Digital Commons Network^™

Hand Hygiene Roles, Challenges, And Intervention Feedback From School Staff: A Qualitative Analysis, Belize, 2022-2023, Anh N Ly, Christina Craig, Dian Maheia, Yolanda Gongora, Vickie Romero, Rosalva Blanco, Allison Lino, Kelsey Mcdavid, Allison Stewart, Victoria Trinies, Alexandra Medley, Francis Morey, Russell Manzanero, Matthew Lozier, Kristy O Murray

Faculty, Staff and Students Publications

Hand hygiene (HH) in school settings can reduce the spread of infectious diseases and student absenteeism due to illness. During the COVID-19 pandemic, the World Health Organization recommended HH as a public health measure to prevent disease transmission. Understanding school staff's experiences with school-based programs is important for future program development and improvement. As part of a mixed-methods study, we conducted in-depth interviews in March 2022 with school administrators and teachers at 12 primary schools in Belize, selected based on high gaps in HH resources, to understand HH responsibilities, supplies, and challenges. An intervention was implemented to increase HH knowledge …

Prevalence, Experience, And Awareness Of Substandard And Falsified Medicines Among The Public And Healthcare Professionals In Jordan., Maysa Falah, Eman Daar, Daniel Zahra, Michael Dillon

Peninsula Medical School

INTRODUCTION: This study aimed to assess the awareness, experiences and perspectives on substandard and falsified (SF) medicines among the general public and healthcare professionals in Jordan. SF medicines pose a global public health concern, yet data on their prevalence and associated risks in Jordan remain limited.

METHODS: A cross-sectional study was conducted between January and June 2023 using a convergent mixed-methods approach. Quantitative data were collected through structured surveys administered to 209 members of the public and 136 healthcare professionals (pharmacists and clinicians) recruited via convenience sampling across Jordan's 12 governorates. Surveys were conducted in English and Arabic. Qualitative data …

A Smart Pill Bottle And Text Messaging Intervention For Promoting Medication Adherence In Patients With Chronic Myeloid Leukemia: A Pilot Study Of Txt4 Tki, Kuang-Yi Wen, Neil Palmisiano, Rita Smith, Rachel Slamon, Gina Keiffer, Christian Fidler, Margaret Kasner, Lindsay Wilde, Md

Department of Medical Oncology Faculty Papers

BACKGROUND: Patients undergoing tyrosine kinase inhibitor (TKI) therapy for chronic myeloid leukemia (CML) often face challenges with adherence, despite the efficacy of the treatment. Theory-guided and evidence-informed interventions addressing psychosocial and adherence barriers are critical for promoting adherence. Using a mixed-method approach, the pilot study developed and evaluated the feasibility and potential impact of an intervention "txt4TKI," to support medication and symptom management among CML patients undergoing TKI therapy.

METHODS: Guided by the Necessity and Concerns framework, the study comprised two phases: Phase 1 involved qualitative patient needs assessment interviews informing intervention design. Phase 2 was a single-arm pilot study …

Decoding Resistance To Immune Checkpoint Inhibitors In Non-Small Cell Lung Cancer: A Comprehensive Analysis Of Plasma Proteomics And Therapeutic Implications, Michal Harel, Nili Dahan, Coren Lahav, Eyal Jacob, Yehonatan Elon, Igor Puzanov, Ronan J. Kelly, Yuval Shaked, Raya Leibowitz, David P. Carbone, David R. Gandara, Adam P. Dicker

Department of Radiation Oncology Faculty Papers

BACKGROUND: Immune checkpoint inhibitors (ICIs) have shown substantial benefit for patients with advanced non-small cell lung cancer (NSCLC). However, resistance to ICIs remains a major clinical challenge. Here, we perform a comprehensive bioinformatic analysis of plasma proteomic profiles to explore the underlying biology of treatment resistance in NSCLC.

METHODS: The analysis was performed on 388 "resistance-associated proteins" (RAPs) that were previously described as pretreatment plasma proteomic predictors within the PROphet computational model designed to predict ICI clinical benefit in NSCLC. Putative tissue origins of the RAPs were explored using publicly available datasets. Enrichment analyses were performed to investigate RAP-related biological …

The Joint Association Of Diet Quality And Sleep Regularity With Incident Cardiovascular Disease In The Multi-Ethnic Study Of Atherosclerosis, Kaitlin S Potts, Claire Veldkamp, Alexis C Wood, Erin D Michos, Raymond Noordam, Tianyi Huang, Susan Redline, Heming Wang

Children’s Nutrition Research Center Staff Publications

Background/objectives: Diet quality and sleep regularity both influence cardiovascular disease (CVD) risk and may influence each other, but there is scarce evidence for their joint or interacting associations in relation to CVD. We assessed these associations in the Multi-Ethnic Study of Atherosclerosis (MESA).

Methods: Participants free of CVD with valid diet and sleep measures in 2010-2013 were included and followed through 2020 for detection of incident CVD (188 events detected over 8.8 years among 1782 participants; 55% women). Sleep timing and duration regularity were assessed via the intra-individual SD of sleep onset time and duration across 5- to 7-day actigraphy. …

Untargeted Proteomics Enables Ultra-Rapid Variant Prioritisation In Mitochondrial And Other Rare Diseases, Daniella H Hock, Nikeisha J Caruana, Liana N Semcesen, Nicole J Lake, Luke E Formosa, Sumudu S C Amarasekera, Tegan Stait, Simone Tregoning, Leah E Frajman, Adam M Bournazos, David R L Robinson, Megan Ball, Boris Reljic, Bryony Ryder, Mathew J Wallis, Anand Vasudevan, Cara Beck, Heidi Peters, Joy Lee, Natalie B Tan, Mary-Louise Freckmann, Mitomdt Diagnostic Network For Genomics And Omics, Vasiliki Karlaftis, Chantal Attard, Paul Monagle, Amanda Samarasinghe, Rosie Brown, Weimin Bi, Monkol Lek, Robert Mcfarland, Robert W Taylor, Michael T Ryan, Sandra T Cooper, Zornitza Stark, John Christodoulou, Alison G Compton, David R Thorburn, David A Stroud

Faculty, Staff and Students Publications

Background: Only half of individuals with suspected rare diseases receive a genetic diagnosis following genomic testing. A genetic diagnosis allows access to appropriate care, restores reproductive confidence and reduces the number of potentially unnecessary interventions. A major barrier is the lack of disease agnostic functional tests suitable for implementation in routine diagnostics that can provide evidence supporting pathogenicity of novel variants, especially those refractory to RNA sequencing.

Methods: Focusing on mitochondrial disease, we describe an untargeted mass-spectrometry based proteomics pipeline that can quantify proteins encoded by > 50% of Mendelian disease genes and > 80% of known mitochondrial disease genes in clinically …

Multicomponent Parenteral Lipid Emulsions Do Not Prevent Liver Injury In Neonatal Pigs With Obstructive Cholestasis, Greg Guthrie, Caitlin Vonderohe, Valeria Meléndez Hebib, Barbara Stoll, Douglas Burrin

Children’s Nutrition Research Center Staff Publications

Biliary atresia (BA) is a pediatric liver disease that often necessitates parenteral nutrition (PN) to support growth due to impaired liver function. While soy-based lipid emulsions (SLE) are commonly used in PN, they may contribute to cholestatic liver injury. In contrast, mixed lipid emulsions (MLE) show promise in preventing cholestasis in infants without BA, potentially by restoring bile flow. However, their effectiveness in patients of complete bile duct obstruction, as seen in BA, remains uncertain. To explore the potential benefits of MLE in BA, we utilized a neonatal pig model of bile duct ligation (BDL). Pigs underwent either BDL or …

The Perk/Atf4 Pathway Is Required For Metabolic Reprogramming And Progressive Lung Fibrosis, Jyotsana Pandey, Jennifer L Larson-Casey, Mallikarjun H Patil, Chao He, Nisarat Pinthong, A Brent Carter

Faculty, Staff and Students Publications

Asbestosis is a prototypical type of fibrosis that is progressive and does not resolve. ER stress is increased in multiple cell types that contribute to fibrosis; however, the mechanism(s) by which ER stress in lung macrophages contributes to fibrosis is poorly understood. Here, we show that ER stress resulted in protein kinase RNA-like ER kinase (PERK; Eif2ak3) activation in humans with asbestosis. Similar results were seen in asbestos-injured mice. Mice harboring a conditional deletion of Eif2ak3 were protected from fibrosis. Lung macrophages from asbestosis individuals had evidence of metabolic reprogramming to fatty acid oxidation (FAO). Eif2ak3fl/fl mice had increased oxygen …

Identification Of Surrogate Biomarkers For Mucopolysaccharidosis Type Iva, Yasuhiko Ago, Shaukat Khan, Kimberly Klipner, Allison Bradford, Shunji Tomatsu

Department of Pediatrics Faculty Papers

Mucopolysaccharidosis type IVA (MPS IVA, Morquio A syndrome) is a rare inherited disorder characterized by skeletal dysplasia due to deficient N-acetylgalactosamine-6-sulfate sulfatase activity, resulting in glycosaminoglycan (GAG) accumulation. Identifying accurate biomarkers reflecting clinical severity and therapeutic response remains challenging. This study evaluated potential surrogate biomarkers, including N-terminal pro-C-type natriuretic peptide (NT-proCNP), collagen types I and II, mono-sulfated keratan sulfate (KS), di-sulfated KS, and chondroitin-6-sulfate (C6S), in blood and urine samples from 60 patients ranging from 1 to 62 years of age. NT-proCNP levels were significantly elevated in patients of all ages and negatively correlated with growth impairment, especially after 8 …

Global Dna Methylation Differences Involving Germline Structural Variation Impact Gene Expression In Pediatric Brain Tumors, Fengju Chen, Yiqun Zhang, Wei Li, Fritz J Sedlazeck, Lanlan Shen, Chad J Creighton

Children’s Nutrition Research Center Staff Publications

The extent of genetic variation and its influence on gene expression across multiple tissue and cellular contexts is still being characterized, with germline Structural Variants (SVs) being historically understudied. DNA methylation also represents a component of normal germline variation across individuals. Here, we combine germline SVs (by short-read sequencing) with tumor DNA methylation across 1292 pediatric brain tumor patients. For thousands of methylation probes for CpG Islands (CGIs) or enhancers, rare and common SV breakpoints upstream or downstream associate with differential methylation in tumors spanning various histologic types, a significant subset involving genes with SV-associated differential expression. Cancer predisposition genes …

Evaluation Of Knowledge, Attitudes And Vaccine Hesitancy Towards Mmr Vaccine Among Parents In The United Arab Emirates, Kamel A. Samara, Hiba Jawdat Barqawi, Deema M. Alhayali, Samah Mohamed Kannas, Rim M. Elmorsy, Eman Abu-Gharbieh

Abington Jefferson Health Papers

BACKGROUND: The Measles, Mumps, and Rubella (MMR) vaccine is highly effective, but vaccine hesitancy (VH) is a key barrier to achieving herd immunity. This study aims to assess the general attitudes and knowledge of UAE parents regarding measles and the MMR vaccine while identifying determinants of VH.

METHODOLOGY: A cross-sectional study was done from 15th April 2024 and 5th June 2024. This study recruited 462 parents residing in the UAE using convenience sampling. Recruitment occurred through various social media platforms including WhatsApp, X, and Instagram, as well as in public by approaching parents in parks and malls. Information collected included …

Histone Methyltransferase Ash1l Primes Metastases And Metabolic Reprogramming Of Macrophages In The Bone Niche, Chenling Meng, Kevin Lin, Wei Shi, Hongqi Teng, Xinhai Wan, Anna Debruine, Yin Wang, Xin Liang, Javier Leo, Feiyu Chen, Qianlin Gu, Jie Zhang, Vivien Van, Kiersten L Maldonado, Boyi Gan, Li Ma, Yue Lu, Di Zhao

Faculty, Staff and Student Publications

Bone metastasis is a major cause of cancer death; however, the epigenetic determinants driving this process remain elusive. Here, we report that histone methyltransferase ASH1L is genetically amplified and is required for bone metastasis in men with prostate cancer. ASH1L rewires histone methylations and cooperates with HIF-1α to induce pro-metastatic transcriptome in invading cancer cells, resulting in monocyte differentiation into lipid-associated macrophage (LA-TAM) and enhancing their pro-tumoral phenotype in the metastatic bone niche. We identified IGF-2 as a direct target of ASH1L/HIF-1α and mediates LA-TAMs' differentiation and phenotypic changes by reprogramming oxidative phosphorylation. Pharmacologic inhibition of the ASH1L-HIF-1α-macrophages axis elicits …

Effect Of Targeting Apoc-Iii With Plozasiran On Lipoprotein Particle Size And Number In Hypertriglyceridemia, Christie M Ballantyne, Daniel Gaudet, Robert S Rosenson, Robert A Hegele, Rong Zhou, Stacey Melquist, Jennifer Hellawell, Nicholas J Leeper

Faculty, Staff and Students Publications

Background: Plozasiran, an investigational siRNA targeting hepatic apoC-III, reduces triglyceride-rich lipoproteins (TRLs). The impact of plozasiran on lipoprotein particle numbers and sizes is unknown. However, reductions in the number of TRL particles (TRL-P) and a shift to possibly less atherogenic large low-density lipoprotein particles (LDL-P) are expected.

Objectives: This study aimed to determine the impact of plozasiran on lipoprotein particle concentration and subclass distribution using nuclear magnetic resonance (NMR) in 2 phase 2 studies.

Methods: Patients (N = 403) from SHASTA-2 (severe hypertriglyceridemia) and MUIR (mixed hyperlipidemia) were administered 2 total subcutaneous doses of plozasiran (10, 25, or 50 mg) …

Epigenome-Wide Dna Methylation Association Study Of Chip Provides Insight Into Perturbed Gene Regulation, Sara Kirmani, Tianxiao Huan, Joseph C Van Amburg, Roby Joehanes, Md Mesbah Uddin, Ngoc Quynh H Nguyen, Bing Yu, Jennifer A Brody, Myriam Fornage, Jan Bressler, Nona Sotoodehnia, David A Ong, Fabio Puddu, James S Floyd, Christie M Ballantyne, Bruce M Psaty, Laura M Raffield, Pradeep Natarajan, Karen N Conneely, Joshua S Weinstock, April P Carson, Leslie A Lange, Kendra Ferrier, Nancy L Heard-Costa, Joanne Murabito, Alexander G Bick, Daniel Levy

Faculty, Staff and Student Publications

With age, hematopoietic stem cells can acquire somatic mutations in leukemogenic genes that confer a proliferative advantage in a phenomenon termed CHIP. How these mutations result in increased risk for numerous age-related diseases remains poorly understood. We conduct a multiracial meta-analysis of EWAS of CHIP in the Framingham Heart Study, Jackson Heart Study, Cardiovascular Health Study, and Atherosclerosis Risk in Communities cohorts (N = 8196) to elucidate the molecular mechanisms underlying CHIP and illuminate how these changes influence cardiovascular disease risk. We functionally validate the EWAS findings using human hematopoietic stem cell models of CHIP. We then use expression quantitative …

Dietary Intake Of Protein By Food Source And Incident Hypertension Among Diverse Us Adults: The Mesa Study, Ji Yun Tark, Ruosha Li, Bing Yu, Alexis C Wood, Nikhil S Padhye, Marcia C De Oliveira Otto

Faculty, Staff and Student Publications

Background: Dietary guidelines recommend adequate protein intake from diverse sources for optimal blood pressure; however, its role in hypertension risk remains unclear. We examined prospective associations of protein intake and diversity, overall and by source, with hypertension risk in the MESA (Multi-Ethnic Study of Atherosclerosis) study.

Methods and results: Among 2294 participants aged 45 to 84 years without hypertension at baseline, total, animal, and plant protein intake was assessed using a 120-item food frequency questionnaire. Protein diversity was evaluated using count and the dissimilarity index. Over a 9-year median follow-up, 1356 hypertension cases were identified through blood pressure measurements and …

Tacrolimus Dosing In Liver Transplant Recipients Using Phenotypic Personalized Medicine: A Phase 2 Randomized Clinical Trial, Jeffrey Khong, Megan Lee, Curtis Warren, Un Kim, Sergio Duarte, Kenneth Andreoni, Sunaina Shrestha, Mark Johnson, Narendra Battula, Danielle Mckimmy, Thiago Beduschi, Ji-Hyun Lee, Derek Li, Chih-Ming Ho, Ali Zarrinpar

Department of Surgery Faculty Papers

Tacrolimus is the most commonly used immunosuppression drug after solid organ transplantation; however, its dosing is challenging due to substantial inter-individual variability, often resulting in blood levels that deviate from the target therapeutic range. We explored whether a dynamically customized, phenotypic-outcome-guided drug dosing method could improve maintenance of drug trough levels within pre-determined target ranges, focusing on tacrolimus immediately after liver transplantation. This single-center, partially blinded, completed clinical trial involved 62 adults undergoing liver transplantation, block randomized into parallel groups: standard-of-care (SOC) clinician-determined or Phenotypic Personalized Medicine (PPM)-guided tacrolimus dosing. The primary outcome was percentage of post-transplant days with large …

Identifying Distinct Subgroups With Severe Pain In Sickle Cell Disease: A Cluster Analysis Of The Grndad Multi-Center Registry, Martha O. Kenney, Samuel Wilson, Morgan Rosser, Sophie Lanzkron, Julie Kanter, Susan Padrino, Payal Desai, Deepa Manwani, Alice Cohen, Stephanie Guarino, Ward Hagar, Joshua Field, Jane Little

Department of Medicine Faculty Papers

Sickle cell disease (SCD) affects millions of individuals worldwide, and is characterized by both acute, episodic pain and chronic, persistent pain. Despite the significant burden of the disease, clinicians continue to face significant challenges in treating SCD pain due to variability in pain experiences. The objectives of this study were (1) to identify distinct pain subgroups based on demographic and biopsychosocial characteristics and (2) to evaluate the relationship between the subgroups and pain impact - a SCD-disease specific measure of pain interference. To achieve these objectives, we performed a hierarchical cluster analysis on a cross-sectional sample of adults with SCD …

Prevalence Of Cardiovascular-Kidney-Metabolic Stages In Us Adolescents And Relationship To Social Determinants Of Health, Carissa M. Baker-Smith, Abigail M. Gauen, Lucia C. Petito, Sadiya S. Khan, Norrina B. Allen

Department of Pediatrics Faculty Papers

BACKGROUND: Risk factors for atherosclerotic cardiovascular disease begin in youth. Knowledge of the prevalence of cardio-kidney-metabolic (CKM) syndrome in adolescents and its risk factors is critical to understanding the cause of atherosclerotic cardiovascular disease risk burden.

METHODS: We conducted a cross-sectional analysis of the 2017 to 2020 US National Health and Nutrition Examination Survey data and determined the prevalence of each CKM stage in adolescents aged 12 to 18 years. We then assessed the relationship between the family income-to-poverty ratio, health insurance, routine health care access, food security, health behaviors, and CKM stage. We quantified associations between social factors, behaviors, …

Functional Brain Connectivity Of The Salience Network In Alcohol Use And Anxiety Disorders, Dhruv M Patel, Guillermo F Poblete, Alexandra Castellanos, Ramiro Salas

Staff and Researcher Publications

The interplay between alcohol use disorder (AUD) and anxiety disorders (ANX) is well-documented, yet the underlying neurobiological mechanisms remain elusive. This study aims to elucidate these mechanisms by examining the resting-state functional connectivity (RSFC) within the salience network and to the amygdala, both implicated in alcohol and anxiety disorders. We analyzed data from 264 inpatient participants culled from a wider group of 518 inpatients at The Menninger Clinic in Houston, TX, categorized into four groups (n = 66 each) based on DSM-IV diagnoses: AUD without ANX (AUD), ANX without AUD (ANX), concurrent AUD and ANX (BOTH), and neither (NEITHER). Our …

Development And Validation Of A Clinical Risk Model For Postoperative Outcome In Newly Diagnosed Glioblastoma: A Report Of The Rano Resect Group, Philipp Karschnia, Jacob S Young, Gilbert C Youssef, Antonio Dono, Levin Häni, Tommaso Sciortino, Francesco Bruno, Stephanie T Juenger, Nico Teske, Jorg Dietrich, Michael Weller, Michael A Vogelbaum, Martin Van Den Bent, Juergen Beck, Niklas Thon, Jasper K W Gerritsen, Shawn Hervey-Jumper, Daniel P Cahill, Susan M Chang, Roberta Rudà, Lorenzo Bello, Oliver Schnell, Yoshua Esquenazi, Maximilian I Ruge, Stefan J Grau, Raymond Y Huang, Patrick Y Wen, Mitchel S Berger, Annette M Molinaro, Joerg-Christian Tonn

Faculty, Staff and Student Publications

Background: Following surgery, patients with newly diagnosed glioblastoma frequently enter clinical trials. Nuanced risk assessment is warranted to reduce imbalances between study arms. Here, we aimed (I) to analyze the interactive effects of residual tumor with clinical and molecular factors on outcome and (II) to define a postoperative risk assessment tool.

Methods: The response assessment in neuro-oncology (RANO) resect group retrospectively compiled an international, seven-center training cohort of patients with newly diagnosed glioblastoma. The combined associations of residual tumor with molecular or clinical factors and survival were analyzed, and recursive partitioning analysis was performed for risk modeling. The resulting model …

Capturing The Intersection Of Black-American, Muslim Males And Education: Exploring Their Attitudes, Perceptions, And Lived Experiences Within An Islamic Consciousness, Kirk A. Talib-Deen

UNLV Theses, Dissertations, Professional Papers, and Capstones

This dissertation explored the lived realities of Black-American, Muslim males and their attitudes, perceptions, histories, and endurances toward higher learning in America. It attempted to join and contribute to the more significant, historical, and extant conversations and literature on Black-American males and education, as well as their successes and failures. This dissertation adds to the dearth of literature on the intersection of Black-American, Muslim males, and education, and using jazz as an epistemological way of navigating and organizing the content, the research works to uncover, locate, and define an Islamic consciousness. While negating racist histories concomitant with the American narrative …

Causes Of Death Among Us Medical Residents, Nicholas A. Yaghmour, William E. Bynum, Frederic W. Hafferty, Karen D. Könings, Thomas Richter, Timothy P. Brigham, Thomas J. Nasca

Division of Nephrology Faculty Papers

IMPORTANCE: From 2000 to 2014, the leading causes of medical resident death in the United States were neoplastic diseases and suicide.

OBJECTIVE: To examine whether US medical resident rates of death have changed since 2014 and whether causes of resident death differ by specialty.

DESIGN, SETTING, AND PARTICIPANTS: In this cross-sectional study, residents and fellows who were enrolled in Accreditation Council for Graduate Medical Education (ACGME)-accredited training programs and who died from January 2015 to December 2021 were submitted to the National Death Index to obtain causes of death. These decedents were compared with residents and fellows who died between …

Theta Oscillons In Behaving Rats, M S Zobaer, Nastaran Lotfi, Carli M Domenico, Clarissa Hoffman, Luca Perotti, Daoyun Ji, Yuri Dabaghian

Faculty, Staff and Students Publications

Recently discovered constituents of the brain waves—the oscillons—provide a high-resolution representation of the extracellular field dynamics. Here, we study the most robust, highest-amplitude oscillons recorded in actively behaving male rats, which underlie the traditional θ-waves. The resemblances between θ-oscillons and the conventional θ-waves are manifested primarily at the ballpark level—mean frequencies, mean amplitudes, and bandwidths. In addition, both hippocampal and cortical oscillons exhibit a number of intricate, behavior-attuned, transient properties that suggest a new vantage point for understanding the θ-rhythms’ structure, origins and functions. In particular, we demonstrate that oscillons are frequency-modulated waves, with speed-controlled …

Genome-Wide Allele-Specific Expression In Multi-Tissue Samples From Healthy Male Baboons Reveals The Transcriptional Complexity Of Mammals, Ramesh Ramasamy, Muthuswamy Raveendran, R Alan Harris, Hiep D Le, Ludovic S Mure, Giorgia Benegiamo, Ouria Dkhissi-Benyahya, Howard Cooper, Jeffrey Rogers, Satchidananda Panda

Faculty, Staff and Students Publications

Allele-specific expression (ASE) is pivotal in understanding the genetic underpinnings of phenotypic variation within species, differences in disease susceptibility, and responses to environmental factors. We processed 11 different tissue types collected from 12 age-matched healthy olive baboons (Papio anubis) for genome-wide ASE analysis. By sequencing their genomes at a minimum depth of 30×, we identified over 16 million single-nucleotide variants (SNVs). We also generated long-read sequencing data, enabling the phasing of all variants present within the coding regions of 96.5% of assayable protein-coding genes as a single haplotype block. Given the extensive heterozygosity of baboons relative to humans, we could …

Developing The Mycancergene Digital Health Portal To Improve Patients' Understanding Of Germline Cancer Genetic Test Results: Development, User, And Usability Testing Study, Phillip Trieu, Dominique Fetzer, Briana Mcleod, Kathryn Schweickert, Lauren Gutstein, Brian Egleston, Susan Domchek, Linda Fleisher, Lynne Wagner, Kuang-Yi Wen, Cara Cacioppo, Jessica E. Ebrahimzadeh, Dana Falcone, Claire Langer, Elisabeth Wood, Kelsey Karpink, Shelby Posen, Enida Selmani, Angela R. Bradbury

Department of Medical Oncology Faculty Papers

BACKGROUND: The use of multigene panels has significantly increased the likelihood that genetic testing will leave patients with uncertainties regarding test interpretation, implications, and recommendations, which will change over time. Effective longitudinal care models are needed to provide patients with updated information and to obtain patient and family history updates.

OBJECTIVE: To bridge this gap, we aimed to develop a patient- and genetic provider-informed digital genetic health portal (GHP), MyCancerGene, to improve longitudinal patient understanding of and responses to genetic testing.

METHODS: We used a 5-step process to develop MyCancerGene. To better understand their interest in and willingness to use …

Physiologically Based And Population Pharmacokinetic Modeling Of Midazolam In Children With Obesity Using Real-World Data, Sean Mccann, Victória E. Helfer, Stephen J. Balevic, William J. Muller, John N. Van Den Anker, Amira Al-Uzri, Marisa L. Meyer, Sarah G. Anderson, Sitora Turdalieva, Andrea N. Edginton, Daniel Gonzalez, Best Pharmaceuticals For Children Act Pediatric Trials Network Steering Committee

Department of Pediatrics Faculty Papers

Children represent a highly complex and variable population for treatment, including interindividual differences in drug dose-exposure. Midazolam has been used as a sedative for hospitalized children on- and off-label; however, factors affecting interindividual variability (IIV) in observed clearance for this population are not fully understood and can result in extreme under- or overexposure. Obesity has been described as a significant influence on midazolam in adolescents, which could potentially alter drug exposure. The goal of this study was to use two modeling strategies to evaluate dose-exposure of midazolam in children with and without obesity. Population pharmacokinetic modeling assessed whether measures of …

Smooth Muscle Cells And Fibroblasts In The Ascending Aorta Exhibit Minor Differences Between Embryonic Origins In Angiotensin Ii-Driven Transcriptional Alterations, Sohei Ito, David B Graf, Yuriko Katsumata, Jessica J Moorleghen, Chen Zhang, Yanming Li, Scott A Lemaire, Ying H Shen, Hong S Lu, Alan Daugherty, Hisashi Sawada

Faculty, Staff and Students Publications

Thoracic aortopathy is influenced by angiotensin II (AngII) and exhibits regional heterogeneity with the ascending aorta being particularly susceptible. In this region, smooth muscle cells (SMCs) and selected fibroblasts originate from the second heart field (SHF) and cardiac neural crest (CNC). While our previous study revealed a critical role of SHF-derived cells in AngII-mediated aortopathy, the contribution of CNC-derived cells remains unclear. To investigate lineage-specific responses to AngII, Mef2c-Cre R26RmT/mG mice were infused with AngII. Ascending aortas were harvested at baseline or after 3 days of infusion, representing the prepathological phase. Cells were sorted based on their embryonic origins and …

Multicentre Analysis Of Seizure Outcome Predicted By Removal Of High-Frequency Oscillations, Vasileios Dimakopoulos, Jean Gotman, Petr Klimes, Nicolas Von Ellenrieder, Shi Bei Tan, Garnett Smith, Stephen V. Gliske, Margarita Maltseva, Minette Krisel Manalo, Martin Pail, Milan Brazdil, Dorien Van Blooijs, Maryse A. Van 'T Klooster, Sarah Johnson, Samantha Laboy, Debora Ledergerber, Lukas Imbach, Christos Papadelis, Michael R. Sperling, Maeike Zijlmans, Jan Cimbalnik, Julia Jacobs, William C. Stacey, Birgit Frauscher, Johannes Sarnthein

Department of Neurology Faculty Papers

In drug-resistant focal epilepsy, planning surgical resection can involve presurgical intracranial EEG (iEEG) recordings to detect seizures and other iEEG patterns to improve postsurgical seizure outcome. We hypothesized that resection of tissue generating interictal high-frequency oscillations (HFOs, 80-500 Hz) in the iEEG predicts surgical outcome. In eight international epilepsy centres, iEEG was recorded during the presurgical evaluation of patients. The patients were of all ages, had epilepsy of all types, and underwent surgical resection of a single focus aiming at seizure freedom. In a prospective analysis, we applied a fully automated definition of HFO that was independent of the dataset. …

Temporal Regulation Of Early-Stage Cytokine Expression In Diabetic Wound Healing Under Negative Pressure Wound Therapy, Hua-Sheng Chiu, Ting-Shuo Huang, Chien-Tzung Chen, Xin-Yu Lin, Po-Cheng Liao, Cai-Cin Liou, Chih-Chin Hsu, Sonal Somvanshi, Pavel Sumazin, Pang-Hung Hsu, Chi-Chin Sun, Yu-Chiau Shyu

Faculty, Staff and Students Publications

Negative pressure wound therapy (NPWT) is widely recognized for its efficacy in treating diabetic wounds, but the mechanisms involved in the wound healing process remain unclear. By examining changes in blood cytokine levels as molecular signaling precursors, we aim to provide a comprehensive cytokine profile to support adjunctive therapy research and clinical applications. A diabetic mouse wound model was established to compare cytokine profiles between NPWT-treated and standard dressing groups, identifying key signaling candidates that may facilitate wound healing. By integrating normal mouse data with large-scale cytokine analysis, we developed a time-stratified NPWT approach to track acute-phase cytokine fluctuations in …

Risk Of Coronary Obstruction In Redo-Transcatheter Aortic Valve Replacement Between Bicuspid And Tricuspid Aortic Valves, Atsushi Okada, Syed Zaid, Miho Fukui, Evan Walser-Kuntz, Larissa I Stanberry, Marcus R Burns, John R Lesser, João L Cavalcante, Paul Sorajja, Vinayak N Bapat

Faculty, Staff and Students Publications

Background: Transcatheter aortic valve replacement (TAVR) is approved across all risk profiles, including patients with bicuspid aortic valves. These patients are generally younger, with a higher chance of reintervention.

Objectives: The aim of this study was to compare the feasibility of redo transcatheter aortic valve (TAV) between bicuspid and tricuspid aortic valves.

Methods: A computed tomographic (CT) simulation of redo-TAV was conducted using 913 post-TAVR CT studies from patients who underwent TAVR with SAPIEN 3 or SAPIEN 3 Ultra (S3; n = 623) or Evolut R, Evolut PRO, or Evolut PRO+ (Evolut; n = 290) valves. Fifty-nine cases were for …