Digital Commons Network^™

Yap Overcomes Mechanical Barriers To Induce Mitotic Rounding And Adult Cardiomyocyte Division, Yuka Morikawa, Jong H Kim, Rich Gang Li, Lin Liu, Shijie Liu, Vaibhav Deshmukh, Matthew C Hill, James F Martin

Faculty, Staff and Students Publications

Background: Many specialized cells in adult organs acquire a state of cell cycle arrest and quiescence through unknown mechanisms. Our limited understanding of mammalian cell cycle arrest is derived primarily from cell culture models. Adult mammalian cardiomyocytes, a classic example of cell cycle arrested cells, exit the cell cycle postnatally and remain in an arrested state for the life of the organism. Cardiomyocytes can be induced to re-enter the cell cycle by YAP5SA, an active form of the Hippo signaling pathway effector YAP.

Methods: We performed clonal analyses to determine the cell cycle kinetics of YAP5SA cardiomyocytes. We also performed …

Plural Molecular And Cellular Mechanisms Of Pore Domain, Timothy J Abreo, Emma C Thompson, Anuraag Madabushi, Kristen L Park, Heun Soh, Nissi Varghese, Carlos G Vanoye, Kristen Springer, Jim Johnson, Scotty Sims, Zhigang Ji, Ana G Chavez, Miranda J Jankovic, Bereket Habte, Aamir R Zuberi, Cathleen M Lutz, Zhao Wang, Vaishnav Krishnan, Lisa Dudler, Stephanie Einsele-Scholz, Jeffrey L Noebels, Alfred L George, Atul Maheshwari, Anastasios Tzingounis, Edward C Cooper

Faculty, Staff and Students Publications

KCNQ2 variants in children with neurodevelopmental impairment are difficult to assess due to their heterogeneity and unclear pathogenic mechanisms. We describe a child with neonatal-onset epilepsy, developmental impairment of intermediate severity, and KCNQ2 G256W heterozygosity. Analyzing prior KCNQ2 channel cryoelectron microscopy models revealed G256 as a node of an arch-shaped non-covalent bond network linking S5, the pore turret, and the ion path. Co-expression with G256W dominantly suppressed conduction by wild-type subunits in heterologous cells. Ezogabine partly reversed this suppression. Kcnq2G256W/+ mice have epilepsy leading to premature deaths. Hippocampal CA1 pyramidal cells from G256W/+ brain slices showed hyperexcitability. G256W/+ pyramidal …

Myo5b And The Polygenic Landscape Of Very Early-Onset Inflammatory Bowel Disease In An Ethnically Diverse Population, Ashleigh Watson, R Alan Harris, Amy C Engevik, Numan Oezguen, Maribeth R Nicholson, Sarah Dooley, Rachel Stubler, Lisa Forbes Satter, Lina B Karam, Richard Kellermayer

Faculty, Staff and Students Publications

Background: Genetic discovery in very early-onset inflammatory bowel disease (VEO-IBD) can elucidate not only the origins of VEO-IBD, but also later-onset inflammatory bowel disease. We aimed to investigate the polygenic origins of VEO-IBD in a cohort with a high proportion of Hispanic patients.

Methods: Patients with VEO-IBD who underwent whole exome sequencing at our center were included. Genes were categorized as genes of interest (GOIs) (129 genes previously described to be associated with VEO-IBD) or non-GOIs. VEO-IBD "susceptibility" single nucleotide variants (SNVs) were identified through enrichment compared with gnomAD (Genome Aggregation Database) and ALFA (Allele Frequency Aggregator) and were scored …

Fluorescence Lifetime Sorting Reveals Tunable Enzyme Interactions Within Cytoplasmic Condensates, Leyla E Fahim, Joshua M Marcus, Noah D Powell, Zachary A Ralston, Katherine Walgamotte, Eleonora Perego, Giuseppe Vicidomini, Alessandro Rossetta, Jason E Lee

Faculty, Staff and Students Publications

Ribonucleoprotein (RNP) condensates partition RNA and protein into multiple liquid phases. The multiphasic feature of condensate-enriched components creates experimental challenges for distinguishing membraneless condensate functions from the surrounding dilute phase. We combined fluorescence lifetime imaging microscopy (FLIM) with phasor plot filtering and segmentation to resolve condensates from the dilute phase. Condensate-specific lifetimes were used to track protein-protein interactions by measuring FLIM-Förster resonance energy transfer (FRET). We used condensate FLIM-FRET to evaluate whether mRNA decapping complex subunits can form decapping-competent interactions within P-bodies. Condensate FLIM-FRET revealed the presence of core subunit interactions within P-bodies under basal conditions and the disruption of …

Mechanisms Underlying Dilated Cardiomyopathy Associated With Fkbp12 Deficiency, Amy D Hanna, Ting Chang, Kevin S Ho, Rachel Sue Zhen Yee, William Cameron Walker, Nadia Agha, Chih-Wei Hsu, Sung Yun Jung, Mary E Dickinson, Md Abul Hassan Samee, Christopher S Ward, Chang Seok Lee, George G Rodney, Susan L Hamilton

Faculty, Staff and Students Publications

Dilated cardiomyopathy (DCM) is a highly prevalent and genetically heterogeneous condition that results in decreased contractility and impaired cardiac function. The FK506-binding protein FKBP12 has been implicated in regulating the ryanodine receptor in skeletal muscle, but its role in cardiac muscle remains unclear. To define the effect of FKBP12 in cardiac function, we generated conditional mouse models of FKBP12 deficiency. We used Cre recombinase driven by either the α-myosin heavy chain, (αMHC) or muscle creatine kinase (MCK) promoter, which are expressed at embryonic day 9 (E9) and E13, respectively. Both conditional models showed an almost total loss of FKBP12 in …

Can Clinical Findings At Admission Allow Withholding Of Antibiotics In Patients Hospitalized For Community Acquired Pneumonia When A Test For A Respiratory Virus Is Positive?, Ryan Ward, Alejandro J Gonzalez, Justin A Kahla, Daniel M Musher

Faculty, Staff and Students Publications

BACKGROUND: Current guidelines recommend empiric antibiotic therapy for patients who require hospitalization for community-acquired pneumonia (CAP). We sought to determine whether clinical, imaging or laboratory features in patients hospitalized for CAP in whom PCR is positive for a respiratory virus enable exclusion of bacterial coinfection so that antibiotics can be withheld.

METHODS: For this prospective study, we selected patients in whom an etiologic diagnosis was likely to be reached, namely those who provided a high-quality sputum sample at or shortly after admission, and in whom PCR was done to test for a respiratory virus. We performed quantitative bacteriologic studies on …

Detection Of Clinically Relevant Monogenic Copy-Number Variants By A Comprehensive Genome-Wide Microarray With Exonic Coverage, Matthew Hoi Kin Chau, Stephanie A Anderson, Rodger Song, Lance Cooper, Patricia A Ward, Bo Yuan, Chad Shaw, Paweł Stankiewicz, Sau Wai Cheung, Liesbeth Vossaert, Yue Wang, Nichole M Owen, Janice Smith, Carlos A Bacino, Katharina V Schulze, Weimin Bi

Faculty, Staff and Students Publications

Background: Disease-causing copy-number variants (CNVs) often encompass contiguous genes and can be detected using chromosomal microarray analysis (CMA). Conversely, CNVs affecting single disease-causing genes have historically been challenging to detect due to their small sizes.

Methods: A custom comprehensive CMA (Baylor College of Medicine - BCM v11.2) containing 400k probes and featuring exonic coverage for >4200 known or candidate disease-causing genes was utilized for the detection of CNVs at single-exon resolution. CMA results across a consecutive clinical cohort of more than 13 000 patients referred for genetic investigation at Baylor Genetics were examined. The genomic characteristics of CNVs impacting single …

Mate-Pair Sequencing Enables Identification And Delineation Of Balanced And Unbalanced Structural Variants In Prenatal Cytogenomic Diagnostics, Jicheng Qian, Huilin Wang, Hailei Liang, Yuting Zheng, Mingyang Yu, Wing Ting Tse, Angel Hoi Wan Kwan, Lo Wong, Natalie Kwun Long Wong, Isabella Yi Man Wah, So Ling Lau, Shuk Yi Annie Hui, Matthew Hoi Kin Chau, Xiaoyan Chen, Rui Zhang, Liona C Poon, Tak Yeung Leung, Pengfei Liu, Kwong Wai Choy, Zirui Dong

Faculty, Staff and Students Publications

Background: Mate-pair sequencing detects both balanced and unbalanced structural variants (SVs) and simultaneously informs in relation to both genomic location and orientation of SVs for enhanced variant classification and clinical interpretation, while chromosomal microarray analysis (CMA) only reports deletion/duplication. Herein, we evaluated its diagnostic utility in a prospective back-to-back prenatal comparative study with CMA.

Methods: From October 2021 to September 2023, 426 fetuses with ultrasound anomalies were prospectively recruited for mate-pair sequencing and CMA in parallel for prenatal genetic diagnosis. Balanced/unbalanced SVs and regions with absence of heterozygosity (AOH) were detected and classified independently, and comparisons were made between mate-pair …

Genomic Data And Privacy, Candace T Myers, Runjun D Kumar, Lisa Pilgram, Luca Bonomi, Mara Thomas, Obi L Griffith, Stephanie M Fullerton, Richard A Gibbs

Faculty, Staff and Students Publications

No abstract provided.

Atrx Silences Cartpt Expression In Osteoblastic Cells During Skeletal Development, Yi-Ting Chen, Ming-Ming Jiang, Carolina Leynes, Mary Adeyeye, Camilla F Majano, Barakat Ibrahim, Urszula Polak, George Hung, Zixue Jin, Denise G Lanza, Lan Liao, Brian Dawson, Yuqing Chen-Evenson, Oscar E Ruiz, Richard J Gibbons, Jason D Heaney, Yangjin Bae, Brendan Lee

Faculty, Staff and Students Publications

ATP-dependent chromatin remodeling protein ATRX is an essential regulator involved in maintenance of DNA structure and chromatin state and regulation of gene expression during development. ATRX was originally identified as the monogenic cause of X-linked α-thalassemia mental retardation (ATR-X) syndrome. Affected individuals display a variety of developmental abnormalities and skeletal deformities. Studies from others investigated the role of ATRX in skeletal development by tissue-specific Atrx knockout. However, the impact of ATRX during early skeletal development has not been examined. Using preosteoblast-specific Atrx conditional knockout mice, we observed increased trabecular bone mass and decreased osteoclast number in bone. In vitro coculture …

Meta-Ea: A Gene-Specific Combination Of Available Computational Tools For Predicting Missense Variant Effects, Panagiotis Katsonis, Olivier Lichtarge

Faculty, Staff and Students Publications

Computational methods for estimating missense variant impact suffer from inconsistent performance across genes, which poses a major challenge for their reliable use in clinical practice. While ensemble scores leverage multiple prediction methods to enhance consistency, the overrepresentation of certain genes in the training data can bias their outcomes. To address this critical limitation, we propose a gene-specific ensemble framework trained on reference computational annotations rather than on clinical or experimental data. Accordingly, we generate Meta-EA ensemble scores that achieve comparable performance to the top individual predicting method for each gene set. Incorporating the effects of splicing and the allele frequency …

How Gps Communicate The Urgent Suspected Cancer Referral Pathway To Patients: A Qualitative Study Of Gp-Patient Consultations, Jessica Russell, Laura Boswell, Athena Ip, Jenny Harris, Hardeep Singh, Ashley Nd Meyer, Traber D Giardina, Afsana Bhuiya, Katriina L Whitaker, Georgia B Black

Faculty, Staff and Students Publications

Background: The UK National Institute for Health and Care (NICE) recommends that GPs inform patients referred onto the urgent suspected cancer (USC) pathway about what to expect from the service. However, there is a lack of evidence on patient experience and information needs at the point of referral. It is a challenge for GPs to communicate the reasons for referral and provide reassurance.

Aim: To examine how GPs communicate a potential cancer diagnosis and USC referral in practice.

Design & setting: This is a secondary analysis of a dataset of 23 audio-recorded GP-patient consultations, selected from a larger dataset of …

Early Versus Late Initiation Of Dialysis In Ckd Stage 5: Time For A Consensus, Emaad M Abdel-Rahman, Irtiza Hasan, Abdallah S Abdelrazeq, Ali Rawabdeh, Mei Liu, Nasrollah Ghahramani, David Sheikh-Hamad, Mariana Murea, Pradeep Kadambi, T Alp Ikizler, Alaa S Awad

Faculty, Staff and Students Publications

Chronic kidney disease (CKD), a major global public health problem, emerged as one of the leading causes of death, affecting over 800 million individuals worldwide, with significant burden to patients and their caregivers, and may lead to end-stage kidney disease (ESKD). The decision on optimal initiation of chronic dialysis is a common problem faced by nephrologists, patients, and caregivers due to lack of adequate data. Determining the ideal time to initiate maintenance dialysis for individuals struggling with ESKD has remained a puzzle. Currently, there is no consensus among guidelines as to the best time to initiate dialysis. Discrepancies in guidelines …

Thromboelastography Versus Thromboelastometry For Unfractionated Heparin Monitoring In Adult Patients On Extracorporeal Membrane Oxygenation, Ellen B Yin, Arthur W Bracey, Subhasis Chatterjee

Faculty, Staff and Students Publications

Background: Monitoring the anticoagulant effect of unfractionated heparin (UFH) in extracorporeal membrane oxygenation (ECMO) patients is complex but critically important to balance the risks of treatment related bleeding and circuit thrombosis. While guidelines recommend using more than one method to monitor UFH activity, the use of thromboelastometry (ROTEM) to monitor UFH in ECMO patients has not been investigated in detail.

Methods: This is an observational, single-center retrospective study looking at adult ECMO patients on UFH that had ROTEM and thromboelastography (TEG) tests obtained concurrently. A total of 20 samples were obtained from nine patients during the study period, …

Mutations In Retinal Cyclic Nucleotide-Gated Channels Identified In Familial Cases Of Inherited Retinal Dystrophies From Pakistan, Zainab Akhtar, Kiran Afshan, Yumei Li, Sumaira Altaf, Aleesha Asghar, Ume Sughra, Wajid Ali Khan, Haiba Kaul, Rui Chen, Sabika Firasat

Faculty, Staff and Students Publications

Purpose: Cyclic nucleotide-gated (CNG) channels are ligand-gated ion channels that transduce light signals into electrical signals in the retinal photoreceptors. Pathogenic variants in CNG channel genes are reported to cause inherited retinal dystrophies (IRDs). The current study used targeted panel sequencing to describe the mutational spectrum of CNG channel genes in familial cases of IRDs from eight consanguineous Pakistani families.

Methods: The current study included consanguineous Pakistani families with at least two affected members. DNA was extracted from whole blood samples by the phenol-chloroform method. Two affected members from each family were initially analyzed using targeted panel sequencing of 344 …

Transposable Element Activity Captures Human Pluripotent Cell States, Florencia Levin-Ferreyra, Srikanth Kodali, Yingzhi Cui, Alison R S Pashos, Patrizia Pessina, Justin Brumbaugh, Bruno Di Stefano

Faculty, Staff and Students Publications

Human pluripotent stem cells (hPSCs) exist in multiple, transcriptionally distinct states and serve as powerful models for studying human development. Despite their significance, the molecular determinants and pathways governing these pluripotent states remain incompletely understood. Here, we demonstrate that transposable elements act as sensitive indicators of distinct pluripotent cell states. We engineered hPSCs with fluorescent reporters to capture the temporal expression dynamics of two state-specific transposable elements, LTR5_Hs, and MER51B. This dual reporter system enables real-time monitoring and isolation of stem cells transitioning from naïve to primed pluripotency and further towards differentiation, serving as a more accurate readout of pluripotency …

Tobacco Exposure Linked To Warthin’S Tumor Being The Most Common Benign Parotid Neoplasm In Veterans: A Retrospective Cohort Study, Louis Abarca, Linda K Green, Ray Y Wang, Vlad C Sandulache, David J Hernandez

Faculty, Staff and Students Publications

Objective: Parotid gland neoplasms account for a large proportion of benign salivary gland tumors, with pleomorphic adenomas (PA) being the most common in the civilian population, followed by Warthin's tumor (WT). However, the distinct risk profiles of Veterans significantly influence the incidence and prevalence of salivary gland neoplasms. We investigated the diagnostic and management algorithms for benign parotid gland neoplasms in Veterans.

< >Methods: Retrospective cohort study. Descriptive statistics were calculated using Microsoft Excel. Categorical variables were compared using chi square tests, and were reported with 95% confidence intervals, with statistical significance set at P <  .05.

Results: The study included 158 patients …

Telemedicine For Under-Resourced Patients With Systemic Lupus Erythematosus: A Qualitative Study Exploring The Views And Experiences Of Patients And Their Healthcare Team, Savannah Bowman, Sandeep K Agarwal, Keshia C Ferguson, Maryjo J Maliekel, Maria A Lopez-Olivo, Maria E Suarez-Almazor, Maria I Danila, Jinoos Yazdany, Sebastian Bruera

Faculty, Staff and Students Publications

Objectives: There is scarce knowledge on the benefits, limitations, and acceptance of telemedicine in patients with systemic lupus erythematosus (SLE), particularly in those from under-resourced groups. We aimed to assess the experiences and views on telemedicine of people with SLE, clinicians, and nursing staff from a safety net healthcare system in Harris County, Texas, defined as a hospital network that primarily serves low-income, uninsured, and vulnerable populations.

Methods: We conducted semi-structured 1:1 in-person interviews of patients with SLE and their clinical team members, in Harris County, Texas. Using Levesque's conceptual framework for healthcare access, semi-structured interviews and content analysis were …

Id-Gba: Subgraph Extension With Information Distance Guilt By Association In Complex Networks, Predrag Obradovic, Vladimir Kovacevic, Aleksandar Milosavljevic, Varduhi Petrosyan

Faculty, Staff and Students Publications

Here, we introduce the ID-GBA (Information Distance Guilt By Association) method to expand highly connected sets of nodes by deploying a novel algorithm for subgraph extension based on the guilt-by-association principle and information distance. In this study, ID-GBA was utilized to expand disease clusters, and identify novel disease genes. We first validate its ability to expand related disease sets from disease/disease graphs built using Open Targets' gene association scores. We then analyze disease/control gene expression networks and show that ID-GBA recaptures known disease genes in nine disease/control graphs. Compared to existing methods such as Random Walk with Restarts and Personalized …

Heterologous Prime-Pull Mucosal Vaccination With An Adjuvanted Rbd Vaccine Elicits Robust Iga Production And Protects Against Sars-Cov-2, Allyson H Hirsch, Calder R Ellsworth, William A Lewis, Ryan Craig, Amy E Meyer, Jonatan Maldonado, Frania Ramirez Lopez, Syamala Rani Thimmiraju, James B Mclachlan, Xuebin Qin, Nicholas J Maness, Jeroen Pollet, Ulrich Strych, Maria Elena Bottazzi, Peter J Hotez, Lisa A Morici

Faculty, Staff and Students Publications

Despite the efficacy of approved severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in preventing severe disease and death, breakthrough infections continue to occur in vaccinated individuals, contributing to further viral mutation and spread. These limitations may be attributable to the poor induction of mucosal immunity by parenteral vaccination. Mucosal adjuvants, such as T-vant, can enhance vaccine-induced immune responses through the generation of antigen-specific antibodies and T cells in the respiratory tract. In this study, we evaluated the protective efficacy of adjuvanted SARS-CoV-2 receptor binding domain (RBD) subunit vaccines administered by homologous and heterologous routes. Immunized mice were challenged with …

Improving Interprofessional Neurology Training Using Tele-Education, Fariha Jamal, Amtul Farheen, Christine Rizk

Faculty, Staff and Students Publications

Background: Neurological disorders are a leading cause of disability and death worldwide. Their burden on the health care system has substantially increased in the past 25 years, due to more effective treatments and longer life expectancies. The Veterans Health Administration has seen increases in neurology referrals and patients with neurologic disorders.

Observations: Collaborative efforts among primary care, geriatrics, neurology, psychiatry, physical medicine and rehabilitation, social work, and other disciplines are needed to properly care for veterans with neurologic disorders. Neurology education is an important tool for clinicians to better care for veterans with neurologic disorders. The use of technology and …

Evaluation Of Real-World Evidence To Assess Effectiveness Outcomes Of Janus Kinase Inhibitors For Rheumatoid Arthritis: A Systematic Review Of Us Studies, Chandler Gandy, Shadi Bazzazzadehgan, Sebastian Bruera, Yinan Huang

Faculty, Staff and Students Publications

Objective: This review summarized the real-world effectiveness outcomes of Janus kinase inhibitors (JAKi) for rheumatoid arthritis (RA) based on observational studies.

Methods: A systematic review followed PRISMA guidelines, with searches conducted in PubMed, Embase, and CINAHL from each database's inception to June 2, 2023. Studies were included if they evaluated real-world effectiveness outcomes of JAKi for US RA patients. Search terms included "RA", "JAKi", and "real-world". All citations were imported into COVIDENCE platform. Two reviewers independently performed title/abstract screening and full-text eligibility. For each article, study characteristics and effectiveness measures focusing on treatment pattern, clinical response, and patient-reported outcomes (PROs) …

Baseline Predictors For 28-Day Covid-19 Severity And Mortality Among Hospitalized Patients: Results From The Impacc Study, Jintong Hou, Benjamin Haslund-Gourley, Joann Diray-Arce, Annmarie Hoch, Nadine Rouphael, Patrice M Becker, Alison D Augustine, Al Ozonoff, Leying Guan, Steven H Kleinstein, Bjoern Peters, Elaine Reed, Matt Altman, Charles R Langelier, Holden Maecker, Seunghee Kim, Ruth R Montgomery, Florian Krammer, Michael Wilson, Walter Eckalbar, Steven E Bosinger, Ofer Levy, Hanno Steen, Lindsey B Rosen, Lindsey R Baden, Esther Melamed, Lauren I R Ehrlich, Grace A Mccomsey, Rafick P Sekaly, Joanna Schaenman, Albert C Shaw, David A Hafler, David B Corry, Farrah Kheradmand, Mark A Atkinson, Scott C Brakenridge, Nelson I Agudelo Higuita, Jordan P Metcalf, Catherine L Hough, William B Messer, Bali Pulendran, Kari C Nadeau, Mark M Davis, Ana Fernandez Sesma, Viviana Simon, Monica Kraft, Chris Bime, Carolyn S Calfee, David J Erle, Impacc Network, Lucy F Robinson, Charles B Cairns, Elias K Haddad, Mary Ann Comunale

Faculty, Staff and Students Publications

Introduction: The coronavirus disease 2019 (COVID-19) pandemic threatened public health and placed a significant burden on medical resources. The Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) study collected clinical, demographic, blood cytometry, serum receptor-binding domain (RBD) antibody titers, metabolomics, targeted proteomics, nasal metagenomics, Olink, nasal viral load, autoantibody, SARS-CoV-2 antibody titers, and nasal and peripheral blood mononuclear cell (PBMC) transcriptomics data from patients hospitalized with COVID-19. The aim of this study is to select baseline biomarkers and build predictive models for 28-day in-hospital COVID-19 severity and mortality with most predictive variables while prioritizing routinely collected variables.

Methods: We analyzed 1102 …

Utility Of Microbial Cell-Free Dna Sequencing In The Diagnosis Of Mycobacterial Infections In A Quaternary Care Center, Fernando H Centeno, Todd Lasco, Ahmed M Hamdi, Mayar Al Mohajer

Faculty, Staff and Students Publications

We examine the performance of microbial cell-free DNA (mcfDNA) next-generation sequencing (NGS) testing on patients admitted to a quaternary care hospital in Houston, Texas. The test was 75.0% sensitive and 97.8% specific for all mycobacterial infections. mcfDNA NGS results led to adjustments in antimicrobial therapy for seven of nine patients with positive results.

Toward Improving Retention In Hiv Care After Pregnancy: Lessons From A Post-Pandemic Cohort In The United States, Alexandra H Latham, Andrea Lugo Morales, Elizabeth Barba Gutierrez, Michael Jochum, Sarah Conrad, Eva H Clark, Kassandra Goytia, Megan Alam, Jessica Gerard, Jennifer Mckinney

Faculty, Staff and Students Publications

Introduction: People living with HIV (PLWH) often experience low rates of retention in HIV care (RIC) and suboptimal viral suppression postpartum. Understanding contemporary barriers to RIC is crucial to identify risk factors for loss to care and thereby improve support during this vulnerable transition. This work aimed to identify factors associated with adequate RIC, defined as two HIV care visits ≥90 days apart in the first year postpartum.

Methods: Electronic records were retrospectively reviewed for PLWH who delivered from 2019 to 2023 and received prenatal care within a single county health system. Variables were collected related to both maternal and …

Inclusion Of Patient-Centered, Non-Microbiological Endpoints And Biomarkers In Tuberculosis Drug Trials, Andrew R Dinardo, Wilbert Sabiiti, Stephen H Gillespie, Sophia B Georghiou, Norbert Heinrich, Norbert Hittel, Sami Taghlabi, Danna Carrero Longlax, Mikashmi Kohli, Ursula Panzner, Collins Musia, Christoph Lange, Anca Vasiliu, Rob J W Arts, Anna M Mandalakas, Morten Ruhwald, Lieven J Stuyver, Reinout Van Crevel

Faculty, Staff and Students Publications

Tuberculosis drug trials are primarily designed to identify antibiotic regimens with the strongest potency to kill Mycobacterium tuberculosis. However, microbiologic cure is not synonymous with improved health and recovery. Beyond antimicrobial efficacy, parameters such as morbidity and mortality related to lung function, cardiovascular health, and cancer should be prioritized. This narrative review emphasizes the critical need to emphasize clinical outcomes as much, if not more, than microbiological endpoints. We examine the underlying pathophysiological mechanisms and determinants of non-microbiological outcomes in tuberculosis, providing a synthesis of current knowledge. While there is growing evidence for some biomarkers to risk stratify TB …

Htr1b Is Necessary For Normal Retinal Function In Mice, Solomon E Gibson, Xiaofeng Tao, Guofu Shen, Justin Ma, Yong H Park, Maria Polo-Prieto, Benjamin J Frankfort

Faculty, Staff and Students Publications

Introduction: Serotonin (5-HT) is a neurotransmitter that is involved in retinal development, physiology, and vision, yet the specific contribution of individual 5-HT receptors to retinal function is poorly characterized. We identified 5-HT receptor 1B (Htr1b) as a potential key regulator of serotonergic signaling in the retina.

Methods: Htr1b localization was examined using RNAseq and in situ labeling. Retinal structure was assessed using histology and SD-OCT. Visual function was evaluated using optomotor behavioral experiments. Retinal function was characterized in vivo using electroretinography (ERG) and ex vivo using multielectrode array (MEA) recordings.

Results: Htr1b transcript and HTR1B protein localized primarily …

The Demodex Expert Panel On Treatment And Eyelid Health (Depth) Consensus Regarding The Preferred Treatment For Demodex Blepharitis, Eric Donnenfeld, Kelly K Nichols, Brandon D Ayres, Marjan Farid, Preeya K Gupta, Richard Lyndon Lindstrom, Stephen Pflugfelder, Christopher E Starr, Nandini Venkateswaran, Ian Benjamin Gaddie, Paul M Karpecki, Cecelia Koetting, Selina Mcgee, Laura M Periman, Elizabeth Yeu

Faculty, Staff and Students Publications

Purpose: To reach consensus on Demodex blepharitis (DB) treatment approaches using a modified Delphi process involving 15 ocular surface disease experts.

Methods: The Demodex Expert Panel on Treatment and Eyelid Health (DEPTH) consisted of 15 well-published ocular surface disease experts. Panelists completed two online surveys, a live consensus meeting, and a follow-up survey. The surveys consisted of scaled and multiple-choice questions related to the clinical and patient-reported outcomes of DB and its treatment. For the scaled questions using a 1 to 9 Likert scale, consensus was defined as weighted mean scores of 1-3 and 7-9, whereas for multiple-choice questions, consensus …

A Natural Small Molecule Isoginkgetin Alleviates Hypercholesterolemia And Atherosclerosis By Targeting Acly, Zhidan Zhang, Meijie Chen, Yitong Xu, Zhihua Wang, Zhenghong Liu, Chenyang He, Fanshun Zhang, Xiaojun Feng, Xiayun Ni, Yuanli Chen, Jixia Wang, Xinmiao Liang, Zhifu Xie, Jingya Li, Maciej Banach, Jaroslav Pelisek, Yuqing Huo, Yunhui Hu, Paul C Evans, Li Wang, Xiao-Yu Tian, Jianbo Xiao, Yuhua Shang, Yijun Zheng, Xunde Xian, Jianping Weng, Suowen Xu

Faculty, Staff and Students Publications

Rationale: Atherosclerotic cardiovascular disease (ASCVD) represents the predominant cause of mortality and morbidity globally. Given the established role of hypercholesterolemia as a significant risk factor for ASCVD, the discovery of new lipid-lowering medications is of paramount importance. ATP citrate lyase (ACLY) is a crucial enzyme in cellular metabolism, providing acetyl-CoA as the building block for the biosynthesis of fatty acids and cholesterol. Consequently, it has emerged as a promising drug target for innovative treatments of lipid metabolic disorders.

Methods: Virtual screening of a natural product library was performed to identify small-molecule ACLY inhibitors, leading to the discovery of isoginkgetin (ISOGK). …

Syndromic Forms Of Inherited Retinal Dystrophies: A Comprehensive Molecular Diagnosis Of Consanguineous Pakistani Families Using Capture Panel Sequencing, Aleesha Asghar, Sumbal Wazir, Shehzeen Fatima, Hussan Bilal, Muhammad Shoaib, Saqib Ur Rehman, Sumaira Altaf, Yumei Li, Kiran Afshan, Rui Chen, Sabika Firasat

Faculty, Staff and Students Publications

Background: Inherited retinal dystrophies (IRDs) represent a clinically and genetically heterogeneous group of genetic disorders that involve photoreceptors and/or retinal pigment epithelium degeneration. IRDs may occur as an isolated condition or may represent an ocular manifestation of a multisystemic disorder referred as syndromic IRD. To increase the understanding of the molecular determinants of syndromic IRD-related genes in the Pakistani population, we revealed the genetic profile of 13 consanguineous Pakistani families using capture panel sequencing.

Methods: We performed comprehensive molecular testing on 72 IRD segregating Pakistani families using targeted capture panel sequencing of 344 known genes. The pathogenicity of candidate variants …