Digital Commons Network^™

Use Of Clinical Competency Examinations For Dental Hygiene Licensure, Jocelyn D. Weinhagen, Tara L. Newcomb, Brenda T. Bradshaw

Dental Hygiene Faculty Publications

Dental hygiene licensure with a clinical competency examination (CCE) using a live patient has been required by state licensing boards since 1929. Clinical competency examinations were initially used when dental training was poorly developed, non-standardized, and largely based on the apprenticeship model. Currently, Canada and the state of California have removed the requirement of passing a CCE for dental hygiene licensure, provided certain requirements have been met. Dentistry is the last health care profession to mandate that graduates pass a CCE. The vast majority of dental licensing boards continue to require that third party testing agencies validate the clinical skills …

Clinician Perspectives On Virtual Reality Use In Physical Therapy Practice In The United States, Danielle T. Felsberg, Jared T. Mcguirt, Scott E. Ross, Louisa D. Raisbeck, Charlend K. Howard, Christopher K. Rhea

Rehabilitation Sciences Faculty Publications

The primary goal of physical rehabilitation is to assess movement impairments and restore function to improve overall quality of life. Virtual reality (VR) may provide the optimal environment to promote these goals due to its motivating and modifiable nature which can be difficult to accomplish through traditional real-world therapeutic methods. Current research of VR for rehabilitation has demonstrated that VR interventions can produce clinically meaningful change in motor outcomes. Despite this, adoption and usage of VR by physical therapy professionals is unclear due to the limited research in this area. Thus, the purpose of this study was to identify the …

American Society Of Hematology/International Society On Thrombosis And Haemostasis 2024 Updated Guidelines For Treatment Of Venous Thromboembolism In Pediatric Patients, Paul Monagle, Muayad Azzam, Rachel Bercovitz, Marisol Betensky, Rukhmi Bhat, Tina Biss, Brian Branchford, Leonardo R. Brandão, Anthony K.C. Chan, E. Vincent S. Faustino, Julie Jaffray, Sophie Jones, Hassan Kawtharany, Bryce A. Kerlin, Nicole Kucine, Riten Kumar, Christoph Male, Marie-Claude Pelland-Marcotte, Leslie Raffini, Chittalsinh M. Raulji, Sarah E. Sartain, Clifford M. Takemoto, Cristina Tarango, C. Heleen Van Ommen, Maria C. Velez, Sara K. Vesely, John Wiernikowski, Suzan Williams, Hope P. Wilson, Gary Woods, Ayesha Zia, Reem A. Mustafa

Journal Articles: Pediatrics

BACKGROUND: The American Society of Hematology (ASH) guidelines on treatment of pediatric venous thromboembolism (VTE) were published in 2018. In the last 6 years, there has been a 10-fold increase in the number of children involved in VTE treatment trials.

OBJECTIVE: The ASH Committee on Quality and Guidelines agreed to update the pediatric guidelines in conjunction with the International Society on Thrombosis and Haemostasis (ISTH). These ASH/ISTH evidence-based guidelines are intended to support patients, clinicians, and other health care professionals in the management of pediatric patients with VTE.

METHODS: ASH/ISTH formed a multidisciplinary guideline panel to minimize potential bias from …

Protein Marker-Dependent Drug Discovery Targeting Breast Cancer Stem Cells, Ashley V. Huang, Yali Kong, Kan Wang, Milton L. Brown, David Mu

Department of Biomedical and Translational Sciences Faculty Publications

Breast cancer is one of the most common cancers globally. Unfortunately, many patients with breast cancer develop resistance to chemotherapy and tumor recurrence, which is primarily driven by breast cancer stem cells (BCSCs). BCSCs behave like stem cells and can self-renew and differentiate into mature tumor cells, enabling the cancer to regrow and metastasize. Key markers like CD44 and aldehyde dehydrogenase-1 (ALDH1), along with pathways like Wingless-related integration site (Wnt), Notch, and Hedgehog, are critical to regulating this stem-like behavior of BCSCs and, thus, are being investigated as targets for various new therapies. This review summarizes marker-dependent strategies for targeting …

Codon Composition In Human Oocyters Reveals Age-Associated Defects In Mrna Decay, Pavla Brachova, Lane K. Christenson, Nehemiah S. Alvarez

Department of Biomedical and Translational Sciences Faculty Publications

Oocytes from women of advanced reproductive age exhibit diminished developmental potential, but the underlying mechanisms remain incompletely defined. Oocyte maturation depends on translational control of maternal mRNA synthesized during growth. We performed a computational analysis on human oocytes from women < 30 versus ≥40 years and observed that mRNA GC content correlates negatively with half-life in oocytes from young (< 30 yr) but positively with oocytes from aged (>40 yr) women. In young oocytes, longer mRNA half-life is associated with lower protein abundance, whereas in aged oocytes GC content correlates positively with protein abundance. During the GV-to-MII transition, codon composition stratifies stability: codons that support rapid translation (optimal) stabilize mRNA, while slow-translating codons (non-optimal) promote decay. With reproductive aging, GC-containing codons become more optimal and align with increased …

Contract To Kill: Gnas Mutation, Pratima Raut, Poompozhil Mathivanan, Surinder K. Batra, Moorthy P. Ponnusamy

Journal Articles: Biochemistry & Molecular Biology

The mutation in Gsα-coding GNAS exons, popular as gsp oncogene, is the most frequent mutation across all heterotrimeric G proteins involved in oncogenesis. GNAS R201, the most frequently mutated, followed by Q227, are found predominantly across various neoplasms and cancers such as IPMN, pituitary, thyroid, appendiceal, colorectal, etc. This review emphasizes the pivotal significance of the gsp oncogene and its ramifications underpinning the sustained addiction to GNAS mutation. Recent studies delineating the mechanistic intricacies that provide solid evidence of the profound impact of oncogenic GNAS on tumor formation, progression, and maintenance are highlighted. We have leveraged the discoveries of Gsα …

A Comprehensive Review On Utilizing Human Brain Organoids To Study Neuroinflammation In Neurological Disorders, Adrian Domene Rubio, Luke Hamilton, Mark Bausch, Mengmeng Jin, Ava Papetti, Peng Jiang, Sowmya V. Yelamanchili

Journal Articles: Anesthesiology

Most current information about neurological disorders and diseases is derived from direct patient and animal studies. However, patient studies in many cases do not allow replication of the early stages of the disease and, therefore, offer limited opportunities to understand disease progression. On the other hand, although the use of animal models allows us to study the mechanisms of the disease, they present significant limitations in developing drugs for humans. Recently, 3D-cultured in vitro models derived from human pluripotent stem cells have surfaced as a promising system. They offer the potential to connect findings from patient studies with those from …

Proteomics Profiling Of Research Models For Studying Pancreatic Ductal Adenocarcinoma, Mathilde Resell, Hanne-Line Rabben, Animesh Sharma, Lars Hagen, Linh Hoang, Nan T. Skogaker, Anne Aarvik, Eirik Knudsen Bjåstad, Magnus K. Svensson, Manoj Amrutkar, Caroline S. Verbeke, Surinder K. Batra, Gunnar Qvigstad, Timothy C. Wang, Anil Rustgi, Duan Chen, Chun-Mei Zhao

Journal Articles: Biochemistry & Molecular Biology

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, with a five-year survival rate of 10-15% due to late-stage diagnosis and limited efficacy of existing treatments. This study utilized proteomics-based systems modelling to generate multimodal datasets from various research models, including PDAC cells, spheroids, organoids, and tissues derived from murine and human samples. Identical mass spectrometry-based proteomics was applied across the different models. The preparation and validation of the research models and the proteomics were described in detail. The assembly datasets we present here contribute to the data collection on PDAC, which will be useful for systems modelling, …

Efficacy And Safety Of 4-Month Rifapentine-Based Tuberculosis Treatments In Persons With Diabetes., Ekaterina V. Kurbatova, William C. Whitworth, Lakshmi Praveena Peddareddy, Patrick P. J. Phillips, Nigel A. Scott, Kia E. Bryant, Rodney Dawson, Sandra Wagner Cardoso, Wadzanai Samaneka, Melissa Engle, Ziyaad Waja, Erin Sizemore, Wendy Carr, Kelly E. Dooley, Radojka Savic, Susan Swindells, Richard E. Chaisson, Susan E. Dorman, Payam Nahid, Nhung V. Nguyen, Aids Clinical Trials Group A5349, Tuberculosis Trials Consortium Study 31

Journal Articles: Infectious Diseases

A previous study demonstrated noninferior efficacy of 4-month rifapentine/moxifloxacin regimen for tuberculosis (TB) treatment compared with the standard regimen. We explored results among study participants with diabetes. Among 2,516 randomized participants, 181 (7.2%) had diabetes. Of 166 participants with diabetes in the microbiologically eligible analysis group, 26.3% (15/57) had unfavorable outcomes in the control regimen, 13.8% (8/58) in the rifapentine/moxifloxacin regimen, and 29.4% (15/51) in the rifapentine regimen. The difference in proportion of unfavorable outcomes between the control and rifapentine/moxifloxacin arms in the microbiologically eligible analysis group was -12.5% (95% CI -27.0% to 1.9%); the difference between the control and …

Efficacy And Safety Of Thrombolysis For Pediatric Venous Thromboembolism: A Systematic Review And Meta-Analysis, Hassan Kawtharany, Muayad Azzam, Aseel Alkhader, Marisol Betensky, Qais Hamarsha, Hadi K. Abou Zeid, Razan Mansour, Carine Tabak, Payal Patel, Sarah L. Baghdadi, Rachel S. Bercovitz, Rukhmi Bhat, Tina Biss, Brian R. Branchford, Leonardo R. Brandão, Anthony K.C. Chan, E. Vincent S. Faustino, Julie Jaffray, Sophie Jones, Bryce A. Kerlin, Nicole Kucine, Riten Kumar, Christoph Male, Marie-Claude Pelland-Marcotte, Leslie Raffini, Chittalsinh M. Raulji, Sarah E. Sartain, Clifford M. Takemoto, Cristina Tarango, C Heleen Van Ommen, Maria C. Velez, Sara K. Vesely, John Wiernikowski, Suzan Williams, Hope P. Wilson, Gary Woods, Ayesha Zia, Paul Monagle, Reem A. Mustafa

Journal Articles: Pediatrics

We conducted this systematic review to evaluate outcomes of thrombolysis followed by anticoagulation vs anticoagulation alone in pediatric patients with venous thromboembolism (VTE). This systematic review addresses mortality, VTE resolution, recurrence, bleeding, and organ-specific outcomes in 5 PICO (population, intervention, comparison, outcomes) questions on thrombolysis across pulmonary embolism (PE), extremity deep vein thrombosis (DVT), right atrial thrombosis (RAT), cerebral sinus venous thrombosis (CSVT), and renal vein thrombosis (RVT). Meta-analysis reported risk ratios or differences (95% confidence intervals [CIs]), and absolute effects per 1000 patients. Certainty of evidence was assessed using GRADE (Grading of recommendation, assessment, Development, and Evaluation) guidelines. Thirteen …

A Scoping Review Of Population Diversity In The Common Genomic Aberrations Of Clear Cell Renal Cell Carcinoma, Sean S. Kumar, Ninad Khandekar, Komal Dani, Saina R. Bhatt, Vinay Duddalwar, Anishka D' Souza

Department of Medicine Faculty Publications

Introduction: Previous literature has shown that clear cell renal cell carcinoma (ccRCC) is becoming a more prevalent diagnosis and that the incidence and mortality differ both regionally and racially. While the molecular profiles for ccRCC are studied regionally through biopsy and sequencing techniques, the genomic landscape and ccRCC diversity data are not well studied. We conducted a review of the known genomic data on 6 of the most clinically relevant DNA biomarkers in ccRCC: von Hippel-Lindau (vHL), Polybromo-1 (PBRM1), Breast Cancer Gene 1-Associated Protein 1 (BAP1), Histone-Lysine N-Methyltransferase Domain-Containing 2 (SETD2), Mammalian Target of Rapamycin (mTOR), and Lysine-Specific Demethylase 5C …

Changes In Cardiovascular Risk Factors And Health Care Expenditures Among Patients Prescribed Semaglutide, Yuan Lu, Yuntian Lu, Tedi Totojani, Chungsoo Kim, Rohan Khera, Hua Xu, John E. Brush Jr., Harlan M. Krumholtz, Jason Abaluck

Department of Medicine Faculty Publications

Importance Semaglutide, a glucagon-like peptide-1 receptor agonist, has demonstrated substantial weight reduction and cardiovascular benefits in clinical trials. However, its association with clinical outcomes and health care expenditures remains underexplored.

Objective To evaluate changes in cardiovascular risk factors and health care expenditures among patients prescribed semaglutide across multicenter cohorts.

Design, Setting, and Participants This retrospective cohort study included 23 522 adults (≥18 years) who received an initial semaglutide prescription between January 1, 2018, and January 1, 2025, at Sentara Healthcare and between January 1, 2018, and May 1, 2025, at Yale New Haven Health System.

Exposure The first prescription of …

Multisociety Guidance For Infection Prevention And Control In Nursing Homes, Lona Mody, Sonali D. Advani, Muhammad Salman Ashraf, Allison H. Bartlett, Suzanne F. Bradley, Deborah P. Burdsall, Jennifer A. Hanrahan, Susan S. Huang, Robert L.P. Jump, Lindsay Nicolle, Mary-Claire Roghmann, Patricia Stone, Rekha K. Murthy

Department of Medicine Faculty Publications

This multisociety guidance was endorsed by SHEA, APIC, IDSA, PALTmed, and AGS. It provides recommendations for infection prevention and control (IPC) in the context of the complexity of nursing home care in the United States: increased medical acuity of residents, the spread of multidrug-resistant organisms, and the threat of emerging pathogens. Recommendations and implementation suggestions address IPC leadership, staffing, and resources, healthcare personnel and residents‘ adherence to precautions and effective hand hygiene, outbreak preparedness, training, occupational health, cleaning and disinfection in the care environment, and the involvement of IPC in the facility. The guidance also addresses the challenges of maintaining …

Reliability Of Popliteal Artery Flow-Mediated Dilation In The Seated Position, Taskina Akhter, Patrick B. Wilson, J. David Branch, Leryn J. Reynolds

Exercise Science Faculty Publications

Flow-mediated dilation (FMD), a noninvasive measure of endothelial function, is commonly measured in the popliteal artery in the supine and upright body positions. However, reliability studies of the measurement in these positions are not well studied. This study aimed to examine the trial-retrial and visit-to-visit reliability of popliteal artery FMD in the seated position. Popliteal artery FMD was measured in 20 healthy adults across two visits in the seated and prone positions to assess visit-to-visit reliability. Two measurements were taken for each body position at each visit to assess trial-retrial reliability. %FMD was calculated as the percent change from baseline …

The Dna Demethylase Tet1 Modifies The Impact Of Maternal Folic Acid Status On Embryonic Brain Development, Lehua Chen, Bernard K Van Der Veer, Qiuying Chen, Spyridon Champeris Tsaniras, Wannes Brangers, Harm H M Kwak, Rita Khoueiry, Yunping Lei, Robert Cabrera, Steven S Gross, Richard H Finnell, Kian Peng Koh

Faculty, Staff and Students Publications

Folic acid (FA) is well known to prevent neural tube defects (NTDs), but we do not know why many human NTD cases still remain refractory to FA supplementation. Here, we investigate how the DNA demethylase TET1 interacts with maternal FA status to regulate mouse embryonic brain development. We determined that cranial NTDs display higher penetrance in non-inbred than in inbred Tet1−/− embryos and are resistant to FA supplementation across strains. Maternal diets that are either too rich or deficient in FA are linked to an increased incidence of cranial deformities in wild type and Tet1+/− offspring and to …

Acute Exacerbations Of Chronic Rhinosinusitis, Robert M. Frederick, Kent Lam, Joseph K. Han

Department of Otolaryngology (ENT) Faculty Publications

Purpose of Review

We aim to highlight recent advancements on the evolving chronic rhinosinusitis (CRS) phenotype: acute exacerbations of chronic rhinosinusitis (AECRS). We focused on studies that expanded the current understanding of its pathophysiology, patient characteristics, and disease burden.

Recent findings

Defining AECRS has been a topic of discussion for many years. A recent regulatory definition of AECRS in the literature incorporates a > 3 day requirement of worsened symptoms and an escalation of treatment. It is important not to rely on patient-reported rescue medication frequency as it was recently demonstrated these are only obtained for 1/3 of reported AECRS episodes. …

From Trials To Practice: Implementing A Clinical Intervention In Community Settings, Elizabeth M Vaughan, Xiaoying Yu, Victor J Cardenas, Craig A Johnston, Salim S Virani, Ashok Balasubramanyam, Christie M Ballantyne, Aanand D Naik

Faculty, Staff and Students Publications

Introduction/objectives: Diabetes increases the risk of complications, especially for vulnerable populations. Our previous randomized clinical trial (RCT), TIME (Telehealth-supported, Integrated Community Health Workers (CHWs), Medication access, group visit Education), showed the efficacy of CHW-led diabetes care. This study aimed to gather data on transitioning TIME from clinical trials to practical implementation.

Methods: We conducted a 12-month RCT at a nonprofit community clinic using the Consolidated Framework for Implementation Research (CFIR). Participants, Hispanic adults without insurance and with type 2 diabetes (N = 58; 29/arm), were randomized to TIME (intervention) or usual care (control). The intervention included monthly group visits and …

Development And Validation Of An Interpretable Longitudinal Preeclampsia Risk Prediction Using Machine Learning, Braden W Eberhard, Raphael Y Cohen, Nolan Wheeler, Ricardo Kleinlein, John Rigoni, David W Bates, Kathryn J Gray, Vesela P Kovacheva

Faculty, Staff and Students Publications

Preeclampsia is a pregnancy-specific disease characterized by new onset hypertension after 20 weeks of gestation that affects 2-8% of all pregnancies and contributes to up to 26% of maternal deaths. Despite extensive clinical research, current predictive tools fail to identify up to 66% of patients who develop preeclampsia. We sought to develop a tool to longitudinally predict preeclampsia risk. In this retrospective model development and validation study, we examined a large cohort of patients who delivered at three hospitals in the New England region between 05/2015 and 05/2023. We used sociodemographic, clinical diagnoses, family history, laboratory, and vital signs data. …

The Clinical Genome Resource (Clingen): Advancing Genomic Knowledge Through Global Curation, Clingen Consortium

Faculty, Staff and Students Publications

The Clinical Genome Resource (ClinGen) is a National Institutes of Health-funded program founded 10 years ago that defines the clinical relevance of genes and variants for medical and research use. ClinGen working groups develop standards for data sharing and curating genomic knowledge. Expert panels, with >2500 active members from 67 countries, curate the validity of monogenic disease relationships, pathogenicity of genetic variation, dosage sensitivity of genes, and actionability of gene-disease interventions using ClinGen standards, infrastructure, and curation interfaces. Results are available on clinicalgenome.org and classified variants are also submitted to ClinVar, a publicly available database hosted by the National Institutes …

Targeted Analysis Of Dyslexia-Associated Regions On Chromosomes 6, 12 And 15 In Large Multigenerational Cohorts, Nicola H Chapman, Patrick A Navas, Michael O Dorschner, Michele Mehaffey, Karen G Wigg, Kaitlyn M Price, Oxana Y Naumova, Elizabeth N Kerr, Sharon L Guger, Maureen W Lovett, Elena L Grigorenko, Virginia Berninger, Cathy L Barr, Ellen M Wijsman, Wendy H Raskind

Faculty, Staff and Students Publications

Dyslexia is a common learning impairment with a genetic basis that affects word reading and spelling. An increasing list of loci and genes have been implicated, but analyses to-date have investigated only limited genomic variation within each locus with no confirmed pathogenic variants identified. Our study is the first to comprehensively sequence both coding and cis-acting regulatory regions of such genes in a large study sample. In a collection of >2000 participants in families from three independent sites, we performed targeted capture and comprehensive sequencing of all exons and some regulatory elements of five candidate risk genes (DNAAF4, CYP19A1, DCDC2, …

Interleukin-15-Armoured Gpc3 Car T Cells For Patients With Solid Cancers, David Steffin, Nisha Ghatwai, Antonino Montalbano, Purva Rathi, Amy N Courtney, Azlann B Arnett, Julien Fleurence, Ramy Sweidan, Tao Wang, Huimin Zhang, Prakash Masand, John M Maris, Daniel Martinez, Jennifer Pogoriler, Navin Varadarajan, Sachin G Thakkar, Deborah Lyon, Natalia Lapteva, Mei Zhuyong, Kalyani Patel, Dolores Lopez-Terrada, Carlos A Ramos, Premal Lulla, Tannaz Armaghany, Bambi J Grilley, Stephen Gottschalk, Gianpietro Dotti, Leonid S Metelitsa, Helen E Heslop, Malcolm K Brenner, Pavel Sumazin, Andras Heczey

Faculty, Staff and Students Publications

Interleukin-15 (IL15) promotes the survival of T lymphocytes and enhances the antitumor properties of CAR T cells in preclinical models of solid neoplasms in which CAR T cells have limited efficacy1-4. Glypican-3 (GPC3) is expressed in a group of solid cancers5-10, and here we report the first evaluation in humans of the effects of IL15 co-expression on GPC3-CAR T cells. Cohort 1 patients (NCT02905188/NCT02932956) received GPC3-CAR T cells, which were safe but produced no objective antitumor responses and reached peak expansion at two weeks. Cohort 2 patients ( …

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 …

Design And Rationale Of Myoflame-19 Randomised Controlled Trial: Myocardial Protection To Reduce Post-Covid Inflammatory Heart Disease Using Cardiovascular Magnetic Resonance Endpoints, Valentina O Puntmann, Dietrich Beitzke, Andreas Kammerlander, Inga Voges, Dominik D Gabbert, Marcus Doerr, Bishwas Chamling, Biykem Bozkurt, Juan Carlos Kaski, Erica Spatz, Eva Herrmann, Gernot Rohde, Philipp Deleuw, Lenka Taylor, Christine Windemuth-Kieselbach, Cornelia Harz, Marta Santiuste, Laura Schoeckel, Juliana Hirayama, Peter C Taylor, Colin Berry, Eike Nagel

Faculty, Staff and Students Publications

Background: Cardiac symptoms due to postacute inflammatory cardiac involvement affect a broad segment of previously well people with only mild acute coronavirus disease 2019 (COVID-19) illness and without overt structural heart disease. Cardiovascular magnetic resonance (CMR) imaging can identify the underlying subclinical disease process, which is associated with chronic cardiac symptoms. Specific therapy directed at reducing postacute cardiac inflammatory involvement before development of myocardial injury and impairment is missing.

Methods: Prospective multicenter randomized placebo-controlled study of myocardial protection therapy (combined immunosuppressive/antiremodeling) of low-dose prednisolone and losartan. Consecutive symptomatic individuals with a prior COVID-19 infection, no pre-existing significant comorbidities or structural …

Zero-Inflated Models For The Evaluation Of Colorectal Polyps In Colon Cancer Screening Studies-A Value-Based Biostatistics Practice, Alok K Dwivedi, Sherif E Elhanafi, Mohamed O Othman, Marc J Zuckerman

Faculty, Staff and Students Publications

Background: Colon cancer screening studies are needed for the early detection of colorectal polyps to reduce the risk of colorectal cancer. Unfortunately, the data generated on colon polyps are typically analyzed in their dichotomized form and sometimes with standard count models, which leads to potentially inaccurate findings in research studies. A more appropriate approach for evaluating colon polyps is zero-inflated models, considering undetected existing polyps at colonoscopy screening.

Method: We demonstrated the application of the zero-inflated and hurdle models including zero-inflated Poisson (ZIP), zero-inflated robust Poisson (ZIRP), zero-inflated negative binomial (ZINB), zero-inflated generalized Poisson (ZIGP), zero hurdle Poisson (ZHP), and …

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 …

Exercise Mitigates High-Fat Diet-Induced Cardiac Dysfunction Via Apoe Genotype- And Immune-Dependent Mechanisms: A Photon-Counting Ct Study In Adult Mice, Rohan Nadkarni, Alex J Allphin, Darin P Clark, Yi Qi, Zay Yar Han, Ketan B Ghaghada, Alexandra Badea, Cristian T Badea

Faculty, Staff and Students Publications

Background: Cardiovascular dysfunction frequently accompanies aging and is often worsened by adverse lifestyle factors and genetic susceptibility. The apolipoprotein E (APOE) gene modulates susceptibility to cardiovascular disease, but how exercise and diet interact with APOE genotype remains insufficiently understood. We investigate the cardioprotective potential of exercise in humanized APOE-targeted replacement mice on control and high-fat diet, using photon-counting computed tomography (PCCT) and deep learning-based image segmentation.

Methods: This study included 251 male and female mice in mid-to-late life of APOE2, APOE3, and APOE4 genotypes with variation in humanized NOS2 (HN) mediated innate immune response, exercise status (exercised vs. sedentary) and …

Towards A Map Of The Immune System Manipulation Network By Trypanosoma Cruzi, Juan Cruz Gamba, Ana Rosa Pérez, Carolina Verónica Poncini, Cristina Poveda, Iván Marcipar, Gabriel Cabrera

Faculty, Staff and Students Publications

No abstract provided.

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). …

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, …

"How Can I Get Out Of This?": A Qualitative Study Of The Phenomenology And Functional Impact Of Misophonia In Youth And Families, Andrew Giles Guzick, Catherine Elizabeth Rast, Brenna Burns Maddox, Servando Rodriguez Barajas, Jane Clinger, Joseph Mcguire, Eric A Storch

Faculty, Staff and Students Publications

Introduction: Misophonia is an increasingly recognized disorder characterized by negative emotional and sensory reactions to specific noises. Although misophonia most often begins in childhood, there has been minimal research on its clinical presentation in youth. This qualitative study explored cognitive behavioral processes that are involved in misophonia and its associated functional impairment in young people and their families.

Methods: Focused interviews were conducted with 20 youth with misophonia (ages 10-17) and their parents. Thematic analyses of these interviews using a cognitive behavioral theoretical framework were conducted.

Results: A number of themes were identified, which included internalizing and externalizing cognitive behavioral …