bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasma amyloid β levels are driven by genetic variants nearAPOE, BACE1, APP, PSEN2:A genome-wide association study in over 12,000 non-demented participants
Authors: Damotte Vincent , van der Lee Sven J , Chouraki Vincent , Grenier-Boley Benjamin , Simino Jeannette , Adams Hieab , Tosto Giuseppe , White Charles , Terzikhan Natalie , Cruchaga Carlos , Knol Maria J. , Li Shuo , Schraen Susanna , Grove Megan L. , Satizabal Claudia , Amin Najaf , Berr Claudine , Younkin Steven ,   Alzheimer’s Disease Neuroimaging Initiative, Gottesman Rebecca F. , Buée Luc , Beiser Alexa , Knopman David S. , Uitterlinden Andre , DeCarli Charles , Bressler Jan , DeStefano Anita , Dartigues Jean-François , Yang Qiong , Boerwinkle Eric , Tzourio Christophe , Fornage Myriam , Ikram M Arfan , Amouyel Philippe , de Jager Phil , Reitz Christiane , Mosley Thomas H , Lambert Jean-Charles , Seshadri Sudha , van Duijn Cornelia 
Published: September 2017

AbstractINTRODUCTIONThere is increasing interest in plasma Aβ as an endophenotype and biomarker of Alzheimer’s disease (AD). Identifying the genetic determinants of plasma Aβ levels may elucidate important processes that determine plasma Aβ measures.METHODSWe included 12,369 non-demented participants derived from eight population-based studies. Imputed genetic data and plasma Aβ1-40, Aβ1-42 levels and Aβ1-42/Aβ1-40 ratio were used to perform genome-wide association studies, gene-based and pathway analyses. Significant variants and genes were followed-up for the association with PET Aβ deposition and AD risk.RESULTSSingle-variant analysis identified associations acrossAPOEfor Aβ1-42 and Aβ1-42/Aβ1-40 ratio, andBACE1for Aβ1-40. Gene-based analysis of Aβ1-40 additionally identified associations forAPP,PSEN2,CCKandZNF397. There was suggestive interaction between aBACE1variant andAPOEε4 on brain Aβ deposition.DISCUSSIONIdentification of variants near/in known major Aβ-processing genes strengthens the relevance of plasma-Aβ levels both as an endophenotype and a biomarker of AD.
Goodness of fit checks for binomial N-mixture models
Authors: Knape Jonas , Arlt Debora , Barraquand Frédéric , Berg Åke , Chevalier Mathieu , Pärt Tomas , Ruete Alejandro , Zmihorski Michał 
Published: September 2017

AbstractBinomial N-mixture models are commonly applied to analyze population survey data. By estimating detection probabilities, N-mixture models aim at extracting information about abundances in terms of actual and not just relative numbers. This separation of detection probability and abundance relies on parametric assumptions about the distribution of individuals among sites and of detections of individuals among repeat visits to sites. Current methods for checking assumptions are limited, and their computational complexity have hindered evaluations of their performances.We develop computationally efficient graphical goodness of fit checks and measures of overdispersion for binomial N-mixture models. These checks are illustrated in a case study, and evaluated in simulations under two scenarios. The two scenarios assume overdispersion in the abundance distribution via a negative binomial distribution or in the detection probability via a beta-binomial distribution. We evaluate the ability of the checks to detect lack of fit, and how lack of fit affects estimates of abundances.The simulations show that if the parametric assumptions are incorrect there can be severe biases in estimated abundances: negatively if there is overdispersion in abundance relative to the fitted model and positively if there is overdispersion in detection. Our goodness of fit checks performed well in detecting lack of fit when the abundance distribution is overdispersed, but struggled to detect lack of fit when detections were overdispersed. We show that the inability to detect lack of fit due to overdispersed detection is caused by a fundamental similarity between N-mixture models with beta-binomial detections and N-mixture models with negative binomial abundances.The strong biases in estimated abundances that can occur in the binomial N-mixture model when the distribution of individuals among sites, or the detection model, is mis-specified implies that checking goodness of fit is essential for sound inference in ecological studies that use these methods. To check the assumptions we provide computationally efficient goodness of fit checks that are available in an R-package nmixgof. However, even when a binomial N-mixture model appears to fit the data well, estimates are not robust in the presence of overdispersion unless additional information about detection is collected.
Rare Variant Burden in Known Dystonia Genes in Population Controls and Sporadic Dystonia Patients
Authors: Cirulli Elizabeth T. , Hickey Patrick , Tracy Samantha , Johnson Julia , Caffall Zachary , Tsukayama Kaylin , Scott Burton , Stacy Mark , Calakos Nicole 
Published: September 2017

AbstractBackgroundRare mutations in genes associated with Mendelian forms of disease are a potential mechanism for sporadic disease. The need to assess the clinical significance of such variants is increasing as personalized medicine and genome sequencing increases.ObjectiveTo evaluate the rate of rare, functional variants in dystonia genes in the general population to improve interpretation of the clinical relevance of potentially pathogenic variants in dystonia cases.MethodsWe performed an “aggregated” collapsing analysis of exome sequence that considered rare coding variants in genes previously associated with dystonia, a rare neurological movement disorder, on 2,372 population controls of European ethnicity. We then performed a pilot study in sporadic dystonia to assess whether there was a substantially greater incidence of individuals with rare variation in dystonia genes.ResultsNearly half of population controls had a rare coding variant when 148 genes associated with a dystonia phenotype were considered. When the subset of genes causing isolated dystonia (14 genes) was evaluated, 3-4% of controls harbored rare qualifying variants. Our pilot study of case exomes was powered to identify a five-fold higher or greater rate of qualifying variants in isolated dystonia genes in sporadic dystonia cases compared to population controls; we did not find such an enrichment.ConclusionsWe provide the first systematic analysis of rare variation in dystonia genes considered collectively. Our findings emphasize the need to consider the overall frequency of variants in rare disease-related genes in the general population when considering their potential role in clinical presentations.
MeDEStrand: an improved method to infer genome-wide absolute methylation level from DNA enrichment experiment
Authors: Xu Jingting , Liu Shimeng , Yin Ping , Bulun Serdar , Dai Yang 
Published: September 2017

AbstractBackgroundDNA methylation of dinucleotide CpG is an essential epigenetic modification that plays a key role in transcription. Bisulfite conversion method is a “gold standard” for DNA methylation profiling that provides single nucleotide resolution. However, whole-genome bisulfite conversion is very expensive. Alternatively, DNA enrichment-based methods offer high coverage of methylated CpG dinucleotides with the lowest cost per CpG covered genome-wide and have been used widely. They measure the DNA enrichment of methyl-CpG binding, therefore do not directly provide absolute methylation levels. Further, the enrichment is influenced by confounding factors besides the methylation status, e.g., CpG density. Computational models that can accurately derive the absolute methylation levels from the enrichment data are necessary.ResultsWe present ‘MeDEStrand’, a method uses sigmoid function to estimate and correct the CpG bias from the numbers of reads that fell within bins that divide the genome. In addition, unlike the previous methods, which estimate CpG bias based on reads mapped at the same genomic loci, ‘MeDEStrand’ processes the reads for the positive and negative DNA strands separately. We compare the performance of ‘MeDEStrand’ with three other state-of-the-art methods ‘MEDIPS’, ‘BayMeth’ and ‘QSEA’ on four independent datasets generated using immortalized cell lines (GM12878 and K562) and human patient primary cells (foreskin fibroblast and mammary epithelial). Based on the comparison between the inferred absolute methylation levels from MeDIP-seq and the corresponding RRBS data, ‘MeDEStrand’ shows the best performance at high resolution of 25, 50 and 100 base pairs.Conclusions‘MeDEStrand’ benefits from the estimation of CpG bias with a sigmoid function and the procedure to process reads mapped to the positive and negative DNA strands separately. ‘MeDEStrand’ is a tool to infer whole-genome absolute DNA methylation level at the cost of enrichment-based methods with adequate accuracy and resolution. R package ‘MeDEStrand’ and its tutorial is freely available for download athttps://github.com/jxu1234/MeDEStrand.git
Inhaled nicotine equivalent to cigarette smoking disrupts systemic and uterine hemodynamics and induces cardiac arrhythmia in pregnant rats
Authors: Shao Xuesi M. , López-Valdés Héctor E. , Liang Jing , Feldman Jack L. 
Published: September 2017

AbstractMaternal smoking with obligatory nicotine inhalation is associated with preterm delivery, low birth weight, fetal growth retardation and developmental defects. We tested the hypothesis that cigarette smoking-relevant nicotine inhalation during pregnancy impairs cardiovascular function and uterine hemodynamics with consequential fetal ischemia. Pregnant rats exposed to episodic inhaled nicotine via a novel lung alveolar region-targeted aerosol method produced nicotine pharmacokinetics resembling cigarette smoking in humans. This clinically relevant nicotine aerosol inhalation (NAI) induced transient reduction and irregular fluctuations in uterine artery blood flow associated with cardiac arrhythmia and high magnitude irregular fluctuations of systemic blood pressure. The arrhythmia included sinoatrial (SA) block, sinus arrest, 2oand 3oatrioventricular (A-V) block and supraventricular escape rhythm. These effects were blocked by the nicotinic receptor (nAChR) antagonist mecamylamine. Resection of the ovarian nerve, which innervates uterine blood vessels, counteracted the NAI-induced reduction in uterine blood flow. We suggest that the rapid rise pattern of arterial blood nicotine concentration stimulates and then desensitizes autonomic nAChRs leading to disruptions of cardiac function as well as systemic and uterine hemodynamics that reduces uteroplacental blood flow, a mechanism underlying maternal smoking-associated pregnancy complications and developmental disorders. These findings challenge the safety of pure nicotine inhalation, i.e., E-cigarettes.
Pay ratio legislation in the United Kingdom: a prospect
Authors: Imai Akihito 
Published: September 2017

Purpose
The article examines a current debate over pay ratio rulemaking in the United Kingdom. In the United States, the Securities and Exchange Commission issued a rule that requires public companies to disclose the ratio of the annual pay of their chief executive officer to the median of their employees’ pay in 2015. The United Kingdom has considered making a similar rule under Prime Minister Theresa May.

Design/methodology/approach
The article provides a concise analysis of the current debate over a rule regarding pay ratio in the United Kingdom. It also highlights characteristics and concerns by comparing pay ratio disclosure in the United States.

Findings
The United Kingdom seems to have taken the first step toward pay ratio rule, similar to Section 953(b) of the Dodd-Frank Wall Street Reform and Consumer Protection Act, the so-called pay ratio disclosure. Some differences can however be found in manifestos and many issues and uncertainties still remain for rulemaking.

Originality/value
This article provides information on a prospect for a pay ratio rule in the United Kingdom.
A review of the SEC Participating Affiliate No-Action Letters’ relief from Investment Advisers Act of 1940 registration for foreign investment advisers
Authors: Cohen Wendy E. , Dickstein David Y. , Hennion Christian B. , Marshall Richard D. , Yacker Allison C. , Zinman Lance A. 
Published: September 2017

Purpose
To explain the US Securities and Exchange Commission (the “SEC”) staff’s (the “Staff”) participating affiliate exemption from investment adviser registration for foreign advisers set forth in a line of Staff no-action letters issued between 1992 and 2005 (the “Participating Affiliate Letters”) and to discuss recent guidance issued by the Staff in an information update published in March 2017 (the “Information Update”) with respect to complying with requirements of the Participating Affiliate Letters.

Design/methodology/approach
Reviews the development of the Staff’s approach regarding the non-registration of foreign advisers that rely on the Participating Affiliate Letters from prior to the issuance of those letters through the Information Update and sets forth recommendations for registered investment advisers and their participating affiliates.

Findings
While there are arguments that the Information Update goes beyond restating established standards and does not clearly explain whether submission of all listed documentation is required, the Information Update will likely standardize the information submitted to the SEC.

Originality/value
Practical guidance for advisers relying on the Participating Affiliate Letters from experienced securities and financial services lawyers.
Fifteen years of social media in emergencies: A retrospective review and future directions for crisis Informatics
Authors: Reuter Christian , Kaufhold Marc‐André 
Published: September 2017

Social media has been established in many larger emergencies and crises. This process has not started just a few years ago, but already 15 years ago in 2001 after the terrorist attacks of 9/11. In the following years, especially in the last 10, sometimes summarized under the term crisis informatics, a variety of studies focusing on the use of ICT and social media before, during or after nearly every crisis and emergency has arisen. This article aimed to recapitulate 15 years of social media in emergencies and its research with a special emphasis on use patterns, role patterns and perception patterns that can be found across different cases to point out what has been achieved so far, and what future potentials exist.
Probiotic Mascarpone‐type cheese: Characterisation and cell viability during storage and simulated gastrointestinal conditions
Authors: de Almeida Júlia dos S Opuski , Dias Carolinne O , Pinto Stephanie S , Pereira Luiza C , Verruck Silvani , Fritzen‐Freire Carlise B , Amante Edna R , Prudêncio Elane S , Amboni Renata D M C 
Published: September 2017

The aim of this study was to evaluate the effects of Bifidobacterium animalis subsp. lactis BB‐12 and the prebiotic inulin in a Mascarpone‐type cheese on its physicochemical parameters during storage, as well as the protective effects of the matrix on the viability of the probiotics and their survival after exposure to simulated gastrointestinal conditions. The incorporation of the probiotic and inulin into the Mascarpone‐type cheese affected specific physicochemical and textural properties. Viable cell counts remained above 6 log cfu/g throughout the whole storage period and after the simulated gastrointestinal conditions, indicating the protective effect of the matrix of the Mascarpone‐type cheese.
Differences in bioactive protein and vitamin status of milk from certified organic and conventional farms
Authors: Brodziak Aneta , Król Jolanta , Litwińczuk Zygmunt , Barłowska Joanna 
Published: September 2017

The aim of the study was to determine differences in the status of selected bioactive whey proteins and lipophilic vitamins in milk obtained from certified organic farms as compared to conventional farms (using traditional and intensive production systems). Significant relationships were noted with regard to production system and individual bioactive milk compounds, that is β‐lactoglobulin, lactoferrin, lysozyme, vitamins A, D3 and E, and β‐carotene (P = 0.001) and bovine serum albumin (BSA) (P = 0.016). Milk obtained from extensive farms, especially certified organic ones, was a valuable source of certain antioxidant compounds: β‐lactoglobulin (3.32 g/L), lactoferrin (123.8 mg/L), vitamin E (2.044 mg/L) and β‐carotene (0.257 mg/L) in the case of organic farms.
IRF7 gene expression profile and methylation of its promoter region in patients with systemic sclerosis
Authors: Rezaei Ramazan , Mahmoudi Mahdi , Gharibdoost Farhad , Kavosi Hoda , Dashti Navid , Imeni Vahideh , Jamshidi Ahmadreza , Aslani Saeed , Mostafaei Shayan , Vodjgani Mohammad 
Published: September 2017

AbstractObjectiveThe aim of the current study was to evaluate if methylation status of CpG sites of interferon regulatory factor 7 (IRF7) promoter in peripheral blood mononuclear cells (PBMCs) of systemic sclerosis (SSc) patients is involved in pathogenesis of the disease.MethodsPBMCs were isolated from whole blood of 50 SSc patients and 30 controls. After the extraction of total RNA and DNA contents from PBMCs, complementary DNA (cDNA) was synthesized. Afterwards, quantitative analysis of IRF7 messenger RNA (mRNA) was conducted by real‐time polymerase chain reaction (PCR). To evaluate the methylation status of the promoter region of IRF7 gene, PCR products of bisulfite‐treated DNA from SSc patients and controls were sequenced.ResultsThe mRNA expression of IRF7 in PBMCs from patients compared with controls was significantly upregulated. While limited cutaneous SSc patients expressed the mRNA of IRF7 higher than controls, the diffuse cutaneous SSc group did not demonstrate significantly increased expression in comparison to controls. Insignificant promoter hypomethylation of IRF7 was observed in SSc patients compared with the control group. However, CpG2 hypomethylation was significantly associated with increased SSc risk. Furthermore, overall promoter methylation and mRNA level of IRF7 were significantly correlated with each other. Nonetheless, none of them correlated with Rodnan score of SSc patients. There was significant difference in IRF7 mRNA expression between CpG8 methylated and unmethylated SSc patients. Moreover, the difference of methylation and expression was not significant between anti‐nuclear antibody (ANA)‐positive and ANA‐negative SSc patients.ConclusionsIt is suggested that hypomethylation of the IRF7 promoter might play a role in SSc pathogenesis, probably through promoting the IRF7 expression in PBMCs of patients with SSc.
Ideal Cricoid Pressure Is Biomechanically Impossible During Laryngoscopy
Authors: Trethewy Christopher E. , Doherty Steven R. , Burrows Julie M. , Clausen Don 
Published: September 2017

AbstractObjectiveThis study was a prospective, randomized controlled trial of rapid sequence intubation (RSI) with cricoid pressure (CP) within the emergency department (ED). The primary aim of the study was to examine the link between ideal CP and the incidence of aspiration.MethodPatients > 18 years of age undergoing RSI in the ED of two hospitals in New South Wales, Australia, were randomly assigned to receive measured CP using weighing scales to target the ideal CP range (3.060–4.075 kg) or control CP where the weighing scales were used, but the CP operator was blinded to the amount of CP applied during the RSI. A data logger recorded all CP delivered during each RSI. Immediately after intubation, tracheal and esophageal samples were taken and underwent pepsin analysis.ResultsFifty‐four RSIs were analyzed (25 measured/29 control). Macroscopic contamination of the larynx at RSI was observed in 14 patients (26%). During induction (0–50 seconds), both groups delivered in‐range CP. During intubation (51–223 seconds), laryngoscopy was associated with a reduction in mean CP below 3.060 kg in both groups. When compared, there was no statistically significant difference between the groups. For 11 patients, pepsin was detected in the oropharyngeal sample, while three were positive for tracheal pepsin. Seven patients (four control/three measured) were treated for clinical aspiration during hospitalization. As a result of the finding that neither group could maintain ideal range CP during laryngoscopy, the trial was abandoned.ConclusionLaryngoscopy provides a counter force to CP, which is negated to facilitate tracheal intubation. The concept that a static 3.060 to 4.075 kg CP could be maintained during laryngoscopy and intubation was rejected by our study. Whether a lower CP range could prevent aspiration during RSI was not explored by this study.
How climate influences the biology and behaviour of Phyllophaga capillata (Coleoptera: Melolonthidae) in the Brazilian Cerrado
Authors: Oliveira Charles M , Frizzas Marina R 
Published: September 2017

AbstractPhyllophaga capillata (Blanchard) is the most important soil pest in soybean crops in Central Brazil (Federal District and Goiás state). The objective of this work was to study the bio‐ecology of P. capillata in the field in the Cerrado of Central Brazil, relating its biology and behaviour to the climatic characteristics of this biome. The study was conducted over three years in a soybean [Glycine max (L.) Merr.] production area (≈6000 ha) in the Federal District. Field samplings were taken to observe the biological stages of P. capillata, preferred oviposition sites and the adult swarming period. Phyllophaga capillata presented an univoltine cycle that lasted about 10 months of egg to inactive adults, and 12 months until the appearance of active adults. Eggs were found in the field in October and November. The larval stage occurred between November and June. Pre‐pupae were observed in June and the pupae between July and August. Inactive adults were observed in August and September, and the swarming period was between September and December. Females preferred to oviposit in sites with taller plants. This species synchronises its active phases (larvae and active adults) with soybean cultivation and the rainy season (October/March) in the Brazilian Cerrado. Alternatives for pest management based on their bio‐ecological characteristics are presented.
Nasal protein profiles in work‐related asthma caused by different exposures
Authors: Suojalehto H. , Lindström I. , Wolff H. , Puustinen A. 
Published: September 2017

AbstractBackgroundThe mechanisms of work‐related asthma (WRA) are incompletely delineated. Nasal cell samples may be informative about processes in the lower airways. Our aim was to determine the nasal protein expression profiles of WRA caused by different kind of exposures.MethodsWe collected nasal brush samples from 82 nonsmoking participants, including healthy controls and WRA patients exposed to (i) protein allergens, (ii) isocyanates and (iii) welding fumes the day after relevant exposure. The proteome changes in samples were analysed by two‐dimensional difference gel electrophoresis, and the differentially regulated proteins found were identified by mass spectrometry. Immunological comparison was carried out using Western blot.ResultsWe detected an average of 2500 spots per protein gel. Altogether, 228 protein spots were chosen for identification, yielding 77 different proteins. Compared to the controls, exposure to protein allergens had the largest effects on the proteome. Hierarchical clustering revealed that protein allergen‐ and isocyanate‐related asthma had similar profiles, whereas asthma related to welding fumes differed. The highly overrepresented functional categories in the asthma groups were defence response, protease inhibitor activity, inflammatory and calcium signalling, complement activation and cellular response to oxidative stress. Immunological analysis confirmed the found abundance differences in galectin 10 and protein S100‐A9 between the groups.ConclusionsWork‐related asthma patients exposed to protein allergens and isocyanates elicit similar nasal proteome responses and the profiles of welders and healthy controls were alike. Revealed biological activities of the protein expression changes are associated with allergic inflammation and asthma.