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Atrial Fibrillation Induced By Anticancer Drugs And Underling Mechanisms., Alexander Burashnikov Oct 2022

Atrial Fibrillation Induced By Anticancer Drugs And Underling Mechanisms., Alexander Burashnikov

Division of Cardiology Faculty Papers

Cancer therapy has made major progress in the past several decades, but treatments are often accompanied by significant side effects. Arrhythmias are a widespread complication of some antineoplastic drugs, with atrial fibrillation (AF) being the most often encountered drug-associated arrhythmia. Preexisting AF risk factors are commonly present in cancer patients who develop drug-associated AF, and active cancer itself may cause or promote AF. Although anticancer drugs may induce AF in cancer patients without AF risk factors, it appears that most drug-associated AF develop when cancer drugs add or aggravate precancer-existing and/or cancer-related pro-AF factors/alterations, additively or synergistically producing AF. Abnormalities …


Influence Of Pregabalin Maintenance On Cannabis Effects And Related Behaviors In Daily Cannabis Users, Joshua A Lile, Joseph L Alcorn, Lon R Hays, Thomas H Kelly, William W Stoops, Michael J Wesley, Philip M Westgate Oct 2022

Influence Of Pregabalin Maintenance On Cannabis Effects And Related Behaviors In Daily Cannabis Users, Joshua A Lile, Joseph L Alcorn, Lon R Hays, Thomas H Kelly, William W Stoops, Michael J Wesley, Philip M Westgate

Faculty, Staff and Student Publications

No medications are approved for cannabis use disorder (CUD), though a small clinical trial demonstrated that the voltage-dependent calcium channel (VDCC) ligand gabapentin reduced cannabis use in treatment seekers. VDCCs are modulated by cannabinoid (CB) ligands, and there are shared effects between CB agonists and VDCC ligands. This overlapping neuropharmacology and the initial clinical results supported the evaluation of pregabalin, a "next-generation" VDCC ligand, as a CUD medication. Two separate placebo-controlled, double-blind, counterbalanced, within-subjects human laboratory studies tested placebo and 300 (N = 2 females, 11 males; Experiment [EXP] 1) or 450 (N = 3 females, 11 males; …


Outcomes Of Children With Low-Grade Gliomas In Low- And Middle-Income Countries: A Systematic Review, Richard Ward, Hannah M Jones, Davis Witt, Frederick Boop, Eric Bouffet, Carlos Rodriguez-Galindo, Ibrahim Qaddoumi, Daniel C Moreira Oct 2022

Outcomes Of Children With Low-Grade Gliomas In Low- And Middle-Income Countries: A Systematic Review, Richard Ward, Hannah M Jones, Davis Witt, Frederick Boop, Eric Bouffet, Carlos Rodriguez-Galindo, Ibrahim Qaddoumi, Daniel C Moreira

Department of Medical Oncology Faculty Papers

Purpose: Pediatric CNS tumors are increasingly a priority, particularly with the WHO designation of low-grade glioma (LGG) as one of six index childhood cancers. There are currently limited data on outcomes of pediatric patients with LGGs in low- and middle-income countries (LMICs).

Methods: To better understand the outcomes of LGGs in LMICs, this systematic review interrogated nine literature databases.

Results: The search identified 14,977 publications. Sixteen studies from 19 countries met the selection criteria and were included for data abstraction and analysis. Eleven studies (69%) were retrospective reviews from single institutions, and one (6%) captured institutional data prospectively. The studies …


Crucial Nuances In Understanding (Mis)Associations Between The Neonatal Microbiome And Cesarean Delivery, Alexa M Sassin, Grace J Johnson, Alison N Goulding, Kjersti M Aagaard Oct 2022

Crucial Nuances In Understanding (Mis)Associations Between The Neonatal Microbiome And Cesarean Delivery, Alexa M Sassin, Grace J Johnson, Alison N Goulding, Kjersti M Aagaard

Faculty, Staff and Students Publications

As rates of Cesarean delivery and common non-communicable disorders (NCDs), such as obesity, metabolic disease, and atopy/asthma, have concomitantly increased in recent decades, investigators have attempted to discern a causal link. One line of research has led to a hypothesis that Cesarean birth disrupts the presumed normal process of colonization of the neonatal microbiome with vaginal microbes, yielding NCDs later in life. However, a direct link between a disrupted microbiota transfer at time of delivery and acute and/or chronic illness in infants born via Cesarean has not been causally established. Microbiota seeding from maternal vaginal or stool sources has been …


Children With Functional Abdominal Pain Disorders Successfully Decrease Fodmap Food Intake On A Low Fodmap Diet With Modest Improvements In Nutritional Intake And Diet Quality, Vishnu Narayana, Ann R Mcmeans, Rona L Levy, Robert J Shulman, Bruno P Chumpitazi Oct 2022

Children With Functional Abdominal Pain Disorders Successfully Decrease Fodmap Food Intake On A Low Fodmap Diet With Modest Improvements In Nutritional Intake And Diet Quality, Vishnu Narayana, Ann R Mcmeans, Rona L Levy, Robert J Shulman, Bruno P Chumpitazi

Faculty, Staff and Students Publications

BACKGROUND: We sought to determine how a low fermentable oligosaccharide, disaccharide, monosaccharide, and polyol (FODMAP) diet (LFD) affected high FODMAP food intake, nutrient intake, and diet quality in children with functional abdominal pain disorders (FAPD).

METHODS: Children (ages 7-13 years) with Rome IV FAPD began a dietitian-guided LFD. Three-day food records were captured at baseline and 2-3 weeks into the LFD. Intake of high FODMAP foods, energy, macronutrients, micronutrients, food groups, and ultra-processed foods were determined.

KEY RESULTS: Median age of participants was 11 years, and 19/31 (61%) were female. Twenty-eight (90%) decreased high FODMAP food intake on the LFD: …


Covid Community-Engaged Testing In Alabama: Reaching Underserved Rural Populations Through Collaboration, Christopher Greer Mccollum, Thomas N Creger, Aadia I Rana, Lynn T Matthews, Stefan D Baral, Greer A Burkholder, William A Curry, Latesha Elopre, Faith E Fletcher, Sydney Grooms, Emily B Levitan, Max Michael, Barbara Van Der Pol, Michael J Mugavero Oct 2022

Covid Community-Engaged Testing In Alabama: Reaching Underserved Rural Populations Through Collaboration, Christopher Greer Mccollum, Thomas N Creger, Aadia I Rana, Lynn T Matthews, Stefan D Baral, Greer A Burkholder, William A Curry, Latesha Elopre, Faith E Fletcher, Sydney Grooms, Emily B Levitan, Max Michael, Barbara Van Der Pol, Michael J Mugavero

Faculty, Staff and Students Publications

Rural communities are often underserved by public health testing initiatives in Alabama. As part of the National Institutes of Health's Rapid Acceleration of Diagnostics‒Underserved Populations initiative, the University of Alabama at Birmingham, along with community partners, sought to address this inequity in COVID-19 testing. We describe the participatory assessment, selection, and implementation phases of this project, which administered more than 23 000 COVID-19 tests throughout the state, including nearly 4000 tests among incarcerated populations. (


The Association Of Baseline Plasma Sars-Cov-2 Nucleocapsid Antigen Level And Outcomes In Patients Hospitalized With Covid-19, Activ-3/Tico Study Group, Angela J Rogers, Deborah Wentworth, Andrew Phillips, Katy Shaw-Saliba, Robin L Dewar, Neil R Aggarwal, Abdel G Babiker, Weizhong Chang, Nila J Dharan, Victoria J Davey, Elizabeth S Higgs, Norman Gerry, Adit A Ginde, J W Awori Hayanga, Helene Highbarger, Jeroen L Highbarger, Mamta K Jain, Virginia Kan, Kami Kim, Perrine Lallemand, Bradley G Leshnower, Joseph K Lutaakome, Gail Matthews, Ahmad Mourad, Eleftherios Mylonakis, Ven Natarajan, Maria L Padilla, Lavannya M Pandit, Roger Paredes, Sarah Pett, Srikanth Ramachandruni, M Tauseef Rehman, Brad T Sherman, D Clark Files, Samuel M Brown, Michael A Matthay, B Taylor Thompson, James D Neaton, H Clifford Lane, Jens D Lundgren Oct 2022

The Association Of Baseline Plasma Sars-Cov-2 Nucleocapsid Antigen Level And Outcomes In Patients Hospitalized With Covid-19, Activ-3/Tico Study Group, Angela J Rogers, Deborah Wentworth, Andrew Phillips, Katy Shaw-Saliba, Robin L Dewar, Neil R Aggarwal, Abdel G Babiker, Weizhong Chang, Nila J Dharan, Victoria J Davey, Elizabeth S Higgs, Norman Gerry, Adit A Ginde, J W Awori Hayanga, Helene Highbarger, Jeroen L Highbarger, Mamta K Jain, Virginia Kan, Kami Kim, Perrine Lallemand, Bradley G Leshnower, Joseph K Lutaakome, Gail Matthews, Ahmad Mourad, Eleftherios Mylonakis, Ven Natarajan, Maria L Padilla, Lavannya M Pandit, Roger Paredes, Sarah Pett, Srikanth Ramachandruni, M Tauseef Rehman, Brad T Sherman, D Clark Files, Samuel M Brown, Michael A Matthay, B Taylor Thompson, James D Neaton, H Clifford Lane, Jens D Lundgren

Faculty, Staff and Students Publications

BACKGROUND: Levels of plasma SARS-CoV-2 nucleocapsid (N) antigen may be an important biomarker in patients with COVID-19 and enhance our understanding of the pathogenesis of COVID-19.

OBJECTIVE: To evaluate whether levels of plasma antigen can predict short-term clinical outcomes and identify clinical and viral factors associated with plasma antigen levels in hospitalized patients with SARS-CoV-2.

DESIGN: Cross-sectional study of baseline plasma antigen level from 2540 participants enrolled in the TICO (Therapeutics for Inpatients With COVID-19) platform trial from August 2020 to November 2021, with additional data on day 5 outcome and time to discharge.

SETTING: 114 centers in 10 countries. …


Imbalanced Il-37/Tnf-Α/Ctss Signaling Disrupts Corneal Epithelial Barrier In A Dry Eye Model In Vitro, Yun Zhang, Jin-Miao Li, Rong Lu, Zhao Liu, Xin Chen, Cintia S De Paiva, Stephen C Pflugfelder, De-Quan Li Oct 2022

Imbalanced Il-37/Tnf-Α/Ctss Signaling Disrupts Corneal Epithelial Barrier In A Dry Eye Model In Vitro, Yun Zhang, Jin-Miao Li, Rong Lu, Zhao Liu, Xin Chen, Cintia S De Paiva, Stephen C Pflugfelder, De-Quan Li

Faculty, Staff and Students Publications

PURPOSE: To explore novel role and molecular mechanism of a natural anti-inflammatory cytokine interleukin (IL) 37 in preventing corneal epithelial barrier disruption from hyperosmolar stress as can occur in dry eye disease.

METHODS: Primary human corneal epithelial cells (HCECs) were cultured from fresh donor limbal explants. An in vitro dry eye model with hyperosmolar stress was established by switching HCECs from isosmolar (312mOsM) to hyperosmolar medium (350-500 mOsM), and some cells were treated with rhIL-37 or rhTNF-α, for different periods (2-48 h). The expression of cytokines and cathepsin S, and barrier protein integrity were evaluated by RT-qPCR, ELISA, and immunofluorescent …


Human Herpesvirus 8-Negative Effusion-Based Large B-Cell Lymphoma: A Distinct Entity With Unique Clinicopathologic Characteristics, Savanah D. Gisriel, Ji Yuan, Ryan C. Braunberger, Danielle L V Maracaja, Xueyan Chen, Xiaojun Wu, Jenna Mccracken, Mingyi Chen, Yi Xie, Laura E. Brown, Peng Li, Yi Zhou, Tarsheen Sethi, Austin Mchenry, Ronald G. Hauser, Nathan Paulson, Haiming Tang, Eric D. Hsi, Endi Wang, Qian-Yun Zhang, Ken H. Young, Mina L. Xu, Zenggang Pan Oct 2022

Human Herpesvirus 8-Negative Effusion-Based Large B-Cell Lymphoma: A Distinct Entity With Unique Clinicopathologic Characteristics, Savanah D. Gisriel, Ji Yuan, Ryan C. Braunberger, Danielle L V Maracaja, Xueyan Chen, Xiaojun Wu, Jenna Mccracken, Mingyi Chen, Yi Xie, Laura E. Brown, Peng Li, Yi Zhou, Tarsheen Sethi, Austin Mchenry, Ronald G. Hauser, Nathan Paulson, Haiming Tang, Eric D. Hsi, Endi Wang, Qian-Yun Zhang, Ken H. Young, Mina L. Xu, Zenggang Pan

Pathology Research and Scholarship

Rare cases of human herpesvirus 8 (HHV8)-negative effusion-based large B-cell lymphoma (EB-LBCL) occur in body cavities without antecedent or concurrent solid mass formation. In contrast to HHV8 + primary effusion lymphoma (PEL), EB-LBCL has no known association with HIV or HHV8 infection. However, the small sample sizes of case reports and series worldwide, especially from non-Japanese regions, have precluded diagnostic uniformity. Therefore, we conducted a retrospective, multi-institutional study of 55 cases of EB-LBCL and performed a comprehensive review of an additional 147 cases from the literature to identify distinct clinicopathologic characteristics. In our study, EB-LBCL primarily affected elderly (median age …


Svat: Secure Outsourcing Of Variant Annotation And Genotype Aggregation, Miran Kim, Su Wang, Xiaoqian Jiang, Arif Harmanci Oct 2022

Svat: Secure Outsourcing Of Variant Annotation And Genotype Aggregation, Miran Kim, Su Wang, Xiaoqian Jiang, Arif Harmanci

Faculty, Staff and Student Publications

BACKGROUND: Sequencing of thousands of samples provides genetic variants with allele frequencies spanning a very large spectrum and gives invaluable insight into genetic determinants of diseases. Protecting the genetic privacy of participants is challenging as only a few rare variants can easily re-identify an individual among millions. In certain cases, there are policy barriers against sharing genetic data from indigenous populations and stigmatizing conditions.

RESULTS: We present SVAT, a method for secure outsourcing of variant annotation and aggregation, which are two basic steps in variant interpretation and detection of causal variants. SVAT uses homomorphic encryption to encrypt the data at …


Development Of The Invasive Candidiasis Discharge [I Can Discharge] Model: A Mixed Methods Analysis, Jinhee Jo, Truc T Tran, Nicholas D Beyda, Debora Simmons, Joshua A Hendrickson, Masaad Saeed Almutairi, Faris S Alnezary, Anne J Gonzales-Luna, Edward J Septimus, Kevin W Garey Oct 2022

Development Of The Invasive Candidiasis Discharge [I Can Discharge] Model: A Mixed Methods Analysis, Jinhee Jo, Truc T Tran, Nicholas D Beyda, Debora Simmons, Joshua A Hendrickson, Masaad Saeed Almutairi, Faris S Alnezary, Anne J Gonzales-Luna, Edward J Septimus, Kevin W Garey

Faculty, Staff and Student Publications

Patients with invasive candidiasis (IC) have complex medical and infectious disease problems that often require continued care after discharge. This study aimed to assess echinocandin use at hospital discharge and develop a transition of care (TOC) model to facilitate discharge for patients with IC. This was a mixed method study design that used epidemiologic assessment to better understand echinocandin use at hospital discharge TOC. Using grounded theory methodology focused on patients given echinocandins during their last day of hospitalization, a TOC model for patients with IC, the invasive candidiasis [I Can] discharge model was developed to better understand discharge barriers. …


Aging After Stroke: How To Define Post-Stroke Sarcopenia And What Are Its Risk Factors?, Sheng Li, Javier Gonzalez-Buonomo, Jaskiran Ghuman, Xinran Huang, Aila Malik, Nuray Yozbatiran, Elaine Magat, Gerard E Francisco, Hulin Wu, Walter R Frontera Oct 2022

Aging After Stroke: How To Define Post-Stroke Sarcopenia And What Are Its Risk Factors?, Sheng Li, Javier Gonzalez-Buonomo, Jaskiran Ghuman, Xinran Huang, Aila Malik, Nuray Yozbatiran, Elaine Magat, Gerard E Francisco, Hulin Wu, Walter R Frontera

Faculty, Staff and Student Publications

BACKGROUND: Sarcopenia, generally described as "aging-related loss of skeletal muscle mass and function", can occur secondary to a systemic disease.

AIM: This project aimed to study the prevalence of sarcopenia in chronic ambulatory stroke survivors and its associated risk factors using the two most recent diagnostic criteria.

DESIGN: A cross-sectional observational study.

SETTING: A scientific laboratory.

POPULATION: Chronic stroke.

METHODS: Twenty-eight ambulatory chronic stroke survivors (12 females; mean age=57.8±11.8 years; time after stroke=76±45 months), hand-grip strength, gait speed, and appendicular skeletal muscle mass (ASM) were measured to define sarcopenia. Risk factors, including motor impairment and spasticity, were identified using regression …


Perspectives Of Zambian Clinical Oncology Trainees In The Md Anderson And Zambia Virtual Clinical Research Training Program (Mozart), Kevin Diao, Darya A Kizub, Noveen Ausat, Catherine K Mwaba, Chidinma P Anakwenze Akinfenwa, Carrie A Cameron, Elizabeth Y Chiao, Dorothy C Lombe, Susan C Msadabwe, Lilie L Lin Oct 2022

Perspectives Of Zambian Clinical Oncology Trainees In The Md Anderson And Zambia Virtual Clinical Research Training Program (Mozart), Kevin Diao, Darya A Kizub, Noveen Ausat, Catherine K Mwaba, Chidinma P Anakwenze Akinfenwa, Carrie A Cameron, Elizabeth Y Chiao, Dorothy C Lombe, Susan C Msadabwe, Lilie L Lin

Faculty, Staff and Student Publications

BACKGROUND: African countries are underrepresented in cancer research, partly because of a lack of structured curricula on clinical research during medical education. To address this need, the MD Anderson and Zambia Virtual Clinical Research Training Program (MOZART) was developed jointly by MD Anderson Cancer Center (MDA) and the Cancer Diseases Hospital in Zambia (CDH) for Zambian clinical oncology trainees. We explored participant perspectives to provide insight for implementation of similar efforts.

MATERIALS AND METHODS: The MD Anderson and Zambia Virtual Clinical Research Training Program consisted of weekly virtual lectures and support of Zambian-led research protocols through longitudinal mentorship groups that …


Brequinar And Dipyridamole In Combination Exhibits Synergistic Antiviral Activity Against Sars-Cov-2 In Vitro: Rationale For A Host-Acting Antiviral Treatment Strategy For Covid-19, James F Demarest, Maryline Kienle, Ruthmabel Boytz, Mary Ayres, Eun Jung Kim, J J Patten, Donghoon Chung, Varsha Gandhi, Robert A Davey, David B Sykes, Nadim Shohdy, John C Pottage, Vikram S Kumar Oct 2022

Brequinar And Dipyridamole In Combination Exhibits Synergistic Antiviral Activity Against Sars-Cov-2 In Vitro: Rationale For A Host-Acting Antiviral Treatment Strategy For Covid-19, James F Demarest, Maryline Kienle, Ruthmabel Boytz, Mary Ayres, Eun Jung Kim, J J Patten, Donghoon Chung, Varsha Gandhi, Robert A Davey, David B Sykes, Nadim Shohdy, John C Pottage, Vikram S Kumar

Faculty, Staff and Student Publications

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19) and the associated global pandemic resulting in >400 million infections worldwide and several million deaths. The continued evolution of SARS-CoV-2 to potentially evade vaccines and monoclonal antibody (mAb)-based therapies and the limited number of authorized small-molecule antivirals necessitates the need for development of new drug treatments. There remains an unmet medical need for effective and convenient treatment options for SARS-CoV-2 infection. SARS-CoV-2 is an RNA virus that depends on host intracellular ribonucleotide pools for its replication. Dihydroorotate dehydrogenase (DHODH) is a ubiquitous host …


Sex-Specific Epigenetic Development In The Mouse Hypothalamic Arcuate Nucleus Pinpoints Human Genomic Regions Associated With Body Mass Index, Harry Mackay, Chathura J Gunasekara, Kit-Yi Yam, Dollada Srisai, Hari Krishna Yalamanchili, Yumei Li, Rui Chen, Cristian Coarfa, Robert A Waterland Sep 2022

Sex-Specific Epigenetic Development In The Mouse Hypothalamic Arcuate Nucleus Pinpoints Human Genomic Regions Associated With Body Mass Index, Harry Mackay, Chathura J Gunasekara, Kit-Yi Yam, Dollada Srisai, Hari Krishna Yalamanchili, Yumei Li, Rui Chen, Cristian Coarfa, Robert A Waterland

Duncan NRI Faculty and Staff Publications

Recent genome-wide association studies corroborate classical research on developmental programming indicating that obesity is primarily a neurodevelopmental disease strongly influenced by nutrition during critical ontogenic windows. Epigenetic mechanisms regulate neurodevelopment; however, little is known about their role in establishing and maintaining the brain's energy balance circuitry. We generated neuron and glia methylomes and transcriptomes from male and female mouse hypothalamic arcuate nucleus, a key site for energy balance regulation, at time points spanning the closure of an established critical window for developmental programming of obesity risk. We find that postnatal epigenetic maturation is markedly cell type and sex specific and …


Neurons Burdened By Dna Double-Strand Breaks Incite Microglia Activation Through Antiviral-Like Signaling In Neurodegeneration, Gwyneth M Welch, Carles A Boix, Eloi Schmauch, Jose Davila-Velderrain, Matheus B Victor, Vishnu Dileep, P Lorenzo Bozzelli, Qiao Su, Jemmie D Cheng, Audrey Lee, Noelle S Leary, Andreas R Pfenning, Manolis Kellis, Li-Huei Tsai Sep 2022

Neurons Burdened By Dna Double-Strand Breaks Incite Microglia Activation Through Antiviral-Like Signaling In Neurodegeneration, Gwyneth M Welch, Carles A Boix, Eloi Schmauch, Jose Davila-Velderrain, Matheus B Victor, Vishnu Dileep, P Lorenzo Bozzelli, Qiao Su, Jemmie D Cheng, Audrey Lee, Noelle S Leary, Andreas R Pfenning, Manolis Kellis, Li-Huei Tsai

Faculty, Staff and Students Publications

DNA double-strand breaks (DSBs) are linked to neurodegeneration and senescence. However, it is not clear how DSB-bearing neurons influence neuroinflammation associated with neurodegeneration. Here, we characterize DSB-bearing neurons from the CK-p25 mouse model of neurodegeneration using single-nucleus, bulk, and spatial transcriptomic techniques. DSB-bearing neurons enter a late-stage DNA damage response marked by nuclear factor κB (NFκB)-activated senescent and antiviral immune pathways. In humans, Alzheimer's disease pathology is closely associated with immune activation in excitatory neurons. Spatial transcriptomics reveal that regions of CK-p25 brain tissue dense with DSB-bearing neurons harbor signatures of inflammatory microglia, which is ameliorated by NFκB knockdown in …


Sequencing Individual Genomes With Recurrent Genomic Disorder Deletions: An Approach To Characterize Genes For Autosomal Recessive Rare Disease Traits, Bo Yuan, Katharina V Schulze, Nurit Assia Batzir, Jefferson Sinson, Hongzheng Dai, Wenmiao Zhu, Francia Bocanegra, Chin-To Fong, Jimmy Holder, Joanne Nguyen, Christian P Schaaf, Yaping Yang, Weimin Bi, Christine Eng, Chad Shaw, James R Lupski, Pengfei Liu Sep 2022

Sequencing Individual Genomes With Recurrent Genomic Disorder Deletions: An Approach To Characterize Genes For Autosomal Recessive Rare Disease Traits, Bo Yuan, Katharina V Schulze, Nurit Assia Batzir, Jefferson Sinson, Hongzheng Dai, Wenmiao Zhu, Francia Bocanegra, Chin-To Fong, Jimmy Holder, Joanne Nguyen, Christian P Schaaf, Yaping Yang, Weimin Bi, Christine Eng, Chad Shaw, James R Lupski, Pengfei Liu

Children’s Nutrition Research Center Staff Publications

Background: In medical genetics, discovery and characterization of disease trait contributory genes and alleles depends on genetic reasoning, study design, and patient ascertainment; we suggest a segmental haploid genetics approach to enhance gene discovery and molecular diagnostics.

Methods: We constructed a genome-wide map for nonallelic homologous recombination (NAHR)-mediated recurrent genomic deletions and used this map to estimate population frequencies of NAHR deletions based on large-scale population cohorts and region-specific studies. We calculated recessive disease carrier burden using high-quality pathogenic or likely pathogenic variants from ClinVar and gnomAD. We developed a NIRD (NAHR deletion Impact to Recessive Disease) score for recessive …


Identification Of An Early Survival Prognostic Gene Signature For Localized Osteosarcoma Patients, Harry Mackay, Chathura J Gunasekara, Kit-Yi Yam, Dollada Srisai, Hari Krishna Yalamanchili, Yumei Li, Rui Chen, Cristian Coarfa, Robert A Waterland Sep 2022

Identification Of An Early Survival Prognostic Gene Signature For Localized Osteosarcoma Patients, Harry Mackay, Chathura J Gunasekara, Kit-Yi Yam, Dollada Srisai, Hari Krishna Yalamanchili, Yumei Li, Rui Chen, Cristian Coarfa, Robert A Waterland

Faculty, Staff and Students Publications

Recent genome-wide association studies corroborate classical research on developmental programming indicating that obesity is primarily a neurodevelopmental disease strongly influenced by nutrition during critical ontogenic windows. Epigenetic mechanisms regulate neurodevelopment; however, little is known about their role in establishing and maintaining the brain's energy balance circuitry. We generated neuron and glia methylomes and transcriptomes from male and female mouse hypothalamic arcuate nucleus, a key site for energy balance regulation, at time points spanning the closure of an established critical window for developmental programming of obesity risk. We find that postnatal epigenetic maturation is markedly cell type and sex specific and …


Modeling Multivariate Age-Related Imaging Variables With Dependencies, Hwiyoung Lee, Chixiang Chen, Peter Kochunov, Liyi Elliot Hong, Shuo Chen Sep 2022

Modeling Multivariate Age-Related Imaging Variables With Dependencies, Hwiyoung Lee, Chixiang Chen, Peter Kochunov, Liyi Elliot Hong, Shuo Chen

Faculty, Staff and Student Publications

Neuroimaging techniques have been increasingly used to understand the neural biology of aging brains. The neuroimaging variables from distinct brain locations and modalities can exhibit age-related patterns that reflect localized neural decline. However, it is a challenge to identify the impacts of risk factors (eg, mental disorders) on multivariate imaging variables while simultaneously accounting for the dependence structure and nonlinear age trajectories using existing tools. We propose a mixed-effects model to address this challenge by building random effects based on the latent brain aging status. We develop computationally efficient algorithms to estimate the parameters of new random effects. The simulations …


Mixed Random And Nonrandom Allocation, And Group Randomization Have Been Mislabeled And Misanalysed, Necessitating Reanalysis Comment On Conner Et Al Kiwic For Vitality: Results Of A Randomized Placebo-Controlled Trial Testing The Effects Of Kiwifruit Or Vitamin C Tablets On Vitality In Adults With Low Vitamin C Levels, Colby J Vorland, Yasaman Jamshidi-Naeini, Lilian Golzarri-Arroyo, Andrew W Brown, David B Allison Sep 2022

Mixed Random And Nonrandom Allocation, And Group Randomization Have Been Mislabeled And Misanalysed, Necessitating Reanalysis Comment On Conner Et Al Kiwic For Vitality: Results Of A Randomized Placebo-Controlled Trial Testing The Effects Of Kiwifruit Or Vitamin C Tablets On Vitality In Adults With Low Vitamin C Levels, Colby J Vorland, Yasaman Jamshidi-Naeini, Lilian Golzarri-Arroyo, Andrew W Brown, David B Allison

Children’s Nutrition Research Center Staff Publications

We read the report by Conner and colleagues that tested whether kiwifruit or vitamin C affected measures of vitality [...].


Public Health Information Seeking, Trust, And Covid-19 Prevention Behaviors: Cross-Sectional Study, Emmanuel Kwabena Tetteh, Todd Combs, Elvin Hsing Geng, Virginia Ruth Mckay Sep 2022

Public Health Information Seeking, Trust, And Covid-19 Prevention Behaviors: Cross-Sectional Study, Emmanuel Kwabena Tetteh, Todd Combs, Elvin Hsing Geng, Virginia Ruth Mckay

2020-Current year OA Pubs

BACKGROUND: Preventative health measures such as shelter in place and mask wearing have been widely encouraged to curb the spread of the COVID-19 disease. People's attitudes toward preventative behaviors may be dependent on their sources of information and trust in the information.

OBJECTIVE: The aim of this study was to understand the relationship between trusting in COVID-19 information and preventative behaviors in a racially and politically diverse metropolitan area in the United States.

METHODS: We conducted a web-based cross-sectional survey of residents in St. Louis City and County in Missouri. Individuals aged ≥18 years were eligible to participate. Participants were …


Video-Urodynamics Efficacy Of Sacral Neuromodulation For Neurogenic Bladder Guided By Three-Dimensional Imaging Ct And C-Arm Fluoroscopy: A Single-Center Prospective Study, Shuaishuai Shan, Wen Zhu, Guoxian Zhang, Qinyong Zhang, Yingyu Che, Jianguo Wen, Qingwei Wang Sep 2022

Video-Urodynamics Efficacy Of Sacral Neuromodulation For Neurogenic Bladder Guided By Three-Dimensional Imaging Ct And C-Arm Fluoroscopy: A Single-Center Prospective Study, Shuaishuai Shan, Wen Zhu, Guoxian Zhang, Qinyong Zhang, Yingyu Che, Jianguo Wen, Qingwei Wang

Faculty, Staff and Student Publications

To assess the efficacy of sacral neuromodulation (SNM) for neurogenic bladder (NB), guided by intraoperative three-dimensional imaging of sacral computed tomography (CT) and mobile C-arm fluoroscopy through video-urodynamics examination. We enrolled 52 patients with NB who underwent conservative treatment with poor results between September 2019 and June 2021 and prospectively underwent SNM guided by intraoperative three-dimensional imaging of sacral CT and mobile C-arm fluoroscopy. Video-urodynamics examination, voiding diary, quality of life questionnaire, overactive bladder symptom scale (OABSS) scoring, and bowel dysfunction exam were completed and recorded at baseline, at SNM testing, and at 6-month follow-up phases. Finally, we calculated the …


Functional Assessment Of Missense Variants In The Abcc6 Gene Implicated In Pseudoxanthoma Elasticum, A Heritable Ectopic Mineralization Disorder., Luke Kowal, Jianhe Huang, Hongbin Luo, Jagmohan Singh, Adam E Snook, Jouni Uitto, Qiaoli Li Sep 2022

Functional Assessment Of Missense Variants In The Abcc6 Gene Implicated In Pseudoxanthoma Elasticum, A Heritable Ectopic Mineralization Disorder., Luke Kowal, Jianhe Huang, Hongbin Luo, Jagmohan Singh, Adam E Snook, Jouni Uitto, Qiaoli Li

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Pseudoxanthoma elasticum, a heritable multisystem ectopic mineralization disorder, is caused by inactivating mutations in the ABCC6 gene. The encoded protein, ABCC6, a transmembrane transporter, has a specialized efflux function in hepatocytes by contributing to plasma levels of inorganic pyrophosphate, a potent inhibitor of mineralization in soft connective tissues. Reduced plasma inorganic pyrophosphate levels underlie the ectopic mineralization in pseudoxanthoma elasticum. In this study, we characterized the pathogenicity of three human ABCC6 missense variants using an adenovirus-mediated liver-specific ABCC6 transgene expression system in an Abcc6


D121 Located Within The Dry Motif Of P2y12 Is Essential For P2y12-Mediated Platelet Function., Carol Dangelmaier, Benjamin Mauri, Akruti Patel, Satya P Kunapuli, John C Kostyak Sep 2022

D121 Located Within The Dry Motif Of P2y12 Is Essential For P2y12-Mediated Platelet Function., Carol Dangelmaier, Benjamin Mauri, Akruti Patel, Satya P Kunapuli, John C Kostyak

Department of Medicine Faculty Papers

Platelets are anucleate cells that mediate hemostasis. This occurs via a primary signal that is reinforced by secreted products such as ADP that bind purinergic receptors (P2Y1 and P2Y12) on the platelet surface. We recently identified a human subject, whom we termed platelet defect subject 25 (PDS25) with a platelet functional disorder associated with the P2Y12 receptor. PDS25 has normal blood cell counts and no history of bleeding diathesis. However, platelets from PDS25 have virtually no response to 2-MeSADP (a stable analogue of ADP). Genetic analysis of P2Y12 from PDS25 revealed a heterozygous mutation of D121N within the DRY motif. …


Identifying Candidate Genes And Drug Targets For Alzheimer’S Disease By An Integrative Network Approach Using Genetic And Brain Region-Specific Proteomic Data, Andi Liu, Astrid M Manuel, Yulin Dai, Brisa S Fernandes, Nitesh Enduru, Peilin Jia, Zhongming Zhao Sep 2022

Identifying Candidate Genes And Drug Targets For Alzheimer’S Disease By An Integrative Network Approach Using Genetic And Brain Region-Specific Proteomic Data, Andi Liu, Astrid M Manuel, Yulin Dai, Brisa S Fernandes, Nitesh Enduru, Peilin Jia, Zhongming Zhao

Faculty, Staff and Student Publications

Genome-wide association studies (GWAS) have identified more than 75 genetic variants associated with Alzheimer's disease (ad). However, how these variants function and impact protein expression in brain regions remain elusive. Large-scale proteomic datasets of ad postmortem brain tissues have become available recently. In this study, we used these datasets to investigate brain region-specific molecular pathways underlying ad pathogenesis and explore their potential drug targets. We applied our new network-based tool, Edge-Weighted Dense Module Search of GWAS (EW_dmGWAS), to integrate ad GWAS statistics of 472 868 individuals with proteomic profiles from two brain regions from two large-scale ad cohorts [parahippocampal gyrus …


Medical Student Sensitivity Training On The Differences In Sex Development, Paul Endres, Deborah Ziring, Dimitrios Papanagnou Sep 2022

Medical Student Sensitivity Training On The Differences In Sex Development, Paul Endres, Deborah Ziring, Dimitrios Papanagnou

Student Papers, Posters & Projects

No abstract provided.


Molecular Pathways Enhance Drug Response Prediction Using Transfer Learning From Cell Lines To Tumors And Patient-Derived Xenografts, Yi-Ching Tang, Reid T Powell, Assaf Gottlieb Sep 2022

Molecular Pathways Enhance Drug Response Prediction Using Transfer Learning From Cell Lines To Tumors And Patient-Derived Xenografts, Yi-Ching Tang, Reid T Powell, Assaf Gottlieb

Faculty, Staff and Student Publications

Computational models have been successful in predicting drug sensitivity in cancer cell line data, creating an opportunity to guide precision medicine. However, translating these models to tumors remains challenging. We propose a new transfer learning workflow that transfers drug sensitivity predicting models from large-scale cancer cell lines to both tumors and patient derived xenografts based on molecular pathways derived from genomic features. We further compute feature importance to identify pathways most important to drug response prediction. We obtained good performance on tumors (AUROC = 0.77) and patient derived xenografts from triple negative breast cancers (RMSE = 0.11). Using feature importance, …


Plasma Protein Biomarkers For Primary Graft Dysfunction After Lung Transplantation: A Single-Center Cohort Analysis, Lourdes Chacon-Alberty, Rupa S Kanchi, Shengbin Ye, Camila Hochman-Mendez, Daoud Daoud, Cristian Coarfa, Meng Li, Sandra L Grimm, Maher Baz, Ivan Rosas, Gabriel Loor Sep 2022

Plasma Protein Biomarkers For Primary Graft Dysfunction After Lung Transplantation: A Single-Center Cohort Analysis, Lourdes Chacon-Alberty, Rupa S Kanchi, Shengbin Ye, Camila Hochman-Mendez, Daoud Daoud, Cristian Coarfa, Meng Li, Sandra L Grimm, Maher Baz, Ivan Rosas, Gabriel Loor

Faculty, Staff and Students Publications

The clinical use of circulating biomarkers for primary graft dysfunction (PGD) after lung transplantation has been limited. In a prospective single-center cohort, we examined the use of plasma protein biomarkers as indicators of PGD severity and duration after lung transplantation. The study comprised 40 consecutive lung transplant patients who consented to blood sample collection immediately pretransplant and at 6, 24, 48, and 72 h after lung transplant. An expert grader determined the severity and duration of PGD and scored PGD at T0 (6 h after reperfusion), T24, T48, and T72 h post-reperfusion using the 2016 ISHLT consensus guidelines. A bead-based …


Nasal Nitric Oxide Levels: Improving The Diagnosis Of Primary Ciliary Dyskinesia In Puerto Rico, Wilfredo De Jesús-Rojas, Francisco Alvarado-Huerta, Jesús M Meléndez-Montañez, José Muñiz-Hernández, Arnaldo Santos-López, Ricardo A Mosquera Sep 2022

Nasal Nitric Oxide Levels: Improving The Diagnosis Of Primary Ciliary Dyskinesia In Puerto Rico, Wilfredo De Jesús-Rojas, Francisco Alvarado-Huerta, Jesús M Meléndez-Montañez, José Muñiz-Hernández, Arnaldo Santos-López, Ricardo A Mosquera

Faculty, Staff and Student Publications

Primary Ciliary Dyskinesia (PCD) is a rare genetic disease characterized by motile cilia dysfunction with a prevalence of 1 in 16,309 individuals in Hispanic populations. In Puerto Rico, the prevalence of PCD is unknown. Diagnosis of PCD in Puerto Rico is challenging due to the lack of diagnostic technology. Algorithms for PCD diagnosis include clinical history, genetic testing, ciliary biopsy, and nasal Nitric Oxide (nNO) levels. For the first time, this study successfully implemented and measured the nNO levels in subjects with the RSPH4A (c.921+3_921+6del (intronic)) as a diagnostic tool to complement the current algorithm for PCD diagnosis on the …


Il-6 And Tnf-Α Responses To Acute And Regular Exercise In Adult Individuals With Multiple Sclerosis (Ms): A Systematic Review And Meta-Analysis, Parnian Shobeiri, Homa Seyedmirzaei, Nastaran Karimi, Fatemeh Rashidi, Antônio L Teixeira, Serge Brand, Dena Sadeghi-Bahmani, Nima Rezaei Sep 2022

Il-6 And Tnf-Α Responses To Acute And Regular Exercise In Adult Individuals With Multiple Sclerosis (Ms): A Systematic Review And Meta-Analysis, Parnian Shobeiri, Homa Seyedmirzaei, Nastaran Karimi, Fatemeh Rashidi, Antônio L Teixeira, Serge Brand, Dena Sadeghi-Bahmani, Nima Rezaei

Faculty, Staff and Student Publications

Background: In both the general population and people with multiple sclerosis (PwMS), physical exercise is associated with improved mental well-being. Moreover, there is evidence of the possible protection of physical activity against disease progression in multiple sclerosis (MS). However, the question arises if acute or regular exercise has any impact on the immune system in PwMS. To answer this question, we performed a systematic review and meta-analysis on both plasma and serum cytokine levels (IL-6 and TNF-α) before and after acute and regular exercise among PwMS and compared to healthy controls.

Method: We performed an online search via PubMed, EMBASE, …