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Full-Text Articles in Medicine and Health Sciences

Phenome-Wide Identification Of Therapeutic Genetic Targets, Leveraging Knowledge Graphs, Graph Neural Networks, And Uk Biobank Data, Lawrence Middleton, Ioannis Melas, Chirag Vasavda, Arwa Raies, Benedek Rozemberczki, Ryan S Dhindsa, Justin S Dhindsa, Blake Weido, Quanli Wang, Andrew R Harper, Gavin Edwards, Slavé Petrovski, Dimitrios Vitsios May 2024

Phenome-Wide Identification Of Therapeutic Genetic Targets, Leveraging Knowledge Graphs, Graph Neural Networks, And Uk Biobank Data, Lawrence Middleton, Ioannis Melas, Chirag Vasavda, Arwa Raies, Benedek Rozemberczki, Ryan S Dhindsa, Justin S Dhindsa, Blake Weido, Quanli Wang, Andrew R Harper, Gavin Edwards, Slavé Petrovski, Dimitrios Vitsios

Faculty, Staff and Students Publications

The ongoing expansion of human genomic datasets propels therapeutic target identification; however, extracting gene-disease associations from gene annotations remains challenging. Here, we introduce Mantis-ML 2.0, a framework integrating AstraZeneca's Biological Insights Knowledge Graph and numerous tabular datasets, to assess gene-disease probabilities throughout the phenome. We use graph neural networks, capturing the graph's holistic structure, and train them on hundreds of balanced datasets via a robust semi-supervised learning framework to provide gene-disease probabilities across the human exome. Mantis-ML 2.0 incorporates natural language processing to automate disease-relevant feature selection for thousands of diseases. The enhanced models demonstrate a 6.9% average classification power …


With Love, ; An Interdisciplinary And Intersectional Look At Why Creativity Is Essential, Theo Starr Gardner May 2024

With Love, ; An Interdisciplinary And Intersectional Look At Why Creativity Is Essential, Theo Starr Gardner

Whittier Scholars Program

My Whittier Scholars Program self-designed major, Teaching Creativity, is a mixture of Art, Literature, and Education classes. My research and praxis classes have been focused on the ‘how?’s and 'why?’s of creativity, so it felt only right that my project should be a constructivist, generative project. The project I have been working on throughout my time at Whittier, and that has just fully come to fruition on April 11th, 2024, was a solo art gallery/open mic event entitled ‘With Love,’. With Love, was conceptually inspired by the research I’ve conducted on creativity and creative arts education over the past few …


Metabarcoding The Mycobiome: An Analysis Of The Gut Mycobiome Of Babies, Daniel B. Colon, Jeremy Seto May 2024

Metabarcoding The Mycobiome: An Analysis Of The Gut Mycobiome Of Babies, Daniel B. Colon, Jeremy Seto

Publications and Research

The human gut mycobiome (the fungus that lives in our gut) has been correlated with overall health and disease in humans. There are several factors that affect the human gut mycobiome including delivery method during birth (vaginal vs. c-section) and the presence or absence of antibiotics at birth. The mycobiome of 140 infants aged newborn to 18 months were tested using fecal samples from 3 different time periods (meconium, 6 months, 18 months). A total of 434 fecal samples were collected. A midwife or nurse collected the meconium samples while the child’s parents collected the samples at the 6-month and …


Mitochondria Regulate Proliferation In Adult Cardiac Myocytes, Gregory B Waypa, Kimberly A Smith, Paul T Mungai, Vincent J Dudley, Kathryn A Helmin, Benjamin D Singer, Clara Bien Peek, Joseph Bass, Lauren Nelson, Sanjiv J Shah, Gaston Ofman, J Andrew Wasserstrom, William A Muller, Alexander V Misharin, G R Scott Budinger, Hiam Abdala-Valencia, Navdeep S Chandel, Danijela Dokic, Elizabeth Bartom, Shuang Zhang, Yuki Tatekoshi, Amir Mahmoodzadeh, Hossein Ardehali, Edward B Thorp, Paul T Schumacker May 2024

Mitochondria Regulate Proliferation In Adult Cardiac Myocytes, Gregory B Waypa, Kimberly A Smith, Paul T Mungai, Vincent J Dudley, Kathryn A Helmin, Benjamin D Singer, Clara Bien Peek, Joseph Bass, Lauren Nelson, Sanjiv J Shah, Gaston Ofman, J Andrew Wasserstrom, William A Muller, Alexander V Misharin, G R Scott Budinger, Hiam Abdala-Valencia, Navdeep S Chandel, Danijela Dokic, Elizabeth Bartom, Shuang Zhang, Yuki Tatekoshi, Amir Mahmoodzadeh, Hossein Ardehali, Edward B Thorp, Paul T Schumacker

Faculty, Staff and Student Publications

Newborn mammalian cardiomyocytes quickly transition from a fetal to an adult phenotype that utilizes mitochondrial oxidative phosphorylation but loses mitotic capacity. We tested whether forced reversal of adult cardiomyocytes back to a fetal glycolytic phenotype would restore proliferative capacity. We deleted Uqcrfs1 (mitochondrial Rieske iron-sulfur protein, RISP) in hearts of adult mice. As RISP protein decreased, heart mitochondrial function declined, and glucose utilization increased. Simultaneously, the hearts underwent hyperplastic remodeling during which cardiomyocyte number doubled without cellular hypertrophy. Cellular energy supply was preserved, AMPK activation was absent, and mTOR activation was evident. In ischemic hearts with RISP deletion, new cardiomyocytes …


How Financial Beliefs And Behaviors Influence The Financial Health Of Individuals Struggling With Opioid Use Disorder, James R Langabeer, Francine R Vega, Marylou Cardenas-Turanzas, A Sarah Cohen, Karima Lalani, Tiffany Champagne-Langabeer May 2024

How Financial Beliefs And Behaviors Influence The Financial Health Of Individuals Struggling With Opioid Use Disorder, James R Langabeer, Francine R Vega, Marylou Cardenas-Turanzas, A Sarah Cohen, Karima Lalani, Tiffany Champagne-Langabeer

Faculty, Staff and Student Publications

The surge in opioid use disorder (OUD) over the past decade escalated opioid overdoses to a leading cause of death in the United States. With adverse effects on cognition, risk-taking, and decision-making, OUD may negatively influence financial well-being. This study examined the financial health of individuals diagnosed with OUD by reviewing financial beliefs and financial behaviors. We evaluated quality of life, perceptions of financial condition during active use and recovery, and total debt. We distributed a 20-item survey to 150 individuals in an outpatient treatment program for OUD in a large metropolitan area, yielding a 56% response rate. The results …


High-Density Genetic Map Construction And Qtl Mapping Of A Zigzag-Shaped Stem Trait In Tea Plant (Camellia Sinensis), Dingding Liu, Yuanyuan Ye, Rongjin Tang, Yang Gong, Si Chen, Chenyu Zhang, Piao Mei, Jiedan Chen, Liang Chen, Chunlei Ma May 2024

High-Density Genetic Map Construction And Qtl Mapping Of A Zigzag-Shaped Stem Trait In Tea Plant (Camellia Sinensis), Dingding Liu, Yuanyuan Ye, Rongjin Tang, Yang Gong, Si Chen, Chenyu Zhang, Piao Mei, Jiedan Chen, Liang Chen, Chunlei Ma

Faculty, Staff and Student Publications

The highly unique zigzag-shaped stem phenotype in tea plants boasts significant ornamental value and is exceptionally rare. To investigate the genetic mechanism behind this trait, we developed BC1 artificial hybrid populations. Our genetic analysis revealed the zigzag-shaped trait as a qualitative trait. Utilizing whole-genome resequencing, we constructed a high-density genetic map from the BC1 population, incorporating 5,250 SNP markers across 15 linkage groups, covering 3,328.51 cM with an average marker interval distance of 0.68 cM. A quantitative trait locus (QTL) for the zigzag-shaped trait was identified on chromosome 4, within a 61.2 to 97.2 Mb range, accounting for a phenotypic …


Physical Activity In Underserved Preadolescents: Characterization Of Accumulation And Patterns, Alma I. Behar, Matthew T. Mahar, Gregory Norman, John P. Elder, Michael Pratt, Patricia Dionicio, Noe C. Crespo May 2024

Physical Activity In Underserved Preadolescents: Characterization Of Accumulation And Patterns, Alma I. Behar, Matthew T. Mahar, Gregory Norman, John P. Elder, Michael Pratt, Patricia Dionicio, Noe C. Crespo

International Journal of Physical Activity and Health

Objectives: The increasing rates of physical inactivity and sedentary behaviors among youth are a significant public health concern. The greatest disparities in physical activity (PA) are experienced by underserved (racial/ethnic minority, low-income) youth. This study aimed to characterize accelerometer-measured PA behaviors in a sample of low-income, predominantly Latino, preadolescents. Methods: Participants wore wrist worn GENEActiv accelerometers for 7 days. PA levels were classified as sedentary (< 50 mg), light (50-150 mg), moderate (> 150-500 mg), vigorous (> 500 mg), and MVPA (≥ 150 mg). Time spent in PA levels and sedentary time (ST), prevalence of meeting MVPA guidelines, and PA volume were estimated from accelerometer data. Three-way …


Characterizing The Expression Of The Sphingosine 1-Phosphate Pathway In Injury And Post-Traumatic Fibrosis, Nicole Cubbage May 2024

Characterizing The Expression Of The Sphingosine 1-Phosphate Pathway In Injury And Post-Traumatic Fibrosis, Nicole Cubbage

Masters Theses, 2020-current

Following injury, tissue repair allows for the restoration of the architecture and function of the injured tissue, while tissue replacement is characterized by severely damaged or non-regenerable tissue that is repaired by the laying down of extensive connective tissue, also known as fibrosis. The fibrotic process should be arrested at its early stage to have the greatest impact on preventing or reversing associate sequelae and promoting the regeneration of normal tissue. Sphingosine 1-phosphate (S1P), a metabolic product of cell membrane sphingolipids, has emerged as a pathway that may be involved in fibrosis. Most of S1P’s actions are mediated through the …


Role Of Dunc-13 Isoforms In Alcohol Sensitivity In Drosophila, Makenzie Havard May 2024

Role Of Dunc-13 Isoforms In Alcohol Sensitivity In Drosophila, Makenzie Havard

Honors Theses

Functional alcohol tolerance is an adaptation made by the nervous system to high doses of alcohol, and is seen by a significant reduction in sensitivity to this drug. This tolerance is a significant contributing factor in the progression to Alcohol Use Disorders. A major goal of alcohol research is to understand how alcohol induces this tolerance. Dunc13 is a presynaptic active zone protein essential in synaptic vesicle docking and priming. Alcohol binds to the C1 domain of Dunc13 at physiological concentrations, which inhibits Dunc13 from binding Diacylglycerol. This inhibition is predicted to reduce Dunc13 activity and presynaptic activity. Yet, genetically …


Casi: A Framework For Cross-Timepoint Analysis Of Single-Cell Rna Sequencing Data, Yizhuo Wang, Christopher R Flowers, Michael Wang, Xuelin Huang, Ziyi Li May 2024

Casi: A Framework For Cross-Timepoint Analysis Of Single-Cell Rna Sequencing Data, Yizhuo Wang, Christopher R Flowers, Michael Wang, Xuelin Huang, Ziyi Li

Faculty, Staff and Student Publications

Single-cell RNA sequencing (scRNA-seq) technology has been widely used to study the differences in gene expression at the single cell level, providing insights into the research of cell development, differentiation, and functional heterogeneity. Various pipelines and workflows of scRNA-seq analysis have been developed but few considered multi-timepoint data specifically. In this study, we develop CASi, a comprehensive framework for analyzing multiple timepoints' scRNA-seq data, which provides users with: (1) cross-timepoint cell annotation, (2) detection of potentially novel cell types emerged over time, (3) visualization of cell population evolution, and (4) identification of temporal differentially expressed genes (tDEGs). Through comprehensive simulation …


Imaging Features Of Primary Intracranial Sarcoma With Dicer1 Mutation: A Multicenter Case Series, Rami W Eldaya, Richard J Fagan, Samir A Dagher, Angshumoy Roy, Sonika Dahyia, Gregory N Fuller, Max Wintermark, Matthew S Parsons, Thierry A G M Huisman May 2024

Imaging Features Of Primary Intracranial Sarcoma With Dicer1 Mutation: A Multicenter Case Series, Rami W Eldaya, Richard J Fagan, Samir A Dagher, Angshumoy Roy, Sonika Dahyia, Gregory N Fuller, Max Wintermark, Matthew S Parsons, Thierry A G M Huisman

Faculty, Staff and Student Publications

Primary intracranial sarcoma, DICER1-mutant, is a rare, recently described entity in the fifth edition of the WHO Classification of CNS Tumors. Given the entity's rarity and recent description, imaging data on primary intracranial sarcoma, DICER1-mutant, remains scarce. In this multicenter case series, we present detailed multimodality imaging features of primary intracranial sarcoma, DICER1-mutant, with emphasis on the appearance of the entity on MR imaging. In total, 8 patients were included. In all 8 patients, the lesion demonstrated blood products on T1WI. In 7 patients, susceptibility-weighted imaging was obtained and demonstrated blood products. Primary intracranial sarcoma, DICER1-mutant, …


Evaluation Of Sleep Outcomes After Traumatic Brain Injury In Children Using Questionnaires And Actigraphy, Connie Tran, Sydney Weese, Cydni Williams Md May 2024

Evaluation Of Sleep Outcomes After Traumatic Brain Injury In Children Using Questionnaires And Actigraphy, Connie Tran, Sydney Weese, Cydni Williams Md

Student Research Symposium

Traumatic brain injuries are the result of a sudden external blunt force to the brain and can result in long-term complications or death. In pediatrics, it is the leading cause of acute and chronic sleep wake disturbances, as well as cognitive deficits, which can lead to a reduction in the quality of life. These impairments can later result in lowered performance in work and school settings or decreased psychosocial function. Although there is sufficient evidence that traumatic brain injuries contribute to is that it is unknown whether or not sleep wake disturbances contribute to an increase in the mentioned cognitive …


Construction And Mutagenesis Of Ssv1 Mutants In Extreme Viruses, Lou Ann F. O'Connor, Jono Abshier, Kenneth M. Stedman May 2024

Construction And Mutagenesis Of Ssv1 Mutants In Extreme Viruses, Lou Ann F. O'Connor, Jono Abshier, Kenneth M. Stedman

Student Research Symposium

Archaeal viruses with unique structures such as spindle-shaped virions are found abundantly in extreme environments like geothermal hot springs around the world. Among all spindle-shaped viruses, the model Sulfolobus Spindle-shaped Virus 1 (SSV1) is best studied. Creating the lemon-shaped or spindle-shaped virion structure are two proteins, VP1 as the major capsid protein, and VP3 as the minor capsid protein. The primary structure of VP1 consists of a proteolytic cleavage site at position 66 that is believed to be necessary for virus evolution. Recent studies showed that genetic mutation of the amino acid, glutamate (E) at position 66 in VP1 which …


Describing Shen & Shen Ming Via A Hybrid Quantum Computational Model, Alex M. Cullen, Johnny Lemau May 2024

Describing Shen & Shen Ming Via A Hybrid Quantum Computational Model, Alex M. Cullen, Johnny Lemau

Student Research Symposium

Definitions for Traditional Chinese Medicine (TCM) terminology within the context of quantum biology (QB) have recently been proposed. These definitions aim to elucidate concepts such as qi meridians in TCM. Our study presents a hypothesis that seeks to provide an operational definition for Spirit (Shen) and Bright Spirit (Shen Ming) in TCM via a scoping review. We propose that Shen represents physical, phenomenological proto-consciousness/consciousness in the forms of computation, such as singular particles/bits/qubits, computers, organisms, or computational strategies, whereas Shen Ming may refer to emergent, quasi-physical meta-proto-consciousness/consciousness formed by coherent relationships of multiple orchestrated/integrated units of computation; manifesting itself as …


Systematic Comparison Of Propensity Score Matching And Structural Causal Modeling For Clinical Applications, With A Case Study Of Albumin Treatment For Acute Kidney Injury (Aki) Patients: Propensity Score Matching Vs. Structural Causal Models, Layaal Khellah May 2024

Systematic Comparison Of Propensity Score Matching And Structural Causal Modeling For Clinical Applications, With A Case Study Of Albumin Treatment For Acute Kidney Injury (Aki) Patients: Propensity Score Matching Vs. Structural Causal Models, Layaal Khellah

Student Research Symposium

Introduction:

Propensity Score Matching (PSM) and Structural Causal Models (SCMs) are key approaches in causal inference for treatment evaluation and clinical decisions, both rooted in the potential outcome framework but differing in their foundations—PSM follows Rubin's Causal Model, while SCMs adhere to the Structural Theory of Causation.

Methods:

Our study compares PSM and SCMs in clinical contexts, focusing on albumin as an AKI treatment. We examine each method's steps, highlighting differences. Using data from AKI patients with cirrhosis, we assess albumin’s treatment efficacy with both PSM and SCMs, offering insights into their performance in estimating causal effects..

Results:

PSM and …


Adapting And Evaluating A Theory-Driven, Non-Pharmacological Intervention To Self-Manage Pain, Jennifer Kawi, Chao Hsing Yeh, Lauren Grant, Johannes Thrul, Hulin Wu, Paul J Christo, Lorraine S Evangelista May 2024

Adapting And Evaluating A Theory-Driven, Non-Pharmacological Intervention To Self-Manage Pain, Jennifer Kawi, Chao Hsing Yeh, Lauren Grant, Johannes Thrul, Hulin Wu, Paul J Christo, Lorraine S Evangelista

Faculty, Staff and Student Publications

BACKGROUND: The existing literature has limited detail on theory-driven interventions, particularly in pain studies. We adapted Bandura's self-efficacy framework toward a theory-driven, non-pharmacological intervention using auricular point acupressure (APA) and evaluated participants' perceptions of this intervention on their pain self-management. APA is a non-invasive modality based on auricular acupuncture principles.

METHODS: We mapped our study intervention components according to Bandura's key sources of self-efficacy (performance accomplishments, vicarious experience, verbal persuasion, and emotional arousal) to facilitate the self-management of pain. Through a qualitative study design, we conducted virtual interviews at one and three months after a 4-week APA intervention among 23 …


Role Of Integrase-Pp2a Interaction In Human T-Cell Leukemia Virus Type-1 Replication And Pathogenesis, Shayna Turbin May 2024

Role Of Integrase-Pp2a Interaction In Human T-Cell Leukemia Virus Type-1 Replication And Pathogenesis, Shayna Turbin

Senior Honors Papers / Undergraduate Theses

Human T-cell leukemia virus type-1 (HTLV-1) is an oncogenic retrovirus that causes multiple disorders, including adult T-cell leukemia and HTLV-1-associated myelopathy/tropical spastic paraparesis. HTLV-1 retroviral integrase binds to the regulatory B’56γ subunit of the host cell Protein Phosphatase 2A (PP2A). Integrase contains a highly conserved LxxIxE motif that is essential for binding, which increases integration efficiency and facilitates HTLV-1 hijack of host cell machinery. We aim to understand how mutations introduced in the highly conserved binding site can affect viral particle production and infectivity. We transfected 729B human lymphoblastoid cells and 293T cells with mutant and wildtype virus. Mutations L213A, …


Immunopathogenesis Of Post-Infectious Hydrocephalus, Sascha Powers Bernier May 2024

Immunopathogenesis Of Post-Infectious Hydrocephalus, Sascha Powers Bernier

Honors Scholar Theses

Hydrocephalus is characterized by the abnormal accumulation of cerebrospinal fluid (CSF) within the brain ventricles. In post-infectious hydrocephalus (PIH) cases, the condition presents challenges in understanding the immune response. PIH is a complex condition, often persisting after the initial infection is treated and thus requiring a deeper understanding of the immune mechanisms involved in its development. This thesis will explore the immunopathogenesis of PIH, elucidating the relationship between the immune response and neurological complications that would succeed infection. The immune response of PIH includes a series of events, beginning with the activation of immune cells and finishing with the release …


Correction: Horne Et Al White Matter Correlates Of Domain-Specific Working Memory, Autumn Horne, Junhua Ding, Tatiana T Schnur, Randi C Martin May 2024

Correction: Horne Et Al White Matter Correlates Of Domain-Specific Working Memory, Autumn Horne, Junhua Ding, Tatiana T Schnur, Randi C Martin

Faculty, Staff and Student Publications

In the original publication [...].


Response To Lao, Guan, Wang, Et Al, Casey Crump, Pär Stattin, James D Brooks, Jan Sundquist, Alexis C Edwards, Kristina Sundquist, Weiva Sieh May 2024

Response To Lao, Guan, Wang, Et Al, Casey Crump, Pär Stattin, James D Brooks, Jan Sundquist, Alexis C Edwards, Kristina Sundquist, Weiva Sieh

Faculty, Staff and Student Publications

No abstract provided.


Exome Sequencing Implicates Ancestry-Related Mendelian Variation At Syne1 In Childhood-Onset Essential Hypertension, Ian Copeland, Edmond Wonkam-Tingang, Monesha Gupta-Malhotra, S Shahrukh Hashmi, Yixing Han, Aarti Jajoo, Nancy J Hall, Paula P Hernandez, Natasha Lie, Dan Liu, Jun Xu, Jill Rosenfeld, Aparna Haldipur, Zelene Desire, Zeynep H Coban-Akdemir, Daryl A Scott, Qing Li, Hsiao-Tuan Chao, Ana M Zaske, James R Lupski, Dianna M Milewicz, Sanjay Shete, Jennifer E Posey, Neil A Hanchard May 2024

Exome Sequencing Implicates Ancestry-Related Mendelian Variation At Syne1 In Childhood-Onset Essential Hypertension, Ian Copeland, Edmond Wonkam-Tingang, Monesha Gupta-Malhotra, S Shahrukh Hashmi, Yixing Han, Aarti Jajoo, Nancy J Hall, Paula P Hernandez, Natasha Lie, Dan Liu, Jun Xu, Jill Rosenfeld, Aparna Haldipur, Zelene Desire, Zeynep H Coban-Akdemir, Daryl A Scott, Qing Li, Hsiao-Tuan Chao, Ana M Zaske, James R Lupski, Dianna M Milewicz, Sanjay Shete, Jennifer E Posey, Neil A Hanchard

Faculty, Staff and Student Publications

Childhood-onset essential hypertension (COEH) is an uncommon form of hypertension that manifests in childhood or adolescence and, in the United States, disproportionately affects children of African ancestry. The etiology of COEH is unknown, but its childhood onset, low prevalence, high heritability, and skewed ancestral demography suggest the potential to identify rare genetic variation segregating in a Mendelian manner among affected individuals and thereby implicate genes important to disease pathogenesis. However, no COEH genes have been reported to date. Here, we identify recessive segregation of rare and putatively damaging missense variation in the spectrin domain of spectrin repeat containing nuclear envelope …


Chronic Stress-Induced Neuroinflammation: Relevance Of Rodent Models To Human Disease., Abigail G White, Elias Elias, Andrea Orozco, Shivon A Robinson, Melissa T Manners May 2024

Chronic Stress-Induced Neuroinflammation: Relevance Of Rodent Models To Human Disease., Abigail G White, Elias Elias, Andrea Orozco, Shivon A Robinson, Melissa T Manners

College of Science & Mathematics Departmental Research

The brain is the central organ of adaptation to stress because it perceives and determines threats that induce behavioral, physiological, and molecular responses. In humans, chronic stress manifests as an enduring consistent feeling of pressure and being overwhelmed for an extended duration. This can result in a persistent proinflammatory response in the peripheral and central nervous system (CNS), resulting in cellular, physiological, and behavioral effects. Compounding stressors may increase the risk of chronic-stress-induced inflammation, which can yield serious health consequences, including mental health disorders. This review summarizes the current knowledge surrounding the neuroinflammatory response in rodent models of chronic stress-a …


Molecular Therapy And Nucleic Acid Adeno-Associated Virus-Based Gene Therapy Delivering Combinations Of Two Growth-Associated Genes To Mps Iva Mice, Estera Rintz, Betul Celik, Nidhi Fnu, Angélica María Herreño-Pachón, Shaukat Khan, Shunji Tomatsu, Eliana Benincore-Flórez May 2024

Molecular Therapy And Nucleic Acid Adeno-Associated Virus-Based Gene Therapy Delivering Combinations Of Two Growth-Associated Genes To Mps Iva Mice, Estera Rintz, Betul Celik, Nidhi Fnu, Angélica María Herreño-Pachón, Shaukat Khan, Shunji Tomatsu, Eliana Benincore-Flórez

Department of Medicine Faculty Papers

Mucopolysaccharidosis type IVA (MPS IVA) is caused by a deficiency of the galactosamine (N-acetyl)-6-sulfatase (GALNS) enzyme responsible for the degradation of specific glycosaminoglycans (GAGs). The progressive accumulation of GAGs leads to various skeletal abnormalities (short stature, hypoplasia, tracheal obstruction) and several symptoms in other organs. To date, no treatment is effective for patients with bone abnormalities. To improve bone pathology, we propose a novel combination treatment with the adeno-associated virus (AAV) vectors expressing GALNS enzyme and a natriuretic peptide C (CNP; NPPC gene) as a growth-promoting agent for MPS IVA. In this study, an MPS IVA mouse model was treated …


Developing And Validating A Nomogram For Early Predicting The Need For Intestinal Resection In Pediatric Intussusception, Yuan-Yang Yu, Jia-Jie Zhang, Ya-Ting Xu, Zheng-Xiu Lin, Shi-Kun Guo, Zhong-Rong Li, Hui-Ya Huang, Xiao-Zhong Huang May 2024

Developing And Validating A Nomogram For Early Predicting The Need For Intestinal Resection In Pediatric Intussusception, Yuan-Yang Yu, Jia-Jie Zhang, Ya-Ting Xu, Zheng-Xiu Lin, Shi-Kun Guo, Zhong-Rong Li, Hui-Ya Huang, Xiao-Zhong Huang

Faculty, Staff and Student Publications

PURPOSE: Develop and validate a nomogram for predicting intestinal resection in pediatric intussusception suspecting intestinal necrosis.

PATIENTS & METHODS: Children with intussusception were retrospectively enrolled after a failed air-enema reduction in the outpatient setting and divided into two groups: the intestinal resection group and the non-intestinal resection group. The enrolled cases were randomly selected for training and validation sets with a split ratio of 3:1. A nomogram for predicting the risk of intestinal resection was visualized using logistic regression analysis with calibration curve, C-index, and decision curve analysis to evaluate the model.

RESULTS: A total of 547 cases were included …


Protein Oxidation In Aging And Alzheimer’S Disease Brain, Rukhsana Sultana, D. Allan Butterfield May 2024

Protein Oxidation In Aging And Alzheimer’S Disease Brain, Rukhsana Sultana, D. Allan Butterfield

Markey Cancer Center Faculty Publications

Proteins are essential molecules that play crucial roles in maintaining cellular homeostasis and carrying out biological functions such as catalyzing biochemical reactions, structural proteins, immune response, etc. However, proteins also are highly susceptible to damage by reactive oxygen species (ROS) and reactive nitrogen species (RNS). In this review, we summarize the role of protein oxidation in normal aging and Alzheimer’s disease (AD). The major emphasis of this review article is on the carbonylation and nitration of proteins in AD and mild cognitive impairment (MCI). The oxidatively modified proteins showed a strong correlation with the reported changes in brain structure, carbohydrate …


Predicting The Pathway Involvement Of Metabolites Based On Combined Metabolite And Pathway Features, Erik D. Huckvale, Hunter N. B. Moseley May 2024

Predicting The Pathway Involvement Of Metabolites Based On Combined Metabolite And Pathway Features, Erik D. Huckvale, Hunter N. B. Moseley

Markey Cancer Center Faculty Publications

A major limitation of most metabolomics datasets is the sparsity of pathway annotations for detected metabolites. It is common for less than half of the identified metabolites in these datasets to have a known metabolic pathway involvement. Trying to address this limitation, machine learning models have been developed to predict the association of a metabolite with a “pathway category”, as defined by a metabolic knowledge base like KEGG. Past models were implemented as a single binary classifier specific to a single pathway category, requiring a set of binary classifiers for generating the predictions for multiple pathway categories. This past approach …


Researching Covid To Enhance Recovery (Recover) Pediatric Study Protocol: Rationale, Objectives And Design, Rachel S. Gross, Tanayott Thaweethai, Erika B. Rosenzweig, James Chan, Lori B. Chibnik, Mine S. Cicek, Amy J. Elliott, Valerie J. Flaherman, Andrea S. Foulkes, Margot Gage Witvliet, Richard Gallagher, Maria Laura Gennaro, Terry L. Jernigan, Elizabeth W. Karlson, Stuart D. Katz, Patricia A. Kinser, Lawrence C. Kleinman, Michelle F. Lamendola-Essel, Joshua D. Milner, Sindhu Mohandas, Praveen C. Mudumbi, Jane W. Newburger, Kyung E. Rhee, Amy L. Salisbury, Jessica N. Snowden, Cheryl R. Stein, Melissa S. Stockwell, Kelan G. Tantisira, Tamara Bradford, Et Al May 2024

Researching Covid To Enhance Recovery (Recover) Pediatric Study Protocol: Rationale, Objectives And Design, Rachel S. Gross, Tanayott Thaweethai, Erika B. Rosenzweig, James Chan, Lori B. Chibnik, Mine S. Cicek, Amy J. Elliott, Valerie J. Flaherman, Andrea S. Foulkes, Margot Gage Witvliet, Richard Gallagher, Maria Laura Gennaro, Terry L. Jernigan, Elizabeth W. Karlson, Stuart D. Katz, Patricia A. Kinser, Lawrence C. Kleinman, Michelle F. Lamendola-Essel, Joshua D. Milner, Sindhu Mohandas, Praveen C. Mudumbi, Jane W. Newburger, Kyung E. Rhee, Amy L. Salisbury, Jessica N. Snowden, Cheryl R. Stein, Melissa S. Stockwell, Kelan G. Tantisira, Tamara Bradford, Et Al

School of Medicine Faculty Publications

Importance The prevalence, pathophysiology, and long-term outcomes of COVID-19 (post-acute sequelae of SARS-CoV-2 [PASC] or “Long COVID”) in children and young adults remain unknown. Studies must address the urgent need to define PASC, its mechanisms, and potential treatment targets in children and young adults. Observations We describe the protocol for the Pediatric Observational Cohort Study of the NIH’s REsearching COVID to Enhance Recovery (RECOVER) Initiative. RECOVER-Pediatrics is an observational meta-cohort study of caregiver-child pairs (birth through 17 years) and young adults (18 through 25 years), recruited from more than 100 sites across the US. This report focuses on two of …


Single Extracellular Vesicle Imaging And Computational Analysis Identifies Inherent Architectural Heterogeneity, Kshipra S Kapoor, Seoyun Kong, Hikaru Sugimoto, Wenhua Guo, Vivek Boominathan, Yi-Lin Chen, Sibani Lisa Biswal, Tanguy Terlier, Kathleen M Mcandrews, Raghu Kalluri May 2024

Single Extracellular Vesicle Imaging And Computational Analysis Identifies Inherent Architectural Heterogeneity, Kshipra S Kapoor, Seoyun Kong, Hikaru Sugimoto, Wenhua Guo, Vivek Boominathan, Yi-Lin Chen, Sibani Lisa Biswal, Tanguy Terlier, Kathleen M Mcandrews, Raghu Kalluri

Faculty, Staff and Student Publications

Evaluating the heterogeneity of extracellular vesicles (EVs) is crucial for unraveling their complex actions and biodistribution. Here, we identify consistent architectural heterogeneity of EVs using cryogenic transmission electron microscopy (cryo-TEM), which has an inherent ability to image biological samples without harsh labeling methods while preserving their native conformation. Imaging EVs isolated using different methodologies from distinct sources, such as cancer cells, normal cells, immortalized cells, and body fluids, we identify a structural atlas of their dominantly consistent shapes. We identify EV architectural attributes by utilizing a segmentation neural network model. In total, 7,576 individual EVs were imaged and quantified by …


Histone Demethylase Kdm5 Regulates Cardiomyocyte Maturation By Promoting Fatty Acid Oxidation, Oxidative Phosphorylation, And Myofibrillar Organization, Manisha Deogharia, Leslye Venegas-Zamora, Akanksha Agrawal, Miusi Shi, Abhinav K Jain, Kevin J Mchugh, Francisco Altamirano, Ali J Marian, Priyatansh Gurha May 2024

Histone Demethylase Kdm5 Regulates Cardiomyocyte Maturation By Promoting Fatty Acid Oxidation, Oxidative Phosphorylation, And Myofibrillar Organization, Manisha Deogharia, Leslye Venegas-Zamora, Akanksha Agrawal, Miusi Shi, Abhinav K Jain, Kevin J Mchugh, Francisco Altamirano, Ali J Marian, Priyatansh Gurha

Faculty, Staff and Student Publications

Aims: Human pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) provide a platform to identify and characterize factors that regulate the maturation of CMs. The transition from an immature foetal to an adult CM state entails coordinated regulation of the expression of genes involved in myofibril formation and oxidative phosphorylation (OXPHOS) among others. Lysine demethylase 5 (KDM5) specifically demethylates H3K4me1/2/3 and has emerged as potential regulators of expression of genes involved in cardiac development and mitochondrial function. The purpose of this study is to determine the role of KDM5 in iPSC-CM maturation.

Methods and results: KDM5A, B, and C proteins were mainly expressed …


Effects Of Improved Amino Acid Balance Diet On Lysine Mammary Utilization, Whole Body Protein Turnover And Muscle Protein Breakdown On Lactating Sows, Sai Zhang, Juan C Marini, Vengai Mavangira, Andrew Claude, Julie Moore, Mahmoud A Mohammad, Nathalie L Trottier May 2024

Effects Of Improved Amino Acid Balance Diet On Lysine Mammary Utilization, Whole Body Protein Turnover And Muscle Protein Breakdown On Lactating Sows, Sai Zhang, Juan C Marini, Vengai Mavangira, Andrew Claude, Julie Moore, Mahmoud A Mohammad, Nathalie L Trottier

Children’s Nutrition Research Center Staff Publications

Background: The study objective was to test the hypothesis that low crude protein (CP) diet with crystalline amino acids (CAA) supplementation improves Lys utilization efficiency for milk production and reduces protein turnover and muscle protein breakdown. Eighteen lactating multiparous Yorkshire sows were allotted to 1 of 2 isocaloric diets (10.80 MJ/kg net energy): control (CON; 19.24% CP) and reduced CP with "optimal" AA profile (OPT; 14.00% CP). Sow body weight and backfat were recorded on d 1 and 21 of lactation and piglets were weighed on d 1, 14, 18, and 21 of lactation. Between d 14 and 18, a …