Medicine and Health Sciences Commons^™

New Inhibitors Of Neuronal Nitric Oxide Synthase For The Treatment Of Melanoma, Amardeep Awasthi, Anika Patel, Huiying Li, Koon Mook Kang, Christine D. Hardy, Anas Ansari, Raghad Nowar, Hasan Alhaddad, Md. Emtiaz Hasan, Sun Yang, Thomas L. Poulos, Richard B. Silverman

Pharmacy Faculty Articles and Research

In 2024, an estimated 100,640 new cases of invasive melanoma were diagnosed in the U.S., with 9290 deaths. Our previous studies revealed that neuronal nitric oxide synthase (nNOS) derived nitric oxide plays a critical role in melanoma progression, making nNOS inhibition a promising strategy. High structural similarity among NOS isoforms requires careful design of nNOS inhibitors to avoid off-target effects. Our previous lead, HH044, demonstrated potent antimelanoma activity but exhibited only moderate nNOS selectivity. Here, we utilized a structure-based approach to design nNOS inhibitors that promote interactions with human nNOS-specific residue His342. Compound 9 exhibited inhibition of both human ( …

Development Of Dirofilaria Immitis Adult Worms In Nsg Mice, Detection Of Parasite-Derived Microrna And Comparative Analysis Of Laboratory Isolates, Mohini Nakhale, Jessica A. Hess, Ellie Oliver, Nathan M. Ryan, Kirsten Mallon, Omair Sultan, Elinor Willis, Esha Banerjee, Enrico Radaelli, Charles-Antoine Assenmacher, Michael Povelones, Duncan Wells, Russ Morphew, Jennifer Willingham-Lane, Christine Henderson, John Harrington, Paul Mcveigh, David Abraham

Department of Surgery Faculty Papers

Global efforts to control heartworm disease are challenged by increasing drug resistance and inadequate early detection methods, which hinder the effective diagnosis and treatment of Dirofilaria immitis infection. This study presents an in vivo model for investigating D. immitis development and host-parasite interactions. The growth and migration of the D. immitis JYD-34 isolate were analyzed in immunodeficient NSG mice over 177 days, revealing parasite migration to the heart and lungs, which mirrors infection dynamics in the natural canine host. Pathophysiological examination of host tissues revealed early adult-stage worms elicited minimal inflammation. However, with chronicity, mild pulmonary hemosiderin accumulation was observed. …

Factors Influencing Match Success In Integrated Vascular Surgery Residency Programs From 2019 To 2023, Antony A. Fuleihan, Melissa C. Xu, Scott H. Koeneman, Paul J. Dimuzio, Babak Abai, Michael Nooromid

Department of Surgery Faculty Papers

INTRODUCTION: Integrated vascular surgery residency (IVSR) programs have grown increasingly competitive. However, the factors influencing successful matching remain unclear. This study evaluates the impact of medical school and applicant characteristics on IVSR match outcomes.

METHODS: A list of ACGME-accredited IVSRs was obtained from the Society for Vascular Surgery, and resident data from the 2019-2023 match cycles were collected from publicly available sources. Applicant characteristics consisted of additional graduate degrees, Alpha Omega Alpha (AOA) status, and research productivity. Medical school characteristics consisted of ranking, research funding, vascular surgery interest group (VSIG) presence, and vascular surgery faculty size. Logistic regression models were …

Novel R Shiny Tool For Survival Analysis With Time-Varying Covariate In Oncology Studies: Overcoming Biases And Enhancing Collaboration, Yimei Li, Yang Qiao, Fei Gao, Jordan Gauthier, Qiang Ed Zhang, Jenna Voutsinas, Wendy Leisenring, Ted Gooley, Corinne Summers, Alexandre Hirayama, Cameron Turtle, Rebecca Gardner, Jarcy Zee, Qian Vicky Wu

Wills Eye Hospital Papers

PURPOSE: Our study is motivated by evaluating the role of hematopoietic cell transplantation (HCT) after chimeric antigen receptor T-cell (CAR-T) therapy for ALL, a debated topic. Because patients may receive HCT at different times after CAR-T infusion or never, HCT post-CAR-T should be considered as a time-varying covariate (TVC).

METHODS: Standard Cox models and Kaplan-Meier (KM) curves (naïve method) assume that TVC status is known and fixed at baseline, which can yield biased estimates. Landmark analysis is a popular alternative but depends on a chosen landmark time. Time-dependent (TD) Cox model is better suited for TVC although visualizing survival curves …

Supercharging-Enhanced Ndia-Ms Enables Global Profiling Of Drug-Induced Proteome Solubility Shifts, Yun Xiong, Huimin Zhang, Lin Tan, Bo Wei, John N Weinstein, Philip L Lorenzi

Faculty, Staff and Student Publications

Mass spectrometry (MS) is indispensable for high-throughput quantitation of protein expression. But protein function is regulated by factors beyond abundance alone. Here, we evaluate two supercharging reagents, dimethyl sulfoxide (DMSO) and m-nitrobenzyl alcohol (mNBA), in narrow-window data-independent acquisition (nDIA)-MS. DMSO markedly enhances MS signal and protein identification, whereas mNBA primarily increases peptide identifications. Optimizating nDIA-MS with 3% DMSO boosts signal intensity by up to 56%, enabling identification of ~9,600 proteins from 1 µg HeLa digest in 15 min. Using this methodology, we quantify solubility and abundance changes in 8,694 proteins across three cell lines following short-term treatment with the proteasome …

Perceived Neighborhood Safety And Firearm Secure Storage: Findings From The 2024 Behavioral Risk Factor Surveillance System, Alexander Testa, Karyn Fu, Muhammed Ahmed, Daniel C Semenza, Dylan B Jackson, Sandra Mckay, Kyle T Ganson, Jason M Nagata

Faculty, Staff and Student Publications

Background: Secure firearm storage (i.e., keeping firearms locked and ammunition stored separately) is a means of reducing risks of suicide, unintentional injury, and homicide. While prior research has examined demographic and household factors associated with storage practices, less is known about how contextual factors, such as perceived neighborhood safety from crime, influence firearm storage behavior.

Methods: Data were from the 2024 Behavioral Risk Factor Surveillance System (BRFSS), a nationally coordinated, state-based survey administered by state health departments with technical and methodological support from the Centers for Disease Control and Prevention. Analyses were restricted to respondents in firearm-owning households from ten …

Upper Hemisternotomy Vs. Full Sternotomy For Hemiarch And Proximal Aortic Replacement, Jeffrey A. Zucker, Vishal N. Shah, Joshua R. Chen, Christopher Pritting, Colin King, Jacqueline Mcgee, Megary Mccoy, Konstadinos A. Plestis

Department of Surgery Faculty Papers

Introduction: Hemiarch replacement with proximal aortic replacement is seldom performed via upper hemisternotomy (UHS). We report our surgical technique and postoperative outcomes in 11 patients who underwent UHS for hemiarch and proximal aortic replacement, compared with 15 patients who underwent the procedure via full sternotomy (FS).

Methods: A UHS was performed at the right third or fourth intercostal space. Cardiopulmonary bypass (CPB) was established via the distal ascending aorta or right axillary artery and right common femoral vein. After aortic cross-clamping (ACC), the heart was arrested with single-dose antegrade crystalloid cardioplegia. After proximal aortic replacement, hypothermic circulatory arrest (HCA) between …

High-Throughput Proteomic Profiling To Evaluate Differentiation Syndrome With Menin Inhibition, Miriam B Garcia, Bofei Wang, Irtiza Sheikh, Georgina El Hajjar, David Mccall, Cesar Nunez, Amber Gibson, Philip L Lorenzi, Ghayas C Issa, Branko Cuglievan, Hussein A Abbas

Faculty, Staff and Student Publications

High-throughput proteomic profiling provides a comprehensive analysis of systemic cancer effects and tumor microenvironment interactions. Characterizing soluble proteins driving inflammation in acute myeloid leukemia (AML) offers insight into inflammatory diseases like differentiation syndrome (DS) related to AML therapies like menin inhibitors. We present our application of NUcleic acid-Linked Immuno-Sandwich Assay (NULISA), a novel technology leveraging next-generation sequencing (NGS) for high-throughput, ultra-sensitive characterization of secreted inflammatory proteins in plasma or serum. Here we report its use to identify dynamic soluble protein changes during treatment and at the time of suspected DS in pediatric AML patients treated with the menin inhibitor revumenib …

Functional Genomic Analysis Of Non-Canonical Dna Regulatory Elements Of The Aryl Hydrocarbon Receptor, Shayan Shahriar, Tajhal D Patel, Manjula Nakka, Sandra L Grimm, Cristian Coarfa, Daniel A Gorelick

Faculty, Staff and Students Publications

The aryl hydrocarbon receptor (AHR) is a ligand-dependent transcription factor activated by environmental toxicants like halogenated and polycyclic aromatic hydrocarbons, which then binds to DNA and regulates gene expression. AHR is implicated in numerous physiological processes, including liver and immune function, cell cycle control, oncogenesis, and metabolism. Traditionally, AHR binds a consensus DNA sequence (GCGTG), the xenobiotic response element (XRE), recruits coregulators, and modulates gene expression. Yet, recent evidence suggests AHR can also regulate gene expression via a non-consensus sequence (GGGA), termed the non-consensus XRE (NC-XRE). The prevalence and functional significance of NC-XRE motifs in the genome have remained unclear. …

Beyond Bile Acids Synthesis: Metabolomics Profiling Highlights Extensive Metabolic Dysregulation And Treatment Response In Ctx, Monte A Del Monte, Jennifer Hanson, Penelope E Bonnen

Faculty, Staff and Students Publications

Background: Cerebrotendinous xanthomatosis (CTX) is an inherited metabolic disorder caused by variants in CYP27A1 leading to loss of sterol-27-hydroxylase activity. Sterol-27-hydroxylase generates two classes of bioactive signaling molecules: bile acids and oxysterols. The broader metabolic consequences resulting from perturbations in bile acid and oxysterol signaling and their reversibility with FDA-approved treatment chenodeoxycholic acid (CDCA), are not fully described.

Methods: To establish a comprehensive map of metabolic consequences of CTX, we performed large-scale, untargeted plasma metabolomics in a single subject with CTX, both before and after 6 months of CDCA therapy, and compared results with a reference cohort of over 1100 …

Two Lysosomal Genes Atp13a2 And Gba1 Interact To Drive Neurodegeneration, Mingxue Gu, Jinghan Zhao, Mingxi Deng, Guang Lin, Xueyang Pan, Wenwen Lin, Mengqi Ma, Jinyong Kim, Seul Kee Byeon, Akhilesh Pandey, Lara M Lange, Chad A Shaw, Jonggeol Kim, Joanne Trinh, Christine Klein, Oguz Kanca, Joshua M Shulman, Hugo J Bellen

Duncan NRI Faculty and Staff Publications

Background: Parkinson’s disease (PD) is a genetically complex disorder in which combinations of heterozygous risk variants may contribute to pathogenesis. Many PD risk loci encode lysosomal genes, such as GBA1, a common and potent risk factor, conferring at least a 5-fold increase. However, the mechanisms of GBA1 penetrance remain poorly understood.

Methods: Using Drosophila melanogaster, we performed a genetic interaction screen of lysosomal storage disorder (LSD) genes to identify dominant modifiers of Gba1b (fly homolog of GBA1). Age-dependent locomotor assessments, electroretinograms (ERG), transmission electron microscopy (TEM) analyses and quantification of dopaminergic (DA) neurons were used to assess …

A Heterogeneous Population Code At The First Synapse Of Vision, Tessa Herzog, Takeshi Yoshimatsu, Jose Moya-Diaz, Ben James, Leon Lagnado, Tom Baden

2020-Current year OA Pubs

Vision begins when photoreceptors convert fluctuations in light intensity into temporal patterns of glutamate release that drive the retinal network. The input-output relation at this first stage has not been studied in vivo so it is not known how it operates across a photoreceptor population. Using glutamate imaging in zebrafish, we find that individual type 1 cones (PR1; ancestral red cones), which dominate daylight vision in non-avian vertebrates, encode visual stimuli with high reliability and time-precision but routinely vary in sensitivity to luminance, contrast and frequency across the population. Variations in input-output relations are generated by feedback from the horizontal …

Taming Psoriatic Inflammation: Targeting The Inos–Oxidative Stress–Necroptosis Axis For Precision Therapy, Tolulope Omotope Omolekan, Tithi Roy, Jean Christopher Chamcheu

Faculty Publications

Necroptosis is increasingly recognized as a central driver of psoriatic inflammation, promoting keratinocyte death and sustaining immune activation. Recent evidence shows that inducible nitric oxide synthase (iNOS) deficiency and exogenous nitric oxide (NO) supplementation ameliorate psoriasis-like dermatitis in mice by reducing oxidative stress and constraining necroptotic signaling. These findings identify iNOS-derived NO as both a mediator of reduction–oxidation (redox) imbalance and a key regulator of necroptosis, thereby advancing mechanistic insight into psoriatic pathogenesis. Importantly, they highlight the iNOS–oxidative stress–necroptosis axis as a translationally actionable therapeutic target. Modulating necroptotic cell death through NO-based interventions may restore epidermal homeostasis and improve clinical …

Clinical Outcomes Of Patients Hospitalized For Conventional Pacemaker Implantation With Protein-Energy Malnutrition, Phuuwadith Wattanachayakul, Pojsakorn Danpanichkul, Chalothorn Wannaphut, Hamza Tahir, John Malin, Thanathip Suenghataiphorn, Kanokphong Suparan, Aman Amanullah

Einstein Health Papers

INTRODUCTION: The impact of protein-energy malnutrition (PEM) on patients hospitalized for conventional pacemaker implantation remains poorly understood.

METHODS: We utilized the 2020 U.S. National Inpatient Sample (NIS) database to evaluate the impact of PEM on the in-hospital outcomes of patients who underwent conventional pacemaker implantation. Patients aged 18 and older were identified by ICD-10 CM and PCS codes. Multivariable survey logistic and linear regression analyses were employed to examine in-hospital outcomes, including in-patient mortality, system-based outcomes, and post-procedural complications.

RESULTS: A total of 108 020 patients were identified with 4315 (3.99%) diagnosed with PEM. The mean age of the cohort …

Retrospective Comparison Of Outcomes Of Osteochondral Allograft Transplantation Of The Knee Using Extended Storage Modality Missouri Osteochondral Preservation System Versus Standard Preservation, Henson Destine, Gaston Davis, Harrison S. Fellheimer, Azra Dees, Nathaniel Kern, Bradford Tucker, Kevin Freedman

Rothman Institute Papers

BACKGROUND: Osteochondral allograft (OCA) transplantation is an established surgical intervention for full-thickness chondral defects. Standard preservation (SP) protocols currently allow for OCAs to be stored for a maximum of 28 days after procurement before significant chondrocyte death. An alternative protocol, the Missouri Osteochondral Allograft Preservation System (MOPS), has been shown to allow for grafts to be stored for twice the maximum time allotment as SP.

PURPOSE: To compare clinical outcomes in patients who have undergone OCA transplantation utilizing the extended storage capabilities of the MOPS versus SP protocols.

STUDY DESIGN: Cohort study; Level of evidence, 3.

METHODS: Patients who underwent …

Partial Versus Full Revision In Cementless Single-Stage Exchange For Hip Periprosthetic Joint Infection: A Multicenter Comparative Study With 10-Year Survivorship Analysis, Wenbo Mu, Atthakorn Jarusriwanna, Boyong Xu, Scot A. Brown, Xiaogang Zhang, Alexander Dawes, Javad Parvizi Md, Li Cao

Rothman Institute Papers

BACKGROUND: Periprosthetic joint infection (PJI) is one of the most challenging complications following total hip arthroplasty (THA). Traditional management typically involves full revision to ensure comprehensive infection eradication. However, for patients with well-fixed implants, partial revision in a single-stage cementless approach may provide a viable alternative, potentially preserving bone stock and reducing operative time. The relative efficacy of this approach compared with full revision remains to be fully explored. This multicenter study aims to determine whether partial revision in cementless single-stage exchange surgery offers comparable infection control outcomes to full revision for select patients with well-fixed implants.

METHODS: We conducted …

Olutasidenib In Recurrent/Relapsed Locally Advanced Or Metastatic Idh1-Mutated Chondrosarcoma: Phase 1b/2 Trial, Robin L Jones, Roman Groisberg, Jean-Yves Blay, Howard Colman, Macarena De La Fuente, Patricia Roxburgh, Mwe Mwe Chao, Hua Tian, Florence Duffaud, Rastislav Bahleda, Brian A Van Tine

2020-Current year OA Pubs

Chondrosarcomas are rare cartilaginous neoplasms with limited treatment options. Isocitrate dehydrogenase 1/2 (mIDH1/2) mutations occur in 65% of chondrosarcomas. Here we report safety and efficacy of olutasidenib, an mIDH1 inhibitor, evaluated in patients with locally advanced or metastatic mIDH1 chondrosarcoma (Clinicaltrials.gov identifier: NCT03684811). The primary endpoint was objective response rate by tumor evaluation; secondary endpoints included adverse events, progression-free and overall survival. Patients received olutasidenib 150 mg twice daily. Twenty-three patients were enrolled; 16 were diagnosed with conventional chondrosarcoma (cCS). Median age was 57 (range, 30-71) years. In 21 response-evaluable patients, 11 (52%) had stable disease, 8 (38%) had progressive …

Establishing T1 And Ecv Mapping Based Nomogram Differentiate Acute Ischemic And Nonischemic Myocardial Injury: A Proof-Of-Concept Study, Yanping Su, Kan Liu, Et Al.

2020-Current year OA Pubs

OBJECTIVES: To develop and validate a nomogram based on T1 and extracellular volume fraction (ECV) mapping derived from cardiovascular magnetic resonance (CMR) for differentiating ischemic from nonischemic cardiomyopathies during the acute phase.

METHODS: This retrospective study included patients who underwent CMR at the Fifth Affiliated Hospital of Wenzhou Medical University (internal dataset) and the Fifth Affiliated Hospital of Sun Yat-sen University (external dataset). Patients were assigned to a training set (n = 73), a test set (n = 30), an internal validation set (n = 28), and an external validation set (n = 16). Six multivariable logistic regression models were …

Leveraging Informatics To Manage Lifelong Monitoring In Childhood Cancer Survivors, Kimberly Davidow, Renee Gresh, E. Anders Kolb, Ellen Guarnieri, Mary R. Cooper

College of Population Health Faculty Papers

Background: Electronic health records (EHR) have long held promise for sharing information efficiently, but this remains challenging. This quality improvement initiative sought to improve the accurate documentation of anthracycline and radiation therapy exposures in pediatric oncology patients who were treated at different institutions through a quality improvement methodology and EHR tools. Methods: A custom-built EHR smartform was previously created. Modifications were made to the smartform, and quality improvement methods were utilized to improve receipt of radiation summaries from other institutions and documentation of chemotherapeutic doses. Results: Three months after interventions, including clinician education and smartform updates, accurate anthracycline documentation improved …

Oncofetal Reprogramming: A New Frontier In Cancer Therapy Resistance, Anh Nguyen, Molly Lausten, Bruce M. Boman

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Oncofetal reprogramming has recently emerged as a critical concept in translational cancer research, particularly for its role in driving therapeutic resistance across a variety of malignancies. This biological process refers to a pattern of gene expression that is restricted to embryogenesis, but becomes expressed again in a subpopulation of cancer cells. These genes are typically suppressed after embryogenesis, and their aberrant re-expression in tumors endows cancer cells with stem-like properties and enhanced adaptability. The goal of this review is the following: (i) comprehensively examine the multifaceted nature of oncofetal reprogramming; (ii) elucidate its underlying molecular mechanisms, including its regulators and …

Comparative Outcomes Of Abdominal, Laparoscopic, And Vaginal Sacral Colpopexy: A National Analysis Of Apical Suspension Procedures (2014–2022), Smit Bharat Solanki, Apurva B Pancholy, Vishal Pancholy

Faculty, Staff and Student Publications

Objective: Sacral colpopexy is a well-established procedure for apical suspension, but the relative outcomes of abdominal, laparoscopic, and vaginal approaches remain debated. This study compared perioperative outcomes across these surgical routes using a national database and evaluated trends in robotic assistance.

Materials and methods: We analyzed sacral colpopexy cases from the American College of Surgeons National Surgical Quality Improvement Program between 2014 and 2022. Patient demographics, complication rates, and surgical outcomes were compared among abdominal, laparoscopic, and vaginal procedures. Relative risks (RR) were adjusted for confounders. The utilization of robotic systems in laparoscopic procedures was examined.

Results: Among 61,524 cases, …

Seipin Expression In Hepatocytes Impairs The Assembly Of Vldls And Exacerbates Steatohepatitis, Qianqian Dong, Yidan Ma, Xin Chen, Xiaowei Wang, Ziwei Liu, Chenxi Liang, Liwen Qiu, Jinye Tang, Jin Wu, Yang Liu, Xiaoqin Wu, Yaru Zhou, Mingming Gao, Hongyuan Yang

Faculty, Staff and Student Publications

VLDLs are crucial for maintaining liver and whole-body lipid homeostasis. Limited knowledge exists regarding the lipidation process of VLDL. Endoplasmic reticulum (ER) luminal lipid droplets (LLDs) have been suggested to provide lipids for VLDL lipidation and maturation. Seipin, an integral membrane protein of the ER, plays key roles in the formation of cytoplasmic LDs (CLDs) and adipocyte differentiation. Surprisingly, seipin is hardly detectable in hepatocytes. Given the critical contribution of seipin in forming CLDs, we hypothesize that the absence of seipin in hepatocytes might ensure the proper formation of LLDs and the lipidation and assembly of VLDLs. To explore the …

Downregulation Of Slc40a1 Leads To Iron Accumulation In Fibrotic Lung Fibroblasts, Quanjin Dang, Chaoqun Huang, Yurong Liang, Akshaya Surendran, Dharanya Muthiah, Kishore Vaddadi, Sankha Hewawasam, Tingting W Mills, Lin Liu

Faculty, Staff and Student Publications

Iron is an essential nutrient for almost all organisms. However, excess iron generates reactive oxygen species and causes tissue injuries. Iron is implicated in idiopathic pulmonary fibrosis (IPF). In this study, we examined iron accumulation in fibrotic lung fibroblasts and the underlying mechanisms. We hypothesize that the downregulation of Solute Carrier Family 40 Member 1 (SLC40A1) results in iron accumulation in lung fibroblasts of IPF patients. Using a Prussian Blue iron staining, we found that iron accumulated in the fibrotic region of the lungs from IPF patients and bleomycin- and asbestos-induced lung fibrosis mice. Iron was partially co-localized with the …

An Application-Based Ontological Knowledge Base Of Medications To Support Health Literacy And Adherence For The Consumer Population: An Aging Population Use Case, Clifford Chen, Muhammad Amith, Kirk Roberts, Rebecca Mauldin, Renata Komalasari, Cui Tao

Faculty, Staff and Student Publications

No abstract provided.

The Origin Of Hepatocellular Carcinoma Depends On Metabolic Zonation, Jason Guo, Roger Liang, Andrew Chung, Zhijie Li, Boyuan Li, Eric Chen, Lin Li, Jingjing Wang, Meng-Hsiung Hsieh, Ivy Xiangyi Fang, Benjamin Kroger, Yunguan Wang, Min Zhu, Xiongzhao Ren, Greg Mannino, Yuemeng Jia, Yonglong Wei, Stephen Moore, Daniel J Siegwart, Stephen S Chung, Zixi Wang, Tripti Sharma, Suman Komjeti, Yi Han, Purva Gopal, Guanghua Xiao, Tao Wang, Hao Zhu

Faculty, Staff and Student Publications

The origin of cancer is poorly understood because premalignant cells are rarely followed in their native environments. Although the spatial compartmentalization of metabolic functions is critical for proper liver function, it is unknown whether cancers arise from some zones but not others and whether there are metabolic determinants of cancer risk. Zone-specific, mosaic introduction of Ctnnb1 (catenin beta 1) and Arid2 (AT-rich interaction domain 2) mutations, commonly co-mutated genes in hepatocellular carcinoma (HCC), in mouse models showed that position and metabolic context determine clone fates. Ctnnb1/Arid2-driven cancers were much more likely to arise in zone 3. The …

Dhodh Links Mitochondrial Bioenergetics, One-Carbon Metabolism, And Dna Repair To Sustain Aggressive Prostate Adenocarcinoma, Saiswaroop Rajaratnam, Danthasinghe Waduge Badrajee Piyarathna, Ranjit K Mehta, Venugopalareddy Mekala, Jun Hyoung Park, Uttam Rasaily, Vani Venkatappa, Karthik Reddy Kami Reddy, Vasanta Putluri, Kaveri Goel, Sandra L Grimm, Sai Manohar Thota, Taylor Morrison, Cristian Coarfa, Benny Abraham Kaipparettu, Chao Cheng, Nagireddy Putluri, Jeffrey A Jones, Mukesh K Nyati, Michael Ittmann, Natalie R Gassman, Arun Sreekumar

Faculty, Staff and Students Publications

Background

Dihydroorotate dehydrogenase (DHODH) is a mitochondrial enzyme that connects de novo pyrimidine biosynthesis with the electron transport chain (ETC) function. However, its broader role in prostate cancer (PCa) signaling and response to therapy remains unclear.

Methods

We combined transcriptomic, metabolomic, epigenomic, and functional analyses with clinical outcome data to explore the effects of DHODH depletion in ancestry-annotated European American (EA) and African American (AA) prostate cancer cell line models.

Results

DHODH was markedly overexpressed in malignant prostate epithelial cells and was abundant in tumors. Its knockdown hindered cell proliferation by causing pyrimidine depletion, while unexpectedly increasing oxidative phosphorylation, ETC …

Use Of Electrocardiograms To Identify Coronary Artery Disease: Cross-Validation Of An Artificial Intelligence Model, Michael Leasure, Indu Poornima, Adam Butchy, Utkars Jain, Devin Vasoya, Michael Warnick, Brent Williams, John Rehder, Prahlad Menon, Veronica A. Covalesky, Gary S. Mintz

Department of Medicine Faculty Papers

BACKGROUND: The current gold standard for the diagnosis of coronary artery disease (CAD) is invasive angiography; however, it is an invasive procedure. Therefore, we developed an artificial intelligence model designed to predict significant CAD from a resting digital 12-lead electrocardiogram (ECG).

OBJECTIVES: This retrospective study assessed the model's ability to predict clinically significant CAD in a patient population presenting for coronary angiography.

METHODS: From 2019 to 2021, 16,476 patients had a resting 12-lead digital ECG recorded within 90 days prior to coronary angiography. The artificial intelligence model was developed using 10-fold cross-validation methodology. Clinically significant disease was defined as angiographic …

Interpretable Linear Models For Heart Disease Prediction: A Comparative Study, Dipok Deb, Emran Hossain

Data Science and Data Mining

Heart disease remains a leading cause of mortality worldwide, underscoring the importance of accurate and transparent methods for early diagnosis. While many machine learning and artificial intelligence models have demonstrated strong predictive performance, their limited interpretability poses challenges for clinical adoption. In this study, we evaluate three interpretable linear classification models—Generalized Linear Model (GLM) logistic regression, L1-regularized (Lasso) logistic regression, and Linear Discriminant Analysis (LDA)—for heart disease prediction using the Cleveland Heart Disease dataset. Following comprehensive data preprocessing, the models are assessed on a held-out test set using standard evaluation metrics, including accuracy, precision, recall, F1-score, and the area under …

Psychological Resilience In The Covid-19 Response: A Systematic Review For Future Public Health Preparedness, Atena Pasha, Abdul-Hanan Saani Inusah, Jannatun Nayem, Xiaoming Li, Shan Qiao

Faculty Publications

Objective: The COVID-19 pandemic has highlighted the importance of psychological resilience for well-being. While several reviews have addressed resilience in specific populations or contexts, few have synthesized global literature across diverse populations. This review examines psychological resilience across diverse populations, focusing on measurement, associated factors, and future public health preparedness strategies. Method: Guided by the PRISMA, a thorough search of PsycINFO, PubMed, ScienceDirect, and Web of Science was conducted in February 2024, including quantitative studies considering psychological resilience during the COVID-19 pandemic published in peer-reviewed English journals from 2020 to 2024, using search terms relevant to psychological resilience and COVID-19. …

From Latent Manifolds To Targeted Molecular Probes: An Interpretable, Kinome-Scale Generative Machine Learning Framework For Family-Based Kinase Ligand Design, Gennady M. Verkhivker, Ryan Kassab, Keerthi Krishnan

Mathematics, Physics, and Computer Science Faculty Articles and Research

Scaffold-aware artificial intelligence (AI) models enable systematic exploration of chemical space conditioned on protein-interacting ligands, yet the representational principles governing their behavior remain poorly understood. The computational representation of structurally complex kinase small molecules remains a formidable challenge due to the high conservation of ATP active site architecture across the kinome and the topological complexity of structural scaffolds in current generative AI frameworks. In this study, we present a diagnostic, modular and chemistry-first generative framework for design of targeted SRC kinase ligands by integrating ChemVAE-based latent space modeling, a chemically interpretable structural similarity metric (Kinase Likelihood Score), Bayesian optimization, and …