Digital Commons Network^™

Macrophage-Derived Il-1Β/Nf-Κb Signaling Mediates Parenteral Nutrition-Associated Cholestasis., Karim C El Kasmi, Padade M Vue, Aimee L Anderson, Michael W Devereaux, Swati Ghosh, Natarajan Balasubramaniyan, Sophie A Fillon, Carola Dahrenmoeller, Ayed Allawzi, Crystal Woods, Sarah Mckenna, Clyde J Wright, Linda Johnson, Angelo D'Alessandro, Julie A Reisz, Eva Nozik-Grayck, Frederick J Suchy, Ronald J Sokol

Articles, Abstracts, and Reports

In infants intolerant of enteral feeding because of intestinal disease, parenteral nutrition may be associated with cholestasis, which can progress to end-stage liver disease. Here we show the function of hepatic macrophages and phytosterols in parenteral nutrition-associated cholestasis (PNAC) pathogenesis using a mouse model that recapitulates the human pathophysiology and combines intestinal injury with parenteral nutrition. We combine genetic, molecular, and pharmacological approaches to identify an essential function of hepatic macrophages and IL-1β in PNAC. Pharmacological antagonism of IL-1 signaling or genetic deficiency in CCR2, caspase-1 and caspase-11, or IL-1 receptor (which binds both IL-1α and IL-1β) prevents PNAC in …

Sall1 Functions As A Tumor Suppressor In Breast Cancer By Regulating Cancer Cell Senescence And Metastasis Through The Nurd Complex, Chunling Ma, Fang Wang, Bing Han, Xiaoli Zhong, Fusheng Si, Jian Ye, Eddy C Hsueh, Lynn Robbins, Susan M Kiefer, Yanping Zhang, Pamela Hunborg, Mark A Varvares, Michael Rauchman, Guangyong Peng

Open Access Publications

BACKGROUND: SALL1 is a multi-zinc finger transcription factor that regulates organogenesis and stem cell development, but the role of SALL1 in tumor biology and tumorigenesis remains largely unknown.

METHODS: We analyzed SALL1 expression levels in human and murine breast cancer cells as well as cancer tissues from different types of breast cancer patients. Using both in vitro co-culture system and in vivo breast tumor models, we investigated how SALL1 expression in breast cancer cells affects tumor cell growth and proliferation, metastasis, and cell fate. Using the gain-of function and loss-of-function strategies, we dissected the molecular mechanism responsible for SALL1 tumor …

Left Frontal Hub Connectivity Delays Cognitive Impairment In Autosomal-Dominant And Sporadic Alzheimer's Disease, Nicolai Franzmeier, Anne M Fagan, Katrina Paumier, Tammie Benzinger, John C Morris, Randall J Bateman, Et Al.

2010-2019 OA Pubs

Patients with Alzheimer's disease vary in their ability to sustain cognitive abilities in the presence of brain pathology. A major open question is which brain mechanisms may support higher reserve capacity, i.e. relatively high cognitive performance at a given level of Alzheimer's pathology. Higher functional MRI-assessed functional connectivity of a hub in the left frontal cortex is a core candidate brain mechanism underlying reserve as it is associated with education (i.e. a protective factor often associated with higher reserve) and attenuated cognitive impairment in prodromal Alzheimer's disease. However, no study has yet assessed whether such hub connectivity of the left …

Hospital-Based Physicians' Intubation Decisions And Associated Mental Models When Managing A Critically And Terminally Ill Older Patient., Shannon Haliko, Julie Downs, Deepika Mohan, Robert Arnold, Amber E Barnato

Articles, Abstracts, and Reports

BACKGROUND: Variation in the intensity of acute care treatment at the end of life is influenced more strongly by hospital and provider characteristics than patient preferences.

OBJECTIVE: We sought to describe physicians' mental models (i.e., thought processes) when encountering a simulated critically and terminally ill older patient, and to compare those models based on whether their treatment plan was patient preference-concordant or preference-discordant.

METHODS: Seventy-three hospital-based physicians from 3 academic medical centers engaged in a simulated patient encounter and completed a mental model interview while watching the video recording of their encounter. We used an "expert" model to code the …

Genetic Variants In Hsd17b3, Smad3, And Ipo11 Impact Circulating Lipids In Response To Fenofibrate In Individuals With Type 2 Diabetes, Daniel M. Rotroff, Sonja S. Pijut, Skylar W. Marvel, John R. Jack, Tammy M. Havener, Aurora Pujol, Agatha Schluter, Gregory A. Graf, Henry N. Ginsberg, Hetal S. Shah, He Gao, Mario-Luca Morieri, Alessandro Doria, Josyf C. Mychaleckyi, Howard L. Mcleod, John B. Buse, Michael J. Wagner, Alison A. Motsinger-Reif, Accord/Accordion Investigators

Pharmaceutical Sciences Faculty Publications

Individuals with type 2 diabetes (T2D) and dyslipidemia are at an increased risk of cardiovascular disease. Fibrates are a class of drugs prescribed to treat dyslipidemia, but variation in response has been observed. To evaluate common and rare genetic variants that impact lipid responses to fenofibrate in statin‐treated patients with T2D, we examined lipid changes in response to fenofibrate therapy using a genomewide association study (GWAS). Associations were followed‐up using gene expression studies in mice. Common variants in SMAD3 and IPO11 were marginally associated with lipid changes in black subjects (P < 5 × 10^‐6). Rare variant and gene expression changes …

A Test Of Multisession Automatic Action Tendency Retraining To Reduce Alcohol Consumption Among Young Adults In The Context Of A Human Laboratory Paradigm., Robert F Leeman, Christine Nogueira, Reinout W Wiers, Janna Cousijn, Kelly Serafini, Kelly S Demartini, John A Bargh, Stephanie S O'Malley

Articles, Abstracts, and Reports

BACKGROUND: Young adult heavy drinking is an important public health concern. Current interventions have efficacy but with only modest effects, and thus, novel interventions are needed. In prior studies, heavy drinkers, including young adults, have demonstrated stronger automatically triggered approach tendencies to alcohol-related stimuli than lighter drinkers. Automatic action tendency retraining has been developed to correct this tendency and consequently reduce alcohol consumption. This study is the first to test multiple iterations of automatic action tendency retraining, followed by laboratory alcohol self-administration.

METHODS: A total of 72 nontreatment-seeking, heavy drinking young adults ages 21 to 25 were randomized to automatic …

Opportunities And Obstacles For Deep Learning In Biology And Medicine, Travers Ching, S Joshua Swamidass, Et Al

2010-2019 OA Pubs

Deep learning describes a class of machine learning algorithms that are capable of combining raw inputs into layers of intermediate features. These algorithms have recently shown impressive results across a variety of domains. Biology and medicine are data-rich disciplines, but the data are complex and often ill-understood. Hence, deep learning techniques may be particularly well suited to solve problems of these fields. We examine applications of deep learning to a variety of biomedical problems-patient classification, fundamental biological processes and treatment of patients-and discuss whether deep learning will be able to transform these tasks or if the biomedical sphere poses unique …

High Sodium Continuous Veno-Venous Hemodialysis With Regional Citrate Anticoagulation And Online Dialysate Generation In Patients With Acute Liver Failure And Cerebral Edema, Tamim Hamdi, Lenar Yessayan, Jerry Yee, Balazs Szamosfalvi

Nephrology Articles

INTRODUCTION: Acute liver failure is associated with a high mortality rate. Induction of plasma hypertonicity with mannitol or hypertonic saline remains the cornerstone in the management of resultant cerebral edema. Significant disadvantages of this approach include poor or unpredictable control of serum sodium concentration and volume expansion, among others.

METHODS: We used high sodium continuous veno-venous hemodialysis with regional citrate anticoagulation and online dialysate generation to accurately control the serum sodium in eleven patients with acute liver failure, renal failure, and cerebral edema. We used a Fresenius 2008 K/K2 machine in hemodialysis mode to deliver a blood flow of 60 …

Validation Of An Icd Code For Accurately Identifying Emergency Department Patients Who Suffer An Out-Of-Hospital Cardiac Arrest., Shelby K. Shelton, Steve B. Chukwulebe, David F. Gaieski, Benjamin S. Abella, Brendan G. Carr, Sarah M. Perman

Department of Emergency Medicine Faculty Papers

AIM: International classification of disease (ICD-9) code 427.5 (cardiac arrest) is utilized to identify cohorts of patients who suffer out-of-hospital cardiac arrest (OHCA), though the use of ICD codes for this purpose has never been formally validated. We sought to validate the utility of ICD-9 code 427.5 by identifying patients admitted from the emergency department (ED) after OHCA.

METHODS: Adult visits to a single ED between January 2007 and July 2012 were retrospectively examined and a keyword search of the electronic medical record (EMR) was used to identify patients. Cardiac arrest was confirmed; and ICD-9 information and location of return …

Differences In Work Environment For Staff As An Explanation For Variation In Central Line Bundle Compliance In Intensive Care Units., Yuna S.H. Lee, Patricia W. Stone, Monika Pogorzelska-Maziarz, Ingrid M. Nembhard

College of Nursing Faculty Papers & Presentations

BACKGROUND: Central line-associated bloodstream infections (CLABSIs) are a common and costly quality problem, and their prevention is a national priority. A decade ago, researchers identified an evidence-based bundle of practices that reduce CLABSIs. Compliance with this bundle remains low in many hospitals.

PURPOSE: The aim of this study was to assess whether differences in core aspects of work environments-workload, quality of relationships, and prioritization of quality-are associated with variation in maximal CLABSI bundle compliance, that is, compliance 95%-100% of the time in intensive care units (ICUs).

METHODOLOGY/APPROACH: A cross-sectional study of hospital medical-surgical ICUs in the United States was done. …

Opioid-Related Critical Care Resource Use In Us Children's Hospitals., Jason M. Kane, Jeffrey D. Colvin, Allison H. Bartlett, Matt Hall

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND AND OBJECTIVES: There has been a rapid increase in the rate of pediatric opioid-related hospitalizations. It is unknown how this increase has impacted the use of pediatric critical care. Our objective in this study was to assess the trends in pediatric hospitalization for opioid ingestions in a cohort of US children's hospitals and, specifically, to evaluate the impact on pediatric critical care resource use.

METHODS: A retrospective cohort study of the Pediatric Health Information System was performed to identify hospitalizations for opioid ingestions from 2004 to 2015. Admission to the PICU and the use of naloxone, vasopressors, and ventilation …

Sickle Cell Disease: Classification Of Clinical Complications And Approaches To Preventive And Therapeutic Management., Samir K. Ballas

Department of Medicine Faculty Papers

Sickle cell disease (SCD) is an inherited disorder of hemoglobin structure that has no established cure in adult patients. Cure has been achieved in selected children with sickle cell anemia (SCA) using allogeneic bone marrow transplantation or cord blood transplantation. SCD is essentially a triumvirate of (1) pain syndromes, (2) anemia and its sequelae and (3) organ failure, including infection. Pain, however, is the hallmark of SCD and dominates its clinical picture throughout the life of the patients. The prevalence of these complications varies with age from infancy through adult life. However, pain, infections and anemia requiring blood transfusion occur …

A Systematic Review Of Consumer Preference For E-Cigarette Attributes: Flavor, Nicotine Strength, And Type, Samane Zare, Mehdi Nemati, Yuqing Zheng

Agricultural Economics Faculty Publications

Objective

Systematic review of research examining consumer preference for the main electronic cigarette (e-cigarette) attributes namely flavor, nicotine strength, and type.

Method

A systematic search of peer-reviewed articles resulted in a pool of 12,933 articles. We included only articles that meet all the selection criteria: (1) peer-reviewed, (2) written in English, and (3) addressed consumer preference for one or more of the e-cigarette attributes including flavor, strength, and type.

Results

66 articles met the inclusion criteria for this review. Consumers preferred flavored e-cigarettes, and such preference varied with age groups and smoking status. We also found that several flavors were …

Cyclin D1-Mediated Microrna Expression Signature Predicts Breast Cancer Outcome, Guangxue Wang, Michael Gormley, Jing Qiao, Qian Zhao, Min Wang, Gabriele Disante, Shengqiong Deng, Lin Dong, Timothy G. Pestell, Xiaoming Ju, Mathew C. Casimiro, Sankar Addya, Adam Ertel, Ayden Tozeren, Qinchuan Li, Zuoren Yu, Richard G. Pestell

Department of Cancer Biology Faculty Papers

Background: Genetic classification of breast cancer based on the coding mRNA suggests the evolution of distinct subtypes. Whether the non-coding genome is altered concordantly with the coding genome and the mechanism by which the cell cycle directly controls the non-coding genome is poorly understood.

Methods: Herein, the miRNA signature maintained by endogenous cyclin D1 in human breast cancer cells was defined. In order to determine the clinical significance of the cyclin D1-mediated miRNA signature, we defined a miRNA expression superset from 459 breast cancer samples. We compared the coding and non-coding genome of breast cancer subtypes.

Results: Hierarchical clustering of …

Subclones Dominate At Mds Progression Following Allogeneic Hematopoietic Cell Transplant, Meagan A Jacoby, Eric J Duncavage, Gue Su Chang, Christopher A Miller, Jin Shao, Kevin Elliott, Joshua Robinson, Robert S Fulton, Catrina C Fronick, Michelle O'Laughlin, Sharon E Heath, Iskra Pusic, John S Welch, Daniel C Link, John F Dipersio, Peter Westervelt, Timothy J Ley, Timothy A Graubert, Matthew J Walter

Open Access Publications

Allogeneic hematopoietic cell transplantation (alloHCT) is a potentially curative treatment for myelodysplastic syndromes (MDS), but patients who relapse after transplant have poor outcomes. In order to understand the contribution of tumor clonal evolution to disease progression,we applied exome and error-corrected targeted sequencing coupled with copy number analysis to comprehensively define changes in the clonal architecture of MDS in response to therapy using 51 serially acquired tumor samples from 9 patients who progressed after an alloHCT. We show that small subclones before alloHCT can drive progression after alloHCT. Notably, at least one subclone expanded or emerged at progression in all patients. …

Physiological Mechanisms Of Sustained Fumagillin-Induced Weight Loss, Jie An, Michael L Patnode, Vanessa K Ridaura, Jeffrey I Gordon, Et Al

Open Access Publications

Current obesity interventions suffer from lack of durable effects and undesirable complications. Fumagillin, an inhibitor of methionine aminopeptidase-2, causes weight loss by reducing food intake, but with effects on weight that are superior to pair-feeding. Here, we show that feeding of rats on a high-fat diet supplemented with fumagillin (HF/FG) suppresses the aggressive feeding observed in pair-fed controls (HF/PF) and alters expression of circadian genes relative to the HF/PF group. Multiple indices of reduced energy expenditure are observed in HF/FG but not HF/PF rats. HF/FG rats also exhibit changes in gut hormones linked to food intake, increased energy harvest by …

Structure Of Full-Length Human Trpm4, Jingjing Duan, Zongli Li, Jian Li, Ana Santa-Cruz, Silvia Sanchez-Martinez, Jin Zhang, David E. Clapham

Molecular and Cellular Biochemistry Faculty Publications

Transient receptor potential melastatin subfamily member 4 (TRPM4) is a widely distributed, calcium-activated, monovalent-selective cation channel. Mutations in human TRPM4 (hTRPM4) result in progressive familial heart block. Here, we report the electron cryomicroscopy structure of hTRPM4 in a closed, Na⁺-bound, apo state at pH 7.5 to an overall resolution of 3.7 Å. Five partially hydrated sodium ions are proposed to occupy the center of the conduction pore and the entrance to the coiled-coil domain. We identify an upper gate in the selectivity filter and a lower gate at the entrance to the cytoplasmic coiled-coil domain. Intramolecular interactions exist …

Factors Associated With End-Of-Life Planning In Huntington Disease., Nancy R Downing, Siera Goodnight, Sena Chae, Joel S Perlmutter, Michael Mccormack, Elizabeth Hahn, Stacey K Barton, Noelle Carlozzi

Rowan-Virtua School of Osteopathic Medicine Departmental Research

OBJECTIVE: Knowledge of one's gene status for adult onset conditions provides opportunity to make advance end-of-life (EOL) plans. The purposes of these analyses were to (1) determine the prevalence of EOL plans, including advance directives (ADs) among persons across 3 stages of Huntington disease (HD) and (2) examine factors associated with having ADs in this sample.

METHODS: Data are from 503 participants in the HD Quality of Life study. Participants completed an online health-related quality-of-life survey that included questions regarding EOL planning and self-reported HD symptoms. Frequencies were calculated for EOL planning by the HD stage. Bivariate analysis and logistic …

Evaluating Cognition In Individuals With Huntington Disease: Neuroqol Cognitive Functioning Measures, Jin-Shei Lai, Siera Goodnight, Nancy R Downing, Rebecca E Ready, Jane S Paulsen, Anna L Kratz, Julie C Stout, Michael K Mccormack, David Cella, Christopher Ross, Jenna Russell, Noelle E Carlozzi

Rowan-Virtua School of Osteopathic Medicine Departmental Research

PURPOSE: Cognitive functioning impacts health-related quality of life (HRQOL) for individuals with Huntington disease (HD). The Neuro-QoL includes two patient-reported outcome (PRO) measures of cognition-Executive Function (EF) and General Concerns (GC). These measures have not previously been validated for use in HD. The purpose of this analysis is to evaluate the reliability and validity of the Neuro-QoL Cognitive Function measures for use in HD.

METHODS: Five hundred ten individuals with prodromal or manifest HD completed the Neuro-QoL Cognition measures, two other PRO measures of HRQOL (WHODAS 2.0 and EQ5D), and a depression measure (PROMIS Depression). Measures of functioning The Total …

Nutrient Intake In The First Two Weeks Of Life And Brain Growth In Preterm Neonates., Juliane Schneider, Céline J Fischer Fumeaux, Emma G Duerden, Ting Guo, Justin Foong, Myriam Bickle Graz, Patric Hagmann, M Mallar Chakravarty, Petra S Hüppi, Lydie Beauport, Anita C Truttmann, Steven P Miller

Brain and Mind Institute Researchers' Publications

BACKGROUND: Optimizing early nutritional intake in preterm neonates may promote brain health and neurodevelopment through enhanced brain maturation. Our objectives were (1) to determine the association of energy and macronutrient intake in the first 2 weeks of life with regional and total brain growth and white matter (WM) maturation, assessed by 3 serial MRI scans in preterm neonates; (2) to examine how critical illness modifies this association; and (3) to investigate the relationship with neurodevelopmental outcomes.

METHODS: Forty-nine preterm neonates (21 boys, median [interquartile range] gestational age: 27.6 [2.3] weeks) were scanned serially at the following median postmenstrual weeks: 29.4, …

The Long-Term Effect Of Erythropoiesis Stimulating Agents Given To Preterm Infants: A Proton Magnetic Resonance Spectroscopy Study On Neurometabolites In Early Childhood, Charles Gasparovic, Arvind Caprihan, Ronald A Yeo, John Phillips, Jean R Lowe, Richard Campbell, Robin K Ohls

Pediatrics Research and Scholarship

BACKGROUND: Erythropoiesis stimulating agents (ESAs) are neuroprotective in cell and animal models of preterm birth. Prematurity has been shown to alter neurometabolite levels in children in studies using proton magnetic resonance spectroscopy (1H-MRS).

OBJECTIVE: We hypothesized that ESA treatment in premature infants would tend to normalize neurometabolites by 4-6 years of age.

MATERIALS AND METHODS: Children in a longitudinal study of neurodevelopment underwent MRI and 1H-MRS at approximately 4 years and 6 years of age. Prematurely born children (500-1,250 g birth weight) received ESAs (erythropoietin or darbepoetin) or placebo during their neonatal hospitalization, and these groups were compared to healthy …

A Longitudinal Analysis Of The Impact Of Child Custody Loss On Drug Use And Crime Among A Sample Of African American Mothers, Kathi L. H. Harp, Carrie B. Oser

Health Management and Policy Faculty Publications

This study examines the influence of child custody loss on drug use and crime among a sample of African American mothers. Two types of custody loss are examined: informal custody loss (child living apart from mother but courts not involved), and official loss (child removed from mother’s care by authorities).

Methods—Using data from 339 African American women, longitudinal random coefficient models analyzed the effects of each type of custody loss on subsequent drug use and crime.

Results—Results indicated that both informal and official custody loss predicted increased drug use, and informal loss predicted increased criminal involvement. Findings demonstrate …

Conserved Brain Myelination Networks Are Altered In Alzheimer's And Other Neurodegenerative Diseases., Mariet Allen, Xue Wang, Jeremy D Burgess, Jens Watzlawik, Daniel J Serie, Curtis S Younkin, Thuy Nguyen, Kimberly G Malphrus, Sarah Lincoln, Minerva M Carrasquillo, Charlotte Ho, Paramita Chakrabarty, Samantha Strickland, Melissa E Murray, Vivek Swarup, Daniel H Geschwind, Nicholas T Seyfried, Eric B Dammer, James J Lah, Allan I Levey, Todd E Golde, Cory Funk, Hongdong Li, Nathan D Price, Ronald C Petersen, Neill R Graff-Radford, Steven G Younkin, Dennis W Dickson, Julia R Crook, Yan W Asmann, Nilüfer Ertekin-Taner

Articles, Abstracts, and Reports

INTRODUCTION: Comparative transcriptome analyses in Alzheimer's disease (AD) and other neurodegenerative proteinopathies can uncover both shared and distinct disease pathways.

METHODS: We analyzed 940 brain transcriptomes including patients with AD, progressive supranuclear palsy (PSP; a primary tauopathy), and control subjects.

RESULTS: We identified transcriptional coexpression networks implicated in myelination, which were lower in PSP temporal cortex (TCX) compared with AD. Some of these associations were retained even after adjustments for brain cell population changes. These TCX myelination network structures were preserved in cerebellum but they were not differentially expressed in cerebellum between AD and PSP. Myelination networks were downregulated in …

Effects Of Adjunctive Eslicarbazepine Acetate On Serum Lipids In Patients With Partial-Onset Seizures: Impact Of Concomitant Statins And Enzyme-Inducing Antiepileptic Drugs., Scott Mintzer, Robert T. Wechsler, Joanne B. Rogin, Barry E. Gidal, Matthias Schwab, Elinor Ben-Menachem, Mar Carreño, Patrício Soares Da Silva, Joana Moreira, Yan Li, David Blum, Todd Grinnell

Department of Neurology Faculty Papers

PURPOSE: To evaluate the effects of eslicarbazepine acetate (ESL) on lipid metabolism and to determine whether reduced statin exposure during ESL therapy has clinical consequences.

SUBJECTS AND METHODS: We conducted a post-hoc analysis of pooled data for serum lipids (laboratory values) from three phase III, multicenter, randomized, double-blind, placebo-controlled trials of adjunctive ESL therapy (400, 800, or 1200 mg once daily) in patients with treatment-refractory partial-onset seizures. Changes from baseline in serum lipid levels were analyzed according to use of statins and/or enzyme-inducing antiepileptic drugs (EIAEDs) during the baseline period.

KEY FINDINGS: In total, 426 and 1021 placebo- and ESL-treated …

Largest Gwas Of Ptsd (N=20 070) Yields Genetic Overlap With Schizophrenia And Sex Differences In Heritability., L E Duncan, A Ratanatharathorn, A E Aiello, L M Almli, A B Amstadter, A E Ashley-Koch, D G Baker, J C Beckham, L J Bierut, J Bisson, B Bradley, C-Y Chen, S Dalvie, L A Farrer, S Galea, M E Garrett, J E Gelernter, G Guffanti, M A Hauser, E O Johnson, R C Kessler, N A Kimbrel, A King, N Koen, H R Kranzler, M W Logue, A X Maihofer, A R Martin, M W Miller, R A Morey, N R Nugent, J P Rice, S Ripke, A L Roberts, N L Saccone, J W Smoller, D J Stein, M B Stein, J A Sumner, M Uddin, R J Ursano, D E Wildman, R Yehuda, H Zhao, M J Daly, I Liberzon, K J Ressler, C M Nievergelt, K C Koenen

Open Access Publications

The Psychiatric Genomics Consortium-Posttraumatic Stress Disorder group (PGC-PTSD) combined genome-wide case-control molecular genetic data across 11 multiethnic studies to quantify PTSD heritability, to examine potential shared genetic risk with schizophrenia, bipolar disorder, and major depressive disorder and to identify risk loci for PTSD. Examining 20 730 individuals, we report a molecular genetics-based heritability estimate (h

Assessment Of Data Transformations For Model-Based Clustering Of Rna-Seq Data., Janelle R. Noel-Macdonnell Phd, Joseph Usset, Ellen L. Goode, Brooke L. Fridley

Manuscripts, Articles, Book Chapters and Other Papers

Quality control, global biases, normalization, and analysis methods for RNA-Seq data are quite different than those for microarray-based studies. The assumption of normality is reasonable for microarray based gene expression data; however, RNA-Seq data tend to follow an over-dispersed Poisson or negative binomial distribution. Little research has been done to assess how data transformations impact Gaussian model-based clustering with respect to clustering performance and accuracy in estimating the correct number of clusters in RNA-Seq data. In this article, we investigate Gaussian model-based clustering performance and accuracy in estimating the correct number of clusters by applying four data transformations (i.e., naïve, …

Decision Aid Use During Post-Biopsy Consultations For Localized Prostate Cancer., Margaret Holmes-Rovner, Akshay Srikanth, Stephen G. Henry, Aisha Langford, David R. Rovner, Angela Fagerlin

Emergency Medicine Articles

BACKGROUND: Decision Aids (DAs) effectively translate medical evidence for patients but are not routinely used in clinical practice. Little is known about how DAs are used during patient-clinician encounters.

OBJECTIVE: To characterize the content and communicative function of high-quality DAs during diagnostic clinic visits for prostate cancer.

PARTICIPANTS: 252 men newly diagnosed with localized prostate cancer who had received a DA, 45 treating physicians at 4 US Veterans Administration urology clinics.

METHODS: Qualitative analysis of transcribed audio recordings was used to inductively develop categories capturing content and function of all direct references to DAs (booklet talk). The presence or absence …

Word-List Intrusion Errors Predict Progression To Mild Cognitive Impairment, Kelsey R Thomas, Joel Eppig, Emily C Edmonds, Diane M Jacobs, David J Libon, Rhoda Au, David P Salmon, Mark W Bondi, Alzheimer’S Disease Neuroimaging Initiative

Rowan-Virtua School of Osteopathic Medicine Departmental Research

OBJECTIVE: Preclinical Alzheimer's disease (AD) defined by a positive AD biomarker in the presence of normal cognition is presumed to precede mild cognitive impairment (MCI). Subtle cognitive deficits and cognitive inefficiencies in preclinical AD may be detected through process and error scores on neuropsychological tests in those at risk for progression to MCI.

METHOD: Cognitively normal participants (n = 525) from the Alzheimer's Disease Neuroimaging Initiative were followed for up to 5 years and classified as either stable normal (n = 305) or progressed to MCI (n = 220). Cox regressions were used to determine whether baseline process scores on …

Auditing Snomed Ct Hierarchical Relations Based On Lexical Features Of Concepts In Non-Lattice Subgraphs, Licong Cui, Olivier Bodenreider, Jay Shi, Guo-Qiang Zhang

Computer Science Faculty Publications

Objective—We introduce a structural-lexical approach for auditing SNOMED CT using a combination of non-lattice subgraphs of the underlying hierarchical relations and enriched lexical attributes of fully specified concept names. Our goal is to develop a scalable and effective approach that automatically identifies missing hierarchical IS-A relations.

Methods—Our approach involves 3 stages. In stage 1, all non-lattice subgraphs of SNOMED CT’s IS-A hierarchical relations are extracted. In stage 2, lexical attributes of fully-specified concept names in such non-lattice subgraphs are extracted. For each concept in a non-lattice subgraph, we enrich its set of attributes with attributes from its ancestor …

Genome-Wide Interactions With Dairy Intake For Body Mass Index In Adults Of European Descent, Caren E. Smith, Jack L. Follis, Hassan S. Dashti, Toshiko Tanaka, Mariaelisa Graff, Amanda M. Fretts, Tuomas O. Kilpeläinen, Mary K. Wojczynski, Kris Richardson, Mike A. Nalls, Christina-Alexandra Schulz, Yongmei Liu, Alexis C. Frazier-Wood, Esther Van Eekelen, Carol Wang, Paul S. De Vries, Vera Mikkilä, Rebecca Rohde, Bruce M. Psaty, Torben Hansen, Mary F. Feitosa, Chao-Qiang Lai, Denise K. Houston, Luigi Ferruci, Ulrika Ericson, Zhe Wang, Renée De Mutsert, Wendy H. Oddy, Ester A. L. De Jonge, Ilkka Seppälä, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

Scope: Body weight responds variably to the intake of dairy foods. Genetic variation may contribute to inter‐individual variability in associations between body weight and dairy consumption.

Methods and results: A genome‐wide interaction study to discover genetic variants that account for variation in BMI in the context of low‐fat, high‐fat and total dairy intake in cross‐sectional analysis was conducted. Data from nine discovery studies (up to 25 513 European descent individuals) were meta‐analyzed. Twenty‐six genetic variants reached the selected significance threshold (p‐interaction <10⁻⁷⁾, and six independent variants (LINC01512‐rs7751666, PALM2/AKAP2‐rs914359, ACTA2‐rs1388, PPP1R12A‐rs7961195, LINC00333‐rs9635058, …