Digital Commons Network^™

Functional Vs Structural Cortical Deficit Pattern Biomarkers For Major Depressive Disorder, Peter Kochunov, Bhim M Adhikari, David Keator, Daniel Amen, Si Gao, Nicole R Karcher, Demetrio Labate, Robert Azencott, Yewen Huang, Hussain Syed, Hongjie Ke, Paul M Thompson, Danny J J Wang, Braxton D Mitchell, Jessica A Turner, Theo G M Van Erp, Neda Jahanshad, Yizhou Ma, Xiaoming Du, William Burroughs, Shuo Chen, Tianzhou Ma, Jair C Soares, L Elliot Hong

Faculty, Staff and Student Publications

Importance: Major depressive disorder (MDD) is a severe mental illness characterized more by functional rather than structural brain abnormalities. The pattern of regional homogeneity (ReHo) deficits in MDD may relate to underlying regional hypoperfusion. Capturing this functional deficit pattern provides a brain pattern-based biomarker for MDD that is linked to the underlying pathophysiology.

Objective: To examine whether cortical ReHo patterns provide a replicable biomarker for MDD that is more sensitive than reduced cortical thickness and evaluate whether the ReHo MDD deficit pattern reflects regional cerebral blood flow (RCBF) deficit patterns in MDD and whether a regional vulnerability index (RVI) thus …

Home-Based Transcranial Direct Current Stimulation For Major Depressive Disorder: 6-Month Follow-Up From Randomised Sham-Controlled Trial And Open-Label Treatment Phases, Rachel D Woodham, Sudhakar Selvaraj, Nahed Lajmi, Harriet Hobday, Gabrielle Sheehan, Ali-Reza Ghazi-Noori, Peter J Lagerberg, Rodrigo Machado-Vieira, Jair C Soares, Allan H Young, Cynthia H Y Fu

Faculty, Staff and Student Publications

Transcranial direct current stimulation (tDCS) is a potential home-based treatment for major depressive disorder (MDD). In our double-blind randomised controlled trial (RCT) (n = 174; UK and USA), a 10-week course of home-based tDCS demonstrated clinical efficacy (clinical response: 58.3 % active treatment arm and 37.8 % sham (p = 0.017). tDCS was delivered in a bifrontal montage, with anode over left dorsolateral prefrontal cortex (DLPFC) and cathode over right DLPFC. Each session was 30 min, with active stimulation at 2 mA and sham at 0 mA, incorporating brief ramp-up and ramp-down phased. Following the 10-week RCT, all participants were …

The Burden Of Burnout: Understanding Its Prevalence And Organizational Drivers In Medical Physics, Deborah Schofield, C Lynn Chevalier, Laurence Court, William Harmsen, Akiva Turner

Faculty, Staff and Student Publications

Background: Burnout is a work-related syndrome characterized by increased levels of emotional exhaustion (EE) and depersonalization (DP) along with decreased levels of personal achievement. In the healthcare setting, higher burnout levels have been associated with negative impacts on personnel, an increased risk of errors, and a decrease in the quality of delivered care.

Purpose: The purpose of this study was to assess the prevalence of burnout among medical physicists working in the United States. Additionally, the impact of personal and organizational features on burnout risk was examined.

Methods: The anonymous survey was distributed to 1962 full members of the American …

The Promising Use Of An Emergency Department Observation Unit To Manage Patients With Opioid Use Disorder, Thai Tran, Nicholas Imperato, Akiva Dym, Anthony Rosania, Lewis Nelson, Christine Ramdin, Cynthia Santos

Faculty, Staff and Student Publications

Introduction: The opioid epidemic continues to grow, placing a significant strain on Emergency Departments (EDs), resulting in patients presenting daily with opioid-related concerns including intoxication, withdrawal, infections, injury, and death. Consequently, in recent years many EDs, including our own, have utilized Emergency Department Observation Units (EDOU) to not only manage withdrawal and overdose, but also initiate long-term treatment. This study aims to evaluate the outcomes of patients with opioid use disorder (OUD) who were managed in our EDOU.

Methods: This was a retrospective study of patients placed in an EDOU who had the primary diagnosis of OUD in a single …

Is There An Association Between Inflammatory Biomarkers And Organ Space Surgical Site Infection After Emergency Laparotomy In Massively Transfused Trauma Patients?, Stephanie Martinez Ugarte, Mokunfayo O Fajemisin, Chelsea J Guy-Frank, James M Klugh, Xu Zhang, Erin E Fox, Charles E Wade, Kimberly A Mankiewicz, Lillian S Kao

Faculty, Staff and Student Publications

Background: The relationship between inflammatory biomarkers (IB) and organ space surgical site infections (OS-SSIs) after emergency laparotomy (EL) is poorly understood.

Methods: Retrospective, single-center analysis of patients in the Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial who underwent EL and survived 48 h after admission was performed. IB levels of IL-6, IL-8, G-CSF, MCP-1, neutrophil to lymphocyte ratio, and platelet to lymphocyte ratio were analyzed. IB and OS-SSIs association was evaluated using the Wilcoxon rank sum test.

Results: Of 74 eligible patients, 80 % were male, 69 % sustained blunt trauma, the injury severity score was 31 (24-41), …

Blockade Of A2ar Improved Brain Perfusion And Cognitive Function In A Mouse Model Of Alzheimer’S Disease, Mariana Sayuri Berto Udo, Julia Zaccarelli-Magalhães, Garrett Alan Clemons, Cristiane Teresinha Citadin, Julia Langman, Drew James Smith, Luiz Henrique Matuguma, Vesna Tesic, Hung Wen Lin

Faculty, Staff and Student Publications

Alzheimer’s disease (AD) is a neurodegenerative disorder that affects more than 6.2 million Americans aged 65 and older, particularly women. Along with AD’s main hallmarks (formation of β-amyloid plaques and tau neurofibrillary tangles), there are vascular alterations that occurs in AD pathology. Adenosine A2 receptor (A2AR) is one of the key factors of brain vascular autoregulation and is overexpressed in AD patients. Our previous findings suggest that protein arginine methyltransferase 4 (PRMT4) is overexpressed in AD, which leads to decrease in cerebral blood flow in aged female 3xTg mice. We aimed to investigate the mechanism behind A2AR signaling in the …

Encoding 3d Information In 2d Feature Maps For Brain Ct-Angiography, Uma M Lal-Trehan Estrada, Sunil Sheth, Arnau Oliver, Xavier Lladó, Luca Giancardo

Faculty, Staff and Student Publications

We propose learnable 3D pooling (L3P), a CNN module designed to compress 3D information into 2D feature maps using anisotropic convolutions and unidirectional max pooling. Specifically, we used L3P followed by a 2D network to generate predictions from 3D brain CT-Angiography (CTA) in the context of large vessel occlusion (LVO). To further demonstrate its versatility, we extended its application to 3D brain MRI analysis for brain age prediction. First, we designed an experiment to classify the LVO-affected hemisphere (left or right), projecting the input CTA into the sagittal plane, which allowed to assess the ability of L3P to encode the …

A Rare Sequela Of Untreated Streptococcus Pharyngitis: A Case Report., Meredith Hiltbrand Lehoe, Emily Cushing

Ambulatory and Primary Care Articles

Pharyngitis is commonly caused by the gram positive bacteria, streptococcus. Given the potential morbid complications of untreated streptococcal pharyngitis, antibiotics are critical. One of the rarer complications is pulmonary-renal syndrome (PRS), defined as rapidly progressive glomerulonephritis and diffuse alveolar hemorrhage. PRS is associated with high rates of morbidity and mortality, making swift diagnosis and treatment imperative for survival. More common causes of PRS are tied to autoimmune diseases. This case describes a novel progression of PRS caused by streptococcus. A 26-year-old male with no significant medical history presented to our emergency department with streptococcal group A-positive sore throat. After discontinuing …

Psychometric Properties Of The Spanish Yale-Brown Obsessive-Compulsive Scale - Second Edition, Eric A Storch, Jessica Sc Cheng, Miranda Higham, Josselyn S Muñoz, Vanessa Zavala Cruz, Dayan Berrones, Diana P Obando, Jacey L Anderberg, Renee M Frederick, Vissente Tapia-Cuevas, Macarena Churruca Muñoz, Constanza Uribe Villar, Pablo R Moya, Marcos E Ochoa-Panaifo, Mayra C Martinez Mallen, Andrew D Wiese, Caitlin M Pinciotti, Melisa N Sagarnaga, Joseph F Mcguire, Ogechi C Onyeka, María B Moyano, Latin American Trans-Ancestry Initiative For Ocd Genomics (Latino), Brazilian Obsessive-Compulsive Spectrum Disorder Working Group (Gttoc), Wayne K Goodman, James J Crowley

Faculty, Staff and Students Publications

The Yale-Brown Obsessive-Compulsive Scale, Second Edition (Y-BOCS-II) is an evidence-based clinician-rated measure for assessing the presence and severity of obsessive-compulsive symptoms. The Spanish version of the Y-BOCS-II has not yet been validated. The present study examines the psychometric properties of the Spanish Y-BOCS-II (Spanish-Y-BOCS-II) in adults with obsessive-compulsive disorder (OCD) who are of Hispanic/Latino ancestry. The Spanish-Y-BOCS-II was administered to 1805 adults with OCD. Participants also completed a battery of measures assessing OCD, depression, and anxiety symptoms. The internal consistency for the Symptom Checklist (Kuder-Richardson-20=0.92), Obsession Severity (α=0.87), Compulsion Severity (α=0.86), and Total Severity (α=0.92) were high. The inter-rater reliability …

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 …

Recreational Outdoor Injury And Mortality In Texas State Parks Between 2012 And 2021, Mohammad I Hirzallah, Ebubechi K Adindu, Julliet C Ogu, Tania Allison, May Kamleh

Faculty, Staff and Students Publications

Introduction

Methods

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 …

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 …

Bile Acid Regulation Of Xenobiotic Nuclear Receptors On The Expressions Of Orosomucoids In The Liver, Ji Ho Suh, Inyoung Cheon, Hyun-Jung Jung, Sung Ho Lee, Mi Jeong Heo, Matthew Deberge, Clavia Ruth Wooton-Kee, Kang Ho Kim

Children’s Nutrition Research Center Staff Publications

The constitutive androstane receptor (CAR) and pregnane X receptor (PXR) are xenobiotic nuclear receptors activated by various xenobiotics, drugs, hormones, and bile acids (BAs). Upon activation, these nuclear receptors play critical roles in regulating systemic energy homeostasis. However, precise mechanisms through which CAR and PXR influence systemic metabolism remain incompletely understood. Here, we investigated the impact of CAR and PXR on the liver-secreted hormone (i.e., hepatokine) expressions in response to BA stress such as cholic acid (CA) feeding. Our analysis revealed that several BA-activated genes, including the well-known CAR/PXR target, aldo-keto reductase family 1, member B7 (Akr1b7 …

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. …

Genome-Wide Analyses Identify 30 Loci Associated With Obsessive-Compulsive Disorder, Nora I Strom, Zachary F Gerring, Marco Galimberti, Dongmei Yu, Matthew W Halvorsen, Abdel Abdellaoui, Cristina Rodriguez-Fontenla, Julia M Sealock, Tim Bigdeli, Jonathan R Coleman, Behrang Mahjani, Jackson G Thorp, Katharina Bey, Christie L Burton, Jurjen J Luykx, Gwyneth Zai, Silvia Alemany, Christine Andre, Kathleen D Askland, Julia Bäckman, Nerisa Banaj, Cristina Barlassina, Judith Becker Nissen, O Joseph Bienvenu, Donald Black, Michael H Bloch, Sigrid Børte, Rosa Bosch, Michael Breen, Brian P Brennan, Helena Brentani, Joseph D Buxbaum, Jonas Bybjerg-Grauholm, Enda M Byrne, Judit Cabana-Dominguez, Beatriz Camarena, Adrian Camarena, Carolina Cappi, Angel Carracedo, Miguel Casas, Maria Cristina Cavallini, Valentina Ciullo, Edwin H Cook, Jesse Crosby, Bernadette A Cullen, Elles J De Schipper, Richard Delorme, Srdjan Djurovic, Jason A Elias, Xavier Estivill, Martha J Falkenstein, Bengt T Fundin, Lauryn Garner, Christina Gironda, Fernando S Goes, Marco A Grados, Jakob Grove, Wei Guo, Jan Haavik, Kristen Hagen, Kelly Harrington, Alexandra Havdahl, Kira D Höffler, Ana G Hounie, Donald Hucks, Christina Hultman, Magdalena Janecka, Eric Jenike, Elinor K Karlsson, Kara Kelley, Julia Klawohn, Janice E Krasnow, Kristi Krebs, Christoph Lange, Nuria Lanzagorta, Daniel Levey, Kerstin Lindblad-Toh, Fabio Macciardi, Brion Maher, Brittany Mathes, Evonne Mcarthur, Nathaniel Mcgregor, Nicole C Mclaughlin, Sandra Meier, Euripedes C Miguel, Maureen Mulhern, Paul S Nestadt, Erika L Nurmi, Kevin S O'Connell, Lisa Osiecki, Olga Therese Ousdal, Teemu Palviainen, Nancy L Pedersen, Fabrizio Piras, Federica Piras, Sriramya Potluri, Raquel Rabionet, Alfredo Ramirez, Scott Rauch, Abraham Reichenberg, Mark A Riddle, Stephan Ripke, Maria C Rosário, Aline S Sampaio, Miriam A Schiele, Anne Heidi Skogholt, Laura G Sloofman, Jan Smit, María Soler Artigas, Laurent F Thomas, Eric Tifft, Homero Vallada, Nathanial Van Kirk, Jeremy Veenstra-Vanderweele, Nienke N Vulink, Christopher P Walker, Ying Wang, Jens R Wendland, Bendik S Winsvold, Yin Yao, Hang Zhou, Estonian Biobank, 23andme Inc, Arpana Agrawal, Pino Alonso, Götz Berberich, Kathleen K Bucholz, Cynthia M Bulik, Danielle Cath, Damiaan Denys, Valsamma Eapen, Howard Edenberg, Peter Falkai, Thomas V Fernandez, Abby J Fyer, J M Gaziano, Dan A Geller, Hans J Grabe, Benjamin D Greenberg, Gregory L Hanna, Ian B Hickie, David M Hougaard, Norbert Kathmann, James Kennedy, Dongbing Lai, Mikael Landén, Stéphanie Le Hellard, Marion Leboyer, Christine Lochner, James T Mccracken, Sarah E Medland, Preben B Mortensen, Benjamin M Neale, Humberto Nicolini, Merete Nordentoft, Michele Pato, Carlos Pato, David L Pauls, John Piacentini, Christopher Pittenger, Danielle Posthuma, Josep Antoni Ramos-Quiroga, Steven A Rasmussen, Margaret A Richter, David R Rosenberg, Stephan Ruhrmann, Jack F Samuels, Sven Sandin, Paul Sandor, Gianfranco Spalletta, Dan J Stein, S Evelyn Stewart, Eric A Storch, Barbara E Stranger, Maurizio Turiel, Thomas Werge, Ole A Andreassen, Anders D Børglum, Susanne Walitza, Kristian Hveem, Bjarne K Hansen, Christian Rück, Nicholas G Martin, Lili Milani, Ole Mors, Ted Reichborn-Kjennerud, Marta Ribasés, Gerd Kvale, David Mataix-Cols, Katharina Domschke, Edna Grünblatt, Michael Wagner, John-Anker Zwart, Gerome Breen, Gerald Nestadt, Jaakko Kaprio, Paul D Arnold, Dorothy E Grice, James A Knowles, Helga Ask, Karin J Verweij, Lea K Davis, Dirk J Smit, James J Crowley, Jeremiah M Scharf, Murray B Stein, Joel Gelernter, Carol A Mathews, Eske M Derks, Manuel Mattheisen

Center for Medical Ethics and Health Policy Staff Publications

Obsessive-compulsive disorder (OCD) affects ~1% of children and adults and is partly caused by genetic factors. We conducted a genome-wide association study (GWAS) meta-analysis combining 53,660 OCD cases and 2,044,417 controls and identified 30 independent genome-wide significant loci. Gene-based approaches identified 249 potential effector genes for OCD, with 25 of these classified as the most likely causal candidates, including WDR6, DALRD3 and CTNND1 and multiple genes in the major histocompatibility complex (MHC) region. We estimated that ~11,500 genetic variants explained 90% of OCD genetic heritability. OCD genetic risk was associated with excitatory neurons in the hippocampus and the cortex, along …

Externally Validated Digital Decision Support Tool For Time-To-Osteoradionecrosis Risk-Stratification Using Right-Censored Multi-Institutional Observational Cohorts, Laia Humbert-Vidan, Serageldin Kamel, Andrew Wentzel, Zaphanlene Kaffey, Moamen Abdelaal, Kyle B Spier, Natalie A West, G Elisabeta Marai, Guadalupe Canahuate, Xinhua Zhang, Melissa M Chen, Kareem A Wahid, Jillian Rigert, Seyedmohammadhossein Hosseinian, Andrew J Schaefer, Kristy K Brock, Mark Chambers, Adegbenga O Otun, Ruth Aponte-Wesson, Vinod Patel, Andrew Hope, Jack Phan, Adam S Garden, Steven J Frank, William H Morrison, Michael T Spiotto, David Rosenthal, Anna Lee, Renjie He, Mohamed A Naser, Erin Watson, Katherine A Hutcheson, Abdallah S R Mohamed, Vlad C Sandulache, Lisanne V Van Dijk, Amy C Moreno, Teresa Guerrero Urbano, Clifton D Fuller, Stephen Y Lai

Faculty, Staff and Student Publications

Background: Existing studies on osteoradionecrosis of the jaw (ORNJ) have primarily used cross-sectional data, assessing risk factors at a single time point. Determining the time-to-event profile of ORNJ has important implications to monitor oral health in head and neck cancer (HNC) long-term survivors.

Methods: Data were retrospectively obtained for a clinical observational cohort of 1129 patients (198 ORNJ cases) with HNC treated with radiotherapy (RT) at The University of Texas MD Anderson Cancer Center. A Weibull Accelerated Failure Time model was trained on previously identified dosimetric, clinical and demographic predictors. External validation was performed using an independent cohort of 265 …

Nf2 Loss-Of-Function And Hypoxia Drive Radiation Resistance In Grade 2 Meningiomas, Bhuvic Patel, Sangami Pugazenthi, Collin W English, Vijay Nitturi, 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, Allegra Petti, Hiroko Yano, Tiemo J Klisch, Akdes S Harmanci, Akash J Patel, Albert H Kim

Duncan NRI Faculty and Staff Publications

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) …

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 …

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. …

Comparing The Performance Of 3 Sarcopenia Definitions For Predicting Adverse Events Prior To Liver Transplant, Heidi E Johnston, Hannah L Mayr, Melita Andelkovic, Tahnie G Takefala, Yanyan Chen, Aaron P Thrift, Graeme A Macdonald, Ingrid J Hickman

Faculty, Staff and Students Publications

Background: Sarcopenia is a syndrome of severe muscle wasting, associated with adverse outcomes related to liver transplantation (LT). There are several approaches used to identify sarcopenia. We aimed to investigate the prevalence of sarcopenia using 3 different criteria and determine how these performed in relation to clinical outcomes.

Methods: The cohort study included 237 adults with cirrhosis referred for LT. Sarcopenia was identified using (1) CT-defined; and the (2) original and (3) updated European Working Group on Sarcopenia in Older People criteria (EWGSOP1 and 2). Logistic regression was used to estimate OR and 95% CI for the relationships between sarcopenia …

Barriers To And Facilitators Of Sustaining A Systemic Lupus Erythematosus (Sle) Patient Decision Aid In Regular Rheumatology Outpatient Care In The Usa, Erin E Blanchard, Allyson G Hall, Ezra Gore, Parvaneh Yaghoubi Jami, Aizhan Karabukayeva, Larry R Hearld, Shelby Gontarz, Jasvinder A Singh

Faculty, Staff and Students Publications

Objective: This study investigates the barriers to and facilitators of sustaining a decision aid (DA) tool for patients with SLE in routine rheumatology outpatient care across the USA. The DA was initially developed for assisting patients with SLE in making informed medication choices by providing personalized information on their treatment process.

Methods: We conducted semi-structured interviews with clinicians, administrators, and information technology (IT) professionals from 15 geographically diverse rheumatology clinics that participated in a large-scale DA implementation trial. Interviews were transcribed and analysed using NVivo, with thematic coding to identify key factors influencing DA sustainability.

Results: The analysis identified several …

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) …

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 …

A Subset Of Cortical Areas Exhibit Adult-Like Functional Network Patterns In Early Childhood, Jiaxin Cindy Tu, Xintian Wang, Donna Dierker, Chloe M. Sobolewski, Evan M Gordon, Timothy O Laumann, Adam T Eggebrecht, Muriah D. Wheelock, Et Al.

2020-Current year OA Pubs

The human cerebral cortex contains groups of areas that support sensory, motor, cognitive, and affective functions, often categorized into functional networks. These networks show stronger internal and weaker external functional connectivity (FC), with FC profiles more similar within the same network. Previous studies have shown these networks develop from nascent forms before birth to their mature, adult-like structures in childhood. However, these analyses often rely on adult functional network definitions. This study assesses the potential misidentification of infant functional networks when using adult models and explores the consequences and possible solutions to this problem. Our findings suggest that although adult …

Eye Catching, Alec B Rezigh, Anand D Jagannath, Austin C Rezigh, Ann Marie Kumfer, Stephanie V Sherman

Faculty, Staff and Students Publications

A 55 year-old man with type 2 diabetes mellitus presented to the emergency department with subacute nausea, vomiting, and abdominal pain. He was found to have epididymitis and hyperglycemia that improved with antibiotics and supportive care. However, he was also discovered to have significant acute kidney injury and chronic, relapsing-remitting bouts of eye pain and redness, confirmed to be uveitis on ophthalmologic evaluation. Despite completing an appropriate course of antibiotics, his pyuria and kidney injury persisted. An extensive infectious, autoimmune, and malignancy work-up was negative. As such, renal biopsy was pursued and revealed findings consistent with tubulointerstitial nephritis. With a …

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, …

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 …

The Metastatic Role Of The Cxcl10-Cxcr3 Axis And Its Therapeutic Potential In Osteosarcoma, Benjamin B Gyau, Junyan Wang, Xiang Chen, Margaret A Clement, Zoe D Man, Angela M Major, Mathew C Weiser, Jun Xu, John Hicks, Tsz-Kwong Man

Faculty, Staff and Students Publications

The CXCL10-CXCR3 axis regulates immunity, tumorigenesis, and metastasis in multiple cancers. Yet, its roles in osteosarcoma (OS), the predominant pediatric malignant bone tumor, are not fully defined. Our prior work has shown that elevated serum CXCL10 levels correlate with poor OS prognosis. The current study delves deeper by investigating how CXCL10-mediated CXCR3 signaling influences OS growth and metastatic spread. In vitro, CXCL10 and related CXCR3 ligands (CXCL4, CXCL9, and CXCL11) enhanced OS tumor cell migration. In an orthotopic xenograft mouse model with a newly created CXCR3 knockout (KO) mutant, tumor growth and lung metastasis decreased significantly when compared with …