Digital Commons Network^™

Influence Of Preoperative Blood Pressure On Postoperative Bleeding Complications Following Mohs Micrographic Surgery, Riyad N H Seervai, Sarah K Friske, Emily Powell, Ida F Orengo, Ikue Shimizu, Suzanne Alkul

Faculty, Staff and Students Publications

Background: Hypertension is a common comorbidity in patients undergoing Mohs micrographic surgery (MMS). Evidence in other surgical fields has suggested that high blood pressure increases the risk of perioperative bleeding, predisposing patients to complications such as hematomas, dehiscence, wound infection, and necrosis.

Methods: We reviewed medical charts of all 530 patients who underwent MMS at our institution in one calendar year to identify whether an association exists between preoperative blood pressure and bleeding outcomes in patients undergoing MMS.

Results: Perioperative variables, including history of diagnosed hypertension, preoperative systolic blood pressure >160 mm Hg, systolic blood pressure >180 mm Hg, anticoagulation/antiplatelet …

Influence Of Preoperative Blood Pressure On Postoperative Bleeding Complications Following Mohs Micrographic Surgery, Riyad N H Seervai, Sarah K Friske, Emily Powell, Ida F Orengo, Ikue Shimizu, Suzanne Alkul

Faculty, Staff and Students Publications

Background: Hypertension is a common comorbidity in patients undergoing Mohs micrographic surgery (MMS). Evidence in other surgical fields has suggested that high blood pressure increases the risk of perioperative bleeding, predisposing patients to complications such as hematomas, dehiscence, wound infection, and necrosis.

Methods: We reviewed medical charts of all 530 patients who underwent MMS at our institution in one calendar year to identify whether an association exists between preoperative blood pressure and bleeding outcomes in patients undergoing MMS.

Results: Perioperative variables, including history of diagnosed hypertension, preoperative systolic blood pressure >160 mm Hg, systolic blood pressure >180 mm Hg, anticoagulation/antiplatelet …

The Utility Of Brain Biomarkers In Predicting Survival And Neurological Outcomes In Pediatric Patients After Cardiac Arrest: A Systematic Review And Meta-Analysis, Halla Kamińska, Krzysztof Kurek, Michał Zembala, Sagar Galwankar, Monika Tomaszewska, Shraddha Singh, Nicola Luigi Bragazzi, Michał Pruc, Basar Cander, Francesco Chirico, Amelia Rizzo, Jacek Kubica, Ayman El-Menyar, Anne Lepetit, Pawel Patrzylas, Zubaid Rafique, W Frank Peacock, Łukasz Szarpak

Faculty, Staff and Students Publications

Background: Cardiac arrest in children is associated with high morbidity and mortality, primarily due to neurological injury. Biomarkers linked to brain injury, released into circulation from compromised elements of the neurovascular unit, act as significant prognostic indicators in patients suffering from hypoxic-ischemic brain injury (HIBI) subsequent to the restoration of spontaneous circulation (ROSC) after pediatric cardiac arrest. The aim of this systematic review and meta-analysis is to evaluate the prognostic utility of brain injury biomarkers in predicting neurological outcomes and survival in patients following cardiac arrest in the pediatric population.

Methods: Bibliographic databases (PubMed, the Cochrane Library, and Embase) were …

Small Molecule Screening Identifies Hsp90 As A Modifier Of Rna Foci In Myotonic Dystrophy Type 1, Sara J Johnson, Hannah L Johnson, Reid T Powell, Clifford Stephan, Fabio Stossi, Thomas A Cooper

Faculty, Staff and Students Publications

Myotonic dystrophy type 1 (DM1) is a multisystemic disorder caused by a CTG triplet repeat expansion within the 3' untranslated region of the DMPK gene. Expression of the expanded allele generates RNA containing long tracts of CUG repeats (CUGexp RNA) that form hairpin structures and accumulate in nuclear RNA foci; however, the factors that control DMPK expression and the formation of CUGexp RNA foci remain largely unknown. We performed an unbiased small molecule screen in an immortalized human DM1 skeletal muscle myoblast cell line and identified HSP90 as a modifier of endogenous RNA foci. Small molecule inhibition of HSP90 leads …

Antithymocyte Globulin Therapy In Chronic Lung Allograft Dysfunction, Akhilesh Ajay Padhye, Danielle Guffey, Andres Leon-Pena, Justin Segraves, Ramiro Fernandez, Gabriel Loor, Puneet Garcha, Tianshi David Wu, Gloria Li

Faculty, Staff and Students Publications

Introduction: Lung transplantation has seen strides in survival over the past few decades, though long-term survival remains poor. Chronic lung allograft dysfunction (CLAD) is a leading cause of graft failure and mortality beyond the first year. Anti-thymocyte globulin (ATG) is commonly used for treating refractory CLAD, though its efficacy remains uncertain.

Methods: This retrospective study evaluated the impact of ATG on lung function decline and mortality among lung transplant recipients diagnosed with CLAD, defined as a persistent >20% decline in forced expiratory volume (FEV1) from baseline. Patients treated with ATG were compared to those who did not receive ATG, using …

Global Consensus On Optimal Exercise Recommendations For Enhancing Healthy Longevity In Older Adults (Icsfr), Mikel Izquierdo, Philipe De Souto Barreto, Hidenori Arai, Heike A Bischoff-Ferrari, Eduardo L Cadore, Matteo Cesari, Liang-Kung Chen, Paul M Coen, Kerry S Courneya, Gustavo Duque, Luigi Ferrucci, Roger A Fielding, Antonio García-Hermoso, Luis Miguel Gutiérrez-Robledo, Stephen D R Harridge, Ben Kirk, Stephen Kritchevsky, Francesco Landi, Norman Lazarus, Teresa Liu-Ambrose, Emanuele Marzetti, Reshma A Merchant, John E Morley, Kaisu H Pitkälä, Robinson Ramírez-Vélez, Leocadio Rodriguez-Mañas, Yves Rolland, Jorge G Ruiz, Mikel L Sáez De Asteasu, Dennis T Villareal, Debra L Waters, Chang Won Won, Bruno Vellas, Maria A Fiatarone Singh

Faculty, Staff and Students Publications

Aging, a universal and inevitable process, is characterized by a progressive accumulation of physiological alterations and functional decline over time, leading to increased vulnerability to diseases and ultimately mortality as age advances. Lifestyle factors, notably physical activity (PA) and exercise, significantly modulate aging phenotypes. Physical activity and exercise can prevent or ameliorate lifestyle-related diseases, extend health span, enhance physical function, and reduce the burden of non-communicable chronic diseases including cardiometabolic disease, cancer, musculoskeletal and neurological conditions, and chronic respiratory diseases as well as premature mortality. Physical activity influences the cellular and molecular drivers of biological aging, slowing aging rates-a foundational …

Circulating Tumor Hpv Dna, Antibodies To Hpv16 Early Proteins, And Oral Hpv16 Dna As Biomarkers For Hpv-Related Oropharyngeal Cancer Screening, Kristina R Dahlstrom, Andrew T Day, Victor M Alvarez, Samantha R Chirinos, Giselle Santillana, Ming Guo, Karen S Anderson, Erich M Sturgis

Faculty, Staff and Students Publications

Background: Oropharyngeal cancer rates continue to rise with no effective screening method. Persistent oral oncogenic human papillomavirus (HPV), antibodies to HPV16 early (E) oncoproteins, and circulating tumor HPV DNA (ctHPVDNA) are biomarkers that show promise for use in HPV-related cancer screening.

Objective: To assess the prevalence of biomarkers for HPV-related cancer and their agreement in middle-aged men.

Methods: Men aged 50–64 years from the general population provided oral rinse and blood samples as well as information about demographics, tobacco/alcohol exposure, sexual behavior, and HPV-related disease history. Oral rinse was tested for HPV16 DNA and plasma was tested for HPV16 E …

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 …

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 …

Quality Of Life In Young Adults With Type 1 Diabetes, Marissa N Baudino, Samantha A Carreon, Randi Streisand, Tricia Tang, Sarah Lyons, Siripoom Mckay, Barbara J Anderson, Charles G Minard, Sridevi Devaraj, Ashley M Butler, Marisa E Hilliard

Faculty, Staff and Students Publications

Introduction: Challenges of young adulthood with type 1 diabetes (T1D) include transitioning to adult care, increased T1D self-management responsibilities, and normal developmental transitions. Recognizing patterns of health-related quality of life (HRQOL) across a demographically and clinically broad range of young adults with T1D may help identify who needs additional support as they transfer to adult healthcare. We hypothesized that young adults from specific demographic and clinical groups would report lower HRQOL.

Methods: At baseline of a behavioral RCT (≤2 months after last pediatric T1D clinic visit), 100 young adults (Mage=19.9 ± 1.3, MA1c=8.8 ± 2.0 %) self-reported demographics and HRQOL; …

High Tumor Cd161 Expression Predicts A Survival Advantage And Marks A Th1-Skewed Microenvironment, Briana Amicarella Burns, Manasvi Chandra, Vanaja Konduri, William K Decker

Faculty, Staff and Students Publications

CD8+CD161+ T-cells exhibit augmented memory and cytolytic properties, mediating enhanced immunity in murine tumor models and improved survival in human non-small cell lung cancer. This T-cell subset might serve as a biomarker of positive response to therapy or even be isolated to augment current immunotherapeutic approaches yet limited knowledge of CD161 expression in human cancers restricts practical application. Here we bioinformatically tested the hypothesis that CD161 expression may be associated with positive outcomes in human cancers and investigated mechanisms underlying any observed advantages. Using TCGA-PANCAN dataset, we analyzed expression of CD161 in over 10,000 human tumors, correlating expression levels with …

The Reprogramming Factor Klf4 In Normal And Malignant Blood Cells, H Daniel Lacorazza

Faculty, Staff and Students Publications

The Krüppel-like factor 4 (KLF4) is an evolutionarily conserved zinc finger transcription factor that regulates cellular processes in stem cells, epithelial cells, and immune blood cells by controlling gene expression through genetic, epigenetic, and chromatin remodeling. The landmark 2006 publication identified KLF4 as one of the factors involved in reprogramming differentiated cells into pluripotent stem cells, sparking increased interest in KLF4 research a decade after its discovery, particularly in the fields of stem cell research, epithelial cell biology, endothelial cell function, and tumorigenesis. Over the years, KLF4 has emerged as a key transcription factor in modulating innate and adaptive immunity, …

Diagnostic Delay In Type I Autoimmune Pancreatitis: Clinical, Imaging, Endoscopic And Histologic Predictors Of Timely Diagnosis, Andres Urias Rivera, Travis Josephs, Shilpa Jain, Wasseem Skef, Tara Keihanian, Salmaan Jawaid, Wasif Abidi, Kalpesh Patel, Mohamed O Othman, Fares Ayoub

Faculty, Staff and Students Publications

Background: The diagnosis of autoimmune pancreatitis (AIP) can be challenging due to nonspecific symptoms, low sensitivity of serologic markers, and some overlap in presentation with pancreatic ductal adenocarcinoma (PDAC). We aimed to quantify delays in the diagnosis of AIP and identify factors associated with diagnostic delay.

Methods: This was a single-center retrospective study between 2013 and 2023 of adult patients diagnosed with type 1 AIP based on HISORt criteria. Patients were compared to a randomly selected group of controls with PDAC. Data on clinical presentation, lab results, imaging, procedures, and initial treatment regimen were collected. Timing to diagnosis and predictive …

Editorial: Exploring Klf4’S Role In Immune Cell Function And Disease Progression, H Daniel Lacorazza, Walden Ai

Faculty, Staff and Students Publications

No abstract provided.

Two-Dimensional Speckle Tracking Of The Ascending Aorta: A Novel Approach To Evaluate Arterial Stiffness In Pediatric Patients With Repaired Conotruncal Anomalies Using Echocardiography, Anmol Goyal, Anitha Parthiban, David A White, Daniel Forsha, Doaa Aly

Faculty, Staff and Students Publications

Background: Children with repaired conotruncal abnormalities (CTA) are at risk of progressive aortic dilation and deteriorating aortic elasticity even after surgical correction. Strain imaging, using a 2-dimensional speckle tracking echocardiography (2D-STE), has been used for arterial stiffness assessment, but pediatric data are still lacking. We investigated the feasibility, reproducibility, and clinical value of 2D-STE derived ascending aorta (AAo) stiffness in children with repaired CTA.

Methods: 22 pediatric patients with repaired CTA were included along with 25 age- and sex- matched healthy controls (mean age 10.2 ± 4.5 years). Conventional 2D echocardiographic and 2D-STE assessment of AAo mechanics was performed. M-mode …

Multidisciplinary Approach To Treating Complex Immune Dysregulation Disorders: An Adaptive Model For Institutional Implementation, Lauren A Henderson, Roshini S Abraham, Aisha Ahmed, Lindsey Blount, Scott W Canna, Natalia S Chaimowitz, Shanmuganathan Chandrakasan, Bria Coates, James A Connelly, Megan A Cooper, Christine N Duncan, Anthony French, Melissa Hazen, Michelle L Hermiston, Brian Nolan, Anish Ray, Melissa J Rose, Lisa Forbes Satter, Grant Schulert, Sara Kristen Sexson Tejtel, Tiphanie Vogel, Kelly Walkovich, Matt S Zinter, Edward M Behrens

Faculty, Staff and Students Publications

Patients with immune dysregulation may present with varying combinations of autoimmunity, autoinflammation, immunodeficiency, atopy, lymphoproliferation, and/or malignancy, often with multisystem involvement. Recognizing specific patterns of immune dysregulation, coordinating and interpreting complex diagnostic testing, and choosing initial (often empiric) treatment can be challenging. Centers are increasingly assembling multidisciplinary teams (MDTs) to standardize evaluation and optimize treatment of patients with complex immune dysregulation (immune dysregulation MDTs [immMDTs]). However, published information on the composition and function of immMDTs is sparse, and there is little guidance for those seeking to establish or optimize an immMDT. To inform this review, we assembled a panel of …

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 …

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) …

Advancing Narcolepsy Advocacy: Bridging Patient Narratives And Systemic Change, Ahmed Salem Bahammam, Lindsay Jesteadt, Hamza Dhafar, Amir Sharafkhaneh

Faculty, Staff and Students Publications

We introduce the Stigma-to-Structure Advocacy Framework, a novel, evidence-based model designed to transform narcolepsy advocacy by systematically bridging patient narratives with structural change. Narcolepsy remains a profoundly underdiagnosed and misunderstood neurological disorder, with persistent diagnostic delays and pervasive cultural stigma undermining patient well-being and access to care. Despite recent progress in awareness and support, advocacy efforts remain fragmented and insufficiently integrated with health policy, particularly in low- and middle-income countries. This perspective advances a strategic evolution of narcolepsy advocacy through the Stigma-to-Structure Advocacy Framework, which is anchored in three pillars: narrative-driven awareness, clinical system integration, and policy activation. Drawing on …

Mice With Lymphatic Dysfunction Develop Pathogenic Lung Tertiary Lymphoid Organs That Model An Autoimmune Emphysema Phenotype Of Copd, Barbara Summers, Kihwan Kim, Anjali Trivedi, Tyler M Lu, Sean Houghton, Jade Palmer-Johnson, Joselyn Rojas-Quintero, Juan Cala-Garcia, Tania Pannellini, Francesca Polverino, Raphaël Lis, Hasina Outtz Reed

Faculty, Staff and Students Publications

We have previously shown that mice with a loss of C-type lectin-like type II (CLEC2), which have lymphatic dysfunction due to the role of CLEC2 in platelets for maintaining separation between the venous and lymphatic system, develop lung tertiary lymphoid organ (TLO) formation and lung injury that resembles an emphysema phenotype of chronic obstructive pulmonary disease (COPD). We now sought to investigate whether and how TLOs in these mice may play a pathogenic role in lung injury that is relevant to human disease. We found that inhibiting TLO formation using an anti-CD20 antibody in CLEC2-deficient mice partially blocked the development …

Gut Microbial Community Structure Of The Adult Citrus Root Weevil Diaprepes Abbreviatus, Imilce A Rodriguez-Fernandez, Tasha M Santiago-Rodriguez, Paola G Figueroa-Pratts, Keislamarí Cintrón-Berríos, Nichole D Rodriguez-Cornier, Gary A Toranzos

Faculty, Staff and Students Publications

Diaprepes abbreviatus is an agricultural pest known to affect around 270 plant species across the Caribbean and the United States, posing significant challenges to pest management. Chemical control dominates management, but environmental and health concerns motivate microbiome-informed alternatives. However, limited information exists on the gut anatomy, physicochemical environment, and microbial composition of D. abbreviatus. In this study, we provide the first comprehensive characterization of the gut morphology, pH, and microbiota of adult D. abbreviatus in both females and males collected in Puerto Rico. Using dye-based gut tracing, we identified foregut, midgut, and hindgut or posterior gut compartments, and confirmed the …

Age-Related Variations In Hba1c Improvemecnts: Insights From A Telehealth-Supported Community-Based Intervention, Laura Porterfield, Xiaoying Yu, Amber B Amspoker, Craig A Johnston, Aanand D Naik, Salim S Virani, Christie M Ballantyne, Ashok Balasubramanyam, Elizabeth M Vaughan

Faculty, Staff and Students Publications

Background and objectives: We previously demonstrated that a telehealth-supported community health worker (CHW) intervention significantly improved clinical outcomes in diabetes care. However, the extent to which these benefits vary across different age groups remains unclear. This study evaluated the effectiveness of a CHW-led multidimensional diabetes intervention in reducing HbA1c across age groups.

Research design and methods: We conducted a retrospective analysis of 10 studies (n = 301) that focused on low-income Hispanic adults with or at risk for type 2 diabetes. The intervention included CHW-participant coaching via mobile Health (mHealth), monthly CHW-led group education, and bidirectional mHealth feedback among …

Promotion Of Hiv Clearance By Sensitization Of Hiv Reservoirs To Cell Death, Min Li, Baichao Sun, Jing Dong, Jian-Rong Li, Laurie J Minze, Min Chen, Chao Cheng, Jin Wang

Faculty, Staff and Students Publications

Introduction: HIV integrates its proviral DNA into the host genome to establish persistent infection. To promote HIV clearance, we have designed an approach for selective elimination of host cells harboring replication-competent HIV (SECH), through inhibition of autophagy and anti-apoptotic molecules during viral reactivation. SECH approach can clear HIV-infected cells in approximately 50% humanized mice. However, the mechanisms for the resistance of reservoirs to depletion in mice with failure in HIV clearance are unclear.

Methods: We have performed single cell transcriptome analyses of HIV-infected T cells that escaped the treatments, in order to identify cellular pathways that could be targeted to …

Relationships Of Personality Traits With The Taxonomic Composition Of The Gut Microbiome Among Psychiatric Inpatients, William Orme, Sandra L Grimm, Divya S N Vella, J Christopher Fowler, B Christopher Frueh, Benjamin L Weinstein, Joseph Petrosino, Cristian Coarfa, Alok Madan

Faculty, Staff and Students Publications

Objective: Through the brain-gut-microbiome axis, myriad psychological functions that affect behavior share a dynamic, bidirectional relationship with the intestinal microbiome. Little is known about the relationship between personality-a stable construct that influences social- and health-related behaviors-and the bacterial ecosystem. The authors of this exploratory study examined the relationship between general and maladaptive personality traits and the composition of the gut microbiome.

Methods: In total, 105 psychiatric inpatients provided clinical data and fecal samples. Personality traits were measured with the five-factor model of personality, the Structured Clinical Interview for DSM-IV Axis II Personality Disorders, and the Personality Inventory for DSM-5; 16S …

Inhibition Of Ribosome Biogenesis In Vivo Causes P53-Dependent Death And P53-Independent Dysfunction, Charles J Cho, Thanh Nguyen, Amala K Rougeau, Yang-Zhe Huang, Sarah To, Xiaobo Lin, Supuni Thalalla Gamage, Jordan L Meier, Jason C Mills

Faculty, Staff and Students Publications

Background & aims: Although it is well-known that ribosomes are critical for cell function, and their synthesis (known as ribosome biogenesis [RiBi]) is energy-intensive, surprisingly little is known about RiBi in vivo in adult tissue.

Methods: Using a mouse model with conditional deletion of Nat10, an essential gene for RiBi and subsequent translation of mRNA, we investigated the effects of RiBi blockade in vivo, with a focus on pancreatic acinar cells during homeostasis and tumorigenesis.

Results: We observed an unexpected latency of several weeks between Nat10 deletion and onset of structural and functional abnormalities and p53-dependent acinar cell death. Although …

Autosomal Dominant Hk1-Related Neurodevelopmental Disorder With Visual Defects And Brain Anomalies (Nedviba): An Emerging Mitochondrial Disorder, Bobby G Ng, Erik A Eklund, Jill A Rosenfeld, Abdallah F Elias, Aya Abu-El-Haija, Celine Bris, Magalie Barth, Jong-Hee Chae, Murim Choi, Holly A Dubbs, Carl Fratter, Nicola Foulds, Candace Gamble, Ralitza H Gavrilova, Jaclyn Haven, Trevor L Hoffman, Jill V Hunter, Austin Larson, Timothy Edward Lotze, Pilar Magoulas, Emily C Magness, Debra M Bootin, Eric D Marsh, Victoria Nesbitt, Matthew T Pastore, Joanna Poulton, Shamima Rahman, Fernando Scaglia, Chaya Murali, Jennifer Posey, Joshua Rotenberg, Betsy Schmalz, Deepali N Shinde, Zöe Powis, Rivka Sukenik-Halevy, Kristen V Truxal, Tami Uster, Matheus Vernet Machado Bressan Wilke, Erik Klee, Hyewon Woo, Donald Younkin, Jianhua Zhao, Jorge Granadillo, Seema Lalani, David Chitayat, Wendy K Chung, Hudson H Freeze, Volkan Okur

Faculty, Staff and Students Publications

Purpose: Hexokinase 1 (HK1) encodes a ubiquitously expressed hexokinase, which is responsible for the first step of glycolysis, phosphorylation of glucose to glucose-6-phosphate. Both autosomal recessive and dominant variants in this gene have previously been shown to cause human disease, and presently, there are clinical data available for 27 individuals with the monoallelic neurodevelopmental disorder with visual defects and brain anomalies. Delineation of the entire phenotypic spectrum and genotype-phenotype relations will aid in management and counseling decisions.

Methods: We present molecular and clinical data on 22 additional individuals with heterozygous, mostly de novo, variants in HK1. We …

Variants In Washc3, A Component Of The Wash Complex, Cause Short Stature, Variable Neurodevelopmental Abnormalities, And Distinctive Facial Dysmorphism, Youn Hee Jee, Julian C Lui, Dana Marafi, Zhi-Jie Xia, Ruchika Bhatia, Elaine Zhou, Isabella Herman, Adrian Temnycky, Philip Whalen, Gene Elliot, Ellen W Leschek, Robin Wijngaard, Ronald Van Beek, Annemarie De Vreugd, Maaike C De Vries, Clara D M Van Karnebeek, Machteld M Oud, Thomas C Markello, Kevin M Barnes, Hadil Alrohaif, Hudson H Freeze, William A Gahl, May Christine V Malicdan, Jennifer E Posey, James R Lupski, Jeffrey Baron

Faculty, Staff and Students Publications

Purpose: Genetic defects that impair growth plate chondrogenesis cause a phenotype that varies from skeletal dysplasia to mild short stature with or without other syndromic features. In many individuals with impaired skeletal growth, the genetic causes remain unknown.

Method: Exome sequence was performed in 3 unrelated families with short stature, distinctive facies, and neurodevelopmental abnormalities. The impact of identified variants was studied in vitro.

Results: Exome sequencing identified variants in WASHC3, a component of the WASH complex. In the first family, a de-novo-dominant missense variant (p.L69F) impaired WASHC3 participation in the WASH complex, altered PTH1R endosomal trafficking, diminished PTH1R …

Genetic Landscape Of Hypertrophic Cardiomyopathy In Hong Kong Chinese Population, Derek P H Lee, Ye Cao, Lilei Zhang

Faculty, Staff and Students Publications

Introduction: Asian populations are underrepresented in the hypertrophic cardiomyopathy (HCM) genomic databases, which are currently largely dominated by Caucasian population. We aim to characterize the genetic landscape of HCM in patients from Hong Kong Chinese population.

Methods: From March 2023 to March 2024, fifty-three unrelated patients with an unequivocal clinical diagnosis of HCM were enrolled at a single tertiary center in Hong Kong and underwent genetic testing using a standardized 19-gene panel.

Results: In this cohort study, we identified 13 patients (24.5%) with a predominant pathogenic or likely pathogenic (P/LP) variant and 12 patients (22.6%) with a predominant variant of …

Whole Exome Sequencing As A Screening Tool In Dogs: A Pilot Study, Fréderique Boeykens, Evelien Bogaerts, Liesbeth Vossaert, Luc Peelman, Filip Van Nieuwerburgh, Jimmy H Saunders, Bart J G Broeckx

Faculty, Staff and Students Publications

Background: Whole-exome sequencing (WES) is used to selectively sequence all exons of protein-coding genes. WES is considered as a cost-effective and direct approach for identifying phenotype-associated variants in protein-coding regions and is as such situated between the traditional Sanger sequencing and whole genome sequencing (WGS). While WES is already widely used as a clinical tool in human and medical genetics, its use in veterinary medicine is currently restricted to research purposes. In this article, we aimed to provide baseline performance characteristics of a WES design to assess its suitability with future applications in veterinary clinical genetics in mind.

Methods: To …

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 …