Neurology Commons^™

Leveraging Snomed Ct For Patient Cohort Identification Over Heterogeneous Ehr Data, Xubing Hao, Yan Huang, Licong Cui, Xiaojin Li

Faculty, Staff and Student Publications

SNOMED CT is extensively employed to standardize data across diverse patient datasets and support cohort identification, with studies revealing its benefits and challenges. In this work, we developed a SNOMED CT-driven cohort query system over a heterogeneous Optum® de-identified COVID-19 Electronic Health Record dataset leveraging concept mappings between ICD-9-CM/ICD-10-CM and SNOMED CT. We evaluated the benefits and challenges of using SNOMED CT to perform cohort queries based on both query code sets and actual patients retrieved from the database, leveraging the original ICD-9-CM and ICD-10-CM as baselines. Manual review of 80 random cases revealed 65 cases containing 148 true positive …

Application Of Telc Model To Better Elucidate Neural Stimulation By Touch, James Weifu Lee

Chemistry & Biochemistry Faculty Publications

Aim: This study is to better understand how the transient ion transport activity of touch receptors could change the graded potential to stimulate an action potential firing.

Methods: The latest transmembrane-electrostatically localized protons/cations charges (TELC) theory is employed for numerical analysis to calculate the neural touch signal transduction responding time required to fire an action potential spike.

Results: A neural action potential spike was constructed successfully using newly developed time-dependent TELC-based neural transmembrane potential integral equations (Equations 5, 6, and 7). The results explicated that the TELC curve has an inverse relationship with neural transmembrane potential since its curve appears …

Leveraging Clinical Standards To Improve The Translational Relevance Of Therapies For Experimental Spinal Cord Injury, Aaron L. Silverstein

Theses and Dissertations--Neuroscience

Efforts to improve treatment of spinal cord injury (SCI) often use animals to develop effective therapeutics, intending to improve the survival and the quality of life of persons with SCI. Over half of all SCIs in the United States occur at the cervical level and often cause locomotor deficits and life-threatening breathing dysfunction. Thus, my dissertation is focused on this important patient population.

After beginning with a description of translational research and surveying SCI from a clinical standpoint, I turned to describe experimental models of cervical SCI and more detailed neuroimmunological findings relevant to my work. Then, I conducted a …

Immune Dynamics And B Cell Contributions To Neuroplasticity And Recovery After Stroke, Thomas A. Ujas

Theses and Dissertations--Neuroscience

This dissertation explores the dynamic interplay between the immune system and the brain across stroke and aging using clinical, post-mortem, and pre-clinical models. The immune system plays critical roles in shaping brain function, responding to injury, and mediating recovery. These studies aim to enhance our understanding of neuroimmune dynamics across spatial and temporal dimensions.

In the first part, we conducted longitudinal sampling of aneurysmal subarachnoid hemorrhage (aSAH) patients to track immune cell and cytokine changes at days 3, 5, 7, 10, and 14 post-stroke, with a focus on delayed cerebral ischemia (DCI), a common complication. We observed distinct temporal patterns, …

Cell-Type Specific Apoe4 To Apoe2 ‘Switching’ In Astrocytes And Microglia Alters Alzheimer’S Disease Neuropathology, Lesley R. Golden

Theses and Dissertations--Physiology

Apolipoprotein E (APOE) is the strongest genetic risk factor for late-onset Alzheimer’s disease (LOAD). APOE exists in three common protein isoforms throughout the population: ApoE2 (E2), ApoE3 (E3), and ApoE4 (E4). While APOE allele frequencies and the degree of AD-associated risk vary across different ethnic groups, when compared to the ‘neutral’ and most common E3 allele, the E4 allele confers up to a 33-fold increase in Alzheimer’s Disease (AD) risk. Conversely, the neuroprotective E2 allele decreases AD risk by up to 67%. Here, we aimed to determine the therapeutic potential of cell-type specific APOE allele ‘switching’ and explore …

Obesity Prediction From Structural Mri Using Conformal Deep Learning With Uncertainty Quantification, W. Farzana, A. G. A. Temtam, B. Humud-Arboleda, L. Ma, M. Bean, F. Gerard Moeller, K. M. Iftekharuddin

Electrical & Computer Engineering Faculty Publications

Obesity arises from a neurobehavioral disorder in which the brain’s regulation of hunger and food intake is impaired, leading to an imbalance between energy consumption and expenditure. One key phenotype associated with obesity is body mass index (BMI). BMI is influenced by multiple causal pathways driven by behavioral, metabolic, and genetic factors. Traditional obesity prediction studies often rely on magnetic resonance imaging (MRI) voxel-based morphometry to correlate BMI with obesity-related clinical measurements and brain structure, predominantly gray matter volume (GMV). However, the altered brain regions are variable and widespread between studies, with some literature presenting contradictory results between BMI and …

Recurrent Carotid Paragangliomas In A Syndromic Patient With A Heterozygous Missense Variant In Dna Methyltransferase 3 Alpha, Ryan J German, Blake Vuocolo, Liesbeth Vossaert, Lisa Saba, Robin Fletcher, Matthew L Tedder, Bekim Sadikovic, Jennifer Kerkhof, Michael Wangler, Carlos A Bacino

Duncan NRI Faculty and Staff Publications

We report a 40-year-old African American female with a novel variant in exon 8 of DNA methyltransferase 3 alpha (DNMT3A), (NM_022552.4: c.905G>C, p.G302A) who presented with a history of recurrent carotid paragangliomas, mediastinal mass, intellectual disability, dysarthria, cholelithiasis, diabetes mellitus, hypertension, and dysmorphic features. We interpret this novel variant as likely pathogenic and causative for the patient's syndromic features of Heyn-Sproul-Jackson syndrome. Heyn-Sproul-Jackson syndrome is a condition caused by gain-of-function genetic changes in DNMT3A. Paragangliomas have also been observed in non-syndromic patients with genetic alterations in DNMT3A. We describe a patient with clinical features of Heyn-Sproul-Jackson syndrome such as …

Drosophila Models Uncover Substrate Channeling Effects On Phospholipids And Sphingolipids In Peroxisomal Biogenesis Disorders, Michael F Wangler, Yu-Hsin Chao, Mary Roth, Ruth Welti, James A Mcnew

Duncan NRI Faculty and Staff Publications

Peroxisomal Biogenesis Disorders Zellweger Spectrum (PBD-ZSD) disorders are a group of autosomal recessive defects in peroxisome formation that produce a multi-systemic disease presenting at birth or in childhood. Well documented clinical biomarkers such as elevated very long chain fatty acids (VLCFA) are key biochemical diagnostic findings in these conditions. Additional, secondary biochemical alterations such as elevated very long chain lysophosphatidylcholines are allowing newborn screening for peroxisomal disease. In addition, a more widespread impact on metabolism and lipids is increasingly being documented by metabolomic and lipidomic studies. Here we utilize Drosophila models of pex2 and pex16 as well as human plasma …

Resort Enhances Reference-Based Cell Type Deconvolution For Spatial Transcriptomics Through Regional Information Integration, Linhua Wang, Ling Wu, Guantong Qi, Chaozhong Liu, Wanli Wang, Xiang H-F Zhang, Zhandong Liu

Duncan NRI Faculty and Staff Publications

Motivation: Spatial transcriptomics (ST) captures positional gene expression within tissues but lacks single-cell resolution. Reference-based cell type deconvolution methods were developed to understand cell type distributions for ST. However, batch/platform discrepancies between references and ST impact their accuracy.

Results: We present Region-based Cell Sorting (ReSort), which utilizes ST's region-level data to lessen reliance on reference data and alleviate these technical issues. In simulation studies, ReSort enhances reference-based deconvolution methods. Applying ReSort to a mouse breast cancer model highlights macrophages M0 and M2 enrichment in the epithelial clone, revealing insights into epithelial-mesenchymal transition and immune infiltration.

Availability and implementation: Source codes …

Survey And Improvement Strategies For Gene Prioritization With Large Language Models, Matthew B Neeley, Guantong Qi, Guanchu Wang, Ruixiang Tang, Dongxue Mao, Chaozhong Liu, Sasidhar Pasupuleti, Bo Yuan, Fan Xia, Pengfei Liu, Zhandong Liu, Xia Hu

Duncan NRI Faculty and Staff Publications

Motivation: Rare diseases remain difficult to diagnose due to limited patient data and genetic diversity, with many cases remaining undiagnosed despite advances in variant prioritization tools. While large language models have shown promise in medical applications, their optimal application for trustworthy and accurate gene prioritization downstream of modern prioritization tools has not been systematically evaluated.

Results: We benchmarked various language models for gene prioritization using multi-agent and Human Phenotype Ontology classification approaches to categorize patient cases by phenotype-based solvability levels. To address language model limitations in ranking large gene sets, we implemented a divide-and-conquer strategy with mini-batching and token limiting …

Glutamatergic Lateral Habenula Neurons Modulate Consolidation Of Associative Memories, Snigdha Srivastava, I-Ching Wang, Mikhail Y Kochukov, Jessica L Swanson, Mauro Costa-Mattioli, Benjamin R Arenkiel

Duncan NRI Faculty and Staff Publications

INTRODUCTION: Despite the rise in psychiatric disorders worldwide, the underlying brain circuits responsible for these devastating conditions remain elusive. The lateral habenula (LHb) has emerged as a key brain structure in depression studies due to its hyperactive state in both patients and animal models. While this aligns with known roles in driving aversive states and regulating serotonin release, it is still unclear how acute and transient activity changes in the LHb can influence higher order cognitive processes such as learning, memory, and behavioral adaptation. Given the importance of these processes to psychiatric conditions, understanding how LHb activity impacts cognitive function …

Small Molecule-Based Regulation Of Gene Expression In Human Astrocytes Switching On And Off The G-Quadruplex Control Systems, Vijay Kumar M J, Jérémie Mitteaux, Zi Wang, Ellery Wheeler, Nitin Tandon, Sung Yun Jung, Robert H E Hudson, David Monchaud, Andrey S Tsvetkov

Faculty, Staff and Student Publications

A great deal of attention is being paid to strategies seeking to uncover the biology of the four-stranded nucleic acid structure G-quadruplex (G4) via their stabilization in cells with G4-specific ligands. The conventional definition of chemical biology implies that a complete assessment of G4 biology can only be achieved by implementing a complementary approach involving the destabilization of cellular G4s by ad hoc molecular effectors. We report here on an unprecedented comparison of the cellular consequences of G4 chemical stabilization by pyridostatin (PDS) and destabilization by phenylpyrrolocytosine (PhpC) at both transcriptome- and proteome-wide scales in patient-derived primary human astrocytes. Our …

Tryptophan Kynurenine Pathway-Based Imaging Agents For Brain Disorders And Oncology-From Bench To Bedside, Erik Stauff, Wenqi Xu, Heidi H. Kecskemethy, Sigrid A. Langhans, Vinay V. R. Kandula, Lauren W. Averill, Xuyi Yue

Jefferson Hospital Staff Papers and Presentations

Tryptophan (Trp)-based radiotracers have excellent potential for imaging many different types of brain pathology because of their involvement with both the serotonergic and kynurenine (KYN) pathways. However, radiotracers specific to the kynurenine metabolism pathway are limited. In addition, historically Trp-based radiopharmaceuticals were synthesized with the short-lived isotope carbon-11. A newer generation of Trp-based imaging agents using the longer half-lived and commercially available isotopes, such as fluorine-18 and iodine-124, are being developed. The newly developed amino acid-based tracers have been demonstrated to have favorable radiochemical and imaging characteristics in pre-clinical studies. However, many barriers still exist in the clinical translation of …

Alpha-Synuclein Interaction With Gedunin, Tony Matundura Nyabayo

Graduate Theses/Dissertations

Parkinson’s disease (PD) and other Proteinopathies develop when α-synuclein misfolds and aggregates into toxic amyloids. While existing treatments for PD are primarily focused on managing its symptoms, a viable solution for slowing down the progress of Parkinson’s disease involves targeting the toxic α-synuclein amyloids. Gedunin, a natural inhibitor of heat shock protein 90, has been extensively used to treat malaria. Also, recent research investigations have shed light on its potential beyond malaria therapy, indicating that Gedunin may offer a possible solution for treating a variety of neurodegenerative diseases. Using plate-based assays, we examined how Gedunin influences α-synuclein fibrillation and its …

The Efficacy Of Physical Activity Or Exercise Among Individuals With Cerebral Palsy: An Umbrella Review Of Systematic Reviews, Majed M. Alhumaid, Faris Yahya I. Asiri, Mohamed A. Said, Justin A. Haegele

Human Movement Studies & Special Education Faculty Publications

Introduction

Cerebral palsy (CP) is the most common childhood disability, affecting 1.5-3 per 1000 live births. Physical exercises have been shown to improve muscle and limb outcomes in CP. This systematic review critically appraises existing systematic reviews on the effects of physical activity and exercise on physical, functional, and psychosocial outcomes in individuals with CP compared to those without.

Methods

Using a PICO framework, the question was: In patients with CP, do physical activity and exercise improve muscle- and limb-related outcomes compared to no intervention or usual care? PubMed, Cochrane, ISI Web of Science, and Embase were searched for systematic …

The Differential Expands: Ataxia From Paraneoplastic Cerebellar Degeneration, Dominic Thomas, Md, Amy Dechet

Books, Presentations, Posters, Etc.

Introduction: Paraneoplastic cerebellar degeneration is a rare cause of cerebellar ataxia with a poor prognosis for neurologic recovery. The management of symptoms is dependent primarily upon timely diag nosis and treatment of the underlying neoplasm. Herein, we present the diagnostic and treatment course of a patient with paraneoplastic cerebellar degeneration. Case: A 72-year-old woman with a past medical history of left mastectomy for high grade ER/PR negative Her2 positive invasive ductal carcinoma presented with progressively worsening dysarthria and ataxia over two months. A metabolic work up by her primary care physician was unrevealing. Breast MRI did not show recurrence of …

Cognitive Rehabilitation Of Brain Tumor Survivors: A Systematic Review, Rabeet Tariq, Hafiza Fatima Aziz, Shahier Paracha, Nida Zahid, Timothy J. Ainger, Farhan A. Mirza, Syed Ather Enam

Neurology Faculty Publications

Background Cognitive decline is commonly seen in brain tumor (BT) patients and is associated with a worsened prognosis. Cognitive rehabilitation (CR) for cancer-related cognitive dysfunction has been widely studied for non-central nervous system cancers; however, recent emerging research has commenced documenting CR strategies for BT patients and survivors. Our objective was to review the current literature on various CR modalities in patients and BT survivors.

Methods The review was conducted in accordance with the PRISMA guidelines. The studies on CR were searched across 3 databases using a predefined search strategy. After removing duplicates, performing initial and full-text screenings, and applying …

Hiv Protein Tat Dysregulates Multiple Pathways In Human Ipscs- Derived Microglia, Liam Liyang Guo, Robert Jiang, Yan Cheng, Brooke Russell, Yan Y. Sanders, Ming-Lei Guo

Department of Biomedical and Translational Sciences Faculty Publications

In the era of combined antiretroviral therapy, around 50% of chronic HIV (+) individuals show varying degrees of memory and cognitive deficiency (NeuroHIV), a phenomenon of accelerated brain aging. HIV protein transactivator of transcription (TAT) has been well-accepted as a risk factor contributing to NeuroHIV through dysregulating microglia (Mg) functions. Previous studies have demonstrated that HIV-TAT can affect lipid metabolism, immune responses, autophagy, and senescence in rodent Mg. However, due to the significant species differences between rodent and human Mg (hMg), it is essential to take caution when interpreting the results obtained from rodent models into human conditions. For the …

Key Brain Region Identification In Obesity Prediction With Structural Mri And Probabilistic Uncertainty Aware Model, Walia Farzana, Megan A. Witherow, Ahmed Temtam, Liangsuo Ma, Melanie Bean, F. Gerry Moeller, K. M. Iftekharuddin

Electrical & Computer Engineering Faculty Publications

Objectives/Goals: Predictive performance alone may not determine a model’s clinical utility. Neurobiological changes in obesity alter brain structures, but traditional voxel-based morphometry is limited to group-level analysis. We propose a probabilistic model with uncertainty heatmaps to improve interpretability and personalized prediction. Methods/Study Population: The data for this study are sourced from the Human Connectome Project (HCP), with approval from the Washington University in St. Louis Institutional Review Board. We preprocessed raw T1-weighted structural MRI scans from 525 patients using an automated pipeline. The dataset is divided into training (357 cases), calibration (63 cases), and testing (105 cases). Our probabilistic model …

Tam Receptors Mediate The Fpr2-Driven Pain Resolution And Fibrinolysis After Nerve Injury, Beate Hartmannsberger, Adel Ben‑Kraiem, Sofia Kramer, Carolina Guidolin, Ida Kazerani, Kathrin Doppler, Dominique Thomas, Robert Gurke, Marco Sisignano, Pranav P. Kalelkar, Andrés J. García, Paula V. Monje, Michael Sammeth, Asma Nusrat, Alexander Brack, Susanne M. Krug, Claudia Sommer, Heike L. Rittner

Markey Cancer Center Faculty Publications

Nerve injury causes neuropathic pain and multilevel nerve barrier disruption. Nerve barriers consist of perineurial, endothe- lial and myelin barriers. So far, it is unclear whether resealing nerve barriers fosters pain resolution and recovery. To this end, we analysed the nerve barrier property portfolio, pain behaviour battery and lipidomics for precursors of specialized pro-resolving meditators (SPMs) and their receptors in chronic constriction injury of the rat sciatic nerve to identify tar- gets for pain resolution by resealing the selected nerve barriers. Of the three nerve barriers—perineurium, capillaries and myelin—only capillary tightness specifically against larger molecules, such as fibrinogen, recuperated with …