bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of CYP2C19 gene polymorphisms on the pharmacokinetics and pharmacodynamics of prasugrel 5-mg, prasugrel 10-mg and clopidogrel 75-mg in patients with coronary artery disease
Authors: Bergmeijer Thomas , Tantry Udaya , ten Berg Jurrien , Angiolillo Dominick , James Stefan , Lindahl Tomas , Svensson Peter , Jakubowski Joseph , Brown Patricia , Duvvuru Suman , Sundseth Scott , Walker Joseph , Small David , Moser Brian , Winters Kenneth , Erlinge David , Gurbel Paul 
Published: July 2014

Summary
CYP2C19 genotype has been shown to impact response to clopidogrel 75-mg but not prasugrel 10-mg. Here, we assessed effects of CYP2C19 metaboliser status on pharmacokinetics (PK) and pharmacodynamic (PD) responses to prasugrel 5-mg and 10-mg and clopidogrel 75-mg using data from two PK/PD studies in stable coronary artery disease (CAD) patients (GENERATIONS and FEATHER). Active metabolite concentrations (area under the curve, AUC[0-tlast]), maximum platelet aggregation (MPA) measured by light transmission aggregometry, vasodilator- stimulated phosphoprotein platelet reactivity index, and VerifyNow P2Y12-platelet reaction units (VN-PRU) were analysed by CYP2C19-predicted phenotype (extensive metaboliser [EM; N=154], *2-*8 non-carriers, vs reduced metaboliser [RM; N=41],*2-*8 carriers/* 17 non-carriers). AUC(0-tlast) was unaffected by metaboliser status for prasugrel 5-mg and 10-mg (geometric mean EM/RM ratios 1.00, 95% confidence interval [CI]: 0.86,1.17, p>0.99; and 0.97, 95% CI:0.85,1.12, p=0.71, respectively), but was lower among RMs receiving clopidogrel 75-mg (1.37, 95% CI:1.14,1.65, p<0.001). Platelet reactivity was not significantly affected by CYP2C19 metaboliser status for prasugrel 5-mg, or for prasugrel 10-mg by MPA and VNPRU, but for clopidogrel 75-mg was significantly higher in reduced metabolisers (all measures p<0.01). Prasugrel 10-mg showed greater antiplatelet effects vs clopidogrel 75-mg (all comparisons p<0.001). Prasugrel 5-mg showed greater antiplatelet effects vs clopidogrel 75-mg in RMs (all p<0.001), and comparable effects in EMs (all p≥0.37). In contrast to clopidogrel, prasugrel active metabolite PK was not influenced by CYP2C19 genotype. Antiplatelet effect for prasugrel 10-mg was greater irrespective of metaboliser status and for prasugrel 5-mg was greater for RMs and comparable for EMs as compared to clopidogrel 75-mg.
Prognostic role of MIR146A polymorphisms for cardiovascular events in atrial fibrillation
Authors: Roldán Vanessa , Arroyo Ana Belen , Salloum-Asfar Sallam , Manzano-Fernández Sergio , García-Barberá Nuria , Marín Francisco , Vicente Vicente , González-Conejero Rocío , Martínez Constantino 
Published: July 2014

SummaryThere are few biomarkers able to forecast new thrombotic events in patients with AF. In this framework, microRNAs have emerged as critical players in cardiovascular biology. In particular, miR-146a-5p is recognised as an important negative regulator of inflammation. This study aims to evaluate the prognostic role and biological effect of functional MIR146A polymorphisms, rs2431697 and rs2910164, in non-valvular atrial fibrillation (AF) patients under oral anticoagulation. We studied 901 patients with permanent/paroxysmal AF stabilized for at least six months. Patients were followed-up for two years and adverse cardiovascular events (ACE) were recorded. In vitro studies were performed in monocytes from healthy homozygous for the two genotypes of rs2431697. Rs2910164 had no association with ACE. However, multivariate analysis (adjusted by CHA2DS2–VASc score) revealed that rs2431697TT was associated with adverse cardiovascular events [HR: 1.64 (1.09–2.47); p=0.017]. The predictive value of usefulness of the CHA2DS2–VASc+IL6+rs2431697 for predicting ACE, was statistically better than that predicted by CHA2DS2–VASc+IL6. Functional studies showed that after 24 hours incubation, monocytes from CC individuals showed a 65 % increase in miR-146a-5p levels, while TT individuals only showed a 28 % increase. Indeed, after 24 hours of LPS activation, TT monocytes showed a higher increase in IL6 mRNA expression than CC (52 % vs 26 %). Our study established MIR146A rs2431697 as a prognostic biomarker for ACE in anticoagulated AF patients. These data suggest that TT individuals, when submitted to an inflammatory stress, may be prone to a highest pro-inflammatory state due, in part, to lower levels of miR-146a-5p.
Identification of a circulating microvesicle protein network involved in ST-elevation myocardial infarction
Authors: Vélez Paula , Parguiña Andrés , Ocaranza-Sánchez Raymundo , Grigorian-Shamagian Lilian , Rosa Isaac , Alonso-Orgaz Sergio , Cuesta Fernando de la , Guitián Esteban , Moreu José , Barderas María , González-Juanatey José Ramón , García Ángel 
Published: July 2014

SummaryMembrane microvesicles (MVs) are released from activated cells, most notably platelets, into the circulation. They represent an important mode of intercellular communication, and their number is increased in patients with acute coronary syndromes. We present here a differential proteomic analysis of plasma MVs from ST-elevation myocardial infarction (STEMI) patients and stable coronary artery disease (SCAD) controls. The objective was the identification of MVs biomarkers/drug targets that could be relevant for the pathogenesis of the acute event. Proteome analysis was based on 2D-DIGE, and mass spectrometry. Validations were by western blotting in an independent cohort of patients and healthy individuals. A systems biology approach was used to predict protein-protein interactions and their relation with disease. Following gel image analysis, we detected 117 protein features that varied between STEMI and SCAD groups (fold change cut-off ≥2; p<0.01). From those, 102 were successfully identified, corresponding to 25 open-reading frames (ORFs). Most of the proteins identified are involved in inflammatory response and cardiovascular disease, with 11 ORFs related to infarction. Among others, we report an up-regulation of α2-macroglobulin isoforms, fibrinogen, and viperin in MVs from STEMI patients. Interestingly, several of the proteins identified are involved in thrombogenesis (e.g. α2-macroglobulin, and fibrinogen). In conclusion, we provide a unique panel of proteins that vary between plasma MVs from STEMI and SCAD patients and that might constitute a promising source of biomarkers/drug targets for myocardial infarction.
Body Mass Index, Sex, and Cardiovascular Disease Risk Factors Among Hispanic/Latino Adults: Hispanic Community Health Study/Study of Latinos
Authors: Kaplan Robert C. , Avilés‐Santa M. Larissa , Parrinello Christina M. , Hanna David B. , Jung Molly , Castañeda Sheila F. , Hankinson Arlene L. , Isasi Carmen R. , Birnbaum‐Weitzman Orit , Kim Ryung S. , Daviglus Martha L. , Talavera Gregory A. , Schneiderman Neil , Cai Jianwen 
Published: July 2014

Background

All major Hispanic/Latino groups in the
United States
have a high prevalence of obesity, which is often severe. Little is known about cardiovascular disease (
CVD
) risk factors among those at very high levels of body mass index (
BMI
).

Methods and Results

Among
US
Hispanic men (N=6547) and women (N=9797), we described gradients across the range of
BMI
and age in
CVD
risk factors including hypertension, serum lipids, diabetes, and C‐reactive protein. Sex differences in
CVD
risk factor prevalences were determined at each level of
BMI
, after adjustment for age and other demographic and socioeconomic variables. Among those with class
II
or
III
obesity (
BMI
≥35 kg/m
2
, 18% women and 12% men), prevalences of hypertension, diabetes, low high‐density lipoprotein cholesterol level, and high C‐reactive protein level approached or exceeded 40% during the fourth decade of life. While women had a higher prevalence of class
III
obesity (
BMI
≥40 kg/m
2
) than did men (7% and 4%, respectively), within this highest
BMI
category there was a >50% greater relative prevalence of diabetes, hypertension, and hyperlipidemia in men versus women, while sex differences in prevalence of these
CVD
risk factors were ≈20% or less at other
BMI
levels.

Conclusions

Elevated
BMI
is common in Hispanic/Latino adults and is associated with a considerable excess of
CVD
risk factors. At the highest
BMI
levels,
CVD
risk factors often emerge in the earliest decades of adulthood and they affect men more often than women.
An ethyl acetate fraction derived from Houttuynia cordata extract inhibits the production of inflammatory markers by suppressing NF-кB and MAPK activation in lipopolysaccharide-stimulated RAW 264.7 macrophages
Authors: Chun Jin Mi , Nho Kyoung Jin , Kim Hyo Seon , Lee A Yeong , Moon Byeong Cheol , Kim Ho Kyoung 
Published: July 2014

Abstract

Background

Houttuynia cordata Thunb. (Saururaceae) has been used in traditional medicine for treatment of inflammatory diseases. This study evaluated the anti-inflammatory effects of an ethyl acetate fraction derived from a Houttuynia cordata extract (HCE-EA) on the production of inflammatory mediators and the activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs) in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages.

Methods
To measure the effects of HCE-EA on pro-inflammatory cytokine and inflammatory mediator’s expression in RAW 264.7 cells, we used the following methods: cell viability assay, Griess reagent assay, enzyme-linked immunosorbent assay, real-time polymerase chain reaction and western blotting analysis.

Results
HCE-EA downregulated nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), and interleukin (IL-6) production in the cells, as well as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression. Furthermore, HCE-EA suppressed nuclear translocation of the NF-κB p65 subunit, which correlated with an inhibitory effect on IκBα (nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha) phosphorylation. HCE-EA also attenuated the activation of MAPKs (p38 and JNK).

Conclusions
Our results suggest that the anti-inflammatory properties of HCE-EA may stem from the inhibition of pro-inflammatory mediators via suppression of NF-κB and MAPK signaling pathways.
The Hippo pathway in disease and therapy: cancer and beyond
Authors: Gomez Marta , Gomez Valenti , Hergovich Alexander 
Published: July 2014

AbstractThe Hippo tumour suppressor pathway co‐ordinates cell proliferation, cell death and cell differentiation to regulate tissue growth control. In mammals, a conserved core Hippo signalling module receives signal inputs on different levels to ensure the proper regulation of YAP/TAZ activities as transcriptional co‐activators. While the core module members MST1/2, Salvador, LATS1/2 and MOB1 have been attributed tumour suppressive functions, YAP/TAZ have been mainly described to have oncogenic roles, although some reports provided evidence supporting growth suppressive roles of YAP/TAZ in certain cancer settings. Intriguingly, mammalian Hippo signalling is also implicated in non‐cancer diseases and plays a role in tissue regeneration following injury. Cumulatively, these findings indicate that the pharmacological inhibition or activation of the Hippo pathway could be desirable depending on the disease context. In this review, we first summarise the functions of the mammalian Hippo pathway in tumour formation, and then discuss non‐cancer diseases involving Hippo signalling core components with a specific focus on our current understanding of the non‐cancer roles of MST1/2 and YAP/TAZ. In addition, the pros and cons of possible pharmacological interventions with Hippo signalling will be reviewed, with particular emphasis on anti‐cancer drug development and regenerative medicine.
A Demand Estimation Procedure for Retail Assortment Optimization with Results from Implementations
Authors: Fisher Marshall , Vaidyanathan Ramnath 
Published: July 2014

We consider the problem of choosing, from a set of N potential stock-keeping units (SKUs) in a retail category, K SKUs to be carried at each store to maximize revenue or profit. Assortments can vary by store, subject to a maximum number of different assortments. We view a SKU as a set of attribute levels and also model possible substitutions when a customer's first choice is not in the assortment. We apply maximum likelihood estimation to sales history of the SKUs currently carried by the retailer to estimate the demand for attribute levels and substitution probabilities, and from this, the demand for any potential SKU, including those not currently carried by the retailer. We specify several alternative heuristics for choosing SKUs to be carried in an assortment. We apply this approach to optimize assortments for three real examples: snack cakes, tires, and automotive appearance chemicals. A portion of our recommendations for tires and appearance chemicals were implemented and produced sales increases of 5.8% and 3.6%, respectively, which are significant improvements relative to typical retailer annual comparable store revenue increases. We also forecast sales shares of 1, 11, and 25 new SKUs for the snack cake, tire, and automotive appearance chemical applications, respectively, with mean absolute percentage errors (MAPEs) of 16.2%, 19.1%, and 28.7%, which compares favorably to the 30.7% MAPE for chain sales of two new SKUs reported by Fader and Hardie (1996). This paper was accepted by Yossi Aviv, operations management.
A Qualitative Analysis of Approaches To Contraceptive Counseling
Authors: Dehlendorf Christine , Kimport Katrina , Levy Kira , Steinauer Jody 
Published: July 2014

CONTEXTUnderuse and inconsistent use of contraceptives contribute to the continued high rate of unintended pregnancy in the United States. High‐quality interaction between patient and provider about contraception is associated with improved contraceptive use, yet little is known about how providers support patients in the decision‐making process.METHODSA random sample of 50 family planning visits by patients in the San Francisco Bay Area was selected from a larger sample of 342 audio‐recorded visits to six clinics between 2009 and 2012. In qualitative analysis guided by grounded theory techniques, transcripts were assessed to determine counseling approaches and patterns in the use of these approaches.RESULTSProviders employed three counseling approaches: foreclosed (in 48% of visits), characterized by discussion of few contraceptive methods and method selection by the patient with no involvement from the provider; informed choice (30%), characterized by detailed description of multiple methods, but little or no interaction between the patient and the provider; and shared decision making (22%), characterized by the provider's interactive and responsive participation with the patient in method selection. Use of these approaches varied by patient's age: Women 25 or younger experienced the foreclosed approach more often than older women, and patients older than 35 were far more likely than their younger counterparts to experience the shared decision‐making approach.CONCLUSIONSMost visits did not include interactive engagement between the patient and the provider. Contraceptive counseling interventions should encourage providers to responsively engage with patients of all ages to better meet their contraceptive needs.
Voltage Balancing Scheme in MMC – A New Approach
Authors: Madichetty Sreedhar , Dasgupta Abhijit , Mishra Sambeet 
Published: July 2014

Abstract
This article proposes an online voltage balancing scheme using a new comparative reference wave modulation technique applied to modified modular multilevel converter (MMMC). Recent applications of modular multilevel converter (MMC) in high-voltage DC systems experience many problems with unbalancing of upper and lower arms, due to which circulating currents are rotating in the legs of MMC. These circulating currents pass through the arm inductors and create power loss across the inductor which consequently affects the efficiency of system. In order to overcome the unbalancing and to reduce the power losses, it proposes a new topology for existing MMC called as MMMC. Its main idea is to the balance the system voltage according to the difference between upper and lower arm currents. The upper and lower arm capacitors voltages can be well balanced by proposed technique. Compared to conventional PWM methods, this method can be realized easily. Particularly, this method has not used any kind of sorting technique, which makes it suitable for MMC with a large number of sub-modules. With experiments, the proposed method has been verified successfully.
Percentile and Percentile-t Bootstrap Confidence Intervals: A Practical Comparison
Authors: Elias Christopher J. 
Published: July 2014

Abstract
This paper employs a Monte Carlo study to compare the performance of equal-tailed bootstrap percentile-t, symmetric bootstrap percentile-t, bootstrap percentile, and standard asymptotic confidence intervals in two distinct heteroscedastic regression models. Bootstrap confidence intervals are constructed with both the XY and wild bootstrap algorithm. Theory implies that the percentile-t methods will outperform the other methods, where performance is based on the convergence rate of empirical coverage to the nominal level. Results are consistent across models, in that in the case of the XY bootstrap algorithm the symmetric percentile-t method outperforms the other methods, but in the case of the wild bootstrap algorithm the two percentile-t methods perform similarly and outperform the other methods. The implication is that practitioners that employ the XY algorithm should utilize the symmetric percentile-t interval, while those who opt for the wild algorithm should use either of the percentile-t methods.
Genome-Wide Regression and Prediction with the BGLR Statistical Package
Authors: Pérez Paulino , de los Campos Gustavo 
Published: July 2014

AbstractMany modern genomic data analyses require implementing regressions where the number of parameters (p, e.g., the number of marker effects) exceeds sample size (n). Implementing these large-p-with-small-n regressions poses several statistical and computational challenges, some of which can be confronted using Bayesian methods. This approach allows integrating various parametric and nonparametric shrinkage and variable selection procedures in a unified and consistent manner. The BGLR R-package implements a large collection of Bayesian regression models, including parametric variable selection and shrinkage methods and semiparametric procedures (Bayesian reproducing kernel Hilbert spaces regressions, RKHS). The software was originally developed for genomic applications; however, the methods implemented are useful for many nongenomic applications as well. The response can be continuous (censored or not) or categorical (either binary or ordinal). The algorithm is based on a Gibbs sampler with scalar updates and the implementation takes advantage of efficient compiled C and Fortran routines. In this article we describe the methods implemented in BGLR, present examples of the use of the package, and discuss practical issues emerging in real-data analysis.
The Impact of Attachment Style on the Family Drawings of School-Aged Children
Authors: Procaccia Rossella , Veronese Guido , Castiglioni Marco 
Published: July 2014

Objective:
Primary school children's representations of themselves and their attachment figures were explored by assessing their family drawings. The main aim of the study was to empirically explore differences in the representations of children with secure versus insecure attachment. The study was theoretically informed by attachment theory and methodologically based on widely-used systems for analysing children’s drawings.

Method:
The Separation Anxiety Test was used to evaluate the attachment styles of 117 children (aged 6-10 years). This led to the identification of three groups, similar in age and gender distribution, with three different attachment styles (secure, anxious-ambivalent and avoidant). Each participant was asked to draw a family and the drawings produced were coded on 8 global scales and evaluated for the presence of 35 specific markers divided into five categories (characteristics of the figures; use of space; completeness of representation; emotional-affective tone; overall characteristics of the representation).

Results:
The drawings of securely attached children featured more positive markers, associated with a stable and well-integrated sense of self and others, whereas insecure children produced more markers of instability and negative emotion, with some interesting differences between anxious-ambivalent and avoidant attachment styles.

Conclusion:
Despite its limitations, the study confirmed that family drawings are a valid instrument for evaluating how children represent attachment, thereby facilitating early intervention to prevent later adjustment difficulties.
Caractéristiques récentes de la fécondité des couples mariés et non mariés en Roumanie
Authors: Hoem Jan M. , Mureşan Cornelia , Hărăguş Mihaela 
Published: July 2014

Jusqu’à la fin des années 1980, l’union libre était rare en Roumanie. Après la chute du régime socialiste, cette proportion a progressivement augmenté pour atteindre environ 10 % en 2005, évolution qui a eu des conséquences sur la fécondité. Cet article présente certaines caractéristiques de la fécondité des couples mariés et non mariés entre 1985 et 2005 à partir des données de l’enquête GGS réalisée en Roumanie en 2005, par le calcul des taux de fécondité par durée de l’union et l’utilisation d’un paramètre synthétique basé sur la somme de ces taux toutes durées d’union confondues, indépendamment de la parité. L’analyse met en évidence les catégories de femmes qui ont eu particulièrement tendance à avoir des enfants sans être mariées : les femmes à faible niveau d’instruction et celles d’origine rurale. Dans ces deux groupes, les femmes qui vivaient en union libre ont été fortement affectées par les changements considérables de la politique familiale dans les années 1990, après quoi leur fécondité totale hors mariage est devenue du même ordre de grandeur que celle des femmes mariées. Pour les femmes de ces deux catégories, le fait d’être mariée ou non ne semble guère avoir d’influence sur leur fécondité.
Corriger les indices de scolarisation par la standardisation des structures par âge
Authors: Barakat Bilal F. , Durham Rachel E. , Rodrigues Clarissa Guimarães 
Published: July 2014

La fréquentation scolaire dépend de l’âge. La composition par âge de la population, par un pur effet de structure, influe sur la valeur des indices agrégés de présence dans le système scolaire tels que les ratios de scolarisation. Ce phénomène n’est généralement pas reconnu et a fortiori pris en compte dans les statistiques scolaires. Au mieux, la question de la structure par âge est simplement considérée comme une source d’erreur de mesure quand on compare des données administratives avec des données d’enquête. En recourant à une technique de standardisation des structures par âge, les auteurs montrent comment cet outil très courant en démographie peut facilement être appliqué aux indicateurs de scolarisation, et comment cela affecte les résultats. Ils observent que l’impact sur les ratios nets et bruts de scolarisation est généralement modéré ; mais quand on compare des contextes différents en termes de croissance des effectifs des générations successives ou de fréquentation scolaire, ne pas tenir compte des structures par âge pourrait biaiser les conclusions.