Medicine and Health Sciences Commons^™

Correlates Of Risk For Disinhibited Behaviors In The Million Veteran Program Cohort, Peter B Barr, Tim B Bigdeli, Jacquelyn L Meyers, Roseann E Peterson, Sandra Sanchez-Roige, Travis T Mallard, Danielle M Dick, K Paige Harden, Anna Wilkinson, David P Graham, David A Nielsen, Alan C Swann, Rachele K Lipsky, Thomas R Kosten, Mihaela Aslan, Philip D Harvey, Nathan A Kimbrel, Jean C Beckham

Faculty, Staff and Students Publications

Importance: Many psychiatric outcomes share a common etiologic pathway reflecting behavioral disinhibition, generally referred to as externalizing (EXT) disorders. Recent genome-wide association studies (GWASs) have demonstrated the overlap between EXT disorders and important aspects of veterans' health, such as suicide-related behaviors and substance use disorders (SUDs).

Objective: To explore correlates of risk for EXT disorders within the Veterans Health Administration (VA) Million Veteran Program (MVP).

Design, setting, and participants: A series of phenome-wide association studies (PheWASs) of polygenic risk scores (PGSs) for EXT disorders was conducted using electronic health records. First, ancestry-specific PheWASs of EXT PGSs were conducted in the …

Herpes Zoster And Risk Of Incident Parkinson's Disease In Us Veterans: A Matched Cohort Study, Louis Tunnicliffe, Rimona S Weil, Judith Breuer, Maria C Rodriguez-Barradas, Liam Smeeth, Christopher T Rentsch, Charlotte Warren-Gash

Faculty, Staff and Students Publications

Background: Although some systemic infections are associated with Parkinson's disease (PD), the relationship between herpes zoster (HZ) and PD is unclear.

Objective: The objective is to investigate whether HZ is associated with incident PD risk in a matched cohort study using data from the US Department of Veterans Affairs.

Methods: We compared the risk of PD between individuals with incident HZ matched to up to five individuals without a history of HZ using Cox proportional hazards regression. In sensitivity analyses, we excluded early outcomes.

Results: Among 198,099 individuals with HZ and 976,660 matched individuals without HZ (median age 67.0 years …

Fibroblast Heterogeneity In Pulmonary Fibrosis: A New Target For Therapeutics Development?, Konstantin Tsoyi, Ivan O Rosas

Faculty, Staff and Students Publications

No abstract provided.

Pediatric Cancer Incidence Among Individuals With Overgrowth Syndromes And Overgrowth Features: A Population-Based Assessment In Seven Million Children, Gillean K Connolly, Rachel D Harris, Charles Shumate, Surya P Rednam, Mark A Canfield, Sharon E Plon, Joanne Nguyen, Jeremy M Schraw, Philip J Lupo

Faculty, Staff and Students Publications

Background: Overgrowth syndromes (e.g., Beckwith-Wiedemann) are associated with an increased risk of pediatric cancer, although there are few population-based estimates of risk. There are also limited studies describing associations between other overgrowth features (e.g., hepatosplenomegaly) and pediatric cancer. Therefore, cancer risk among children with these conditions was evaluated with data from a large, diverse population-based registry linkage study.

Methods: This study includes all live births in Texas during the years 1999-2017. Children with overgrowth features and syndromes were identified from the Texas Birth Defects Registry; children with cancer were identified by linkage to the Texas Cancer Registry. Cox regression models …

Role Of Camk2d In Neurodevelopment And Associated Conditions, Pomme M F Rigter, Charlotte De Konink, Matthew J Dunn, Martina Proietti Onori, Jennifer B Humberson, Matthew Thomas, Caitlin Barnes, Carlos E Prada, K Nicole Weaver, Thomas D Ryan, Oana Caluseriu, Jennifer Conway, Emily Calamaro, Chin-To Fong, Wim Wuyts, Marije Meuwissen, Eva Hordijk, Carsten N Jonkers, Lucas Anderson, Berfin Yuseinova, Sarah Polonia, Diane Beysen, Zornitza Stark, Elena Savva, Cathryn Poulton, Fiona Mckenzie, Elizabeth Bhoj, Caleb P Bupp, Stéphane Bézieau, Sandra Mercier, Amy Blevins, Ingrid M Wentzensen, Fan Xia, Jill A Rosenfeld, Tzung-Chien Hsieh, Peter M Krawitz, Miriam Elbracht, Danielle C M Veenma, Howard Schulman, Margaret M Stratton, Sébastien Küry, Geeske M Van Woerden

Faculty, Staff and Students Publications

The calcium/calmodulin-dependent protein kinase type 2 (CAMK2) family consists of four different isozymes, encoded by four different genes-CAMK2A, CAMK2B, CAMK2G, and CAMK2D-of which the first three have been associated recently with neurodevelopmental disorders. CAMK2D is one of the major CAMK2 proteins expressed in the heart and has been associated with cardiac anomalies. Although this CAMK2 isoform is also known to be one of the major CAMK2 subtypes expressed during early brain development, it has never been linked with neurodevelopmental disorders until now. Here we show that CAMK2D plays an important role in neurodevelopment not only in mice but also in …

Adverse Metabolic Phenotypes In Parenterally Fed Neonatal Pigs Do Not Persist Into Adolescence, Sarah K Elefson, Barbara Stoll, Teresa A Davis, Marta L Fiorotto, Samer W El-Kadi, Kenneth Genovese, Thomas Thymann, Per T Sangild, Douglas G Burrin

Faculty, Staff and Students Publications

BACKGROUND: Nutrition during fetal and neonatal life is an important determinant for the risk of adult-onset diseases, especially type 2 diabetes and obesity.

OBJECTIVES: We aimed to determine whether total parenteral nutrition (TPN) compared with enteral formula feeding [enteral nutrition (EN)] in term piglets during the first 2 wk after birth would increase the long-term (5-mo) development of metabolic syndrome phenotypes with adverse glucose homeostasis, fatty liver disease, and obesity.

METHODS: Neonatal female pigs were administered TPN (n = 12) or fed enterally with a liquid enteral milk-replacer formula (EN, n = 12) for 14 d. After transitioning TPN pigs …

Evolving Concepts In Helicobacter Pylori Management, Steven F Moss, Shailja C Shah, Mimi C Tan, Hashem B El-Serag

Faculty, Staff and Students Publications

Helicobacter pylori is the most common chronic bacterial infection worldwide and the most significant risk factor for gastric cancer, which remains a leading cause of cancer-related death globally. H pylori and gastric cancer continue to disproportionately impact racial and ethnic minority and immigrant groups in the United States. The approach to H pylori case-finding thus far has relied on opportunistic testing based on symptoms or high-risk indicators, such as racial or ethnic background and family history. However, this approach misses a substantial proportion of individuals infected with H pylori who remain at risk for gastric cancer because most infections remain …

Circadian Dysfunction Induces Nafld-Related Human Liver Cancer In A Mouse Model, Jennifer Padilla, Noha M Osman, Beatrice Bissig-Choisat, Sandra L Grimm, Xuan Qin, Angela M Major, Li Yang, Dolores Lopez-Terrada, Cristian Coarfa, Feng Li, Karl-Dimiter Bissig, David D Moore, Loning Fu

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Chronic circadian dysfunction increases the risk of non-alcoholic fatty liver disease (NAFLD)-related hepatocellular carcinoma (HCC), but the underlying mechanisms and direct relevance to human HCC have not been established. In this study, we aimed to determine whether chronic circadian dysregulation can drive NAFLD-related carcinogenesis from human hepatocytes and human HCC progression.

METHODS: Chronic jet lag of mice with humanized livers induces spontaneous NAFLD-related HCCs from human hepatocytes. The clinical relevance of this model was analysed by biomarker, pathological/histological, genetic, RNA sequencing, metabolomic, and integrated bioinformatic analyses.

RESULTS: Circadian dysfunction induces glucose intolerance, NAFLD-associated human HCCs, and human …

Generation Of Five Induced Pluripotent Stem Cell Lines From Patients With Mecp2 Duplication Syndrome, Danielle Mendonca, Gerarda Cappuccio, Jennifer Sheppard, Magdalena Delacruz, Jesse Bengtsson, Claudia M B Carvalho, Aleksandar Bajic, Hyekyung Park, Jean J Kim, Paymaan Jafar-Nejad, Christine Coquery, Davut Pehlivan, Bernhard Suter, Mirjana Maletic-Savatic

Faculty, Staff and Students Publications

MECP2 Duplication Syndrome (MDS) is a rare, severe neurodevelopmental disorder arising from duplications in the Xq28 region containing the MECP2 gene that predominantly affects males. We generated five human induced pluripotent stem cell (iPSC) lines from the fibroblasts of individuals carrying between 0.355 and 11.2 Mb size duplications in the chromosomal locus containing MECP2. All lines underwent extensive testing to confirm MECP2 duplication and iPSC-related features such as morphology, pluripotency markers, and trilineage differentiation potential. These lines are a valuable resource for molecular and functional studies of MDS as well as screening for a variety of therapeutic approaches.

Leptin Reduction As A Required Component For Weight Loss, Shangang Zhao, Na Li, Wei Xiong, Guannan Li, Sijia He, Zhuzhen Zhang, Qingzhang Zhu, Nisi Jiang, Christian Ikejiofor, Yi Zhu, May-Yun Wang, Xianlin Han, Ningyang Zhang, Carolina Solis-Herrera, Christine Kusminski, Zhiqiang An, Joel K Elmquist, Philipp E Scherer

Faculty, Staff and Students Publications

Partial leptin reduction can induce significant weight loss, while weight loss contributes to partial leptin reduction. The cause-and-effect relationship between leptin reduction and weight loss remains to be further elucidated. Here, we show that FGF21 and the glucagon-like peptide 1 receptor (GLP-1R) agonist liraglutide rapidly induced a reduction in leptin. This leptin reduction contributed to the beneficial effects of GLP-1R agonism in metabolic health, as transgenically maintaining leptin levels during treatment partially curtailed the beneficial effects seen with these agonists. Moreover, a higher degree of leptin reduction during treatment, induced by including a leptin neutralizing antibody with either FGF21 or …

Genetic Architecture And Biology Of Youth-Onset Type 2 Diabetes, Soo Heon Kwak, Shylaja Srinivasan, Ling Chen, Jennifer Todd, Josep M Mercader, Elizabeth T Jensen, Jasmin Divers, Amy K Mottl, Catherine Pihoker, Rachelle G Gandica, Lori M Laffel, Elvira Isganaitis, Morey W Haymond, Lynne L Levitsky, Toni I Pollin, Jose C Florez, Jason Flannick, Progress In Diabetes Genetics In Youth (Prodigy) Consortium

Faculty, Staff and Students Publications

The prevalence of youth-onset type 2 diabetes (T2D) and childhood obesity has been rising steadily1, producing a growing public health concern1 that disproportionately affects minority groups2. The genetic basis of youth-onset T2D and its relationship to other forms of diabetes are unclear3. Here we report a detailed genetic characterization of youth-onset T2D by analysing exome sequences and common variant associations for 3,005 individuals with youth-onset T2D and 9,777 adult control participants matched for ancestry, including both males and females. We identify monogenic diabetes variants in 2.4% of individuals and three exome-wide significant ( …

Number Of Children In The Household Influences Respiratory Morbidities In Children With Bronchopulmonary Dysplasia In The Outpatient Setting, Joseph M Collaco, Katharine R Tsukahara, Michael C Tracy, Catherine A Sheils, Jessica L Rice, Lawrence M Rhein, Antonia P Popova, Leif Nelin, Audrey N Miller, Winston M Manimtim, Jonathan C Levin, Khanh Lai, Jacob A Kaslow, Lystra P Hayden, Manvi Bansal, Eric D Austin, Brianna Aoyama, Gangaram Akangire, Amit Agarwal, Natalie Villafranco, Sharon A Mcgrath-Morrow

Faculty, Staff and Students Publications

BACKGROUND: Bronchopulmonary dysplasia (BPD), a common complication of prematurity, is associated with outpatient morbidities, including respiratory exacerbations. Daycare attendance is associated with increased rates of acute and chronic morbidities in children with BPD. We sought to determine if additional children in the household conferred similar risks for children with BPD.

METHODS: The number of children in the household and clinical outcomes were obtained via validated instruments for 933 subjects recruited from 13 BPD specialty clinics in the United States. Clustered logistic regression models were used to test for associations.

RESULTS: The mean gestational age of the study population was 26.5 …

The Potential Epidemiologic, Clinical, And Economic Value Of A Universal Coronavirus Vaccine: A Modelling Study, Sarah M Bartsch, Kelly J O'Shea, Danielle C John, Ulrich Strych, Maria Elena Bottazzi, Marie F Martinez, Allan Ciciriello, Kevin L Chin, Colleen Weatherwax, Kavya Velmurugan, Jessie Heneghan, Sheryl A Scannell, Peter J Hotez, Bruce Y Lee

Faculty, Staff and Students Publications

BACKGROUND: With efforts underway to develop a universal coronavirus vaccine, otherwise known as a pan-coronavirus vaccine, this is the time to offer potential funders, researchers, and manufacturers guidance on the potential value of such a vaccine and how this value may change with differing vaccine and vaccination characteristics.

METHODS: Using a computational model representing the United States (U.S.) population, the spread of SARS-CoV-2 and the various clinical and economic outcomes of COVID-19 such as hospitalisations, deaths, quality-adjusted life years (QALYs) lost, productivity losses, direct medical costs, and total societal costs, we explored the impact of a universal vaccine under different …

Quality Assurance For Stereotactic Body Radiation Therapy For Gynecologic Malignancies, Samuel N Andersen, Mark D Bonnen, Michelle S Ludwig, Shraddha M Dalwadi

Faculty, Staff and Students Publications

The use of stereotactic body radiation therapy (SBRT) is not well studied or reported in the treatment of gynecologic malignancies, despite its success in the definitive management of other cancer sites. This report describes a rigorous quality assurance process for patients to undergo dose escalation to the pelvis via stereotactic photon beam irradiation. Patients who receive SBRT must be ineligible for conventional brachytherapy boost and undergo comprehensive informed consent. Fiducial placement, bowel prep, Foley catheter placement with standardized bladder filling, computerized tomography (CT) simulation with whole-body immobilization, magnetic resonance imaging (MRI)-assisted target delineation, planning aims based on the established brachytherapy …

Outcomes Of Minimally Invasive Isolated Tricuspid Valve Repair And Replacement Through Right Mini-Thoracotomy, Ahmed Alnajar, Subhasis Chatterjee, Jacqueline K Olive, Mahmut S Kaymakci, Lauren Gray, Zachary Gray, Joao R Breda, Joseph Lamelas

Faculty, Staff and Students Publications

OBJECTIVE: Isolated tricuspid valve surgery is uncommon and associated with high perioperative morbidity and mortality. We aimed to study the overall outcomes of patients who underwent minimally invasive right thoracotomy tricuspid valve surgery (Mini-TVS), consisting of either tricuspid valve repair (TVre) or replacement (TVR).

METHODS: We performed a retrospective analysis of all Mini-TVS procedures (2017-2022), through which we identified isolated tricuspid valve surgeries. We examined in-hospital outcomes, survival analysis over a 4-year period, and competing risk analysis for reoperative surgery.

RESULTS: Among a total of 51 patients, the average age was 60 ± 16 years, and 67% (n = 34) …

Social Determinants Of Health Framework To Identify And Reduce Barriers To Imaging In Marginalized Communities, Mohab M Elmohr, Zulqarnain Javed, Prachi Dubey, John E Jordan, Lubdha Shah, Khurram Nasir, Eric M Rohren, Christie M Lincoln

Faculty, Staff and Students Publications

Social determinants of health (SDOH) are conditions influencing individuals' health based on their environment of birth, living, working, and aging. Addressing SDOH is crucial for promoting health equity and reducing health outcome disparities. For conditions such as stroke and cancer screening where imaging is central to diagnosis and management, access to high-quality medical imaging is necessary. This article applies a previously described structural framework characterizing the impact of SDOH on patients who require imaging for their clinical indications. SDOH factors can be broadly categorized into five sectors: economic stability, education access and quality, neighborhood and built environment, social and community …

Regulation Of Androgen Receptor Stability By The Β1pix/Stub1 Complex, Ahmed Chahdi, Carolina Jorgez, Abhishek Seth

Faculty, Staff and Students Publications

The Androgen Receptor (AR) is essential in the development and differentiation of testes and male genitalia. AR expression is tightly regulated at the translational and posttranslational levels. AR posttranscriptional regulation is a major determinant of AR availability since AR is a direct target of E3 ubiquitin ligase STUB1. Our work indicated that the Rac/Cdc42 guanosine triphosphatase guanine nucleotide exchange factor, β1Pix, enhanced AR levels after AR stimulation in HEK293 and HeLa cells. AR stimulation decreased AR ubiquitination which is accompanied by increased β1Pix binding to AR. Ectopic expression of β1Pix decreased AR ubiquitination in Tm4 and HEK293 cells. We demonstrated …

Prediction Of Adverse Events Risk In Patients With Comorbid Post-Traumatic Stress Disorder And Alcohol Use Disorder Using Electronic Medical Records By Deep Learning Models, Oshin Miranda, Peihao Fan, Xiguang Qi, Haohan Wang, M Daniel Brannock, Thomas Kosten, Neal David Ryan, Levent Kirisci, Lirong Wang

Faculty, Staff and Students Publications

Background: Identifying co-occurring mental disorders and elevated risk is vital for optimization of healthcare processes. In this study, we will use DeepBiomarker2, an updated version of our deep learning model to predict the adverse events among patients with comorbid post-traumatic stress disorder (PTSD) and alcohol use disorder (AUD), a high-risk population.

Methods: We analyzed electronic medical records of 5565 patients from University of Pittsburgh Medical Center to predict adverse events (opioid use disorder, suicide related events, depression, and death) within 3 months at any encounter after the diagnosis of PTSD+AUD by using DeepBiomarker2. We integrated multimodal information including: lab tests, …

Distribution Of P2y And P2x Purinergic Receptor Expression Within The Intestine, Kristen A Engevik, Francesca J Scribano, J Thomas Gebert, Jacob L Perry, Sue E Crawford, Joseph M Hyser

Faculty, Staff and Students Publications

Nucleotides are potent extracellular signaling molecules during homeostasis, infection, and injury due to their ability to activate purinergic receptors. The nucleotide ATP activates P2X receptors (P2RXs), whereas the nucleotides ADP, ATP, UTP, and UDP-glucose selectively activate different P2Y receptors (P2RYs). Several studies have established crucial roles for P2 receptors during intestinal inflammatory and infectious diseases, yet the most extensive characterization of purinergic signaling has focused on immune cells and the central and enteric nervous systems. As epithelial cells serve as the first barrier against irritants and infection, we hypothesized that the gut epithelium may express multiple purinergic receptors that respond …

Acss3 Regulates The Metabolic Homeostasis Of Epithelial Cells And Alleviates Pulmonary Fibrosis, Lan Wang, Hongmei Yuan, Wenwen Li, Peishuo Yan, Mengxia Zhao, Zhongzheng Li, Huabin Zhao, Shenghui Wang, Ruyan Wan, Yajun Li, Juntang Yang, Xin Pan, Ivan Rosas, Guoying Yu

Faculty, Staff and Students Publications

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease of unknown etiology. The emerging evidence demonstrates that metabolic homeostatic imbalance caused by repetitive injuries of the alveolar epithelium is the potential pathogenesis of IPF. Proteomic analysis identified that Acetyl-CoA synthetase short chain family member 3 (ACSS3) expression was decreased in IPF patients and mice with bleomycin-induced fibrosis. ACSS3 participated in lipid and carbohydrate metabolism. Increased expression of ACSS3 downregulated carnitine palmitoyltransferase 1A (CPT-1A) and resulted in the accumulation of lipid droplets, while enhanced glycolysis which led to an increase in extracellular lactic acid levels in A549 cells. …

Endothelial Cells Adopt A Pro-Reparative Immune Responsive Signature During Cardiac Injury, Hali Long, Jeffrey D Steimle, Francisco Jose Grisanti Canozo, Jong Hwan Kim, Xiao Li, Yuka Morikawa, Minjun Park, Diwakar Turaga, Iki Adachi, Joshua D Wythe, Md Abul Hassan Samee, James F Martin

Faculty, Staff and Students Publications

Modulation of the heart’s immune microenvironment is crucial for recovery after ischemic events such as myocardial infarction (MI). Endothelial cells (ECs) can have immune regulatory functions; however, interactions between ECs and the immune environment in the heart after MI remain poorly understood. We identified an EC-specific IFN responsive and immune regulatory gene signature in adult and pediatric heart failure (HF) tissues. Single-cell transcriptomic analysis of murine hearts subjected to MI uncovered an EC population (IFN-ECs) with immunologic gene signatures similar to those in human HF. IFN-ECs were enriched in regenerative-stage mouse hearts and expressed genes encoding immune responsive transcription factors …

Publisher Correction: Long-Term Labeling And Imaging Of Synaptically Connected Neuronal Networks In Vivo Using Double-Deletion-Mutant Rabies Viruses, Lei Jin, Heather A Sullivan, Mulangma Zhu, Thomas K Lavin, Makoto Matsuyama, Xin Fu, Nicholas E Lea, Ran Xu, Yuanyuan Hou, Luca Rutigliani, Maxwell Pruner, Kelsey R Babcock, Jacque Pak Kan Ip, Ming Hu, Tanya L Daigle, Hongkui Zeng, Mriganka Sur, Guoping Feng, Ian R Wickersham

Faculty, Staff and Students Publications

This corrects the article "Long-term labeling and imaging of synaptically connected neuronal networks in vivo using double-deletion-mutant rabies viruses" on page 373.

Anticoagulation With Osocimab In Patients With Kidney Failure Undergoing Hemodialysis: A Randomized Phase 2 Trial, Jeffrey I Weitz, László B Tankó, Jürgen Floege, Keith A A Fox, Deepak L Bhatt, Ravi Thadhani, James Hung, Ákos F Pap, Dagmar Kubitza, Wolfgang C Winkelmayer

Faculty, Staff and Students Publications

Individuals with kidney failure undergoing hemodialysis are at elevated risk for thromboembolic events. Factor (F) XI, which is in the intrinsic pathway of coagulation, is emerging as an attractive target for new anticoagulants that may be safer than existing agents. Osocimab-an inhibitory FXIa antibody-is a potential treatment option for such patients. We conducted a phase 2b, double-blind, placebo-controlled trial, in which 704 participants (448 male, 256 female) with kidney failure undergoing hemodialysis were randomized to receive lower- or higher-dose osocimab or placebo. In total, 686 participants (436 male, 250 female) received treatment for ≤18 months (planned minimal treatment period of …

In Vivo Cardiac Electrophysiology In Mice: Determination Of Atrial And Ventricular Arrhythmic Substrates, Jose Alberto Navarro-Garcia, Florian Bruns, Oliver M Moore, Marcel A Tekook, Dobromir Dobrev, Christina Y Miyake, Xander H T Wehrens

Faculty, Staff and Students Publications

Cardiac arrhythmias are a common cardiac condition that might lead to fatal outcomes. A better understanding of the molecular and cellular basis of arrhythmia mechanisms is necessary for the development of better treatment modalities. To aid these efforts, various mouse models have been developed for studying cardiac arrhythmias. Both genetic and surgical mouse models are commonly used to assess the incidence and mechanisms of arrhythmias. Since spontaneous arrhythmias are uncommon in healthy young mice, intracardiac programmed electrical stimulation (PES) can be performed to assess the susceptibility to pacing-induced arrhythmias and uncover the possible presence of a proarrhythmogenic substrate. This procedure …

Cardiac Magnetic Resonance Imaging In Detection Of Progressive Graft Dysfunction In Pediatric Heart Transplantation, Kae Watanabe, Nicoleta C Arva, Joshua D Robinson, Cynthia Rigsby, Michael Markl, Melanie Sojka, Paul Tannous, Jennifer Arzu, Nazia Husain

Faculty, Staff and Students Publications

BACKGROUND: Chronic graft failure (CGF) in pediatric heart transplant (PHT) is multifactorial and may present with findings of fibrosis and microvessel disease (MVD) on endomyocardial biopsy (EMB). There is no optimal CGF surveillance method. We evaluated associations between cardiac magnetic resonance imaging (CMR) and historical/EMB correlates of CGF to assess CMR's utility as a surveillance method.

METHODS: Retrospective analysis of PHT undergoing comprehensive CMR between September 2015 and January 2022 was performed. EMB within 6 months was graded for fibrosis (scale 0-5) and MVD (number of capillaries with stenotic wall thickening per field of view). Correlation analysis and logistic regression …

Rates, Patterns, And Predictors Of Specialty Palliative Care Consultation Among Patients With Acute-On-Chronic Liver Failure, Arpan Patel, Anne Walling, Fasiha Kanwal, Marina Serper, Ruben Hernaez, Vinay Sundaram, David Kaplan, Tamar Taddei, Nadim Mahmud

Faculty, Staff and Students Publications

BACKGROUND & AIMS: There is growing acceptance that principles of palliative care should be integrated into the management of serious illnesses affecting the liver, such as acute-on-chronic liver failure (ACLF). However, rates, patterns, and predictors of specialty palliative care consultation among patients with ACLF have not been well-described.

METHODS: We performed a retrospective cohort study of patients hospitalized with ACLF between 1/1/2008 and 12/31/2018 using the VOCAL cohort. Patients were followed until 6/2021. We used mixed-effects regression analyses to identify significant patient and facility factors associated with palliative care consultation. We examined timing of consultation, the influence of ACLF characteristics, …

Mapping Gray And White Matter Volume Abnormalities In Early-Onset Psychosis: An Enigma Multicenter Voxel-Based Morphometry Study, Shuqing Si, Anbreen Bi, Zhaoying Yu, Cheryl See, Sinead Kelly, Sonia Ambrogi, Celso Arango, Inmaculada Baeza, Nerisa Banaj, Michael Berk, Josefina Castro-Fornieles, Benedicto Crespo-Facorro, Jacob J Crouse, Covadonga M Díaz-Caneja, Anne-Kathrin Fett, Adriana Fortea, Sophia Frangou, Benjamin I Goldstein, Ian B Hickie, Joost Janssen, Kody G Kennedy, Lydia Krabbendam, Marinos Kyriakopoulos, Bradley J Macintosh, Pedro Morgado, Stener Nerland, Saül Pascual-Diaz, Maria Picó-Pérez, Fabrizio Piras, Bjørn Rishovd Rund, Elena De La Serna, Gianfranco Spalletta, Gisela Sugranyes, Chao Suo, Diana Tordesillas-Gutiérrez, Daniela Vecchio, Joaquim Radua, Philip Mcguire, Sophia I Thomopoulos, Neda Jahanshad, Paul M Thompson, Claudia Barth, Ingrid Agartz, Anthony James, Matthew J Kempton

Faculty, Staff and Students Publications

INTRODUCTION: Regional gray matter (GM) alterations have been reported in early-onset psychosis (EOP, onset before age 18), but previous studies have yielded conflicting results, likely due to small sample sizes and the different brain regions examined. In this study, we conducted a whole brain voxel-based morphometry (VBM) analysis in a large sample of individuals with EOP, using the newly developed ENIGMA-VBM tool.

METHODS: 15 independent cohorts from the ENIGMA-EOP working group participated in the study. The overall sample comprised T1-weighted MRI data from 482 individuals with EOP and 469 healthy controls. Each site performed the VBM analysis locally using the …

Nonchromosomal Birth Defects And Risk Of Childhood Acute Leukemia: An Assessment In 15 000 Leukemia Cases And 46 000 Controls From The Childhood Cancer And Leukemia International Consortium, Philip J Lupo, Tiffany M Chambers, Beth A Mueller, Jacqueline Clavel, John D Dockerty, David R Doody, Friederike Erdmann, Sameera Ezzat, Tommaso Filippini, Johnni Hansen, Julia E Heck, Claire Infante-Rivard, Alice Y Kang, Corrado Magnani, Carlotta Malagoli, Erin L Marcotte, Catherine Metayer, Helen D Bailey, Ana M Mora, Evangelia Ntzani, Eleni Th Petridou, Maria S Pombo-De-Oliveira, Wafaa M Rashed, Eve Roman, Joachim Schüz, Catharina Wesseling, Logan G Spector, Michael E Scheurer

Faculty, Staff and Students Publications

Although recent studies have demonstrated associations between nonchromosomal birth defects and several pediatric cancers, less is known about their role on childhood leukemia susceptibility. Using data from the Childhood Cancer and Leukemia International Consortium, we evaluated associations between nonchromosomal birth defects and childhood leukemia. Pooling consortium data from 18 questionnaire-based and three registry-based case-control studies across 13 countries, we used multivariable logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between a spectrum of birth defects and leukemia. Our analyses included acute lymphoblastic leukemia (ALL, n = 13 115) and acute myeloid leukemia …

Generation Of A Dcx-Creert2 Knock-In Mouse For Genetic Manipulation Of Newborn Neurons, Gabriella A Perez, Kyung-Won Park, Denise Lanza, Jenna Cicardo, M Danish Uddin, Joanna L Jankowsky

Faculty, Staff and Students Publications

A wide variety of CreERT2 driver lines are available for genetic manipulation of adult-born neurons in the mouse brain. These tools have been instrumental in studying fate potential, migration, circuit integration, and morphology of the stem cells supporting lifelong neurogenesis. Despite a wealth of tools, genetic manipulation of adult-born neurons for circuit and behavioral studies has been limited by poor specificity of many driver lines targeting early progenitor cells and by the inaccessibility of lines selective for later stages of neuronal maturation. We sought to address these limitations by creating a new CreERT2 driver line targeted to the endogenous mouse …

The Importance Of Considering Competing Risks In Recurrence Analysis Of Intracranial Meningioma, Christian Mirian, Lasse Rehné Jensen, Tareq A Juratli, Andrea Daniela Maier, Sverre H Torp, Helen A Shih, Ramin A Morshed, Jacob S Young, Stephen T Magill, Luca Bertero, Walter Stummer, Dorothee Cäcilia Spille, Benjamin Brokinkel, Soichi Oya, Satoru Miyawaki, Nobuhito Saito, Martin Proescholdt, Yasuhiro Kuroi, Konstantinos Gousias, Matthias Simon, Jennifer Moliterno, Ricardo Prat-Acin, Stéphane Goutagny, Vikram C Prabhu, John T Tsiang, Johannes Wach, Erdem Güresir, Junkoh Yamamoto, Young Zoon Kim, Joo Ho Lee, Matthew Koshy, Karthikeyan Perumal, Mustafa K Baskaya, Donald M Cannon, Dennis C Shrieve, Chang-Ok Suh, Jong Hee Chang, Maria Kamenova, Sven Straumann, Jehuda Soleman, Ilker Y Eyüpoglu, Tony Catalan, Austin Lui, Philip V Theodosopoulos, Michael W Mcdermott, Fang Wang, Fuyou Guo, Pedro Góes, Manoel Antonio De Paiva Neto, Aria Jamshidi, Ricardo Komotar, Michael Ivan, Evan Luther, Luis Souhami, Marie-Christine Guiot, Tamás Csonka, Toshiki Endo, Olivia Claire Barrett, Randy Jensen, Tejpal Gupta, Akash J Patel, Tiemo J Klisch, Jun Won Kim, Francesco Maiuri, Valeria Barresi, María Dolores Tabernero, Simon Skyrman, Anders Broechner, Mathias Jacobsen Bach, Ian Law, David Scheie, Bjarne Winther Kristensen, Tina Nørgaard Munch, Torstein Meling, Kåre Fugleholm, Paul Blanche, Tiit Mathiesen

Faculty, Staff and Students Publications

BACKGROUND: The risk of recurrence is overestimated by the Kaplan-Meier method when competing events, such as death without recurrence, are present. Such overestimation can be avoided by using the Aalen-Johansen method, which is a direct extension of Kaplan-Meier that accounts for competing events. Meningiomas commonly occur in older individuals and have slow-growing properties, thereby warranting competing risk analysis. The extent to which competing events are considered in meningioma literature is unknown, and the consequences of using incorrect methodologies in meningioma recurrence risk analysis have not been investigated.

METHODS: We surveyed articles indexed on PubMed since 2020 to assess the usage …