Digital Commons Network^™

Random C-Peptide And Islet Antibodies At Onset Predict Β Cell Function Trajectory And Insulin Dependence In Pediatric Diabetes, Mustafa Tosur, Saima Deen, Xiaofan Huang, Serife Uysal, Marcela Astudillo, Richard A Oram, Maria J Redondo, Farook Jahoor, Ashok Balasubramanyam

Children’s Nutrition Research Center Staff Publications

Objective: Identification of prognostic biomarkers in pediatric diabetes is important for precision medicine. We assessed whether C-peptide and islet autoantibodies are useful to predict the natural history of children with new-onset diabetes.

Methods: We prospectively studied 72 children with new-onset diabetes (median follow-up: 8 months) by applying the Aβ classification system ("A+": islet autoantibody positive, "β+": random serum C-peptide ≥1.3 ng/mL at diagnosis). Beta-cell function was assessed longitudinally with 2 hours postprandial/stimulated urinary C-peptide-to-creatinine ratio (UCPCR) 3-12 weeks (V1) and 6 to 12 months after diagnosis (V2). We obtained a type 1 diabetes genetic risk score for each participant, and …

Efficacy And Feasibility Of Intradialytic Plantar Electrical Stimulation In Patients With Diabetes: A Randomized Double-Blind Controlled Trial, Myeounggon Lee, Abdullah Hamad, Mehrnaz Azarian, Jaewon Beom, Abderrahman Ouattas, Mohammad Dehghan Rouzi, Naima Rodriguez, Nhi Quach, Rania Ibrahim, Mincy Mathew, Talal Talal, Fadwa Al-Ali, Bijan Najafi

Center on Aging Staff Publications

Objective: This study investigates the efficacy and feasibility of electrical stimulation (E-Stim) on sensory fibers of the plantar region during hemodialysis sessions, aiming to improve mobility in patients with diabetes by providing a connection between E-Stim and enhanced mobility with minimal patient effort required.

Research design and methods: Participants aged ≥18 years with diabetes undergoing hemodialysis and able to walk at least 10 m with or without aid were recruited and divided into an intervention group receiving 1-h intradialytic E-Stim three times a week and a control group using an identical nonfunctional device for 12 weeks. Gait, physical activity, patient-reported …

Delivery Of Hand Care To Patients With High Anxiety Burden, Caellagh D Catley, Sarah C Romans, Abby L Cheng, Ryan P Calfee

2020-Current year OA Pubs

PURPOSE: To determine whether patients presenting with Patient-Reported Outcome Measurement Information System (PROMIS) anxiety scores at >95th percentile of the US population undergo elective hand surgery at rates different from patients with less anxiety. Secondarily, we aimed to assess surgeon notation of these patients' emotional states and incidences of postoperative complications.

METHODS: This single-center retrospective cohort study analyzed data from new adult patients presenting for hand care between January 2019 and December 2020. Patients with initial PROMIS anxiety scores ≥70 were identified as the high anxiety burden (HAB) group. For each patient with HAB presenting with carpal tunnel syndrome, trigger …

Quantifying Brain Development In The Healthy Brain And Child Development (Hbcd) Study: The Magnetic Resonance Imaging And Spectroscopy Protocol, Douglas C Dean 3rd, Chad M Sylvester, Michael P Harms, Christopher D Smyser, Et Al.

2020-Current year OA Pubs

The HEALthy Brain and Child Development (HBCD) Study, a multi-site prospective longitudinal cohort study, will examine human brain, cognitive, behavioral, social, and emotional development beginning prenatally and planned through early childhood. The acquisition of multimodal magnetic resonance-based brain development data is central to the study's core protocol. However, application of Magnetic Resonance Imaging (MRI) methods in this population is complicated by technical challenges and difficulties of imaging in early life. Overcoming these challenges requires an innovative and harmonized approach, combining age-appropriate acquisition protocols together with specialized pediatric neuroimaging strategies. The HBCD MRI Working Group aimed to establish a core acquisition …

The Sodium-Proton Exchangers Snhe And Nhe1 Control Plasma Membrane Hyperpolarization In Mouse Sperm, Analia G Novero, Celia M Santi, Et Al.

2020-Current year OA Pubs

Sperm capacitation is a complex process that takes place in the female reproductive tract and empowers mammalian sperm with the competence to fertilize an egg. It consists of an intricate cascade of events that can be mimicked in vitro through incubation in a medium containing essential components, such as bicarbonate, albumin, Ca

The Effects Of Mosaicism On Biological And Clinical Markers Of Alzheimer's Disease In Adults With Down Syndrome, Laura Xicota, Rachel L Henson, Beau Ances, Et Al.

2020-Current year OA Pubs

BACKGROUND: Individuals with Down syndrome (DS) are at high risk of early-onset Alzheimer's disease (AD); yet, some 20 percent do not develop any signs of dementia until after 65 years or in their lifetime. Mosaicism could contribute to this phenotypic variation, where some disomic cells could lead to lower levels of gene products from chromosome 21.

METHODS: We examined longitudinal neuropsychological and biomarker data from two large studies of DS: the Alzheimer Biomarker Consortium-Down syndrome study (ABC-DS) (n = 357); and a legacy study (n = 468). We assessed mosaicism using karyotyping or GWAS data. Participants had data on plasma …

Nuclear Expression Of Dynamin 2 Is Associated With Tumor Aggressiveness In Bladder Cancer Patients: A Bioinformatics And Experimental Approach, Mahdieh Razmi, Leili Saeednejad Zanjani, Mandana Rahimi, Roya Sajed, Sadegh Safaei, Zahra Madjd, Roya Ghods

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Dynamin 2 (DNM2) is aberrantly expressed in different malignancies and exerts a function in tumor progression.

AIMS: This study, for the first time, aimed to evaluate the clinical and prognostic value of DNM2 in the pathophysiology of bladder cancer using bioinformatics analysis and experimental evaluation.

METHODS AND RESULTS: We analyzed gene expression of DNM2 in bladder tumor by GEPIA2 and GENT2 platforms. Cluster subnetworks were recognized from the protein-protein interaction (PPI) network using the MCODE plugin to screen the key genes. Subsequently, the pathway enrichment analysis was evaluated. Then, the immunohistochemical examination was conducted on 209 paraffin-embedded bladder cancer …

Inferring Allele-Specific Copy Number Aberrations And Tumor Phylogeography From Spatially Resolved Transcriptomics, Cong Ma, Metin Balaban, Jingxian Liu, Siqi Chen, Michael J Wilson, Christopher H Sun, Li Ding, Benjamin J Raphael

2020-Current year OA Pubs

Analyzing somatic evolution within a tumor over time and across space is a key challenge in cancer research. Spatially resolved transcriptomics (SRT) measures gene expression at thousands of spatial locations in a tumor, but does not directly reveal genomic aberrations. We introduce CalicoST, an algorithm to simultaneously infer allele-specific copy number aberrations (CNAs) and reconstruct spatial tumor evolution, or phylogeography, from SRT data. CalicoST identifies important classes of CNAs-including copy-neutral loss of heterozygosity and mirrored subclonal CNAs-that are invisible to total copy number analysis. Using nine patients' data from the Human Tumor Atlas Network, CalicoST achieves an average accuracy of …

Development And Validation Of A Prechiasmatic Mouse Model Of Subarachnoid Hemorrhage To Measure Long-Term Cognitive Deficits, Deepti Diwan, Jogender Mehla, James W Nelson, James D Quirk, Sheng-Kwei Song, Sarah Cao, Benjamin Meron, Aminah Mostofa, Gregory J Zipfel

2020-Current year OA Pubs

Controllable and reproducible animal models of aneurysmal subarachnoid hemorrhage (SAH) are crucial for the systematic study of the pathophysiology and treatment of this debilitating condition. However, current animal models have not been successful in replicating the pathology and disabilities seen in SAH patients, especially the long-term neurocognitive deficits that affect the survivor's quality of life. Therefore, there is an unmet need to develop experimental models that reliably replicate the long-term clinical ramifications of SAH - especially in mice where genetic manipulations are straightforward and readily available. To address this need, a standardized mouse SAH model is developed that reproducibly produced …

Identifying Dose Constraints For The Parotid Ducts To Minimize Patient-Reported Xerostomia: Is Conventional Mean Dose Sparing Of The Parotid Glands Sufficient?, Manal Ahmidouch, Shiva K Das, Tong Zhu, Colette Shen, Lawrence B Marks, Bhishamjit S Chera, David V Fried

2020-Current year OA Pubs

BACKGROUND AND PURPOSE: The aim of this study was to identify dose constraints for the parotid ducts that limit patient-reported xerostomia and estimate whether these constraints are achieved during conventional parotid gland sparing radiation therapy (PGS-RT).

METHODS AND MATERIALS: Thirty-eight oropharyngeal squamous cell carcinoma patients were treated prospectively on trial with MRI sialography-guided parotid duct sparing radiation therapy (PDS-RT). PDS-RT explicitly minimizes dose to the parotid ducts in addition to PGS-RT. Parotid duct dose constraints were identified that distinguished patients reporting high and low rates of xerostomia. Atlas-based parotid duct contours were generated on a retrospective cohort of similar patients …

Lenvatinib Plus Ifosfamide And Etoposide In Children And Young Adults With Relapsed Osteosarcoma: A Phase 2 Randomized Clinical Trial, Nathalie Gaspar, Giun-Yi Hung, Sandra J Strauss, Quentin Campbell-Hewson, Filemon S Dela Cruz, Julia L Glade Bender, Kyung-Nam Koh, Sarah B Whittle, Godfrey Chi-Fung Chan, Nicolas U Gerber, Sauli Palmu, Daniel A Morgenstern, Alessandra Longhi, Fredrik Baecklund, Jun Ah Lee, Franco Locatelli, Catalina Márquez Vega, Katherine A Janeway, Geoffrey Mccowage, Martin G Mccabe, Behzad Bidadi, Jie Huang, Jodi Mckenzie, Chinyere E Okpara, Francisco Bautista, Olie Study Investigators

Faculty, Staff and Students Publications

IMPORTANCE: The combination of ifosfamide and etoposide (IE) is commonly used to treat relapsed or refractory osteosarcoma; however, second-line treatment recommendations vary across guidelines.

OBJECTIVE: To evaluate whether the addition of lenvatinib to IE (LEN-IE) improves outcomes in children and young adults with relapsed or refractory osteosarcoma.

DESIGN, SETTING, AND PARTICIPANTS: The OLIE phase II, open-label, randomized clinical trial was conducted globally across Europe, Asia and the Pacific, and North America. From March 22, 2020, through November 11, 2021, the trial enrolled patients aged 2 to 25 years with high-grade osteosarcoma, measurable or evaluable disease per Response Evaluation Criteria in …

Machine Learning-Based Prediction Model For Icu Mortality After Continuous Renal Replacement Therapy Initiation In Children, Sameer Thadani, Tzu-Chun Wu, Danny T Y Wu, Aadil Kakajiwala, Danielle E Soranno, Gerard Cortina, Rachana Srivastava, Katja M Gist, Shina Menon, Worldwide Exploration Of Renal Replacement Outcomes Collaborative In Kidney Diseases (We-Rock) Collaborators

Faculty, Staff and Students Publications

BACKGROUND: Continuous renal replacement therapy (CRRT) is the favored renal replacement therapy in critically ill patients. Predicting clinical outcomes for CRRT patients is difficult due to population heterogeneity, varying clinical practices, and limited sample sizes.

OBJECTIVE: We aimed to predict survival to ICUs and hospital discharge in children and young adults receiving CRRT using machine learning (ML) techniques.

DERIVATION COHORT: Patients less than 25 years of age receiving CRRT for acute kidney injury and/or volume overload from 2015 to 2021 (80%).

VALIDATION COHORT: Internal validation occurred in a testing group of patients from the dataset (20%).

PREDICTION MODEL: Retrospective international …

Individual Dynamic Prediction For Cure And Survival Based On Longitudinal Biomarkers, Can Xie, Xuelin Huang, Ruosha Li, Alexander Tsodikov, Kapil Bhalla

Faculty, Staff and Student Publications

To optimize personalized treatment strategies and extend patients' survival times, it is critical to accurately predict patients' prognoses at all stages, from disease diagnosis to follow-up visits. The longitudinal biomarker measurements during visits are essential for this prediction purpose. Patients' ultimate concerns are cure and survival. However, in many situations, there is no clear biomarker indicator for cure. We propose a comprehensive joint model of longitudinal and survival data and a landmark cure model, incorporating proportions of potentially cured patients. The survival distributions in the joint and landmark models are specified through flexible hazard functions with the proportional hazards as …

Langerhans Cell Histiocytosis In Children Born After Assisted Reproductive Technology, Carrie L Williams, Kathryn J Bunch, Charles Stiller, Michael F G Murphy, Beverley J Botting, Melanie C Davies, Barbara Luke, Philip J Lupo, Alastair G Sutcliffe

Center for Medical Ethics and Health Policy Staff Publications

Research question: Are children born after assisted reproductive technology (ART) at higher risk of developing Langerhans cell histiocytosis (LCH)?

Design: Records of children born after ART recorded by the UK Human Fertilisation & Embryology Authority were linked to National Registry of Childhood Tumours records to determine the number of children developing LCH. Calculated person-years at risk were used in conjunction with the incidence of LCH in the general population to determine the expected number of cases if the cohort had the same incidence as the general population with similar age and sex, over the same calendar years. The standardized incidence …

Chronic Β3-Ar Stimulation Activates Distinct Thermogenic Mechanisms In Brown And White Adipose Tissue And Improves Systemic Metabolism In Aged Mice, Duraipandy Natarajan, Bhuvana Plakkot, Kritika Tiwari, Shoba Ekambaram, Weidong Wang, Michael Rudolph, Mahmoud A Mohammad, Shaji K Chacko, Madhan Subramanian, Stefano Tarantini, Andriy Yabluchanskiy, Zoltan Ungvari, Anna Csiszar, Priya Balasubramanian

Faculty, Staff and Students Publications

Adipose thermogenesis has been actively investigated as a therapeutic target for improving metabolic dysfunction in obesity. However, its applicability to middle-aged and older populations, which bear the highest obesity prevalence in the United States (approximately 40%), remains uncertain due to age-related decline in thermogenic responses. In this study, we investigated the effects of chronic thermogenic stimulation using the β3-adrenergic (AR) agonist CL316,243 (CL) on systemic metabolism and adipose function in aged (18-month-old) C57BL/6JN mice. Sustained β3-AR treatment resulted in reduced fat mass, increased energy expenditure, increased fatty acid oxidation and mitochondrial activity in adipose depots, improved glucose homeostasis, and a …

Randomized, Observer-Blind, Controlled Phase 1 Study Of The Safety And Immunogenicity Of The Na-Gst-1/Alhydrogel Hookworm Vaccine With Or Without A Cpg Odn Adjuvant In Hookworm-Naïve Adults, David J Diemert, Maria Zumer, Mark Bova, Christina Gibbs-Tewary, Elissa M Malkin, Doreen Campbell, Lara Hoeweler, Guangzhao Li, Maria Elena Bottazzi, Peter J Hotez, Jeffrey M Bethony

Faculty, Staff and Students Publications

BACKGROUND: Recombinant Necator americanus Glutathione-S-Transferase-1 (Na-GST-1) formulated on Alhydrogel (Na-GST-1/Alhydrogel) is being developed to prevent anemia and other complications of N. americanus infection. Antibodies induced by vaccination with recombinant Na-GST-1 are hypothesized to interfere with the blood digestion pathway of adult hookworms in the host. Phase 1 trials have demonstrated the safety of Na-GST-1 formulated on Alhydrogel, but further optimization of the vaccine adjuvant formulation may improve humoral immune responses, thereby increasing the likelihood of vaccine efficacy.

METHODS: A randomized, observer-blind, dose escalation Phase 1 trial was conducted in 24 healthy, hookworm-naïve adults. In each cohort of 12 participants, 4 …

Effects Of Trauma Exposure And Posttraumatic Stress Disorder On Perceived Social Support In Youth: A Longitudinal Investigation, Erin Logue, John Leri, Jeffrey D Shahidullah, Caitlin M Pinciotti, Paul J Rathouz, Josh M Cisler, D Jeffrey Newport, Karen Dineen Wagner, Charles B Nemeroff

Faculty, Staff and Students Publications

The aim of this study was to examine relationships among trauma burden, post-traumatic stress disorder, and perceived social support in a large, diverse group of trauma-exposed children and adolescents followed longitudinally. Specifically, we tested the social erosion hypothesis (i.e., mental health challenges negatively affect the quality of social relationships and contribute to reduced social support over time) using a sample of 1,829 trauma-exposed youth (aged 8-21) recruited through the multi-site Texas Childhood Trauma Research Network. Youth who reported more trauma burden (i.e., a greater number of traumas) perceived significantly lower levels of social support from family and peers, and those …

Global And Risk-Group Stratified Well-Being And Mental Health During The Covid-19 Pandemic In Adults: Results From The International Coh-Fit Study, Marco Solmi, Trevor Thompson, Andrés Estradé, Agorastos Agorastos, Joaquim Radua, Samuele Cortese, Elena Dragioti, Davy Vancampfort, Lau Caspar Thygesen, Harald Aschauer, Monika Schlögelhofer, Elena Aschauer, Andres Schneeberger, Christian G Huber, Gregor Hasler, Philippe Conus, Kim Q Do Cuénod, Roland Von Känel, Gonzalo Arrondo, Paolo Fusar-Poli, Philip Gorwood, Pierre-Michel Llorca, Marie-Odile Krebs, Elisabetta Scanferla, Taishiro Kishimoto, Golam Rabbani, Karolina Skonieczna-Żydecka, Paolo Brambilla, Angela Favaro, Akihiro Takamiya, Leonardo Zoccante, Marco Colizzi, Julie Bourgin, Karol Kamiński, Maryam Moghadasin, Soraya Seedat, Evan Matthews, John Wells, Emilia Vassilopoulou, Ary Gadelha, Kuan-Pin Su, Jun Soo Kwon, Minah Kim, Tae Young Lee, Oleg Papsuev, Denisa Manková, Andrea Boscutti, Cristiano Gerunda, Diego Saccon, Elena Righi, Francesco Monaco, Giovanni Croatto, Guido Cereda, Jacopo Demurtas, Natascia Brondino, Nicola Veronese, Paolo Enrico, Pierluigi Politi, Valentina Ciappolino, Andrea Pfennig, Andreas Bechdolf, Andreas Meyer-Lindenberg, Kai G Kahl, Katharina Domschke, Michael Bauer, Nikolaos Koutsouleris, Sibylle Winter, Stefan Borgwardt, Istvan Bitter, Judit Balazs, Pál Czobor, Zsolt Unoka, Dimitris Mavridis, Konstantinos Tsamakis, Vasilios P Bozikas, Chavit Tunvirachaisakul, Michael Maes, Teerayuth Rungnirundorn, Thitiporn Supasitthumrong, Ariful Haque, Andre R Brunoni, Carlos Gustavo Costardi, Felipe Barreto Schuch, Guilherme Polanczyk, Jhoanne Merlyn Luiz, Lais Fonseca, Luana V Aparicio, Samira S Valvassori, Merete Nordentoft, Per Vendsborg, Sofie Have Hoffmann, Jihed Sehli, Norman Sartorius, Sabina Heuss, Daniel Guinart, Jane Hamilton, John Kane, Jose Rubio, Michael Sand, Ai Koyanagi, Aleix Solanes, Alvaro Andreu-Bernabeu, Antonia San José Cáceres, Celso Arango, Covadonga M Díaz-Caneja, Diego Hidalgo-Mazzei, Eduard Vieta, Javier Gonzalez-Peñas, Lydia Fortea, Mara Parellada, Miquel A Fullana, Norma Verdolini, Eva Andrlíková, Karolina Janků, Mark J Millan, Mihaela Honciuc, Anna Moniuszko-Malinowska, Igor Łoniewski, Jerzy Samochowiec, Łukasz Kiszkiel, Maria Marlicz, Paweł Sowa, Wojciech Marlicz, Georgina Spies, Brendon Stubbs, Joseph Firth, Sarah Sullivan, Asli Enez Darcin, Hatice Aksu, Nesrin Dilbaz, Onur Noyan, Momoko Kitazawa, Shunya Kurokawa, Yuki Tazawa, Alejandro Anselmi, Cecilia Cracco, Ana Inés Machado, Natalia Estrade, Diego De Leo, Jackie Curtis, Michael Berk, Andre F Carvalho, Philip Ward, Scott Teasdale, Simon Rosenbaum, Wolfgang Marx, Adrian Vasile Horodnic, Liviu Oprea, Ovidiu Alexinschi, Petru Ifteni, Serban Turliuc, Tudor Ciuhodaru, Alexandra Bolos, Valentin Matei, Dorien H Nieman, Iris Sommer, Jim Van Os, Therese Van Amelsvoort, Ching-Fang Sun, Ta-Wei Guu, Can Jiao, Jieting Zhang, Jialin Fan, Liye Zou, Xin Yu, Xinli Chi, Philippe De Timary, Ruud Van Winkel, Bernardo Ng, Edilberto Peña De León, Ramon Arellano, Raquel Roman, Thelma Sanchez, Larisa Movina, Pedro Morgado, Sofia Brissos, Oleg Aizberg, Anna Mosina, Damir Krinitski, James Mugisha, Dena Sadeghi-Bahmani, Farshad Sheybani, Masoud Sadeghi, Samira Hadi, Serge Brand, Antonia Errazuriz, Nicolas Crossley, Dragana Ignjatovic Ristic, Carlos López-Jaramillo, Dimitris Efthymiou, Praveenlal Kuttichira, Roy Abraham Kallivayalil, Afzal Javed, Muhammad Iqbal Afridi, Bawo James, Omonefe Joy Seb-Akahomen, Jess Fiedorowicz, Jeff Daskalakis, Lakshmi N Yatham, Lin Yang, Tarek Okasha, Aïcha Dahdouh, Jari Tiihonen, Jae Il Shin, Jinhee Lee, Ahmed Mhalla, Lotfi Gaha, Takoua Brahim, Kuanysh Altynbekov, Nikolay Negay, Saltanat Nurmagambetova, Yasser Abu Jamei, Mark Weiser, Christoph U Correll

Faculty, Staff and Students Publications

International studies measuring wellbeing/multidimensional mental health before/ during the COVID-19 pandemic, including representative samples for >2 years, identifying risk groups and coping strategies are lacking. COH-FIT is an online, international, anonymous survey measuring changes in well-being (WHO-5) and a composite psychopathology P-score, and their associations with COVID-19 deaths/restrictions, 12 a-priori defined risk individual/cumulative factors, and coping strategies during COVID-19 pandemic (26/04/2020-26/06/2022) in 30 languages (representative, weighted non-representative, adults). T-test, χ2, penalized cubic splines, linear regression, correlation analyses were conducted. Analyzing 121,066/142,364 initiated surveys, WHO-5/P-score worsened intra-pandemic by 11.1±21.1/13.2±17.9 points (effect size d=0.50/0.60) (comparable results in representative/weighted non-probability samples). Persons with …

Efficacy Of Letermovir For Cytomegalovirus Prophylaxis Following Alemtuzumab T-Cell Depleted Allogeneic Hematopoietic Stem Cell Transplant, Ibrahim N Muhsen, Kristen E Shaver, Tao Wang, Mengfen Wu, Premal Lulla, Carlos A Ramos, Rammurti T Kamble, Helen E Heslop, George Carrum, Laquisa C Hill

Faculty, Staff and Students Publications

In vivo T-cell depletion (TCD) using alemtuzumab decreases the risk of Graft vs Host Disease (GvHD) in recipients of allogeneic hematopoietic stem cell transplant (allo-HSCT). However, this approach increases the risk of infections post-allo-HSCT, including Cytomegalovirus (CMV). Letermovir is approved for the use in CMV prophylaxis post-allo-HSCT. Few studies have investigated the efficacy of letermovir in patients receiving alemtuzumab. This is a single-center retrospective study describing our institutional experience using letermovir in recipients of alemtuzumab TCD allo-HSCT from unrelated donors (URD). The primary outcome was the cumulative incidence of significant CMV infection (defined as viremia leading to preemptive antiviral therapy …

Diabetter Together: Clinical Trial Protocol For A Strengths-Based Peer Mentor Intervention For Young Adults With Type 1 Diabetes Transitioning To Adult Care, Samantha A Carreon, Charles G Minard, Sarah K Lyons, Wendy Levy, Stephanie Camey, Kishan Desai, Brenda Duran, Randi Streisand, Barbara J Anderson, Siripoom V Mckay, Tricia S Tang, Sridevi Devaraj, Ryan Ramphul, Marisa E Hilliard

Faculty, Staff and Students Publications

Background: Type 1 diabetes (T1D) management is challenging for young adults, who are expected to transfer from the pediatric to adult T1D healthcare system while also managing typical developmental demands (e.g., social, financial, work/school, residential). Many young adults have extended gaps in care before following up in adult care, increasing risk for poor health outcomes. There are few evidence-based programs to support young adults with T1D to promote a timelier transition during this period. This paper reports on the design of DiaBetter Together, a randomized controlled trial to evaluate a 12-month Peer Mentor-delivered intervention compared to usual care among young …

Persistent Growth-Promoting Effects Of Vosoritide In Children With Achondroplasia Are Accompanied By Improvements In Physical And Social Aspects Of Health-Related Quality Of Life, Ravi Savarirayan, Melita Irving, William R Wilcox, Carlos A Bacino, Julie E Hoover-Fong, Paul Harmatz, Lynda E Polgreen, Klaus Mohnike, Carlos E Prada, Takuo Kubota, Paul Arundel, Antonio Leiva-Gea, Richard Rowell, Andrea Low, Ian Sabir, Alice Huntsman-Labed, Jonathan Day

Faculty, Staff and Students Publications

Purpose: Evaluate the impact of vosoritide on health-related quality of life in children with achondroplasia.

Methods: Participants received vosoritide (15 μg/kg/day) in an extension trial (NCT03424018) after having participated in a placebo-controlled trial (NCT03197766).

Results: The population comprised 119 participants (mean [SD] age 9.7 [2.6] years). Mean treatment duration was 4 (0.78) years. At year 3, the largest mean (SD) changes were observed in the Quality of Life of Short Stature Youth physical score (5.99 [19.41], caregiver reported; 6.32 [20.15], self-reported) and social score (2.85 [8.29] and 6.76 [22.64], respectively). Changes were greatest in participants with …

Normative Neuroimaging Library: Designing A Comprehensive And Demographically Diverse Dataset Of Healthy Controls To Support Traumatic Brain Injury Diagnostic And Therapeutic Development, Allyson T Gage, James R Stone, Elisabeth A Wilde, Stephen R Mccauley, Robert C Welsh, John P Mugler, Nick Tustison, Brian Avants, Christopher T Whitlow, Lee Lancashire, Seema D Bhatt, Magali Haas

Faculty, Staff and Students Publications

The past decade has seen impressive advances in neuroimaging, moving from qualitative to quantitative outputs. Available techniques now allow for the inference of microscopic changes occurring in white and gray matter, along with alterations in physiology and function. These existing and emerging techniques hold the potential of providing unprecedented capabilities in achieving a diagnosis and predicting outcomes for traumatic brain injury (TBI) and a variety of other neurological diseases. To see this promise move from the research lab into clinical care, an understanding is needed of what normal data look like for all age ranges, sex, and other demographic and …

Genome-Derived Ampullary Adenocarcinoma Classifier And Postresection Prognostication, Brett L Ecker, Kenneth Seier, Austin M Eckhoff, Gabriella N Tortorello, Peter J Allen, Vinod P Balachandran, Nicola Blackburn, Michael I D'Angelica, Ronald P Dematteo, Daniel G Blazer, Jeffrey A Drebin, William E Fisher, Danielle Fortuna, Anthony J Gill, Marie-Claude Gingras, T Peter Kingham, Major K Lee, Michael E Lidsky, Daniel P Nussbaum, Michael J Overman, Jaswinder S Samra, Ronglai Shen, Carlie S Sigel, Kevin C Soares, Charles M Vollmer, Alice C Wei, Sabino Zani, Robert E Roses, Mithat Gonen, William R Jarnagin

Faculty, Staff and Students Publications

Importance: Ampullary adenocarcinoma (AA) is characterized by clinical and genomic heterogeneity. A previously developed genomic classifier defined biologically distinct phenotypes with greater accuracy than standard histologic classification. External validation is needed before routine clinical use.

Objective: To test external validity of the prognostic value of the hidden genome classifier of AA.

Design, setting, and participants: This retrospective cohort study took place at 6 international academic institutions. Consecutive patients (n = 192) who underwent curative-intent resection of histologically confirmed AA were included. The data were analyzed from January 2005 through July 2020.

Exposures: The multilevel meta-feature regression model previously trained on …

Lack Of Association Of First And Second-Line Medication Dosing And Progression To Refractory Status Epilepticus In Children, Cristina Barcia Aguilar, Marta Amengual-Gual, J Nicholas Brenton, Kevin E Chapman, Justice Clark, William D Gaillard, Joshua L Goldstein, Howard P Goodkin, Robert Kahoud, Yi-Chen Lai, Mohamad A Mikati, Lindsey A Morgan, Eric T Payne, Craig A Press, Latania Reece, Tristan T Sands, Kumar Sannagowdara, Theodore Sheehan, Renée A Shellhaas, Robert C Tasker, Mark S Wainwright, Bo Zhang, Tobias Loddenkemper

Faculty, Staff and Students Publications

Purpose: Evaluate the relationship between first and second-line medication dosing and progression to refractory status epilepticus (RSE) in children.

Methods: This is a retrospective analysis of prospectively collected data from September 2014 to February 2020 of children with status epilepticus (SE) who received at least two antiseizure medications (ASMs). We evaluated the risk of developing RSE after receiving a low total benzodiazepine dose (lower than 100 % of the minimum recommended dose for each benzodiazepine dose administered within 10 min) and a low first non-benzodiazepine ASM dose (lower than 100 % of the minimum recommended dose of non-benzodiazepine ASM given …

Parental Report Of Indoor Air Pollution Is Associated With Respiratory Morbidities In Bronchopulmonary Dysplasia, Jessica L Rice, Joseph M Collaco, Michael C Tracy, Catherine A Sheils, Lawrence M Rhein, Antonia P Popova, Paul E Moore, Audrey N Miller, Winston M Manimtim, Khanh Lai, Jacob A Kaslow, Lystra P Hayden, Julie L Fierro, Manvi Bansal, Eric D Austin, Brianna Aoyama, Stamatia Alexiou, Gangaram Akangire, Amit Agarwal, Natalie Villafranco, Roopa Siddaiah, Joanne M Lagatta, Mehtap Haktanir Abul, A Ioana Cristea, Christopher D Baker, Steven H Abman, Sharon A Mcgrath-Morrow

Faculty, Staff and Students Publications

Objective: To determine the association between indoor air pollution and respiratory morbidities in children with bronchopulmonary dysplasia (BPD) recruited from the multicenter BPD Collaborative.

Study design: A cross-sectional study was performed among participants < 3 years old in the BPD Collaborative Outpatient Registry. Indoor air pollution was defined as any reported exposure to tobacco or marijuana smoke, electronic cigarette emissions, gas stoves, and/or wood stoves. Clinical data included acute care use and chronic respiratory symptoms in the past 4 weeks.

Results: A total of 1011 participants born at a mean gestational age of 26.4 ± 2.2 weeks were included. Most (66.6%) had severe BPD. More than 40% of participants were exposed to ≥1 source of indoor air pollution. The odds of reporting an emergency department visit (OR, 1.7; 95% CI, 1.18-2.45), antibiotic use (OR, 1.9; 95% CI, 1.12-3.21), or a systemic steroid course (OR, 2.18; 95% CI, …

Understanding Health-Related Quality Of Life After Hypospadias Repair: A Qualitative Study With Pre-Adolescent Males And Parents, Vinaya Bhatia, Shannon Cannon, Anjali N Patel, Heidi W Brown, Walid A Farhat, Marisa E Hilliard

Faculty, Staff and Students Publications

Introduction: Hypospadias is a common disease that affects approximately 1 in every 200 live male births in the United States, and long-term studies of individuals who have undergone repair demonstrate complication rates of 15%-70%. The Hypospadias-Specific Health-related Quality of Life (HRQOL) Conceptual Framework for youth and adults suggests that additional morbidity may be incurred from poor psychological, social, and sexual health. The current study sought to clarify hypospadias-specific HRQOL and care priorities in a pre-pubertal population.

Material and methods: This IRB-approved, semi-structured interview study used rigorous qualitative research methods. Eligible patients were English-speaking 8-12-year-old males with hypospadias and their parents. …

Analysis Of Dna Methylation In Gliomas: Assessment Of Preanalytical Variables, Karol Bomsztyk, Daniel Mar, Oleg Denisenko, Suzanne Powell, Monika Vishnoi, Zheng Yin, Jennifer Delegard, Caroline Hadley, Nitin Tandon, Akash J Patel, Anoop P Patel, Richard G Ellenbogen, Rohan Ramakrishna, Robert C Rostomily

Faculty, Staff and Students Publications

Precision oncology is driven by biomarkers. For glioblastoma multiforme (GBM), the most common malignant adult primary brain tumor, O6-methylguanine-DNA methyltransferase (MGMT) gene promoter methylation is an important prognostic and treatment clinical biomarker. Time consuming pre-analytical steps such as biospecimen storage, fixation, sampling, and processing are sources of data irreproducibility, and all these pre-analytical variables are confounded by intratumor heterogeneity of MGMT promoter methylation. To assess the effect of pre-analytical variables on GBM DNA methylation, tissue storage/sampling (CryoGrid), sample preparation multi-sonicator (PIXUL), and 5-methylcytosine (5mC) DNA immunoprecipitation (Matrix MeDIP-qPCR/seq) platforms were used. MGMT promoter methylation status assayed by MeDIP-qPCR was …

Veterans' Experiences Of And Preferences For Patient-Centered, Measurement-Based Ptsd Care, Marcela C Weber, Ashlyn M Jendro, Ellen P Fischer, Karen L Drummond, Trenton M Haltom, Natalie E Hundt, Michael A Cucciare, Jeffrey M Pyne

Faculty, Staff and Students Publications

Background: Up to 50% of veterans drop out of trauma-focused evidence-based psychotherapies (TF-EBP) without completing treatment or recovering; evidence suggests this is in part because their posttraumatic stress disorder (PTSD) care is insufficiently patient-centered. There is also evidence that measurement-based care (MBC) for mental health should be personalized to the patient, yet this is not common practice in VA PTSD care.

Objectives: To explore veterans' experiences and preferences for aligning measurement-based PTSD care with their own treatment goals.

Method: Qualitative interviews were conducted with veterans (n=15) with PTSD who had received at least 2 sessions of a TF-EBP.

Measures: Survey …

Association Of Left Atrial Function With Frailty: The Atherosclerosis Risk In Communities (Aric) Study, Daokun Sun, Romil R Parikh, Wendy Wang, Anne Eaton, Pamela L Lutsey, B Gwen Windham, Riccardo M Inciardi, Scott D Solomon, Christie M Ballantyne, Amil M Shah, Lin Yee Chen

Faculty, Staff and Students Publications

Background: Frailty is common in people with cardiovascular disease. Worse left atrial (LA) function is an independent risk factor for cardiovascular disease. However, whether worse LA function is associated with frailty is unclear.

Methods: We included 3292 older adults from the Atherosclerosis Risk in Communities study who were non-frail at baseline (visit 5, 2011-2013) and had LA function (reservoir, conduit, and contractile strain) measured from two-dimensional speckle-tracking echocardiography. LA stiffness index was calculated as a ratio of E/e' to LA reservoir strain. Frailty was defined using the validated Fried frailty phenotype. Incident frailty was assessed between 2016 and 2019 during …

Rfc2 May Contribute To The Pathogenicity Of Williams Syndrome Revealed In A Zebrafish Model, Ji-Won Park, Tae-Ik Choi, Tae-Yoon Kim, Yu-Ri Lee, Dilan Wellalage Don, Jaya K George-Abraham, Laurie A Robak, Cristina C Trandafir, Pengfei Liu, Jill A Rosenfeld, Tae Hyeong Kim, Florence Petit, Yoo-Mi Kim, Chong Kun Cheon, Yoonsung Lee, Cheol-Hee Kim

Faculty, Staff and Students Publications

Williams syndrome (WS) is a rare multisystemic disorder caused by recurrent microdeletions on 7q11.23, characterized by intellectual disability, distinctive craniofacial and dental features, and cardiovascular problems. Previous studies have explored the roles of individual genes within these microdeletions in contributing to WS phenotypes. Here, we report five patients with WS with 1.4 Mb-1.5 Mb microdeletions that include RFC2, as well as one patient with a 167-kb microdeletion involving RFC2 and six patients with intragenic variants within RFC2. To investigate the potential involvement of RFC2 in WS pathogenicity, we generate a rfc2 knockout (KO) zebrafish using CRISPR-Cas9 technology. Additionally, we generate …