Medical Specialties Commons^™

Longer Time To Recovery From Acute Kidney Injury Is Associated With Major Adverse Kidney Events In Patients With Cirrhosis, Kavish R Patidar, Mobasshir A Naved, Shaowli Kabir, Ananth Grama, Andrew S Allegretti, Giuseppe Cullaro, Sumeet K Asrani, Astin Worden, Archita P Desai, Marwan S Ghabril, Lauren D Nephew, Eric S Orman

Faculty, Staff and Students Publications

BACKGROUND: In patients with cirrhosis and acute kidney injury (AKI), longer time to AKI-recovery may increase the risk of subsequent major-adverse-kidney-events (MAKE).

AIMS: To examine the association between timing of AKI-recovery and risk of MAKE in patients with cirrhosis.

METHODS: Hospitalised patients with cirrhosis and AKI (n = 5937) in a nationwide database were assessed for time to AKI-recovery and followed for 180-days. Timing of AKI-recovery (return of serum creatinine7-days. Primary outcome was MAKE at 90-180-days. MAKE is an accepted clinical endpoint in AKI and defined as the composite outcome of ≥25% decline in estimated-glomerular-filtration-rate (eGFR) compared with baseline with …

Derivation And Validation Of A Clinical Risk Assessment Model For Cancer-Associated Thrombosis In Two Unique Us Health Care Systems, Ang Li, Jennifer La, Sarah B May, Danielle Guffey, Wilson L Da Costa, Christopher I Amos, Raka Bandyo, Emily M Milner, Karen M Kurian, Daniel C R Chen, Nhan V Do, Carolina Granada, Nimrah Riaz, Mary T Brophy, Vipul Chitalia, J Michael Gaziano, David A Garcia, Marc Carrier, Christopher R Flowers, Neil A Zakai, Nathanael R Fillmore

Faculty, Staff and Students Publications

PURPOSE: Venous thromboembolism (VTE), especially pulmonary embolism (PE) and lower extremity deep vein thrombosis (LE-DVT), is a serious and potentially preventable complication for patients with cancer undergoing systemic therapy.

METHODS: Using retrospective data from patients diagnosed with incident cancer from 2011-2020, we derived a parsimonious risk assessment model (RAM) using least absolute shrinkage and selection operator regression from the Harris Health System (HHS, n = 9,769) and externally validated it using the Veterans Affairs (VA) health care system (n = 79,517). Bootstrapped c statistics and calibration curves were used to assess external model discrimination and fit. Dichotomized risk strata using …

Assessing The Contributions Of Modifiable Risk Factors To Serious Falls And Fragility Fractures Among Older Persons Living With Hiv, Julie A Womack, Terrence E Murphy, Linda Leo-Summers, Jonathan Bates, Samah Jarad, Thomas M Gill, Evelyn Hsieh, Maria C Rodriguez-Barradas, Phyllis C Tien, Michael T Yin, Cynthia A Brandt, Amy C Justice

Faculty, Staff and Students Publications

BACKGROUND: Although 50 years represents middle age among uninfected individuals, studies have shown that persons living with HIV (PWH) begin to demonstrate elevated risk for serious falls and fragility fractures in the sixth decade; the proportions of these outcomes attributable to modifiable factors are unknown.

METHODS: We analyzed 21,041 older PWH on antiretroviral therapy (ART) from the Veterans Aging Cohort Study from 01/01/2010 through 09/30/2015. Serious falls were identified by Ecodes and a machine-learning algorithm applied to radiology reports. Fragility fractures (hip, vertebral, and upper arm) were identified using ICD9 codes. Predictors for both models included a serious fall within …

Test-Retest Reliability Of Virtual Reality Devices In Quantifying For Relative Afferent Pupillary Defect, Prithul Sarker, Nasif Zaman, Joshua Ong, Phani Paladugu, Molly Aldred, Ethan Waisberg, Andrew G. Lee, Alireza Tavakkoli

Student Papers, Posters & Projects

Background: The swinging flashlight test (SFT) is one of the most prominent clinical tests for detecting the relative afferent pupillary defect (RAPD). A positive RAPD localizes the lesion to the affected afferent pupil pathway and is a critical part of any ophthalmic exam. Testing for an RAPD, however, can be challenging (especially when small), and there is significant intrarater and interrater variability.

Methods: Prior studies have shown that the pupillometer can improve the detection and measurement of RAPD. In our previous research, we have demonstrated an automatic SFT by utilizing virtual reality (VR), named VR-SFT. We applied our methods to …

Association Of Diet Quality With Metabolic (Dysfunction) Associated Fatty Liver Disease In Veterans In Primary Care, Natalia I Heredia, Aaron P Thrift, David J Ramsey, Rohit Loomba, Hashem B El-Serag

Faculty, Staff and Student Publications

BACKGROUND: Diet is associated with metabolic (dysfunction)-associated fatty liver disease (MAFLD), but the dietary composition associated with MAFLD risk has not been well-examined.

AIM: The purpose of this study was to assess the association of two healthy eating indices with the presence and severity of MAFLD in a sample of Veterans in a primary care setting.

METHODS: This was a single center cross-sectional study using a random stratified sample of Veterans enrolled in primary care. Participants underwent a Fibroscan and completed an interviewer-administered Diet History Questionnaire II from which we calculated the Healthy Eating Index-2015 and Alternate Mediterranean Diet Score. …

Long Non-Coding Rnas: Definitions, Functions, Challenges And Recommendations, John S Mattick, Paulo P Amaral, Piero Carninci, Susan Carpenter, Howard Y Chang, Ling-Ling Chen, Runsheng Chen, Caroline Dean, Marcel E Dinger, Katherine A Fitzgerald, Thomas R Gingeras, Mitchell Guttman, Tetsuro Hirose, Maite Huarte, Rory Johnson, Chandrasekhar Kanduri, Philipp Kapranov, Jeanne B Lawrence, Jeannie T Lee, Joshua T Mendell, Timothy R Mercer, Kathryn J Moore, Shinichi Nakagawa, John L Rinn, David L Spector, Igor Ulitsky, Yue Wan, Jeremy E Wilusz, Mian Wu

Faculty, Staff and Students Publications

Genes specifying long non-coding RNAs (lncRNAs) occupy a large fraction of the genomes of complex organisms. The term 'lncRNAs' encompasses RNA polymerase I (Pol I), Pol II and Pol III transcribed RNAs, and RNAs from processed introns. The various functions of lncRNAs and their many isoforms and interleaved relationships with other genes make lncRNA classification and annotation difficult. Most lncRNAs evolve more rapidly than protein-coding sequences, are cell type specific and regulate many aspects of cell differentiation and development and other physiological processes. Many lncRNAs associate with chromatin-modifying complexes, are transcribed from enhancers and nucleate phase separation of nuclear condensates …

The Impact Of Covid-19 On A Large Pragmatic Clinical Trial Embedded In Primary Care, Sarah M Leatherman, Cynthia Hau, Alison Klint, Peter A Glassman, Addison A Taylor, Ryan E Ferguson, William C Cushman, Areef Ishani

Faculty, Staff and Students Publications

INTRODUCTION: The COVID-19 pandemic had significant impact on clinical care and clinical trial operations, but the impact on decentralized pragmatic trials is unclear. The Diuretic Comparison Project (DCP) is a Point-of Care (POC) pragmatic trial testing whether chlorthalidone is superior to hydrochlorothiazide in preventing major cardiovascular (CV) events and non-cancer death. DCP utilized telephone consent, data collection from the electronic health record and Medicare, forwent study visits, and limited provider commitment beyond usual care. We assessed the impact of COVID-19 on recruitment, follow-up, data collection, and outcome ascertainment in DCP.

METHODS: We compared data from two 8-month periods: Pre-Pandemic (July …

Pediatric Swine Model Of Methicillin-Resistant Staphylococcus Aureus Sepsis-Induced Coagulopathy, Disseminated Microvascular Thrombosis, And Organ Injuries, Trung C Nguyen, Juan C Marini, Bobby Guillory, Christian Valladolid-Brown, Marina Martinez-Vargas, Deepika Subramanyam, Daniel Cohen, Sonya C Cirlos, Fong Lam, Barbara Stoll, Inka C Didelija, Caitlin Vonderohe, Renan Orellana, Arun Saini, Subhashree Pradhan, Dalia Bashir, Moreshwar S Desai, Saul Flores, Manpreet Virk, Hossein Tcharmtchi, Amir Navaei, Sheldon Kaplan, Linda Lamberth, Kristina G Hulten, Brooks P Scull, Carl E Allen, Ayse Akcan-Arikan, K Vinod Vijayan, Miguel A Cruz

Faculty, Staff and Students Publications

Sepsis-induced coagulopathy leading to disseminated microvascular thrombosis is associated with high mortality and has no existing therapy. Despite the high prevalence of Gram-positive bacterial sepsis, especially methicillin-resistant

HYPOTHESIS: Our objective is to develop a pediatric sepsis-induced coagulopathy swine model that last 70 hours.

METHODS AND MODELS: Ten 3 weeks old piglets, implanted with telemetry devices for continuous hemodynamic monitoring, were IV injected with MRSA (

RESULTS: Compared with the saline treated piglets (control), the septic piglets within 24 hours had significantly lower neurologic and respiratory scores. Over time, PT, d-dimer, and fibrinogen increased, while platelet counts and activities of factors …

Changes In Local Tissue Microenvironment In Response To Subcutaneous Long-Acting Delivery Of Tenofovir Alafenamide In Rats And Non-Human Primates, Fernanda P Pons-Faudoa, Nicola Di Trani, Simone Capuani, Nathanael Hernandez, Anthony M Wood, Bharti Nehete, Jean Niles, Kathryn A Shelton, Sarah Kezar, Lane R Bushman, Corrine Ying Xuan Chua, Michael M Ittmann, Peter L Anderson, Pramod N Nehete, Roberto C Arduino, Joan E Nichols, Alessandro Grattoni

Faculty, Staff and Student Publications

Several implantable long-acting (LA) delivery systems have been developed for sustained subcutaneous administration of tenofovir alafenamide (TAF), a potent and effective nucleotide reverse transcriptase inhibitor used for HIV pre-exposure prophylaxis (PrEP). LA platforms aim to address the lack of adherence to oral regimens, which has impaired PrEP efficacy. Despite extensive investigations in this field, tissue response to sustained subcutaneous TAF delivery remains to be elucidated as contrasting preclinical results have been reported in the literature. To this end, here we studied the local foreign body response (FBR) to sustained subdermal delivery of three forms of TAF, namely TAF free base …

De Novo Variants In Mrtfb Have Gain-Of-Function Activity In Drosophila And Are Associated With A Novel Neurodevelopmental Phenotype With Dysmorphic Features, Jonathan C Andrews, Jung-Wan Mok, Oguz Kanca, Sharayu Jangam, Cynthia Tifft, Ellen F Macnamara, Bianca E Russell, Lee-Kai Wang, Undiagnosed Diseases Network, Stanley F Nelson, Hugo J Bellen, Shinya Yamamoto, May Christine V Malicdan, Michael F Wangler

Duncan NRI Faculty and Staff Publications

Purpose: Myocardin-related transcription factor B (MRTFB) is an important transcriptional regulator, which promotes the activity of an estimated 300 genes but is not known to underlie a Mendelian disorder.

Methods: Probands were identified through the efforts of the Undiagnosed Disease Network. Because the MRTFB protein is highly conserved between vertebrate and invertebrate model organisms, we generated a humanized Drosophila model expressing the human MRTFB protein in the same spatial and temporal pattern as the fly gene. Actin binding assays were used to validate the effect of the variants on MRTFB.

Results: Here, we report 2 pediatric probands with de novo …

Implication Of Chromosomal Microarray Analysis Prior To In-Utero Repair Of Fetal Open Neural Tube Defect, R Zemet, E Krispin, R M Johnson, N R Kumar, L E Westerfield, S Stover, D G Mann, J Castillo, H A Castillo, A A Nassr, M Sanz Cortes, R Donepudi, J Espinoza, W E Whitehead, M A Belfort, A A Shamshirsaz, I B Van Den Veyver

Duncan NRI Faculty and Staff Publications

Objective: In-utero repair of open neural tube defects (ONTD) is an accepted treatment option with demonstrated superior outcome for eligible patients. While current guidelines recommend genetic testing by chromosomal microarray analysis (CMA) when a major congenital anomaly is detected prenatally, the requirement for an in-utero repair, based on the Management of Myelomeningocele Study (MOMS) criteria, is a normal karyotype. In this study, we aimed to evaluate if CMA should be recommended as a prerequisite for in-utero ONTD repair.

Methods: This was a retrospective cohort study of pregnancies complicated by ONTD that underwent laparotomy-assisted fetoscopic repair or open-hysterotomy fetal surgery at …

Conjugated Bile Acids Are Nutritionally Re-Programmable Antihypertensive Metabolites, Saroj Chakraborty, Anju Lulla, Xi Cheng, Ji-Youn Yeo, Juthika Mandal, Tao Yang, Xue Mei, Piu Saha, Rachel M Golonka, Beng San Yeoh, Blair Mell, Wei Jia, Vasanta Putluri, Danthasinghe Waduge Badrajee Piyarathna, Nagireddy Putluri, Arun Sreekumar, Katie Meyer, Matam Vijay-Kumar, Bina Joe

Faculty, Staff and Students Publications

BACKGROUND: Hypertension is the largest risk factor affecting global mortality. Despite available medications, uncontrolled hypertension is on the rise, whereby there is an urgent need to develop novel and sustainable therapeutics. Because gut microbiota is now recognized as an important entity in blood pressure regulation, one such new avenue is to target the gut-liver axis wherein metabolites are transacted via host-microbiota interactions. Knowledge on which metabolites within the gut-liver axis regulate blood pressure is largely unknown.

METHOD: To address this, we analyzed bile acid profiles of human, hypertensive and germ-free rat models and report that conjugated bile acids are inversely …

Bi-Allelic Variants In Hmgcr Cause An Autosomal-Recessive Progressive Limb-Girdle Muscular Dystrophy, Joel A Morales-Rosado, Tanya L Schwab, Sarah K Macklin-Mantia, A Reghan Foley, Filippo Pinto E Vairo, Davut Pehlivan, Sandra Donkervoort, Jill A Rosenfeld, Grace E Boyum, Ying Hu, Anh T Q Cong, Timothy E Lotze, Carrie A Mohila, Dimah Saade, Diana Bharucha-Goebel, Katherine R Chao, Christopher Grunseich, Christine C Bruels, Hannah R Littel, Elicia A Estrella, Lynn Pais, Peter B Kang, Michael T Zimmermann, James R Lupski, Brendan Lee, Matthew J Schellenberg, Karl J Clark, Klaas J Wierenga, Carsten G Bönnemann, Eric W Klee

Faculty, Staff and Students Publications

Statins are a mainstay intervention for cardiovascular disease prevention, yet their use can cause rare severe myopathy. HMG-CoA reductase, an essential enzyme in the mevalonate pathway, is the target of statins. We identified nine individuals from five unrelated families with unexplained limb-girdle like muscular dystrophy and bi-allelic variants in HMGCR via clinical and research exome sequencing. The clinical features resembled other genetic causes of muscular dystrophy with incidental high CPK levels (>1,000 U/L), proximal muscle weakness, variable age of onset, and progression leading to impaired ambulation. Muscle biopsies in most affected individuals showed non-specific dystrophic changes with non-diagnostic immunohistochemistry. …

Impact Of Race And Ethnicity On Presentation And Outcomes Of Patients Treated On Rhabdomyosarcoma Clinical Trials: A Report From The Children’S Oncology Group, Senna R Munnikhuysen, Princess A Ekpo, Wei Xue, Zhengya Gao, Philip J Lupo, Rajkumar Venkatramani, Christine M Heske

Faculty, Staff and Students Publications

BACKGROUND: Racial and ethnic disparities have been demonstrated in pediatric and adult cancers. However, there is no consensus on whether such disparities exist in the presentation, treatment, and outcome of patients with rhabdomyosarcoma (RMS).

METHODS: Patient information from the seven most recent RMS clinical trials was obtained from the Children's Oncology Group (COG). Chi-squared analyses were used to compare patient, tumor, and treatment characteristics across racial and ethnic groups. Pairwise analyses comparing Non-Hispanic Black (NHB) versus Non-Hispanic White (NHW) racial groups and Hispanic versus NHW ethnic groups were conducted for significant characteristics. Kaplan-Meier method and Wilcoxon signed-rank tests were performed …

Optimising Clinical Care Through Cdh1-Specific Germline Variant Curation: Improvement Of Clinical Assertions And Updated Curation Guidelines, Xi Luo, Jamie L Maciaszek, Bryony A Thompson, Huei San Leong, Katherine Dixon, Sónia Sousa, Michael Anderson, Maegan E Roberts, Kristy Lee, Amanda B Spurdle, Arjen R Mensenkamp, Terra Brannan, Carolina Pardo, Liying Zhang, Tina Pesaran, Sainan Wei, Grace-Ann Fasaye, Chimene Kesserwan, Brian H Shirts, Jeremy L Davis, Carla Oliveira, Sharon E Plon, Kasmintan A Schrader, Rachid Karam, Clingen Cdh1 Variant Curation Expert Panel

Faculty, Staff and Students Publications

BACKGROUND: Germline pathogenic variants in CDH1 are associated with increased risk for diffuse gastric cancer and lobular breast cancer. Risk-reduction strategies include consideration of prophylactic surgery, thereby making accurate interpretation of germline CDH1 variants critical for physicians deciding upon these procedures. The Clinical Genome Resource (ClinGen) CDH1 Variant Curation Expert Panel (VCEP) developed specifications for CDH1 variant curation with a goal to resolve variants of uncertain significance (VUS) and with ClinVar conflicting interpretations and continues to update these specifications.

METHODS:CDH1 variant classification specifications were modified based on updated genetic testing clinical criteria, new recommendations from ClinGen, and expert knowledge …

Differentially Expressed Tear Proteins In Sjögren's Syndrome Keratoconjunctivitis Sicca, Stephen P Yoon, Zhiyuan Yu, Stephen C Pflugfelder, Cintia S De Paiva

Faculty, Staff and Students Publications

Purpose: The purpose of this study was to determine if there are significant differences in the concentrations of tear proteins in Sjögren's syndrome keratoconjunctivitis sicca (SS KCS) compared to healthy controls.

Methods: Tear samples were collected with unmarked Schirmer strips from 15 patients with SS KCS and 21 healthy controls. Tear protein was eluted and the concentration measured. Inflammatory mediators were assayed with a Raybiotech L-507 glass slide array and normalized by strip wetting length. All patients underwent an ocular surface exam to evaluate tear break-up time (TBUT), corneal fluorescein (CF) staining, and conjunctival (CJ) staining. The symptom assessment questionnaire …

When Patient Rudeness Impacts Care: A Review Of Incivility In Healthcare, Alexandra Townsley, Jennifer Li-Wang, Rajani Katta

Faculty, Staff and Students Publications

Healthcare workers increasingly face incivility and rude behaviors from patients, families, and visitors. Although these are less severe than other types of mistreatment, studies have documented that they may still impact healthcare worker well-being and patient care. Defining and measuring incivility can be challenging because current research relies on the perceptions of the targets. Furthermore, there is often overlap among different types of mistreatment, and much of it goes unreported by those who experience it. Nevertheless, multiple studies have documented that incivility is common in healthcare and has been associated with burnout and intent to leave. In clinical settings, multiple …

Cost-Effective Microscopic Draping: Covid-19 Umbrella, Yusif Hajiyev, Ronald J Vilela

Faculty, Staff and Students Publications

We describe a cost-effective solution to limit aerosol transmission to the surgeon and other personnel in the operating room during otologic surgery.

Tumour Infiltrating Lymphocytes (Tils) And Immune Composition In Breast Cancer Patients From Kenya: Spatial Distributions And Associations With Risk Factors And Tumour Characteristics, Shahin Sayed, Hela Koka, Mustapha Abubakar, Kevin Gardner, Roberto Salgado, Zahir Moloo, Ambar Beatriz Caban-Ureña, Daniel Rosen, Patricia Castro, Mansoor Saleh, Asim Jamal Shaikh, Jasmit Shah, Jonine Figueroa, Francis Makokha, Hien Khanh Ha, Zhong Wang, Pumza Magangane, Richard Naidoo, Veronica Ngundo, Xiaohong Rose Yang, Dhirendra Govender

Faculty, Staff and Students Publications

Background: The immune landscape of breast cancer (BC) in patients from Sub Saharan Africa is understudied. Our aims were to describe the distribution of Tumour Infiltrating Lymphocytes (TILs) within the intratumoural stroma (sTILs) and the leading/invasive edge stroma (LE-TILs), and to evaluate TILs across BC subtypes with established risk factors and clinical characteristics in Kenyan women.

Methods: Visual quantification of sTILs and LE-TILs were performed on Haematoxylin and eosin -stained pathologically confirmed BC cases based on the International TIL working group guidelines. Tissue Microarrays were constructed and stained with immunohistochemistry (IHC) for CD3, CD4, CD8, CD68, CD20, and FOXP3. Linear …

Synapse-Specific Changes In Arc And Bdnf In Rat Hippocampus Following Chronic Temporal Lobe Epilepsy, Daniel L Egbenya, Suleman Hussain, Yi-Chen Lai, Anne E Anderson, Svend Davanger

Faculty, Staff and Students Publications

Expression of immediate early genes (IEGs) in the brain is important for synaptic plasticity, and probably also in neurodegenerative conditions. To understand the cellular mechanisms of the underlying neuropathophysiological processes in epilepsy, we need to pinpoint changes in concentration of synaptic plasticity-related proteins at subsynaptic levels. In this study, we examined changes in synaptic expression of Activity-regulated cytoskeleton-associated (Arc) and Brai Derived Neurotrophic Factor (BDNF) in a rat model of kainate-induced temporal lobe epilepsy (TLE). Western blotting showed reduced concentrations of Arc and increased concentrations of BDNF in hippocampal synaptosomes in chronic TLE rats. Then, using quantitative electron microscopy, we …

Physiological Age By Artificial Intelligence-Enhanced Electrocardiograms As A Novel Risk Factor Of Mortality In Kidney Transplant Candidates, Elizabeth C Lorenz, Isabella Zaniletti, Bradley K Johnson, Tanya M Petterson, Walter K Kremers, Carrie A Schinstock, Hatem Amer, Andrea L Cheville, Nathan K Lebrasseur, Wolfgang C Winkelmayer, Sankar D Navaneethan, Abraham Baez-Suarez, Zachi I Attia, Francisco Lopez-Jimenez, Paul A Friedman, Cassie C Kennedy, Andrew D Rule

Faculty, Staff and Students Publications

BACKGROUND: Mortality risk assessment before kidney transplantation (KT) is imperfect. An emerging risk factor for death in nontransplant populations is physiological age as determined by the application of artificial intelligence to the electrocardiogram (ECG). The aim of this study was to examine the relationship between ECG age and KT waitlist mortality.

METHODS: We applied a previously developed convolutional neural network to the ECGs of KT candidates evaluated 2014 to 2019 to determine ECG age. We used a Cox proportional hazard model to examine whether ECG age was associated with waitlist mortality.

RESULTS: Of the 2183 patients evaluated, 59.1% were male, …

Prognostic Value Of Severe Acute Respiratory Syndrome Coronavirus-2 Viral Load And Antibodies In Patients Hospitalized With Covid-19, Rebecca N Bauer, Anastasia Teterina, Haridha Shivram, Jacqueline Mcbride, Carrie M Rosenberger, Fang Cai, Min Bao, Larry Tsai, Oliver Gordon, Ivan T Lee, Jeffrey J Wallin, Danielle Porter, Kavita Juneja, Gregory Camus, Ivan O Rosas, Steffen Wildum

Faculty, Staff and Students Publications

Observational studies have identified the potential prognostic value for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) viral load and anti-SARS-CoV-2 antibodies in coronavirus disease 2019 (COVID-19). However, viral load in nasopharyngeal (NP) swabs produced inconsistent results in prognostic analyses, and the prognostic value of viral load or antibodies has not been confirmed in large clinical trials. COVACTA and REMDACTA were double-blind, randomized, controlled trials with a combined enrollment of 1078 patients hospitalized with COVID-19 treated with tocilizumab or placebo in COVACTA or tocilizumab plus remdesivir or placebo plus remdesivir in REMDACTA. We assessed the potential prognostic value of NP and serum …

Gpr43 Stimulation On Tcrαβ+ Intraepithelial Colonic Lymphocytes Inhibits The Recruitment Of Encephalitogenic T-Cells Into The Central Nervous System And Attenuates The Development Of Autoimmunity, Carolina Prado, Alexandra Espinoza, J Eduardo Martínez-Hernández, Joseph Petrosino, Erick Riquelme, Alberto J M Martin, Rodrigo Pacheco

Faculty, Staff and Students Publications

INTRODUCTION: Gut microbiota plays a critical role in the regulation of immune homeostasis. Accordingly, several autoimmune disorders have been associated with dysbiosis in the gut microbiota. Notably, the dysbiosis associated with central nervous system (CNS) autoimmunity involves a substantial reduction of bacteria belonging to Clostridia clusters IV and XIVa, which constitute major producers of short-chain fatty acids (SCFAs). Here we addressed the role of the surface receptor-mediated effects of SCFAs on mucosal T-cells in the development of CNS autoimmunity.

METHODS: To induce CNS autoimmunity, we used the mouse model of experimental autoimmune encephalomyelitis (EAE) induced by immunization with the myelin …

Exome-Wide Assessment Of Isolated Biliary Atresia: A Report From The National Birth Defects Prevention Study Using Child-Parent Trios And A Case-Control Design To Identify Novel Rare Variants, Pagna Sok, Aniko Sabo, Lynn M Almli, Mary M Jenkins, Wendy N Nembhard, A J Agopian, Michael J Bamshad, Elizabeth E Blue, Lawrence C Brody, Austin L Brown, Marilyn L Browne, Mark A Canfield, Suzan L Carmichael, Jessica X Chong, Shannon Dugan-Perez, Marcia L Feldkamp, Richard H Finnell, Richard A Gibbs, Denise M Kay, Yunping Lei, Qingchang Meng, Cynthia A Moore, James C Mullikin, Donna Muzny, Andrew F Olshan, Faith Pangilinan, Jennita Reefhuis, Paul A Romitti, Jeremy M Schraw, Gary M Shaw, Martha M Werler, Sanjiv Harpavat, Philip J Lupo, University Of Washington Center For Mendelian Genomics, Nisc Comparative Sequencing Program, The National Birth Defects Prevention Study

Faculty, Staff and Students Publications

The etiology of biliary atresia (BA) is unknown, but recent studies suggest a role for rare protein-altering variants (PAVs). Exome sequencing data from the National Birth Defects Prevention Study on 54 child-parent trios, one child-mother duo, and 1513 parents of children with other birth defects were analyzed. Most (91%) cases were isolated BA. We performed (1) a trio-based analysis to identify rare de novo, homozygous, and compound heterozygous PAVs and (2) a case-control analysis using a sequence kernel-based association test to identify genes enriched with rare PAVs. While we replicated previous findings on PKD1L1, our results do not suggest that …

Evaluation Of An Automated Genome Interpretation Model For Rare Disease Routinely Used In A Clinical Genetic Laboratory, Linyan Meng, Ruben Attali, Tomer Talmy, Yakir Regev, Niv Mizrahi, Pola Smirin-Yosef, Liesbeth Vossaert, Christian Taborda, Michael Santana, Ido Machol, Rui Xiao, Hongzheng Dai, Christine Eng, Fan Xia, Shay Tzur

Faculty, Staff and Students Publications

Purpose: The analysis of exome and genome sequencing data for the diagnosis of rare diseases is challenging and time-consuming. In this study, we evaluated an artificial intelligence model, based on machine learning for automating variant prioritization for diagnosing rare genetic diseases in the Baylor Genetics clinical laboratory.

Methods: The automated analysis model was developed using a supervised learning approach based on thousands of manually curated variants. The model was evaluated on 2 cohorts. The model accuracy was determined using a retrospective cohort comprising 180 randomly selected exome cases (57 singletons, 123 trios); all of which were previously diagnosed and solved …

Static Perimetry In The Rate Of Progression In Ush2a-Related Retinal Degeneration (Rush2a) Study: Assessment Through 2 Years, Jacque L Duncan, Peiyao Cheng, Maureen G Maguire, Allison A Ayala, David G Birch, Janet K Cheetham, Todd A Durham, Abigail T Fahim, Carel B Hoyng, Hiroshi Ishikawa, Michel Michaelides, Mark E Pennesi, José-Alain Sahel, Katarina Stingl, Christina Y Weng

Faculty, Staff and Students Publications

PURPOSE: To evaluate disease progression using static perimetry (SP) in patients with USH2A-related retinal degeneration, including Usher syndrome type 2 (USH2) and nonsyndromic autosomal recessive retinitis pigmentosa.

DESIGN: Prospective, observational cohort study.

METHODS: A total of 102 patients with biallelic disease-causing sequence variants in USH2A with baseline best-corrected visual acuity (BCVA) letter score ≥54 were recruited from 16 clinical sites in Europe and North America. SP, BCVA, full-field stimulus thresholds, spectral domain optical coherence tomography macular scans, and fundus-guided mesopic microperimetry were performed at baseline and annually. The main outcome measures were total hill of vision (V

RESULTS: The average …

An International Delphi Consensus Statement On Metabolic Dysfunction-Associated Fatty Liver Disease And Risk Of Chronic Kidney Disease, Dan-Qin Sun, Giovanni Targher, Christopher D Byrne, David C Wheeler, Vincent Wai-Sun Wong, Jian-Gao Fan, Herbert Tilg, Wei-Jie Yuan, Christoph Wanner, Xin Gao, Michelle T Long, Mehmet Kanbay, Mindie H Nguyen, Sankar D Navaneethan, Yusuf Yilmaz, Yuli Huang, Rino A Gani, Pierluigi Marzuillo, Jérôme Boursier, Huijie Zhang, Chan-Young Jung, Jin Chai, Luca Valenti, George Papatheodoridis, Giovanni Musso, Yu-Jun Wong, Mohamed El-Kassas, Nahum Méndez-Sánchez, Silvia Sookoian, Michael Pavlides, Ajay Duseja, Adriaan G Holleboom, Junping Shi, Wah-Kheong Chan, Yasser Fouad, Junwei Yang, Sombat Treeprasertsuk, Helena Cortez-Pinto, Masahide Hamaguchi, Manuel Romero-Gomez, Mamun Al Mahtab, Ponsiano Ocama, Atsushi Nakajima, Chunsun Dai, Mohammed Eslam, Lai Wei, Jacob George, Ming-Hua Zheng

Faculty, Staff and Students Publications

BACKGROUND: With the rising global prevalence of fatty liver disease related to metabolic dysfunction, the association of this common liver condition with chronic kidney disease (CKD) has become increasingly evident. In 2020, the more inclusive term metabolic dysfunction-associated fatty liver disease (MAFLD) was proposed to replace the term non-alcoholic fatty liver disease (NAFLD). The observed association between MAFLD and CKD and our understanding that CKD can be a consequence of underlying metabolic dysfunction support the notion that individuals with MAFLD are at higher risk of having and developing CKD compared with those without MAFLD. However, to date, there is no …

Pediatric Ercp In The Setting Of Acute Pancreatitis: A Secondary Analysis Of An International Multicenter Cohort Study, Carolena Trocchia, Racha Khalaf, Ernest Amankwah, Wenly Ruan, Douglas S Fishman, Bradley A Barth, Quin Y Liu, Matthew Giefer, Kyung Mo Kim, Mercedes Martinez, Luigi Dall'oglio, Filippo Torroni, Paola De Angelis, Simona Faraci, Sam Bitton, Steven L Werlin, Kulwinder Dua, Roberto Gugig, Clifton Huang, Petar Mamula, J Antonio Quiros, Yuhua Zheng, Travis Piester, Amit Grover, Victor L Fox, Michael Wilsey, David M Troendle

Faculty, Staff and Students Publications

Previous studies have demonstrated the safety of performing endoscopic retrograde cholangiopancreatography (ERCP) in the pediatric population; however, few have addressed the outcomes of children undergoing ERCP during acute pancreatitis (AP). We hypothesize that ERCP performed in the setting of AP can be executed with similar technical success and adverse event profiles to those in pediatric patients without pancreatitis. Using the Pediatric ERCP Database Initiative, a multi-national and multi-institutional prospectively collected dataset, we analyzed 1124 ERCPs. One hundred and ninety-four (17%) of these procedures were performed in the setting of AP. There were no difference in the procedure success rate, procedure …

Clinical Spectrum And Genetic Causes Of Mitochondrial Hepatopathy Phenotype In Children, James E Squires, Alexander G Miethke, C Alexander Valencia, Kieran Hawthorne, Lisa Henn, Johan L K Van Hove, Robert H Squires, Kevin Bove, Simon Horslen, Rohit Kohli, Jean P Molleston, Rene Romero, Estella M Alonso, Jorge A Bezerra, Stephen L Guthery, Evelyn Hsu, Saul J Karpen, Kathleen M Loomes, Vicky L Ng, Philip Rosenthal, Krupa Mysore, Kasper S Wang, Marisa W Friederich, John C Magee, Ronald J Sokol, Childhood Liver Disease Research Network (Children)

Faculty, Staff and Students Publications

BACKGROUND: Alterations in both mitochondrial DNA (mtDNA) and nuclear DNA genes affect mitochondria function, causing a range of liver-based conditions termed mitochondrial hepatopathies (MH), which are subcategorized as mtDNA depletion, RNA translation, mtDNA deletion, and enzymatic disorders. We aim to enhance the understanding of pathogenesis and natural history of MH.

METHODS: We analyzed data from patients with MH phenotypes to identify genetic causes, characterize the spectrum of clinical presentation, and determine outcomes.

RESULTS: Three enrollment phenotypes, that is, acute liver failure (ALF, n = 37), chronic liver disease (Chronic, n = 40), and post-liver transplant (n = 9), were analyzed. …

Examination Of Parent-Reported Differences In Children’S Daily Screen Use, Sleep, And Sleep Hygiene Behaviors During The School Year And Summer And Their Association With Bmi, Jennette P Moreno, Alexis C Wood, Brooke Reichek, Hafza Dadabhoy, Tom Baranowski, Debbe Thompson, Teresia M O'Connor

Faculty, Staff and Students Publications

OBJECTIVE: The current study examined school-summer differences in children's sleep patterns and sleep hygiene. Cross-sectional relationships with children's sleep, sleep hygiene, and weight status were explored during the school year and summer.

METHODS: Children (5-8 years) and their parents (n = 197 dyads) were recruited from 4 schools in southeastern Texas and via Facebook. Parents reported children's school year and summer sleep, sleep hygiene, and screen media use. Children's body mass index (BMI) was objectively assessed at the beginning and end of the summer. Associations between children's sleep hygiene and screen media use, sleep duration, and weight status were explored. …