Medicine and Health Sciences Commons^™

Chronic Obstructive Pulmonary Disease: Thoracic Ct Texture Analysis And Machine Learning To Predict Pulmonary Ventilation, Andrew Westcott, Dante P I Capaldi, David G Mccormack, Aaron D Ward, Aaron Fenster, Grace Parraga

Medical Biophysics Publications

Background Fixed airflow limitation and ventilation heterogeneity are common in chronic obstructive pulmonary disease (COPD). Conventional noncontrast CT provides airway and parenchymal measurements but cannot be used to directly determine lung function. Purpose To develop, train, and test a CT texture analysis and machine-learning algorithm to predict lung ventilation heterogeneity in participants with COPD. Materials and Methods In this prospective study (

Hyperpolarized Helium 3 Mri In Mild-To-Moderate Asthma: Prediction Of Postbronchodilator Reversibility, Rachel L Eddy, Sarah Svenningsen, Christopher Licskai, David G Mccormack, Grace Parraga

Medical Biophysics Publications

Background: Longitudinal progression to irreversible airflow limitation occurs in approximately 10% of patients with asthma, but it is difficult to identify patients who are at risk for this transition.

Purpose: To investigate 6-year longitudinal changes in hyperpolarized helium 3 (3He) MRI ventilation defects in study participants with mild-to-moderate asthma and identify predictors of longitudinal changes in postbronchodilator forced expiratory volume in 1 second (FEV1) reversibility

Materials and Methods: Spirometry and hyperpolarized 3He MRI were evaluated in participants with mild-to-moderate asthma in two prospectively planned visits approximately 6 years apart. Participants underwent methacholine challenge at baseline (January 2010 to April 2011) …

Rheumatoid Arthritis-Relevant Dna Methylation Changes Identified In Acpa-Positive Asymptomatic Individuals Using Methylome Capture Sequencing., Xiaojian Shao, Marie Hudson, Ines Colmegna, Celia M T Greenwood, Marvin J. Fritzler, Philip Awadalla, T Pastinen, Sasha Bernatsky

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: To compare DNA methylation in subjects positive vs negative for anti-citrullinated protein antibodies (ACPA), a key serological marker of rheumatoid arthritis (RA) risk.

METHODS: With banked serum from a random subset (N = 3600) of a large general population cohort, we identified ACPA-positive samples and compared them to age- and sex-matched ACPA-negative controls. We used a custom-designed methylome panel to conduct targeted bisulfite sequencing of 5 million CpGs located in regulatory or hypomethylated regions of DNA from whole blood (red blood cell lysed). Using binomial regression models, we investigated the differentially methylated regions (DMRs) between ACPA-positive vs ACPA-negative subjects. …

Assessment Of Physical Fitness After Bariatric Surgery And Its Association With Protein Intake And Type Of Cholecalciferol Supplementation, Hendrika J M Smelt, Sjaak Pouwels, Alper Celik, Adarsh Gupta, Johannes F Smulders

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Background: Several studies showed that there is a relationship between vitamin and mineral status and muscle strength. In particular this is the case for handgrip strength (HS) and vitamin D deficiency. In bariatric surgery there is a risk of decrease in muscle strength after surgery and also vitamin and mineral deficiencies are not uncommon. The aim of this study is to assess the effect of low vitamin 25 (OH) cholecalciferol levels, high dose cholecalciferol supplementation regime and protein intake on physical fitness, measured using handgrip strength (HS) and the shuttle walk run test (SWRT). Methods: For this retrospective …

Splice-Altering Variant In Col11a1 As A Cause Of Nonsyndromic Hearing Loss Dfna37., Kevin T. Booth, James W. Askew, Zohreh Talebizadeh, Patrick L M Huygen, James Eudy, Judith Kenyon, Denise Hoover, Michael S. Hildebrand, Katherine R. Smith, Melanie Bahlo, William J. Kimberling, Richard J H Smith, Hela Azaiez, Shelley D. Smith

Manuscripts, Articles, Book Chapters and Other Papers

PURPOSE: The aim of this study was to determine the genetic cause of autosomal dominant nonsyndromic hearing loss segregating in a multigenerational family.

METHODS: Clinical examination, genome-wide linkage analysis, and exome sequencing were carried out on the family.

RESULTS: Affected individuals presented with early-onset progressive mild hearing impairment with a fairly flat, gently downsloping or U-shaped audiogram configuration. Detailed clinical examination excluded any additional symptoms. Linkage analysis detected an interval on chromosome 1p21 with a logarithm of the odds (LOD) score of 8.29: designated locus DFNA37. Exome sequencing identified a novel canonical acceptor splice-site variant c.652-2A>C in the COL11A1 …

Dissecting Features Of Epigenetic Variants Underlying Cardiometabolic Risk Using Full-Resolution Epigenome Profiling In Regulatory Elements., Fiona Allum, Åsa K. Hedman, Xiaojian Shao, Warren A. Cheung, Jinchu Vijay, Frédéric Guénard, Tony Kwan, Marie-Michelle Simon, Bing Ge, Cristiano Moura, Elodie Boulier, Lars Rönnblom, Sasha Bernatsky, Mark Lathrop, Mark I. Mccarthy, Panos Deloukas, André Tchernof, T Pastinen, Marie-Claude Vohl, Elin Grundberg

Manuscripts, Articles, Book Chapters and Other Papers

Sparse profiling of CpG methylation in blood by microarrays has identified epigenetic links to common diseases. Here we apply methylC-capture sequencing (MCC-Seq) in a clinical population of ~200 adipose tissue and matched blood samples (Ntotal~400), providing high-resolution methylation profiling (>1.3 M CpGs) at regulatory elements. We link methylation to cardiometabolic risk through associations to circulating plasma lipid levels and identify lipid-associated CpGs with unique localization patterns in regulatory elements. We show distinct features of tissue-specific versus tissue-independent lipid-linked regulatory regions by contrasting with parallel assessments in ~800 independent adipose tissue and blood samples from the general population. We follow-up …

Saturated Fatty Acid Activates T Cell Inflammation Through A Nicotinamide Nucleotide Transhydrogenase (Nnt)-Dependent Mechanism, Grace Mccambridge, Madhur Agrawal, Alanna Keady, Philip A. Kern, Hatice Hasturk, Barbara S. Nikolajczyk, Leena P. Bharath

Pharmacology and Nutritional Sciences Faculty Publications

Circulating fatty acids (FAs) increase with obesity and can drive mitochondrial damage and inflammation. Nicotinamide nucleotide transhydrogenase (NNT) is a mitochondrial protein that positively regulates nicotinamide adenine dinucleotide phosphate (NADPH), a key mediator of energy transduction and redox homeostasis. The role that NNT-regulated bioenergetics play in the inflammatory response of immune cells in obesity is untested. Our objective was to determine how free fatty acids (FFAs) regulate inflammation through impacts on mitochondria and redox homeostasis of peripheral blood mononuclear cells (PBMCs). PBMCs from lean subjects were activated with a T cell-specific stimulus in the presence or absence of generally pro-inflammatory …

Oscillometry And Pulmonary Magnetic Resonance Imaging In Asthma And Copd, Rachel L Eddy, Andrew Westcott, Geoffrey N Maksym, Grace Parraga, Ronald J Dandurand

Medical Biophysics Publications

Developed over six decades ago, pulmonary oscillometry has re-emerged as a noninvasive and effort-independent method for evaluating respiratory-system impedance in patients with obstructive lung disease. Here, we evaluated the relationships between hyperpolarized

Optimum Recording Time Of Routine Electroencephalogram For Adults With Epilepsy*, Kemal Tutkavul, Yilmaz Çeti̇nkaya

Turkish Journal of Medical Sciences

Background/aim: This study aimed to reveal the optimum recording time of routine electroencephalogram (EEG) for adults with epilepsy.Materials and methods: In this clinical observational study we investigated features of paroxysms that emerged in EEGs recorded for 45 min in adults with epilepsy.Results: Paroxysms were detected in 38.14% of 97 patients. The probability of occurrence of paroxysm during the first 10 min was found to be statistically significantly low in comparison to the first 30 and 45 min (respectively P = 0.004, P = 0.0001). This probability was found to increase insignificantly when comparing the first 20 min with the first …

Genomic Prediction Of Relapse In Recipients Of Allogeneic Haematopoietic Stem Cell Transplantation., J Ritari, K Hyvärinen, S Koskela, M Itälä-Remes, R Niittyvuopio, A Nihtinen, U Salmenniemi, M Putkonen, L Volin, T Kwan, T Pastinen, J Partanen

Manuscripts, Articles, Book Chapters and Other Papers

Allogeneic haematopoietic stem cell transplantation currently represents the primary potentially curative treatment for cancers of the blood and bone marrow. While relapse occurs in approximately 30% of patients, few risk-modifying genetic variants have been identified. The present study evaluates the predictive potential of patient genetics on relapse risk in a genome-wide manner. We studied 151 graft recipients with HLA-matched sibling donors by sequencing the whole-exome, active immunoregulatory regions, and the full MHC region. To assess the predictive capability and contributions of SNPs and INDELs, we employed machine learning and a feature selection approach in a cross-validation framework to discover the …