zhongming Zhao

Faculty, Staff and Student Publications

Introduction: Accurate detection of gastrointestinal diseases from endoscopic images remains challenging due to substantial inter-class similarity, intra-class variability, and heterogeneous lesion presentation. While convolutional neural networks (CNNs) effectively capture fine mucosal textures, their limited receptive field restricts global contextual reasoning. Conversely, transformer architectures model long-range dependencies but may underrepresent localized structural detail.

Methods: This study proposes a dual-branch hybrid transformer framework that integrates global token-level reasoning from ViT-L/32 with hierarchical spatial modeling from MaxViT-L. An adaptive gated fusion mechanism is introduced to dynamically regulate the relative contribution of local and global representations on a per-sample basis, enabling content-aware cross-scale integration. …

Overcoming Egfr-Mediated Dendritic Cell Dysfunction To Enhance Anti-Tumor Immunity In Egfr-Mutant Nsclc By Precisely Targeting Cd73 With Ph-Responsive Nanocarriers., Xiaoling Shang, Xudong Geng, Zixu Wang, Shumin Yuan, Shanshan Ding, Ni Liu, Xinchun Ma, Xuan Sun, Huimin Wang, Ying Sun, Xun Qu, Guangwen Ren, Yong Qiang Li, Xiuwen Wang, Yanguo Liu

Faculty Research 2026

EGFR mutations remain a major challenge in immunotherapy for non-small cell lung cancer (NSCLC), with poor responses to immune checkpoint inhibitors driven by mechanisms associated with EGFR mutation-mediated tumor microenvironment (TME) modulation. This study reveals that EGFR mutations prominently impaired dendritic cell (DC) maturation, disrupting their capacity to effectively prime CD8+ T cells and thereby compromising anti-tumor immune responses. By application of clinical specimen analyses, multi-omics approaches, and in vivo mouse models, this work demonstrates that EGFR mutations elicited adenosine production through the ERK/c-Jun signaling axis in tumor cells, establishing an immunosuppressive TME that impeded maturation and antigen presentation of …

Cxcr6+ Natural Killer Cell Immunotherapy Preserves Cd4+ T Helper Cells In Humanized Mice, Naushad Khan, Kayla Frank, Silke Paust

Faculty Research 2026

Human immunodeficiency virus (HIV) persists despite antiretroviral therapy because long-lived viral reservoirs are not eliminated, and ongoing or rebound infection contributes to progressive loss of CD4⁺ T helper cells. Natural killer (NK) cells can acquire adaptive, antigen-experienced functions, including recall responses to HIV envelope protein, suggesting that defined NK-cell subsets may be therapeutically useful against HIV. Because HIV-responsive adaptive NK-cell activity is enriched among CXC chemokine receptor 6-positive (CXCR6⁺) NK cells, we tested whether CXCR6⁺ NK cells provide enhanced antiviral activity and CD4⁺ T-cell protection compared with CXCR6⁻ NK cells. In co-cultures with HIV-infected …

Wearable Sensor-Based Phase Segmentation Analysis Of Front Crawl Swimming: A Scoping Review, Jonathan Simoes, Samuel Aylward, Daniel Hamze, Daniel James Goble, Daniel M. Russell, Joshua Haworth

Exercise Science Faculty Publications

Front crawl swimming stroke phase segmentation has historically relied on video analysis, but the development of wearable sensor technology has created new opportunities for automated phase segmentation. This scoping review mapped the available evidence on wearable sensor-based stroke phase segmentation methods in front crawl swimming, following PRISMA-ScR guidelines. A systematic search of SPORTDiscus, Web of Science, and IEEE Xplore conducted from January to June 2026, identified 15 eligible peer-reviewed studies published between 2000 and 2024. The review revealed an emerging field of research that has converged methodologically around inertial measurement units (IMUs) and the Chollet phase segmentation framework while remaining …

Peculiarities Of Phosphatidylserine Externalization By Nano- And Microsecond Electric Pulses, Mantas Silkunas, Alayna Enos, Iurii Semenov, Giedre Silkuniene, Eleni Zivla, Olga N. Pakhomova, Andrei G. Pakhomov

Bioelectrics Publications

Phosphatidylserine (PS) externalization is a hallmark of apoptosis but can also be triggered within seconds by pulsed electric fields (PEFs). Whether PS reaches the outer leaflet by lateral migration through electropores or indirectly through Ca²⁺-dependent signaling and scramblase activation remains debated. We used total internal reflection fluorescence (TIRF) microscopy with Annexin V-Alexa Fluor 568 and/or bovine lactadherin-FITC to resolve PS externalization in HEK293 cells placed on an indium tin oxide (ITO) transparent electrode. PEF exposures produced discrete PS-positive puncta ("freckles") within ~ 10 s after a 20-µs pulse (1.2-2.5 kV/cm) or with a ~ 1-min delay after a …

Clinical Test Cases For Commissioning, Qa, And Benchmarking Of Model-Based Dose Calculation Algorithms In 1⁹2ir Hdr Gynecologic Tandem And Ring Brachytherapy, Vasiliki Peppa, Maude Robitaille, Fatemeh Akbari, Shirin Enger, Rowan Thomson, Firas Mourtada, Gabriel Fonseca

Department of Radiation Oncology Faculty Papers

PURPOSE: To develop clinically relevant test cases for commissioning Model-Based Dose Calculation Algorithms (MBDCAs) for ¹⁹²Ir High Dose Rate (HDR) gynecologic brachytherapy following the workflow proposed by the TG-186 report and the WGDCAB report 372.

ACQUISITION AND VALIDATION METHODS: Two cervical cancer intracavitary HDR brachytherapy models were developed based on a real patient, using either uniformly structured regions or realistic segmentation. The patient's computed tomography (CT) images were processed, converted to a series of digital imaging and communications in medicine (DICOM) CT images, and imported into two treatment planning systems (TPSs), the Oncentra Brachy and BrachyVision. The original segmentation …

Synergistic Sensitization Of Pancreatic Cancer Cells By Nanosecond Pulsed Electric Fields And Cold Atmospheric Plasma Via Amplifying Ros And Apoptotic Signaling, Zobia Minhas, Edwin A. Oshin, Lifang Yang, Chunqi Jiang, Siqi Guo

Bioelectrics Publications

Pancreatic cancer remains a highly lethal malignancy, with standard therapies offering limited benefits in advanced stages; thus, novel strategies that exploit specific cancer cell vulnerabilities are urgently needed. Building on our previous findings that nanosecond pulsed electric fields (nsPEF) combined with cold atmospheric plasma (CAP) produce enhanced cytotoxicity, this study investigates the molecular mechanisms underlying this synergy. Pan02 pancreatic cancer cells were subjected to nsPEF, CAP, or a combination of both. We assessed cell viability, reactive oxygen species (ROS) production, and mitochondrial integrity using metabolic assays, flow cytometry, and fluorescence microscopy. Apoptotic markers were evaluated via Western blotting and caspase …

Nanofibrous Materials And Nanoparticles For Combating Antimicrobial Resistance: Synthesis, Integration, And Translational Perspectives, Rewati Raman Ujjwal, Ashish Dilip Sutar, Rahul Shukla, Gymama Slaughter

Center for Bioelectronics Publications

Antimicrobial resistance (AMR) is a major global health challenge driven by mechanisms such as biofilm formation, efflux pumps, and genetic mutations. Nanoparticulate and fibrous materials have emerged as promising strategies to overcome these limitations through multimodal antimicrobial action and controlled drug delivery. This review highlights recent advances in electrospun nanofibrous systems, including natural and synthetic polymer-based scaffolds, stimuli-responsive nanofibers, and functionalized patches. Nanoparticle-loaded nanofiber systems demonstrate enhanced performance, including bacterial eradication, sustained drug release, and significant biofilm disruption. Multifunctional systems combining antimicrobial, antioxidant, and immunomodulatory properties further show synergism. Emerging innovations, such as piezoelectric and smart sensing systems, enable self-powered …

Epithelial-Mesenchymal Transition And Stress Adaptations Underlie Yttrium-90 Resistance In Liver Cancer Cell Lines, Alexander Zheleznyak, Dhanusha Duraiyan, Prasanth Thunuguntla, Jessica Camacho, Shuang Wu, Jingxia Liu, Jason D Weber, Daniel L J Thorek, Benjamin S Strnad, Ryan C Fields, Matthew A Ciorba, Christine Yoon, Valerie Blanc, Nicholas Davidson, Jessica Silva-Fisher, Christopher D Malone

2020-Current year OA Pubs

UNLABELLED: Molecular signatures predict prognosis in hepatocellular carcinoma, but their relevance to transarterial radioembolization (TARE) with yttrium-90 (90Y) is unknown. We aimed to identify baseline and treatment-induced pathways associated with response and nominate biomarkers. Ten transcriptomically diverse human liver cancer cell lines were exposed to escalating activities of glass 90Y microspheres for 10 days. Normalized AUC values quantified sensitivity. Whole-transcriptome RNA sequencing at baseline and after treatment was analyzed with elastic net regression and gene set enrichment. Findings were corroborated by qRT-qPCR and exploratory analysis of pretreatment tumor samples from patients undergoing TARE. Liver cancer cell line responses to 90Y …

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

Center for Medical Ethics and Health Policy Staff Publications

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

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

Center for Medical Ethics and Health Policy Staff Publications

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

Eeg And Imu Gait Signal Processing: A Comparative Assessment Of The "Reza" Exponential Filter And Classic Filters, Reza Pousti, Daniel M. Russell, Derek C. Monroe, Christopher K. Rhea

Rehabilitation Sciences Faculty Publications

Noise degrades both EEG and gait signals, and classical IIR filters (Butterworth, Chebyshev, elliptic) involve trade-offs between passband flatness, ripple, and roll-off. This study compared a novel exponential "Reza" filter with these designs for neural and locomotor data. We analyzed an open-source mobile brain-body imaging dataset with EEG and gait data from 49 healthy adults (EEG: 256-channel, 512 Hz; IMUs: six APDM Opals, 128 Hz). EEG channels were grand-averaged and band-pass filtered at 0.5-50 Hz, while IMU axes were averaged and band-pass filtered at 0.5-5 Hz. The outcomes were signal-to-noise ratio SNR (dB) and band-integrated Welch PSD (EEG:0.5-50 Hz; IMU:0.5-5 …