Medical Sciences Commons^™

The Infected Diabetic Foot: Risk Factors For Re-Infection After Treatment For Diabetic Foot Osteomyelitis, Lawrence A Lavery, Mario C Reyes, Bijan Najafi, Tyler L Coye, Matthew Sideman, Michael C Siah, Arthur N Tarricone

Center on Aging Staff Publications

Our objective was to evaluate risk factors for re-infection in patients after treatment for diabetic foot osteomyelitis (OM). We used pooled patient level data from two RTCs that evaluated patients with diabetic foot infections. We evaluated 171 patients with OM. OM was confirmed with bone culture or histopathology. Data from the 12-month follow-up were used to determine clinical outcomes. Re-infection occurred in 47 (27.5%) patients. Risk factors for re-infection were Toe Brachial Index < 0.40 (25.7% vs. 9.8%, p = 0.02), skin perfusion pressure < 40 mmHg (6.3% vs. 5.9%, p = 0.04), wound healing (55.3% vs. 75.0%, p = 0.01), time to heal (156.0, 69.5-365 vs. 91.5, 38.8-365, p = 0.001), and history of MI (14.9% vs. 3.2%, p = 0.005). During 12-month follow-up, patients with re-infections were 198.8 times more likely to require a foot related hospitalisation (81.8% vs. 0.0%, p = 0.001), 10.4 times more likely have an all-cause hospitalisation (70.2% vs. 18.5%, p = 0.001) and 9.4 times more likely to need an amputation (36.2% vs. 5.6%, p = 0.001). Patients with re-infection had a significantly longer median length of hospitalisation (20.0, 13.5-34.5 vs. 14.0, 10.0-22.0, p = 0.003) and median length of antibiotic duration (55.0, 35.0-87.0 vs. 46.0, 22.8-68.0, p = 0.03). Patients with re-infection are less likely to heal and have more foot-related hospitalizations and amputations.

Flyphonedb2: A Computational Framework For Analyzing Cell-Cell Communication In Drosophila Scrna-Seq Data Integrating Alphafold-Multimer Predictions, Mujeeb Qadiri, Ying Liu, Ah-Ram Kim, Myeonghoon Han, Eric Zhou, Austin Veal, Tzu-Chiao Lu, Hongjie Li, Yanhui Hu, Norbert Perrimon

Center on Aging Staff Publications

Cell-cell communication (CCC) plays a critical role in the physiological regulation of organisms and has been implicated in numerous diseases. Previously, we introduced FlyPhoneDB, a tool designed to explore CCC in Drosophila single-cell RNA-sequencing datasets. The core algorithm of FlyPhoneDB infers tissue-specific signaling events between cell types by calculating cell-cell interaction scores based on curated ligand-receptor (L-R) expression across major signaling pathways. However, the utility of FlyPhoneDB was limited by the relatively small number of available L-R pairs.

Here, we present FlyPhoneDB2, a major upgrade featuring a significantly expanded knowledgebase that includes a greater number of L-R pairs, incorporating annotations …

Lis1 Depletion In Adult Mouse Projection Neurons Causes Neurodegeneration And Severe Neurological Phenotypes, Anne Ventrone

Theses and Dissertations

Proper LIS1 function is crucial for human brain development, as mutations in LIS1 lead to lissencephaly, a severe neurodevelopmental disorder caused by defective proliferation, differentiation and migration of neural precursors. Our understanding of LIS1's functions after brain development is limited. LIS1 regulates cytoplasmic dynein 1 (dynein), an essential microtubule motor protein in cell division and migration, but also a cellular transport motor. We previously showed that tamoxifen (TX)-induced global knockout of LIS1 using a Cre/Lox system (Act-Lis1iKO) in young adult mice results in severe neurological defects and rapid lethality. This strongly supports LIS1's critical post- developmental role, but the underlying …

Delayed Tooth Eruption As An Early Clinical Indicator Of Genetical Tooth Agenesis: A Family-Based Study Of Cases With Whole-Exome Sequencing, Yu-Chen Jeng, I-Ting Chen, Hui-Ching Cheng, Hsin-Yu Huang, Chao-Kai Hsu, Yu-Fen Yen

Journal of Dental Sciences

Delayed tooth eruption is frequently considered a benign developmental variation but may represent an early sign of genetically driven tooth agenesis. We evaluated a 22-month-old female presenting with markedly delayed eruption (only eight primary teeth) and a positive family history of ectodermal features. Given the inconclusive early radiographic findings, whole-exome sequencing (WES) was utilized. WES revealed the proband carried a heterozygous EDARADD variant (NM_080738:c.328G>T; p.Asp110Tyr). Subsequent familial segregation analysis identified an additional heterozygous WNT10A variant (NM_025216:c.637G>A; p.Gly213Ser) within the broader family. The EDARADD variant alone was associated with varying presentations from normal dentition to delayed eruption. Furthermore, the …

Reelin Regulation Of Striatal Physiology And Cocaine Reward, Kasey Lynn Brida

All ETDs from UAB

Drugs of abuse activate defined neuronal populations in brain reward structures such as the nucleus accumbens (NAc), which are thought to promote the enduring synaptic, circuit, and behavioral consequences of drug exposure. While the molecular and cellular effects arising from experience with drugs like cocaine are increasingly well understood, the mechanisms that sculpt NAc neuron participation are largely unknown. Here, we leveraged unbiased single-nucleus transcriptional profiling to identify expression of the secreted glycoprotein Reelin (encoded by the Reln gene) as a marker of cocaine-activated neurons within the rat NAc. Multiplexed in situ detection confirmed selective expression of the immediate early …

Investigating Potential Therapeutic Vulnerabilities And Elucidating Molecular Mechanisms For The Tumor Suppressors Nfkbia And Anxa7 In Diffuse Gliomas, Aran Merati

All ETDs from UAB

Gliomas, and especially diffuse gliomas, can be a devastating disease when attempting treatment in the clinic. Diffuse gliomas are typically malignant and pose definitive problems with respect to patient care predominantly due to their ability to exist outside of the bulk tumor by invading into the surrounding brain parenchyma. Consequently, not every cancerous cell can be fully removed by surgical resection and therapeutic resistance, so the stem-like population left behind can repopulate a recurrent tumor from a single cell. There is a desperate need for pinpointing novel therapeutic vulnerabilities in diffuse gliomas, which could potentially involve the targeting of key …

Maternal Immune Activation Causes Oligodendrocyte Deficits In The Hypothalamus, Kate Miller

All ETDs from UAB

Maternal immune activation (MIA) refers to the occurrence of an inflammatory immune response during any stage of pregnancy. This manifests as the upregulation of proinflammatory cytokines and can be caused by air pollution, obesity, or viral infection. When this occurs during the first trimester in humans, it increases the offspring’s susceptibility to developing neuropsychiatric disorders such as autism (ASD) and schizophrenia (SZ), in males more commonly than females. In addition to behavioral manifestations of neuropsychiatric disorders, metabolic syndrome (MetS) is a common comorbidity, defined as the co-occurrence of three or more symptoms including but not limited to hyperlipidemia, hypertension, and …

Parsing Clinical And Neurobiological Heterogeneity In First-Episode Psychosis Patients With And Without Features Of The Deficit Syndrome Of Schizophrenia, Matheus Teles Gomes De Araujo

All ETDs from UAB

Schizophrenia is highly heterogeneous in its neurobiological and clinical presentations, which hinders attempts to understand its pathophysiology, limits efforts to identify biomarkers, and deters optimal patient care. A way to parse clinical heterogeneity is to subtype patients based on clinical presentations. The deficit syndrome (DS) is a possible subtype, characterized by primary and enduring negative symptoms. Evidence for neurobiological abnormalities dissociating DS from other forms of schizophrenia is inconsistent as most studies do not account for heterogeneity within patient groups due to limitations of group-level comparisons. The question remains whether DS presents a unique and less heterogeneous neurobiological phenotype. The …

Blood Culture Utilization: How Many Follow-Up Cultures Are Needed?, George Jones, Jennifer Hanrahan

Department of Medicine Faculty Publications

Background: Follow-up blood cultures (BCx) are ordered after an initial positive culture in many instances. The number of follow-up cultures needed is not clear. Obtaining unnecessary BCx may cause unintended consequences. The optimal balance between stewardship and patient safety warrants investigation. We sought to assess the frequency with which a third set is positive after a negative second BCx. Methods: We conducted a retrospective study of BCx submitted to the microbiology laboratory from 1/1/18-11/1/23. We included all patients ≥18 years who had at least two follow-up BCx drawn 24-72 hours after an initial positive culture. Data were collected from electronic …

A Novel D-Peptide Modulates Dclk1 Gelsolin Interactions, Reducing Pdac Tumor Growth, Landon L. Moore, Dongfeng Qu, Parthasarathy Chandrekesan, Kamille Pitts, Randal May, Byron E. Anderson, Milton L. Brown, Courtney W. Houchen

Department of Medicine Faculty Publications

What drives inflammation-associated tumorigenesis and progression in pancreatic ductal adenocarcinoma (PDAC)? Doublecortin-like kinase 1 (DCLK1) is a central driver of inflammation-associated tumorigenesis, with elevated expression linked to worse clinical outcomes. Two isoforms of DCLK1 possess a unique extracellular domain (ECD). DCLK1 isoform 2 contains two microtubule-binding domains, while isoform 4, lacks the microtubule-binding domains but, plays a pivotal role in tumor progression. We identified novel D-peptides that selectively target this ECD, significantly suppressing PDAC cell proliferation in vitro and tumor growth in xenograft models without inducing cell death. In silico modeling and binding assays revealed DCLK1 isoform 4 interacts with …

Dance-Related Fractures Occur In The Upper And Lower Extremities At Similar Rates: An Analysis Of The 2004-2023 National Electronic Injury Surveillance System Database, Senah E. Stephens, Joshua F. Edwards, Lisa K. Cannada

Department of Medicine Faculty Publications

Introduction

In the United States, 21% of adolescents participate in dance. Dancers are susceptible to injuries, particularly of the lower extremity, due to extreme positioning, dynamic overload, and repetitive movements.

Objectives

(1) to report the prevalence and describe demographic characteristics of dance-related fractures and (2) to analyze variables associated with disposition status.

Methods

The National Electronic Injury Surveillance System (NEISS) database, published by the US Consumer Product Safety Commission, was used to investigate dance-related fractures diagnosed in a sample of 100 emergency departments over 20 years. Descriptive statistics and demographic variables were analyzed using chi square tests. Age was analyzed …

Late Diagnosis Of Klinefelter Syndrome: Overcoming Phenotypic Variability And Diagnostic Oversights, Amna Kamran, Chinelo Okigbo

Department of Medicine Faculty Publications

We report a case of Klinefelter syndrome (KS) diagnosed in adulthood, emphasizing the impact of phenotypic variability and the declining reliance on physical examination in delayed recognition. A 27-year-old male with obesity, low libido, and biochemical and clinical primary hypogonadism was found to have 47, XXY karyotype, consistent with KS. His hypogonadism was initially attributed to obesity and overlooked, despite classic signs of a micropenis and small testes. The case highlights the importance of physical examination, comprehensive history, and clinician awareness in diagnosing KS, particularly in atypical presentations. KS is associated with increased risks of osteoporosis, cardiovascular disease, and psychosocial …

Weighted Family History Density Of Substance Use: Influence On Participant Substance Use Onset, Escalation, And Duration, Carleigh A. Litteral

Theses and Dissertations--Psychology

Substance use disorders impose a staggering toll on the United States (U.S.), straining healthcare systems, destabilizing communities, and profoundly impacting both individuals and families. Approximately one in six Americans aged 12 and older had a past-year substance use disorder in 2022 (Key Substance Use, 2022), and nearly one-third of adults experience a substance use disorder in their lifetime (Wu, 2010), contributing to an economic burden exceeding $400 billion annually (National Drug Threat Assessment, 2011). Family history of substance use disorders is a key predictor of vulnerability, with individuals who have affected relatives being 2–8 times more …

Identification Of Fiducial Points In Seismocardiographic Cycles Using Manual And Automated Annotation Methods, Jasmine-Vy T. Truong

Honors Undergraduate Theses

There is currently a need for complementary methods for non-invasive cardiac monitoring. Seismocardiography (SCG), the measurement of cardiac-induced vibrations at the chest surface, has shown potential clinical utility. Improving the reliability of detecting fiducial points of electrocardiography (ECG) and SCG, which collectively capture the electro-mechanical cardiac activities, could expand ECG/SCG utility as a low-cost, accessible tool for clinical assessment. This study identifies commonly accepted criteria for fiducial point detection in SCG and ECG through an extensive literature review and signal processing techniques. The previous criteria were evaluated to identify their strengths and weaknesses. Based on the findings, an improved set …

The Bacterial Sensing Nuclear-Oligomerization Domain 2 Receptor In The Brain: Location And Potential Function, Julia Smyth

Dissertations

Nucleotide-binding oligomerization domain-2 (NOD2) is a cytosolic receptor, activated by bacterial peptides that initiates innate immune responses through nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPK), and Caspase-1 pathways. While the role of NOD2 in inflammation outside the central nervous system (CNS) is well-established, especially in the gastrointestinal system, its expression and function in the brain remain poorly defined. Previous genetic studies suggest a link between NOD2 and neurological and psychiatric conditions, including stroke, Parkinson’s disease, and schizophrenia. However, information regarding NOD2 expression, localization, and function in the CNS is limited. In this work, we investigated NOD2 expression, localization, and regulation …

Pattern Integration And Differentiation: Dual Process Model Of Episodic Memory, Hallvard Røe Evensmoen, Lars M. Rimol, Henning Stople Rise, Tor Ivar Hansen, Hamed Nili, Anderson M. Winkler, Asta K. Håberg

Human Genetics Publications

The role of precise timing in episodic memory remains obscure. We showed 139 participants episodes consisting of objects, and tested subsequent memory for the precise timing and order of the objects and episodes. Temporal compression of the episode enhanced memory for relative but not absolute timing of the objects’ presentation and their order. Conversely, temporal expansion between neighboring episodes was associated with successful memory for episode order. fMRI in 36 participants revealed that temporal compression of the episode was associated with more similar activation patterns within episodes in several brain regions including the posterior hippocampus. However, the activation pattern in …

To Discard Or Not To Discard 1pns? A Systematic Review And Meta-Analysis On 291,474 Embryos, T. Lee, F. Qi, K. Peirce, J. Natalwala, V. Chapple, P. J. Mark, K. Sanders, Y. Liu

Research outputs 2022 to 2026

Unlike embryos that display two pronuclei (2PN), monopronucleated (1PN) embryos are assumed to be haploid and can be routinely discarded. Although there are reports of live births after 1PN embryo transfer, the developmental and clinical prognosis of 1PN embryos has not been systematically evaluated. The aim of this review was to elucidate the developmental, clinical and neonatal outcomes of 1PN embryos compared with 2PN embryos. Twenty-four studies met the inclusion criteria. The blastulation rate was lower in 1PN embryos compared with 2PN embryos [risk ratio (RR) 0.50, 95% CI 0.48–0.51]. The live birth rate was lower in 1PN blastocysts when …

Automating The Amino Acid Identification In Elliptical Dichroism Spectrometer With Machine Learning, Ridhanya Sree Balamurugan, Yusuf Asad, Tommy Gao, Dharmakeerthi Nawarathna, Umamaheswara Rao Tida, Dali Sun

Electrical & Computer Engineering Faculty Publications

Amino acid identification is crucial across various scientific disciplines, including biochemistry, pharmaceutical research, and medical diagnostics. However, traditional methods such as mass spectrometry require extensive sample preparation and are time-consuming, complex and costly. Therefore, this study presents a pioneering Machine Learning (ML) approach for automatic amino acid identification by utilizing the unique absorption profiles from an Elliptical Dichroism (ED) spectrometer. Advanced data preprocessing techniques and ML algorithms to learn patterns from the absorption profiles that distinguish different amino acids were investigated to prove the feasibility of this approach. The results show that ML can potentially revolutionize the amino acid analysis …

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 …

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 …

An Overview Of Video Game Biometrics Collection And Considerations For Cyberbiosecurity, Lucas Potter, Christen Westberry, Xavier-Lewis Palmer

Electrical & Computer Engineering Faculty Publications

Over the past fifty years, the global cost of consumer electronics has significantly decreased, leading to greater accessibility to both biosensing systems and interactive entertainment platforms. This increased access has naturally resulted in higher usage of medical and entertainment electronics. However, the intersection of these technologies, combined with invasive data harvesting practices, has raised concerns about the potential misuse of biological signals to manipulate individuals' behavior both within and beyond the video game environment. Currently, biometric data in video games are employed in various ways, such as using Heart Rate Variability (HRV) as a performance metric and integrating eye tracking …

Diagnosis Of Hypertensive Disorders In Pregnancy, Rebecca Horgan, Yara Hage Diab, Maged Costantine, George Saade, Baha Sibai

Department of Obstetrics & Gynecology Faculty Publications

Hypertensive disorders of pregnancy, including chronic hypertension, superimposed preeclampsia, gestational hypertension, and preeclampsia, affect 10-20% of pregnancies and are a significant cause of maternal and perinatal mortality. The incidence of these disorders is rising due to factors such as advanced maternal age, obesity, assisted reproductive technology, and increased rates of preexisting comorbidities. Differentiating pregnancy-associated hypertension from pre-existing chronic hypertension is challenging, as the overlap between the two may be broadening due to the changing demographics of the pregnant population. This review critically evaluated the evidence regarding the current time periods recommended to make a diagnosis of a hypertensive disorder of …

Sex Differences In Inter-Temporal Decision Making And Cortical Thickness Of The Orbitofrontal And Insula In Young Adult Cannabis Users: Evidence From 1111 Subjects, Alan N. Francis, Joan A. Camprodon, Francesca Filbey

School of Medicine Publications

To test for sex differences in the impact of cannabis use on decision-making and brain correlates, we employed cortical thickness (CT) analysis of brain regions involved in intertemporal decision-making namely bilateral orbitofrontal cortex(OFC) and insula in young adult nondependent cannabis-users(CU) and non-users(NU) and their scores on delay discounting task. Neuroimaging analyzes of previously collected data were performed on 608CU and 503NU. CT analysis was performed on MRI images. OFC and insula thickness, scores on the delay discounting test were compared between groups and correlated. Controlling alcohol-use and intra-cranial-volume, CU exhibited sex differences in CT. The bilateral insula was significantly thinner …

Potentiation Of Gelonin Cytotoxicity By Pulsed Electric Fields, Olga N. Pakhomova, Eleni Zivla, Giedre Silkuniene, Mantas Silkunas, Andrei G. Pakhomov

Bioelectrics Publications

Gelonin is a ribosome-inactivating protein with extreme intracellular toxicity but poor permeation into cells. Targeted disruption of cell membranes to facilitate gelonin entry is explored for cancer and tissue ablation. We demonstrate a hundreds- to thousands-fold enhancement of gelonin cytotoxicity by pulsed electric fields in the T24, U-87, and CT26 cell lines. The effective gelonin concentration to kill 50% of cells (EC₅₀) after electroporation ranged from <1 nM to about 100 nM. For intact cells, the EC₅₀ was unattainable even at the highest gelonin concentration of 1000 nM, which reduced cell survival by only 5–15%. For isoeffective electroporation treatments using 300 ns, 9 µs, and 100 µs pulses, longer pulses were more efficient at lowering gelonin EC₅₀. Increasing the electric field strength of 8, 100 µs pulses from 0.65 to 1.25 kV/cm reduced gelonin EC₅₀ from 128 nM to 0.72 nM. Conversely, the presence of 100 nM gelonin enabled a more than 20-fold reduction in the number of pulses required for equivalent cell killing. Pulsed electric field-mediated delivery of gelonin shows promise for hyperplasia ablation at concentrations sufficiently low to minimize or avoid systemic toxicity.

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 …

Establishing A Conventional Linac-Based Electron Flash Beam, Justin Defrancisco

Theses and Dissertations

Problems: A rediscovered radiotherapy technique, FLASH, involves increasing the dose rate to >40 Gy/s. For a given dose, FLASH is shown to decrease the normal tissue complication probability without affecting the tumor control probability. More preclinical studies are necessary to confirm and enable these desirable properties on humans. Current preclinical investigations have diverse constraints, requiring FLASH apparatuses with flexible parameters and accurate control. However, there are limited FLASH platforms available, the existing ones are costly. Our institution is not in possession of any such infrastructure. Even if available, dosimetry and beam control in FLASH are extremely lacking. There is …

Development Of A Mediation Model Of Pain Cognition In Adult Patients With Sickle Cell Disease, Daniel M. Sop

Theses and Dissertations

Pain is a hallmark of Sickle Cell Disease (SCD), a genetic hemoglobinopathy characterized by chronic hemolytic anemia, vaso-occlusion, and organ damage. While acute vaso-occlusive crises (VOC) have been extensively studied, the mechanisms underlying chronic pain and its interplay with brain function remain unclear. This dissertation investigates the relationships between cerebral blood flow (CBF), fluid cognition, and pain sensitivity in adults with SCD, utilizing advanced imaging techniques and validated assessment tools.

Arterial spin labeling (ASL) and functional magnetic resonance imaging (fMRI) were employed to measure CBF and brain activity, respectively. Pain sensitivity was assessed using the Pain Sensitivity Questionnaire (PSQ), and …

Enhancing Clinical Trial Matching In Molecular Diagnostics: Using Natural Language Processing And Clustering Approaches In Hematological Malignancies, Gillian Fanning

Theses and Dissertations

Clinical trial matching is a critical component of personalized medicine, particularly in the management of hematologic malignancies. At Virginia Commonwealth University (VCU) Health, the Molecular Diagnostics (MDX) Lab produces somatic variant reports and recommends clinical trials based on the presence of clinically significant mutations. However, the current manual trial recommendation process is time-intensive and lacks scalability.

This study introduces a computational framework to streamline and standardize clinical trial matching using natural language processing (NLP) and unsupervised clustering. Trial brief descriptions were analyzed to extract frequent terms, and trials were grouped based on term similarity using joint dimensionality reduction and clustering. …

Rare Variant Analysis Of Electronic Health Record-Defined Major Depressive Disorder In The All Of Us Research Program, Stephen Emil Vieno

Theses and Dissertations

The underlying pathogenesis of MDD remains poorly understood, with multiple competing hypotheses regarding its exact etiology. As a heterogeneous disorder with relatively low heritability, large-scale genome-wide association studies of MDD have relied on increasingly large sample sizes to identify common genetic variants associated with the disorder. However, the rare variant genetic architecture of MDD is still largely unknown. The aim of the present analysis was to use the AoU—a United States-based biobank that integrates healthcare records from over 50 healthcare systems and possesses whole genome sequencing data for participants—to perform a gene set–based analysis of MDD. This analysis presented several …