Digital Commons Network^™

Plasma Mtbr-Tau243 Biomarker Identifies Tau Tangle Pathology In Alzheimer's Disease, Kanta Horie, Rama K Koppisetti, Nicolas R Barthélemy, Yingxin He, Chihiro Sato, Brian A Gordon, Hong Jiang, Tammie L S Benzinger, David M Holtzman, John C Morris, Suzanne E Schindler, Randall J Bateman, Et Al.

2020-Current year OA Pubs

Insoluble tau aggregates within neurofibrillary tangles are a defining neuropathological feature of Alzheimer's disease (AD) and closely correlate with clinical symptoms. Although tau pathology can be assessed using tau positron emission tomography, a more accessible biomarker is needed for diagnosis, prognosis and tracking treatment effects. Here we present a new plasma tau species, the endogenously cleaved, microtubule-binding region containing residue 243 (eMTBR-tau243), which specifically reflects tau tangle pathology. Across the AD spectrum in three different cohorts (n = 108, 55 and 739), plasma eMTBR-tau243 levels were significantly elevated at the mild cognitive impairment stage and increased further in dementia. Plasma …

Protocol For A Multisite, Parallel-Group, Randomized Clinical Trial Comparing A Brief Tele-Cognitive Behavioral Therapy Intervention (Bright) With Attention Control For The Reduction Of Body Image-Related Distress Among Head And Neck Cancer Survivors, Evan M Graboyes, Jessica R Vanderlan, Patrik Pipkorn, Sidharth V Puram

2020-Current year OA Pubs

One in four head and neck cancer (HNC) survivors experience clinically significant body image distress (BID), a devastating psychosocial morbidity that adversely affects quality of life. To date, effective interventions for these patients are lacking. BRIGHT (Building a Renewed ImaGe after Head and neck cancer Treatment), a brief cognitive behavioral treatment (CBT), has shown potential efficacy as a novel treatment paradigm for HNC survivors with BID. The primary objective of this randomized clinical trial (RCT) is to test the hypothesis that BRIGHT improves BID among HNC survivors relative to an Attention Control (AC) intervention. In this multisite RCT, N = …

Burst Steroid Therapy And Quality Of Life In Patients With Acute Heart Failure: Insights From The Cortahf Trial, Matteo Pagnesi, Douglas L Mann, Et Al.

2020-Current year OA Pubs

AIMS: Patients hospitalized with acute heart failure (AHF) treated with a 7 day prednisone course in the CORTAHF pilot trial had a greater improvement in health-related quality of life (QoL) at Day 7 in both the overall population and in patients with baseline interleukin 6 > 13 pg/mL. This post-hoc analysis examines the specific QoL domains and the relationship between clinical signs of congestion and QoL.

METHODS: In the CORTAHF pilot trial, patients with AHF and high-sensitivity C-reactive protein (hsCRP) > 20 mg/L were randomized 1:1 to once-daily oral 40 mg prednisone for 7 days plus usual care or usual care alone. …

Nf2 Loss-Of-Function And Hypoxia Drive Radiation Resistance In Grade 2 Meningiomas, Bhuvic Patel, Sangami Pugazenthi, Shree S Pari, Tatenda Mahlokozera, William A Leidig, Hsiang-Chih Lu, Alicia Yang, Kaleigh Roberts, Patrick Desouza, Kyle P Mcgeehan, Diane D Mao, Namita Sinha, Joseph E Ippolito, Sonika Dahiya, Hiroko Yano, Albert H Kim, Et Al.

2020-Current year OA Pubs

BACKGROUND: World Health Organization Grade 2 meningiomas (G2Ms) often recur and resist therapies. Grade 2 meningiomas with histopathological necrosis have been associated with worse local control (LC) after radiation therapy, but the drivers and biomarkers of radiation resistance in G2Ms remain unknown.

METHODS: We performed genetic sequencing and histopathological analysis of 113 G2Ms and investigated the role of genetic and microenvironmental factors on clonogenic survival after ionizing radiation. We performed transcriptional profiling of our in vitro model and 18 human G2M tumors by bulk RNA sequencing as well as 8 G2Ms by single nuclei RNA sequencing.

RESULTS: NF2 loss-of-function (LOF) …

Phase 2 Open-Label Study Of Sacituzumab Govitecan As Second-Line Therapy In Patients With Extensive-Stage Sclc: Results From Tropics-03, Afshin Dowlati, Anne C Chiang, Andrés Cervantes, Sunil Babu, Erika Hamilton, Shu Fen Wong, Andrea Tazbirkova, Ivana Gabriela Sullivan, Cédric Van Marcke, Antoine Italiano, Jilpa Patel, Sabeen Mekan, Tia Wu, Saiama N Waqar

2020-Current year OA Pubs

INTRODUCTION: The phase 2 TROPiCS-03 study evaluated the efficacy/safety of sacituzumab govitecan (SG) as second-line treatment in patients with previously treated extensive-stage SCLC (ES-SCLC).

METHODS: TROPiCS-03 (NCT03964727) is a multicohort, open-label, phase 2 basket study of solid tumors, including ES-SCLC. Adults with ES-SCLC that progressed after one previous line of platinum-based chemotherapy and anti-programmed death-(ligand) 1 (PD-[L]1) therapy received SG 10 mg/kg on days 1 and 8 of a 21-day cycle. The primary end point was the investigator-assessed objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors version 1.1. Key secondary end points included investigator-assessed duration of …

Age-Related Mesenchymal Stromal Cell Senescence Is Associated With Progression From Mgus To Multiple Myeloma, Natalya Plakhova, Sheila A Stewart, Et Al.

2020-Current year OA Pubs

The risk of progression of monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma (MM) increases with advancing age, suggesting that progression may be influenced by age-related changes within the bone marrow (BM) microenvironment. We hypothesise that senescent mesenchymal stromal cells (MSCs), which accumulate in the BM with age, may contribute to MGUS progression to MM. Here, we show that, like BM MSCs from aged non-cancer controls, BM MSCs from both MM and MGUS patients exhibit a senescent phenotype characterised by enlarged, flattened morphology, increased β-galactosidase activity and CDKN2A expression, and decreased proliferation rate compared with BM MSCs from healthy …

White Matter Microstructure In School-Age Children With Down Syndrome, Dea Garic, Robert C Mckinstry, Natasha Marrus, Kelly N Botteron, Et Al.

2020-Current year OA Pubs

Down syndrome (DS) is the most common genetic cause of intellectual disability, but our understanding of white matter microstructure in children with DS remains limited. Previous studies have reported reductions in white matter integrity, but nearly all studies to date have been conducted in adults or relied solely on diffusion tensor imaging (DTI), which lacks the ability to disentangle underlying properties of white matter organization. This study examined white matter microstructural differences in 7- to 12-year-old children with DS (n = 23), autism (n = 27), and typical development (n = 50) using DTI as well as High Angular Resolution …

Cardiovascular And Renal Treatment In Heart Failure Patients With Hyperkalemia Or High Risk Of Hyperkalemia: Rationale And Design Of The Care-Hk In Hf Registry, Stephen J Greene, Michael Böhm, Biykem Bozkurt, Javed Butler, John G F Cleland, Andrew J S Coats, Nihar R Desai, Diederick E Grobbee, Ellie Kelepouris, Fausto Pinto, Giuseppe Rosano, Isabelle Morin, Peter Szecsödy, Solenn Fabien, Sandra Waechter, Maria G Crespo-Leiro, Martin Hülsmann, Tibor Kempf, Otmar Pfister, Anne-Catherine Pouleur, Andrew J Sauer, Manish Saxena, Martin Schulz, Maurizio Volterrani, Stefan D Anker, Mikhail N Kosiborod

Faculty, Staff and Students Publications

Background: Despite guideline recommendations, many patients with heart failure (HF) do not receive target dosages of renin-angiotensin-aldosterone system inhibitors (RAASis) in clinical practice due, in part, to concerns about hyperkalemia (HK).

Methods and results: This noninterventional, multinational, multicenter registry (NCT04864795; 111 sites in Europe and the USA) enrolled 2558 eligible adults with chronic HF (mostly with reduced ejection fraction [HFrEF]). Eligibility criteria included use of angiotensin-converting-enzyme inhibitor/angiotensin-II receptor blocker/angiotensin-receptor-neprilysin inhibitor, being a candidate for or treatment with a mineralocorticoid receptor antagonist, and increased risk of HK (eg, current serum potassium > 5.0 mmol/L), history of HK in the previous …

Claustrum Volume Is Reduced In Multiple Sclerosis And Predicts Disability, Nicole Shelley, Bradley Judge, Dmitriy A Yablonskiy, Robert T Naismith, Matthew R Brier, Anne H Cross

2020-Current year OA Pubs

OBJECTIVE: The claustrum is a small, thin structure of predominantly gray matter with broad connectivity and enigmatic function. Little is known regarding the impact of claustrum pathology in multiple sclerosis (MS).

METHODS: This study assessed whether claustrum volume was reduced in MS and whether reductions were associated with specific disability domains. We compared the impact of claustrum volume reductions on neurological disability versus the well-studied thalamus. Data from the 15,793 participants in the MS PATHS study were used for primary analyses. A second cohort of 71 people with MS and healthy controls from our center was used for validation.

RESULTS: …

Detection Of Enterovirus Rna In Pancreas And Lymphoid Tissues Of Organ Donors With Type 1 Diabetes, Jutta E Laiho, Sami Oikarinen, Sofia Morfopoulou, Maarit Oikarinen, Ashlie Renner, Daniel Depledge, Matthew C Ross, Ivan C Gerling, Judith Breuer, Joseph F Petrosino, Vincent Plagnol, Alberto Pugliese, Antonio Toniolo, Richard E Lloyd, Heikki Hyöty, Npod-Virus Group

Center for Medical Ethics and Health Policy Staff Publications

Aims/hypothesis: The nPOD-Virus group collaboratively applied innovative technologies to detect and sequence viral RNA in pancreas and other tissues from organ donors with type 1 diabetes. These analyses involved the largest number of pancreas samples collected to date. The aim of the current work was to examine the presence of enterovirus RNA in pancreas and lymphoid tissues of organ donors with and without type 1 diabetes.

Methods: We analysed pancreas, spleen, pancreatic lymph nodes and duodenum samples from the following groups: (1) donors with type 1 diabetes (n=71) with (n=35) or without (n=36) insulin-containing islets; (2) donors with single or …

Joint Analysis Of The Npod-Virus Group Data: The Association Of Enterovirus With Type 1 Diabetes Is Supported By Multiple Markers Of Infection In Pancreas Tissue, Sarah J Richardson, Teresa Rodriguez-Calvo, Jutta E Laiho, John S Kaddis, Julius O Nyalwidhe, Irina Kusmartseva, Sofia Morfopoulou, Joseph F Petrosino, Vincent Plagnol, Kathrin Maedler, Margaret A Morris, Jerry L Nadler, Mark A Atkinson, Matthias Von Herrath, Richard E Lloyd, Heikki Hyoty, Noel G Morgan, Alberto Pugliese, Npod-Virus Group

Center for Medical Ethics and Health Policy Staff Publications

Aims/hypothesis: Previous pathology studies have associated enterovirus infections with type 1 diabetes by examining the enterovirus capsid protein 1 (VP1) in autopsy pancreases obtained near diabetes diagnosis. The Network for Pancreatic Organ Donors with Diabetes (nPOD) has since obtained pancreases from organ donors with type 1 diabetes (with broad age and disease duration) and donors with disease-associated autoantibodies (AAbs), the latter representing preclinical disease. Two accompanying manuscripts from the nPOD-Virus Group report primary data from a coordinated analysis of multiple enterovirus indices. We aimed to comprehensively assess the association of multiple enterovirus markers with type 1 diabetes.

Methods: The nPOD-Virus …

Histologic- And Genomic-Directed Adjuvant Therapy For Ampullary Adenocarcinoma: A Hidden Genome-Derived Analysis, Brett L Ecker, Kenneth Seier, Ankur Choubey, Austin M Eckhoff, Gabriella N Tortorello, Vinod P Balachandran, Nicola Blackburn, Michael I D'Angelica, Ronald P Dematteo, Daniel G Blazer, Jeffrey A Drebin, William E Fisher, 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, Charles M Vollmer, Alice C Wei, Sabino Zani, Australian Pancreatic Genome Initiative, Robert E Roses, Mithat Gonen, William R Jarnagin

Faculty, Staff and Students Publications

Background: The benefit of adjuvant chemotherapy (AC) for ampullary adenocarcinoma is unclear. The Hidden Genome model classifies prognostic subtypes with greater accuracy than standard histologic classification (intestinal [INT] vs pancreatobiliary [PB]), but its predictive capacity to guide the use of AC remains unstudied.

Methods: We applied the Hidden Genome model to an international cohort of 183 patients with resected ampullary adenocarcinoma who underwent genomic sequencing. The model quantified the predicted cell of origin (colorectal vs pancreas/distal bile duct) in all specimens. Overall survival (OS) was compared using Kaplan-Meier estimates, stratified by AC use versus surgery alone (SA).

Results: Most patients …

Changes In The Fxr-Cistrome And Alterations In Bile Acid Physiology In Wilson Disease, Clavia Ruth Wooton-Kee, Hari K Yalamanchili, Islam Mohamed, Manal Hassan, Kenneth D R Setchell, Monica Narvaez Rivas, Ayse K Coskun, Vasanta Putluri, Nagireddy Putluri, Prasun Jalal, Michael L Schilsky, David D Moore

Children’s Nutrition Research Center Staff Publications

Background: Wilson disease (WD) is an autosomal recessive disorder that results in excessive hepatic copper, causing hepatic steatosis, inflammation, fibrosis, cirrhosis, and liver failure. Previous studies have revealed dysregulation of many farnesoid X receptor (FXR) metabolic target genes in WD, including the bile salt exporter pump, the major determinant of bile flow.

Methods: We tested the hypothesis that the FXR-cistrome is decreased in Atp7b-/- mice in accord with dysregulated bile acid homeostasis.

Results: FXR binding within Atp7b-/- mouse livers displayed surprising complexity: FXR binding was increased in distal intergenic regions but decreased in promoter regions in Atp7b-/- versus wild-type mice. …

Functional Mobility And Pain Are Improved For 6 Years After Adolescent Bariatric Surgery, Neil Thivalapill, Todd M Jenkins, Thomas H Inge, Changchun Xie, Anita P Courcoulas, Carroll M Harmon, Michael A Helmrath, Stephanie Sisley, Marc P Michalsky, Justin R Ryder, Teen‐Longitudinal Assessment Of Bariatric Surgery (Teen‐Labs) Consortium

Faculty, Staff and Students Publications

Objective: The long-term durability of improvements in functional mobility and musculoskeletal pain for adolescents after metabolic and bariatric surgery (MBS) is unknown.

Methods: We used the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) study to determine the change in mobility and pain among adolescents who underwent MBS. From standardized 400-m walk tests, we analyzed walk time, heart rate (HR) parameters, and musculoskeletal pain.

Results: The mean walk time improved from 383 s (95% CI: 368-399) prior to surgery to 351 s (95% CI: 330-372) by 6 years. The mean resting HR was 90 beats per minute (bpm; 95% CI: 87-93) preoperatively …

Severe Gastrointestinal Manifestations In Childhood-Onset Lupus: A Single-Center Cohort And Review Of The Literature, James Orozco, Jessica Nguyen, Sara Mm Yasrebi, Marnie Blalock, Sara L Grisales, Craig L Jensen, Marietta M Deguzman

Faculty, Staff and Students Publications

Objective

Systemic lupus erythematosus (SLE) is a complex autoimmune condition with diverse manifestations. Childhood-onset SLE (cSLE) presents more severely than adult-onset disease with a higher incidence of severe neurologic or renal manifestations and lower estimated survival rates. There is limited literature on the range of severe gastrointestinal manifestations at presentation in cSLE, and this lack of information results in underappreciation of these potentially life-threatening complications and little guidance regarding management of these patients.

Methods

We reviewed cases of patients with cSLE and severe GI manifestations at presentation diagnosed at our institution and additionally provide a comprehensive review of existing cases …

Epidemiology Of Intestinal Parasite Infections And Multiparasitism And Their Impact On Growth And Hemoglobin Levels During Childhood In Tropical Ecuador: A Longitudinal Study Using Molecular Detection Methods, Rojelio Mejia, Irina Chis Ster, Martha E Chico, Irene Guadalupe, Andrea Arévalo-Cortés, Andrea Lopez, Aida Y Oviedo-Vera, Philip J Cooper

Faculty, Staff and Students Publications

Background: There are few longitudinal epidemiological studies of intestinal parasitic infections (IPI) and their health effects. We studied the epidemiology and determinants of IPI and multiparasitism during childhood using molecular methods for parasite detection and analysed their effects on growth and hemoglobin levels.

Methods: Random sample of 401 children from an Ecuadorian birth cohort followed up to 8 years of age. Data on environmental and sociodemographic characteristics were collected by questionnaires. Stool samples were collected, and weight, height, and hemoglobin levels were measured at 7 and 13 months, and 2, 3, 5, and 8 years. Stool samples were analysed using …

Protein Biomarkers Of Interstitial Lung Abnormalities In Relatives Of Patients With Pulmonary Fibrosis, Jonathan A Rose, Mark P Steele, Esteban J Kosak Lopez, Gisli Thor Axelsson, Andrea G Galecio Chao, Alan Waich, Katie Regan, Swati Gulati, Anthony H Maeda, Sharmin Sultana, Claire Cutting, Ann-Marcia C Tukpah, Andrew J Synn, Mary B Rice, Hilary J Goldberg, Joyce S Lee, David A Lynch, Rachel K Putman, Hiroto Hatabu, Benjamin A Raby, David A Schwartz, Ivan O Rosas, Gary M Hunninghake

Faculty, Staff and Students Publications

Rationale: First-degree relatives of patients with pulmonary fibrosis (referred to here as relatives) are at high risk for interstitial lung abnormalities (ILA), highlighting the need for biomarkers for risk prediction. We aimed to identify blood proteins associated with and predictive of ILA among relatives of patients with pulmonary fibrosis.

Methods: Relatives enrolled in two independent cohorts had protein levels measured using an aptamer-based proteomic platform. ILA were assessed with computed tomography scans as per Fleischner Society recommendations. Protein associations with ILA were assessed using regression. Significant proteins were used with clinical variables to detect ILA.

Results: Of 237 relatives from …

The Aging Ovary Stands On The Shoulders Of Giant Multinucleated Cells, Avery A Ahmed, Stephanie A Pangas

Faculty, Staff and Students Publications

Reproductive aging is associated with declining fertility and increasing inflammation, though these events are not well understood. An exciting new study in PLOS Biology utilizes cutting-edge technologies to characterize the role of multinucleated giant cells in ovarian aging.

Impact Of Length Of Stay On Diagnostic Yield In The Epilepsy Monitoring Unit: A Multi-Center Retrospective 12-Year Veterans Health Administration Study, Maximillian S Feygin, Autumn Smith, Sruthi Gopinath Karicheri, Khadar Haroun, Omar Khan, Maria R Lopez, Stephan Eisenschenk, John Jones, Stephanie Reeder, Alan R Towne, Christopher Ransom, Karen Medin, James Chen, Tung Tran, Nina I Garga, Noemi Rincon-Flores, Marissa Kellogg, Steven Tobochnik, Zulfi Haneef

Faculty, Staff and Students Publications

Objective: Epilepsy Monitoring Units (EMUs) in Veterans Health Administration (VHA) Epilepsy Centers of Excellence (ECoE) are critical for the diagnosis and management of seizure disorders. Whether a shorter length of stay (LOS) in the EMU due to scheduling impacts diagnostic yield is unclear.

Methods: Data from 7074 EMU visits across 15 VHA EMUs (2012-2024) were analyzed. Based on usual admission schedules, EMUs were divided into "fixed" (typically Monday-Friday) or "flexible" subgroups. Diagnostic outcomes were classified as epileptic seizures (ES), psychogenic non-epileptic seizures (PNES), other non-epileptic events, and inconclusive. Diagnostic rates were compared between fixed and flexible sites using cumulative distribution …

Baseline Characteristics Of The Us Study To Protect Brain Health Through Lifestyle Intervention To Reduce Risk (Us Pointer): Successful Enrollment Of A Diverse Clinical Trial Cohort At Risk For Cognitive Decline, Rachel A Whitmer, Laura D Baker, Maria C Carrillo, Heather M Snyder, Maryjo L Cleveland, Darren R Gitelman, Miia Kivipelto, Xiaoyan I Leng, Laura Lovato, Kathryn V Papp, Valory N Pavlik, Stephen P Salloway, Christy C Tangney, Sarah Tomaszewski Farias, Jeff D Williamson, Sharon Wilmoth, Nancy Woolard, Melissa Yu, Mark Andrew Espeland, U.S. Pointer Study Group

Faculty, Staff and Students Publications

Introduction: The U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER) is a 2-year randomized controlled trial of two lifestyle interventions in 2111 older adults at increased risk for cognitive decline.

Methods: Sociodemographic and clinical characteristics and rates of ancillary study participation were described with means and frequencies.

Results: U.S. POINTER successfully enrolled a cohort, ages 60-79 years, which was ethno-racially inclusive (>30% individuals from groups often under-represented in clinical trials with cognitive outcomes) and 18% residing in neighborhoods with moderate or high levels of socioeconomic deprivation. Enrollees were cognitively intact but at increased …

Assessment Of Frailty In Patients With Heart Failure: A New Heart Failure Frailty Score Developed By Delphi Consensus, Cristiana Vitale, Emmanuelle Berthelot, Andrew J S Coats, Hill Loreena, Nancy M Albert, Michal Tkaczyszyn, Stamatis Adamopoulos, Lisa Anderson, Markus S Anker, Stefan D Anker, Derek Bell, Tuvia Ben-Gal, Vasiliki Bistola, Biykem Bozkurt, Poppy Brooks, Miguel Camafort, Juan Jesus Carrero, Ovidiu Chioncel, Dong-Ju Choi, Wook-Jin Chung, Wolfram Doehner, Daniel Fernández-Bergés, Roberto Ferrari, Mona Fiuzat, Juan Esteban Gomez-Mesa, Finn Gustafsson, Ewa Jankowska, Seok-Min Kang, Koichiro Kinugawa, Kamlesh Khunti, F D Richard Hobbs, Christopher Lee, Yuri Lopatin, Matthew Maddocks, Giuseppe Maltese, Elena Marques-Sule, Yuya Matsue, Òscar Miró, Brenda Moura, Massimo Piepoli, Piotr Ponikowski, Giovanni Pulignano, Amina Rakisheva, Robin Ray, Angela Sciacqua, Petar Seferovic, Trinidad Sentandreu-Mañó, Shirley Sze, Alan Sinclair, Anna Strömberg, Olga Theou, Hiroyuki Tsutsui, Izabella Uchmanowicz, Maria Teresa Vidan, Maurizio Volterrani, Stephan Von Haehling, Byungsu Yoo, Jian Zhang, Yuhui Zhang, Marco Metra, Giuseppe Massimo Claudio Rosano

Faculty, Staff and Students Publications

Aims: The Heart Failure Frailty Score (HFFS) is a novel, multidimensional tool to assess frailty in patients with heart failure (HF). It has been developed to overcome limitations of existing frailty assessment tools while being practical for clinical use. The HFFS reflects the concept of frailty as a multidimensional, dynamic and potentially reversible state, which increases vulnerability to stressors and risk of poor outcomes in patients with HF.

Methods and results: The HFFS was developed through a Delphi consensus process involving 54 international experts. This approach involved iterative rounds of questionnaires and interviews, where a panel of experts provided their …

Interactions Between Adgrf1 (Gpr110) And Extracellular Matrix Proteins Govern Its Effects On Tumorigenesis In Her2-Positive Breast Cancer, Noor Mazin Abdulkareem, Raksha Bhat, Micah Castillo, Sung Yun Jung, Suhas Vasaikar, Sarmistha Nanda, Alexis Ruiz, Martin Shea, Wangjia Cao, Jamunarani Veeraraghavan, Hee-Yong Kim, Tasneem Bawa-Khalfe, Tahir Hussain, Xinli Liu, Preethi Gunaratne, Rachel Schiff, Meghana V Trivedi

Faculty, Staff and Students Publications

Background and purpose: We and others have previously shown that ADGRF1, an adhesion G protein-coupled receptor, is overexpressed and associated with poor survival in many cancers, including human epidermal growth factor receptor-2 (HER2) breast cancer (BC). Also, we have reported the tumour-promoting function of ADGRF1 using preclinical models of HER2+ BC. In this study, we investigated the effect of ADGRF1 overexpression in an orthotopic in vivo model as well as downstream signalling of ADGRF1 in HER2+ BC.

Experimental approach: We utilized a doxycycline (Dox)-induced ADGRF1 overexpression system in HER2+ BC cell lines and performed various in vitro and in vivo …

Sci – U: Validation Of An Updated Self-Care Inventory For Contemporary Diabetes Management In Adolescents With Type 1 Diabetes, Sarah S Jaser, Tamim A Hamdan, Marisa E Hilliard, Joyce P Yi-Frazier, Randi Streisand, Faisal S Malik, Daniel J Desalvo, Maeve B O'Donnell, Annette M La Greca

Faculty, Staff and Students Publications

Aims: The Self-Care Inventory is a widely used measure to assess diabetes self-management behaviors. We sought to adapt and streamline the measure to reflect advances in diabetes management, including increased use of continuous glucose monitor and automated insulin delivery systems.

Methods: Through an expert-driven, iterative process, the updated Self-Care Inventory (SCI-U) was created by modifying items to reflect modern diabetes management and reducing the measure to 8 items. The measure was administered to 369 adolescents with type 1 diabetes in 4 regions of the United States, at baseline of two separate intervention trials (mean age = 15.5 ± 1.5, 56 …

Genome-Wide Association Studies Of Down Syndrome Associated Congenital Heart Defects Suggests A Genetically Heterogeneous Risk For Chd In Ds, Elizabeth R Feldman, Yunqi Li, David J Cutler, Tracie C Rosser, Stephanie B Wechsler, Lauren Sanclemente, Angela L Rachubinski, Natalina Elliott, Paresh Vyas, Irene Roberts, Karen R Rabin, Michael Wagner, Bruce D Gelb, Joaquin M Espinosa, Philip J Lupo, Adam J De Smith, Stephanie L Sherman, Elizabeth J Leslie-Clarkson

Faculty, Staff and Students Publications

Congenital heart defects (CHDs) are the most common structural birth defect and are present in 40-50% of children born with Down syndrome (DS). To characterize the genetic architecture of DS-associated CHD, we sequenced genomes of a multiethnic group of children with DS and a CHD (n=886: atrioventricular septal defects (AVSD), n=438; atrial septal defects (ASD), n=122; ventricular septal defects (VSD), n=170; other types of CHD, n=156) and DS with a structurally normal heart (DS+NH, n=572). We performed four GWAS for common variants (MAF>0.05) comparing DS with CHD, stratified by CHD-subtype, to DS+NH controls. Although no SNP achieved genome-wide significance, …

Worldwide Prevalence Of Chagas Cardiomyopathy-An Analysis From The Global Burden Of Disease Dataset, Abdul Mannan Khan Minhas, Rachel Marcus, Salim S Virani, Michael D Shapiro, Robert J Mentz, Luis E Echeverria, Jonathan T Arcobello, Dmitry Abramov

Faculty, Staff and Students Publications

Purpose: The worldwide prevalence of Chagas Cardiomyopathy (CCM) as well as the trends in the prevalence of CCM over time have not been well characterized.

Methods: An analysis of the Global Burden of Disease (GBD) data from 1990 to 2019 was conducted to assess the burden of CCM. This study focused on determining the prevalence of CCM, along with its age-standardized prevalence rate (ASR) per 1,00,000 people, considering various patient demographics and geographical regions as defined in the GBD. Additionally, the study examined the temporal trends over this 30-year period by calculating the estimated annual percentage change (EAPC) in CCM …

Managing Hypercholesterolemia In Adults Older Than 75 Years Without A History Of Atherosclerotic Cardiovascular Disease: An Expert Clinical Consensus From The National Lipid Association And The American Geriatrics Society, Vera Bittner, Sunny A Linnebur, Dave L Dixon, Daniel E Forman, Ariel R Green, Terry A Jacobson, Ariela R Orkaby, Joseph J Saseen, Salim S Virani

Faculty, Staff and Students Publications

The risk of atherosclerotic cardiovascular disease increases with advancing age. Elevated LDL-cholesterol and non-HDL-cholesterol levels remain predictive of incident atherosclerotic cardiovascular events among individuals older than 75 years. Risk prediction among older individuals is less certain because most current risk calculators lack specificity in those older than 75 years and do not adjust for co-morbidities, functional status, frailty, and cognition which significantly impact prognosis in this age group. Data on the benefits and risks of lowering LDL-cholesterol with statins in older patients without atherosclerotic cardiovascular disease are also limited since most primary prevention trials have included mostly younger patients. Available …

Is Less More? Maximizing Outcomes By Tailoring Treatments To Patients: Oncofertility And Oncomenopause, Janice S Kwon, Marie Plante, Martha Hickey, Annabelle Huguenin, Sarah Hmaidan, Terri Lynn Woodard

Faculty, Staff and Students Publications

Notable advances have been made in improving survival outcomes in various cancers, but some have incurred undesirable costs and effects to patients with respect to fertility and menopause. Patients are living longer with cancer, and patient reported outcomes are influencing decision-making by individuals and their health care providers. It is essential to evaluate existing standards of care on an ongoing basis and prioritize quality of life and long-term survivorship, particularly for interventions in early-stage cancers and risk-reducing strategies that often yield long-term life expectancy.

Speech Delay And Hearing Rehabilitation Disparities In Children With Hearing Loss, Lacey C Magee, Malek Bouzaher, Mihika Thapliyal, Yi-Chun Liu, Samantha Anne

Faculty, Staff and Students Publications

Objectives: To investigate the influence of race and insurance type on speech delay rates and hearing rehabilitation access in children with bilateral hearing loss (HL).

Study design: Retrospective cross-sectional study of pediatric patients with bilateral HL who received cochlear implants (CIs) or hearing aids (HAs).

Setting: This study used the national Pediatric Health Information System (PHIS) database to identify patients with HL across 52 tertiary care pediatric hospitals in the United States.

Methods: Data collected included demographics, CI/HA use, speech delay/disorders, and type of insurance coverage.

Results: This study identified 18,422 patients with bilateral HL (40.1% female, 66.3% white, 66.3% …

Dietary Interventions To Support And Improve Sleep Disturbances And Insomnia Disorder In Menopause: From Bench To Bedside, Rosie H Musgrave, Sara Nowakowski, Tamlyn J Watermeyer, Emily J Arentson-Lantz, Greg J Elder

Faculty, Staff and Students Publications

Sleep is essential for maintaining physical and psychological health, and also cognitive health (referred to as 'brain health'). However, the transition to menopause has a direct impact upon sleep. Sleep disturbances are reported by approximately 40%-60% of menopausal women, and insomnia disorder is also prevalent. Diet-based interventions could potentially be used to improve subjective sleep quality in this population, and although there are several promising interventions which have been used in other groups that could be trialled, the evidence base is currently lacking. One particularly promising area for future research is that these interventions might be used alongside, or instead …

Aged Regulatory T Cells Fail To Control Autoimmune Lacrimal Gland Pathogenic Cd4+ T Cells, Kaitlin K Scholand, Laura Schaefer, Gowthaman Govindarajan, Zhiyuan Yu, Jeremias G Galletti, Cintia S De Paiva

Faculty, Staff and Students Publications

CD25KO mice are a model of Sjögren disease. CD25KO mice have severe inflammation and infiltrating lymphocytes to the lacrimal glands (LG). Whether the pathogenicity of CD25KO CD4+ T cells can be controlled in vivo by Tregs is unknown. Eight-week-old B6 and CD25KO mice LGs were submitted for RNA bulk sequencing. A total of 3481 genes were differentially expressed in CD25KO LG compared to B6. Tear washing analysis identified CD25KO mice had elevated protein levels of TNF, IFN-γ, and CCL5 and decreased protein levels of IL-12p40 and VEGF-A. Co-adoptive transfer of CD25KO CD4+ T cells with either young or aged B6 …