bluuebunny/crossref_metadata_2025_split huggingface dataset:
Studying the Genetics of Complex Disease With Ancestry‐Specific Human Phenotype Networks: The Case of Type 2 Diabetes in East Asian Populations
Authors: Qiu Jingya , Moore Jason H. , Darabos Christian 
Published: April 2016

ABSTRACTGenome‐wide association studies (GWAS) have led to the discovery of over 200 single nucleotide polymorphisms (SNPs) associated with type 2 diabetes mellitus (T2DM). Additionally, East Asians develop T2DM at a higher rate, younger age, and lower body mass index than their European ancestry counterparts. The reason behind this occurrence remains elusive. With comprehensive searches through the National Human Genome Research Institute (NHGRI) GWAS catalog literature, we compiled a database of 2,800 ancestry‐specific SNPs associated with T2DM and 70 other related traits. Manual data extraction was necessary because the GWAS catalog reports statistics such as odds ratio and P‐value, but does not consistently include ancestry information. Currently, many statistics are derived by combining initial and replication samples from study populations of mixed ancestry. Analysis of all‐inclusive data can be misleading, as not all SNPs are transferable across diverse populations. We used ancestry data to construct ancestry‐specific human phenotype networks (HPN) centered on T2DM. Quantitative and visual analysis of network models reveal the genetic disparities between ancestry groups. Of the 27 phenotypes in the East Asian HPN, six phenotypes were unique to the network, revealing the underlying ancestry‐specific nature of some SNPs associated with T2DM. We studied the relationship between T2DM and five phenotypes unique to the East Asian HPN to generate new interaction hypotheses in a clinical context. The genetic differences found in our ancestry‐specific HPNs suggest different pathways are involved in the pathogenesis of T2DM among different populations. Our study underlines the importance of ancestry in the development of T2DM and its implications in pharmocogenetics and personalized medicine.
Review of the Gene‐Environment Interaction Literature in Cancer: What Do We Know?
Authors: Simonds Naoko I. , Ghazarian Armen A. , Pimentel Camilla B. , Schully Sheri D. , Ellison Gary L. , Gillanders Elizabeth M. , Mechanic Leah E. 
Published: April 2016

ABSTRACTBackgroundRisk of cancer is determined by a complex interplay of genetic and environmental factors. Although the study of gene‐environment interactions (G×E) has been an active area of research, little is reported about the known findings in the literature.MethodsTo examine the state of the science in G×E research in cancer, we performed a systematic review of published literature using gene‐environment or pharmacogenomic flags from two curated databases of genetic association studies, the Human Genome Epidemiology (HuGE) literature finder and Cancer Genome‐Wide Association and Meta Analyses Database (CancerGAMAdb), from January 1, 2001, to January 31, 2011. A supplemental search using HuGE was conducted for articles published from February 1, 2011, to April 11, 2013. A 25% sample of the supplemental publications was reviewed.ResultsA total of 3,019 articles were identified in the original search. From these articles, 243 articles were determined to be relevant based on inclusion criteria (more than 3,500 interactions). From the supplemental search (1,400 articles identified), 29 additional relevant articles (1,370 interactions) were included. The majority of publications in both searches examined G×E in colon, rectal, or colorectal; breast; or lung cancer. Specific interactions examined most frequently included environmental factors categorized as energy balance (e.g., body mass index, diet), exogenous (e.g., oral contraceptives) and endogenous hormones (e.g., menopausal status), chemical environment (e.g., grilled meats), and lifestyle (e.g., smoking, alcohol intake). In both searches, the majority of interactions examined were using loci from candidate genes studies and none of the studies were genome‐wide interaction studies (GEWIS). The most commonly reported measure was the interaction P‐value, of which a sizable number of P‐values were considered statistically significant (i.e., <0.05). In addition, the magnitude of interactions reported was modest.ConclusionObservations of published literature suggest that opportunity exists for increased sample size in G×E research, including GWAS‐identified loci in G×E studies, exploring more GWAS approaches in G×E such as GEWIS, and improving the reporting of G×E findings.
Across‐Platform Imputation of DNA Methylation Levels Incorporating Nonlocal Information Using Penalized Functional Regression
Authors: Zhang Guosheng , Huang Kuan‐Chieh , Xu Zheng , Tzeng Jung‐Ying , Conneely Karen N. , Guan Weihua , Kang Jian , Li Yun 
Published: April 2016

ABSTRACTDNA methylation is a key epigenetic mark involved in both normal development and disease progression. Recent advances in high‐throughput technologies have enabled genome‐wide profiling of DNA methylation. However, DNA methylation profiling often employs different designs and platforms with varying resolution, which hinders joint analysis of methylation data from multiple platforms. In this study, we propose a penalized functional regression model to impute missing methylation data. By incorporating functional predictors, our model utilizes information from nonlocal probes to improve imputation quality. Here, we compared the performance of our functional model to linear regression and the best single probe surrogate in real data and via simulations. Specifically, we applied different imputation approaches to an acute myeloid leukemia dataset consisting of 194 samples and our method showed higher imputation accuracy, manifested, for example, by a 94% relative increase in information content and up to 86% more CpG sites passing post‐imputation filtering. Our simulated association study further demonstrated that our method substantially improves the statistical power to identify trait‐associated methylation loci. These findings indicate that the penalized functional regression model is a convenient and valuable imputation tool for methylation data, and it can boost statistical power in downstream epigenome‐wide association study (EWAS).
Testing Allele Transmission of an SNP Set Using a Family‐Based Generalized Genetic Random Field Method
Authors: Li Ming , Li Jingyun , He Zihuai , Lu Qing , Witte John S. , Macleod Stewart L. , Hobbs Charlotte A. , Cleves Mario A. ,   the National Birth Defects Prevention Study
Published: April 2016

ABSTRACTFamily‐based association studies are commonly used in genetic research because they can be robust to population stratification (PS). Recent advances in high‐throughput genotyping technologies have produced a massive amount of genomic data in family‐based studies. However, current family‐based association tests are mainly focused on evaluating individual variants one at a time. In this article, we introduce a family‐based generalized genetic random field (FB‐GGRF) method to test the joint association between a set of autosomal SNPs (i.e., single‐nucleotide polymorphisms) and disease phenotypes. The proposed method is a natural extension of a recently developed GGRF method for population‐based case‐control studies. It models offspring genotypes conditional on parental genotypes, and, thus, is robust to PS. Through simulations, we presented that under various disease scenarios the FB‐GGRF has improved power over a commonly used family‐based sequence kernel association test (FB‐SKAT). Further, similar to GGRF, the proposed FB‐GGRF method is asymptotically well‐behaved, and does not require empirical adjustment of the type I error rates. We illustrate the proposed method using a study of congenital heart defects with family trios from the National Birth Defects Prevention Study (NBDPS).
Performance of iron ore oxygen carrier modified by biomass ashes in coal‐fueled chemical looping combustion
Authors: Zhang Shuai , Xiao Rui 
Published: April 2016

AbstractThe modification of oxygen carrier by low‐cost biomass ash shows great potential to reduce the economic and environmental costs associated with oxygen carrier preparation and biomass ash disposal. In this study, three biomass ashes ‒ a wheat stalk ash (WSA), a corn stalk ash (CSA), and a soybean stalk ash (SSA) ‒ were selected as the modifiers to evaluate their potential to improve the reactivity of a iron ore produced from the Mining Area C (MAC) of Western Australia. A lignite coal ash‐modified MAC iron ore was also prepared to make a comparison. The reactivity performance of ash‐modified samples and the cyclic behavior of the selected best candidate were evaluated in a laboratory‐scale fluidized‐bed reactor system with coal as fuel. The results showed that MAC iron ore loaded with different ashes showed different degrees of improvement in its reactivity. SSA‐modified MAC iron ore behaved the best due to the highest K2O content and the total contents of K2O, CaO, and Na2O in SSA as well as its great resistance to melting. The higher loading content of SSA in MAC iron ore resulted in more coal gasification products converted to CO2 and H2O at a faster reaction rate. The cyclic test of MAC‐20SSA showed that it performed well both in its reactivity and physical structure. Stable outlet gas concentrations were achieved and MAC‐20SSA exhibited good resistance to sintering. It can be inferred that SSA is a promising low‐cost modifying agent to enhance the performance of oxygen carrier while reducing the environmental impact associated with its disposal. © 2016 Society of Chemical Industry and John Wiley & Sons, Ltd
Personality and reported quality of life in Parkinson's disease
Authors: Pontone Gregory M. , Mari Zoltan , Perepezko Kate , Weiss Howard D , Bassett Susan S 
Published: April 2016

ObjectivePersonality affects an individual's ability to cope with the burden of chronic disease. However, the impact of personality on quality of life (QoL) in Parkinson's disease (PD) is not well characterized. The goal of this study is to determine the effect of personality on QoL in PD.MethodsThe study included 92 patients with idiopathic PD from Baltimore‐Washington area movement disorder neurology clinics. QoL was assessed using the 37‐item Parkinson's disease Quality of Life Questionnaire (PDQL) total score, and the Neuroticism–Extraversion–Openness Inventory was used to determine personality traits.ResultsStep‐wise regression models examined the contribution of personality, depression, demographic, and PD variables on PDQL‐assessed QoL. Neuroticism, conscientiousness, years of education, and depression explained 42% of the variance in the PDQL total score after adjusting for other disease variables. High neuroticism (β = −0.727, 95% confidence interval (CI) −1.125, −0.328, p < 0.0001) and depression (β = −9.058, 95%CI −17.46, −0.657, p = 0.035) negatively affected the PDQL, while high conscientiousness (β = 0.468, 95%CI 0.078, 0.858, p = 0.019), and years of education (β = 1.441, 95%CI 0.371, 2.510, p = 0.009) were positive factors.ConclusionsPersonality can have a positive or negative influence on QoL in PD. PD patients with otherwise similar disease burdens and depressive symptoms may experience different levels of QoL depending on the level of neurotic or conscientious personality traits. Therefore, when interpreting patient responses on the PDQL, it is important to understand whether they reflect aspects of PD, that is, motor impairment and depression, which are amenable to treatment or whether they reflect personality traits.
Perceived stress and cognitive function in older adults: which aspect of perceived stress is important?
Authors: Korten Nicole C.M. , Comijs Hannie C. , Penninx Brenda W.J.H. , Deeg Dorly J.H. 
Published: April 2016

ObjectiveFew studies examined the association between perceived stress and cognitive function in older adults. This study will examine which aspects of perceived stress especially impact cognitive function.MethodsCross‐sectional data of 1099 older adults between 64 and 100 years from the Longitudinal Aging Study Amsterdam were used. Perceived stress and its subscales perceived helplessness and perceived self‐efficacy were measured with the Perceived Stress Scale. Cognitive function was assessed regarding memory, processing speed and executive function. Univariate and multivariate linear regression analyses were performed between the stress measures and the domains of cognitive function.ResultsPerceived stress was associated with worse processing speed, direct and delayed recall, semantic fluency and digit span backwards (rangeβ = −0.10; −0.11;p < 0.01). The subscale perceived helplessness showed negative associations only with processing speed (β = −0.06,p < 0.05) and delayed recall (β = −0.06,p < 0.05), which became nonsignificant after the adjustment for depressive symptoms or sense of mastery. The subscale perceived self‐efficacy was significantly associated with better cognitive function, also after adjustment for depressive symptoms or sense of mastery (rangeβ = 0.10; 0.18;p < 0.01).ConclusionsIn older adults, especially perceived self‐efficacy showed independent associations with a broad range of cognitive functions. Perceived self‐efficacy might be an important factor in reducing stress and the prevention of cognitive decline. Copyright © 2016 John Wiley & Sons, Ltd.
Alteration of the regional cerebral glucose metabolism in healthy subjects by glucose loading
Authors: Ishibashi Kenji , Wagatsuma Kei , Ishiwata Kiichi , Ishii Kenji 
Published: April 2016

AbstractHigh plasma glucose (PG) levels can reduce fluorine‐18‐labeled fluorodeoxyglucose (18F‐FDG) uptake, especially in the Alzheimer's disease (AD)‐related regions. This fact is supported by studies showing that the resting‐state activity in diabetes can be altered in the default mode network (DMN)‐related regions, which considerably overlap with the AD‐related regions. In order to expand the current knowledge, we aimed to investigate the relationship between increasing PG levels and the regional cerebral metabolic rates for glucose (CMRglc) as a direct index of brain activity. We performed dynamic 18F‐FDG positron emission tomography with arterial blood sampling once each in the fasting and glucose‐loading conditions on 12 young, healthy volunteers without cognitive impairment or insulin resistance. The absolute CMRglc values were calculated for the volume‐of‐interest (VOI) analysis, and normalized CMRglc maps were generated for the voxelwise analysis. The normalized measurement is known to have smaller intersubject variability than the absolute measurement, and may, thus, lead to greater statistical power. In VOI analysis, no regional difference in the CMRglc was found between the two conditions. In exploratory voxelwise analysis, however, significant clusters were identified in the precuneus, posterior cingulate, lateral parietotemporal, and medial prefrontal regions where the CMRglc decreased upon glucose loading (P < 0.05, corrected). These regions include the representative components of both the DMN and AD pathology. Taken together with the previous knowledge on the relationships between the DMN, AD, and diabetes, it may be inferred that glucose loading induces hypometabolism in the AD‐related and DMN‐related regions. Hum Brain Mapp 37:2823–2832, 2016. © 2016 Wiley Periodicals, Inc.
Who Gained Insurance Coverage in 2014, the First Year of Full ACA Implementation?
Authors: Courtemanche Charles , Marton James , Yelowitz Aaron 
Published: April 2016

AbstractThe most significant pieces of the Affordable Care Act (exchanges, subsidies, Medicaid expansion, and individual mandate), implemented in 2014, were associated with sizable gains in coverage nationally that were divided equally between gains in Medicaid and private coverage. These national trends mask heterogeneity in gains by state Medicaid expansion status, age, income level, and source of coverage. © 2016 The Authors. Health Economics published by John Wiley & Sons Ltd.
Concurrent cetuximab and postoperative radiation in resected high‐risk squamous cell carcinomas of the head and neck: A single‐institution experience
Authors: Araki Daisuke , Redman Mary W. , Martins Renato , Eaton Keith , Baik Christina , Chow Laura , Goulart Bernardo , Lee Sylvia , Santana–Davila Rafael , Liao Jay , Parvathaneni Upendra , Laramore George , Futran Neal , Mendez Eduardo , Bhrany Amit , Rodriguez Cristina P. 
Published: April 2016

AbstractBackgroundPostoperative cisplatin and radiation is the standard of care for high‐risk squamous cell carcinoma of the head and neck (SCCHN). We have used cetuximab and radiation in the postoperative setting for patients deemed poor candidates for cisplatin.MethodsWe retrospectively identified 40 patients who received cetuximab and radiation for resected locoregionally advanced SCCHN between 2006 and 2013 at our institution.ResultsThe 2‐year Kaplan–Meier estimates were: overall survival (OS) 41%, recurrence‐free survival (RFS) 34%, locoregional control 63%, and distant metastatic control 59%. Eastern Cooperative Oncology Group (ECOG) performance status ≥1 predicted for inferior OS (hazard ratio [HR] = 5.43; p = .003), RFS (HR = 4.07; p = .007), and locoregional control (HR = 4.92; p = .04) in multivariate analysis.ConclusionPatients with resected high‐risk SCCHN treated with postoperative cetuximab and radiation have suboptimal therapeutic outcomes. Further study of the efficacy and cost‐effectiveness compared to radiation alone is warranted. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1318–1323, 2016
Prognostic role of the Bethesda System for conventional papillary thyroid carcinoma
Authors: Gweon Hye Mi , Koo Hye Ryoung , Son Eun Ju , Kim Jeong‐Ah , Youk Ji Hyun , Hong Soon Won , Lim Beom Jin 
Published: April 2016

AbstractBackgroundThe purpose of this study was to investigate the role of the Bethesda System for Reporting Thyroid Cytopathology (BSRTC) as a prognostic marker in conventional papillary thyroid carcinoma (PTC).MethodsA total of 397 patients who underwent ultrasound‐guided fine‐needle aspiration biopsy (FNAB) and surgery for conventional PTCs were enrolled. The association between the Bethesda category and histopathologic result was evaluated.ResultsAmong the Bethesda categories, a significant difference was found in the presence of extrathyroidal extension (Bethesda category III, 3.2% [7 of 220]; category V, 19.1% [42 of 220]; and category VI, 77.7% [171 of 220]; p < .001) and lymph node metastasis (Bethesda category III, 3.8% [6 of 156]; category V, 16.7% [26 of 156]; and category VI, 79.5% [124 of 156]; p < .001). Multivariate analysis showed that the Bethesda category was independently predictive of extrathyroidal extension (p = .013) and lymph node metastasis (p = .035).ConclusionConventional PTC with a higher Bethesda category at the time of cytology diagnosis would be poor prognosis. © 2016 Wiley Periodicals, Inc. Head Neck 38: First–1514, 2016
Successful intraoperative electrophysiologic monitoring of the recurrent laryngeal nerve, a multidisciplinary approach: The Massachusetts Eye and Ear Infirmary monitoring collaborative protocol with experience in over 3000 cases
Authors: Macias Alvaro A. , Eappen Sunil , Malikin Ilya , Goldfarb Jeremy , Kujawa Sharon , Konowitz Paul M. , Kamani Dipti , Randolph Gregory W. 
Published: April 2016

AbstractBackgroundAlthough intraoperative nerve monitoring (IONM) is utilized increasingly, the information on the related anesthesia technique is limited. This study presents an up‐to‐date clinical algorithm, including setup and troubleshooting of an IONM system, endotracheal tube placement, and anesthetic parameters. To our knowledge, this is the first interdisciplinary collaborative protocol for monitored neck surgery based on the published evidence and clinical experience.MethodsThe Departments of Otolaryngology Head and Neck Surgery, Anesthesiology, and Audiology collaboratively developed a protocol for IONM of the recurrent laryngeal nerve (RLN) based on published evidence and our experience with 3000 patients over a 16‐year period.ResultsNo complications related to monitoring or endotracheal tube placement were noted when the IONM protocol was implemented at Massachusetts Eye and Ear Infirmary (MEEI). The IONM protocol has proven to be vital in standardizing care and in avoiding intraoperative errors.ConclusionAn IONM system entails an anesthesiologist who understands the challenges posed by this technique; muscle relaxation must be minimized/eliminated to optimize IONM. © 2016 Wiley Periodicals, Inc. Head Neck 38: First–1494, 2016
Clinical outcomes of patients with hypercalcitoninemia after initial treatment for medullary thyroid cancer and postoperative serum calcitonin cutoffs for predicting structural recurrence
Authors: Cho Yoon Young , Jang Hye Won , Jang Ju Young , Kim Tae Hyuk , Choe Jun‐Ho , Kim Jung‐Han , Kim Jee Soo , Kim Sun Wook , Chung Jae Hoon 
Published: April 2016

AbstractBackgroundPersistent hypercalcitoninemia is reported in 40% to 60% of patients with medullary thyroid cancer (MTC) after initial therapy, but their clinical outcomes have not been clearly studied. We evaluated the outcomes of MTC with hypercalcitoninemia and assessed the cutoffs of postoperative serum calcitonin for predicting structural recurrence.MethodsA dynamic risk assessment system was used to categorize clinical outcomes in this retrospective study. Receiver operating characteristic (ROC) curve analysis was used to calculate the calcitonin cutoffs for predicting structural recurrence.ResultsAmong 120 patients operated on, 30 (25%) had persistent hypercalcitoninemia. Of that group, 18 (60%) had biochemical persistent disease and 11 (37%) developed structural identified disease, including 1 death (3%). Postoperative calcitonin <29 pg/mL predicted structural disease with 100% sensitivity, 90.5% specificity, and 100% negative predictive value.ConclusionOne third of the patients with MTC with hypercalcitoninemia experienced structural recurrence, and postoperative basal serum calcitonin might be a simple tumor marker to predict structural recurrence. © 2016 Wiley Periodicals, Inc. Head Neck 38: First–1508, 2016
Not very NICE: deviance, stigma and nutritional guidelines related to healthy weight and obesity
Authors: Hann Alison , Frawley Ashley , Spedding Gillian 
Published: April 2016

SummaryThis paper critically examines the current National Institute for Health and Clinical Excellence and National Health Service guidelines on weight management and the avoidance of obesity (NG7). We demonstrate that the guidance is unlikely to produce the desired effect of enabling people to reduce or control their weight through the twin strategies of dieting (primarily using the calories‐in, calories‐out approach) and increasing their levels of exercise. The paper provides a critical examination of these guidelines and concludes that they are unlikely to encourage maintenance of ‘healthy’ weights or prevent obesity, are not based upon particularly strong evidence and are misguided in maintaining a persistent focus upon weight rather than other indicators of health. Moreover, we suggest their promotion may produce a number of unintended consequences, including perpetuating body‐related stigmatisation and anxieties. Copyright © 2016 John Wiley & Sons, Ltd.