bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prescription patterns of angiotensin‐converting enzyme inhibitors for various indications: A UK population‐based study
Authors: Mahmoudpour Seyed Hamidreza , Asselbergs Folkert W. , Souverein Patrick C. , de Boer Anthonius , Maitland‐van der Zee Anke H. 
Published: June 2018

AimAngiotensin‐converting enzyme inhibitors (ACEIs) are widely prescribed for several cardiovascular indications. This study investigated patterns of ACEI use for various indications.MethodsA descriptive, retrospective population‐based study was conducted using data from the UK Clinical Practice Research Datalink. Patients starting ACEIs (2007–2014) were selected and ACEI indications were retrieved from electronically recorded medical records. Stratified by indication, we distinguished between persistent and nonpersistent ACEI use, considering a 6‐month interval between two prescription periods as a maximum for persistent use. Five‐year persistence rates for various indications were calculated using the Kaplan–Meier method and compared in a log‐rank test. Nonpersistent users were subdivided into three groups: (i) stop; (ii) restart; and (iii) switch to an angiotensin II‐receptor blocker. Patients who received ACEIs for hypertension who switched to other classes of antihypertensive medications were further investigated.ResultsIn total, 254 002 ACEI initiators were identified with hypertension (57.6%), myocardial infarction (MI; 4.2%), renal disease (RD; 3.7%), heart failure (HF; 1.5%), combinations of the above (17.2%) or none of the above (15.8%). Five‐year persistence rates ranged from 43.2% (RD) to 68.2% (MI; P < 0.0001). RD and HF patients used ACEIs for the shortest time (average 23.6 and 25.0 months, respectively). For the nonpersistent group, the percentage of switchers to angiotensin II‐receptor blockers ranged from 27.6% (RD) to 42.2% (MI) and the restarters ranged from 15.0% (HF) to 18.1% (group without indication).ConclusionsDepending on the indication, there are various rates of ACEI nonpersistence. Patients with RD are most likely to discontinue treatment.
Activating the pregnane X receptor by imperatorin attenuates dextran sulphate sodium‐induced colitis in mice
Authors: Liu Meijing , Zhang Guohui , Zheng Chunge , Song Meng , Liu Fangle , Huang Xiaotao , Bai Shasha , Huang Xinan , Lin Chaozhan , Zhu Chenchen , Hu Yingjie , Mi Suiqing , Liu Changhui 
Published: June 2018

Background and PurposeActivation of the human pregnane X receptor (PXR; NR1I2) has potential therapeutic uses for inflammatory bowel disease (IBD). Imperatorin (IMP), a naturally occurring coumarin, is the main bioactive ingredient of Angelica dahurica Radix, which is regularly used to treat the common cold and intestinal disorders. However, there are no data on the protective effects of IMP against IBD.Experimental ApproachThe effects of IMP on PXR‐modulated cytochrome P450 3A4 (CYP3A4) expression were assessed using a PXR transactivation assay, a mammalian two‐hybrid assay, a competitive ligand‐binding assay, analysis of CYP3A4 mRNA and protein expression levels and measurement of CYP3A4 activity using a cell‐based reporter gene assay and in vitro model. The inhibitory effects of IMP on NF‐κB activity were evaluated by a reporter assay and NF‐κB p65 nuclear translocation. The anti‐IBD effects of IMP were investigated in a dextran sulphate sodium (DSS)‐induced colitis mouse model. Colon inflammatory cytokines were assessed by elisa.Key ResultsIMP activated CYP3A4 promoter activity, recruited steroid receptor coactivator 1 to the ligand‐binding domain of PXR and increased the expression and activity of CYP3A4. PXR knockdown substantially reduced IMP‐induced increase in CYP3A4 expression. Furthermore, IMP‐mediated PXR activation suppressed the nuclear translocation of NF‐κB and down‐regulated LPS‐induced expression of pro‐inflammatory genes. Nevertheless, PXR knockdown partially reduced the IMP‐mediated inhibition of NF‐κB. IMP ameliorated DSS‐induced colitis by PXR/NF‐κB signalling.Conclusions and ImplicationsIMP acts as a PXR agonist to attenuate DSS‐induced colitis by suppression of the NF‐κB‐mediated pro‐inflammatory response in a PXR/NF‐κB‐dependent manner.
Digital third parties: Understanding the technological challenge to Canada's third party advertising regime
Authors: Small Tamara A. 
Published: June 2018

AbstractSome scholars proclaim that social media can make third party advertising regulations “technologically obsolete.” Since social media are essentially free, financial resources are no longer an obstacle to the participation in elections. These claims, however, lack empirical consideration. Using original data on third party election advertising from 2004 ‐ 2015, this article argues that digital technologies have not made advertising regulations obsolete. Analysis shows that third parties are increasingly engaged in paid internet advertising. For many third parties, money matters in the digital age as it did in the broadcast age.
Policy versus practice: Third party behaviour in Canadian elections
Authors: Lawlor Andrea , Crandall Erin 
Published: June 2018

AbstractThird party campaigners are widely noted to have the power to change the landscape of an election. Yet, in Canada, we know little about whether there is consistency behind third parties' motivations, expectations and strategies, or how these motivations parse with those of the legislators who are attempting to regulate their behaviour. This article explores these factors using data from Canadian federal elections from 2004 to 2015. Merging qualitative interviews and survey data of third parties with quantitative evaluations of third party and political party campaign spending, we assess whether the strategic motivations of third parties reflect the intentions and design of campaign policies that regulate their actions. The United Kingdom regulatory regime is briefly reviewed as an example of an alternative policy approach.
Third party political participation and anti‐collusion rules
Authors: Pal Michael 
Published: June 2018

AbstractOne of the enduring questions regarding third parties is how to prevent collusion between them and political parties. Collusion raises the spectre of third parties being used as vehicles to evade the spending and contribution limits imposed on political parties. I will argue in this article that federal election laws are inadequate at deterring collusion. The episode involving the “HarperPAC” and similar groups around the 2015 election helped to shine a spotlight on the vulnerabilities of the Canada Elections Act. I argue that the model deployed by the U.S. Federal Election Commission to regulate independent expenditures represents a promising path for reform if carefully adapted to the Canadian context.
Interindividual differences in the clinical effectiveness of liraglutide in Type 2 diabetes: a real‐world retrospective study conducted in Spain
Authors: Gomez‐Peralta F. , Lecube A. , Fernández‐Mariño A. , Alonso Troncoso I. , Morales C. , Morales‐Pérez F. M. , Guler I. , Cadarso‐Suárez C. 
Published: June 2018

AbstractAimsTo study the response of clinical variables (HbA1c, body weight, lipid profile and blood pressure) over 24 months of liraglutide treatment in a real‐world clinical setting, and to describe the evolution of HbA1c and body weight reduction in response to liraglutide treatment by employing generalized additive mixed models (GAMMs).MethodsWe included people aged ≥ 18 years with Type 2 diabetes mellitus that initiated liraglutide treatment between November 2011 and May 2015. Demographic and clinical data were retrieved retrospectively over 24 months from electronic medical records with a median duration of observation of 7.0 (IQR 3.0–12.0) months.ResultsIndividuals that initiated liraglutide therapy were obese (BMI 39.1 kg/m2), with inadequate HbA1c (68 mmol/mol [8.4%]), blood pressure and lipid levels. Upon liraglutide treatment, HbA1c, body weight, mean systolic and diastolic blood pressure, and lipid levels decreased gradually. GAMMs demonstrated that longer treatment with liraglutide was a predictor of improved HbA1c response, whereas higher baseline HbA1c, longer Type 2 diabetes duration and treatment with insulin were predictors of worse HbA1c response. Higher baseline weight, longer treatment with liraglutide and the interaction between metformin and time were predictors of improved weight response.ConclusionsIn this real‐world study, we showed the effectiveness of liraglutide in improving body weight, HbA1c, mean systolic and diastolic blood pressure, and lipid levels. GAMMs indicated that baseline HbA1c and weight, time of treatment with liraglutide, diabetes duration and the use of metformin or insulin are predictors of clinical response to liraglutide.
Plasma levels of free fatty acids correlate with type 2 diabetes mellitus
Authors: Spiller Sandro , Blüher Matthias , Hoffmann Ralf 
Published: June 2018

AimsFree fatty acids (FFA) mediate adverse metabolic effects such as downregulated carbohydrate metabolisms, providing causal links between obesity and the development of type 2 diabetes mellitus (T2DM). Here, we investigated the plasma concentrations of FFA alone and in combination with protein glycation as potential diagnostic and prognostic biomarkers of T2DM.Materials and methodsEDTA‐plasma obtained from 48 newly diagnosed male T2DM patients, 48 long‐term controlled (24 male and 24 female) T2DM patients, 20 prediabetic male T2DM patients and two age‐matched control cohorts (48 non‐diabetic (ND) men; 24 male and 24 female ND partipants) were analysed for a set of clinical parameters including FFA. Glycation sites were quantified after tryptic digestion using tandem mass spectrometry.ResultsMedian plasma concentrations of FFA were almost three‐fold higher in samples obtained from newly diagnosed (long‐term controlled) T2DM patients than in those obtained from the control group, providing diagnostic sensitivity (SN) of 92% (85%) and specificity (SP) of 90% (88%). When combined with the glycation level of lysine‐141 of haptoglobin, diagnostic accuracy improved further for newly diagnosed (SN, 94%; SP 96%) and long‐term controlled (SN, 85%; SP, 94%) T2DM patients (HbA1c: SN, 88%; SP, 96%). A prospective pilot study evaluating the prognostic value revealed initially low FFA levels for pre‐diabetic patients that increased in the following four years in patients whose prediabetic state worsened or who developed T2DM.ConclusionsFFA levels are elevated in newly diagnosed and long‐term controlled T2DM patients, providing high diagnostic accuracy of 87% and 91%, respectively, which improved further when combined with the glycation degree of lysine‐141 in haptoglobin. Additionally, FFA showed higher mean fold‐changes than HbA1c or FPG in subjects developing T2DM, indicating higher sensitivity towards the progression of the disease.
Left atrial function: Correlation with left ventricular function and contractile reserve in patients with hypertension
Authors: Fung Matle J. , Thomas Liza , Leung Dominic Y. 
Published: June 2018

AimsAlterations in left atrial (LA) and left ventricular (LV) function have been documented in hypertensive patients. However, the correlation of LA with LV functional changes has not been established. Using normotensive controls, we examined LA functional changes in hypertensive patients by strain deformation analysis, and their relationship to LV functional changes including contractile reserve (CR).MethodsOne hundred and sixteen patients (61 men, aged 57.6 ± 9.1 years, 67 with hypertension) underwent dobutamine echocardiography. Patients with significant coronary or valvular disease, previous myocardial infarction or coronary revascularization, and diabetes were excluded. LA reservoir (Ɛs), conduit (Ɛe), and atrial contractile (Ɛa) strain were measured at rest. LV global longitudinal strain (GLS) and ejection fraction (LVEF) were measured at rest and at low‐dose dobutamine. LV CR was calculated as the difference in GLS and LVEF between the low dose and their corresponding resting values.ResultsHypertensive patients, compared with controls, had significantly impaired LA Ɛs (30.7 ± 3.9% vs 42.4 ± 4.9%), Ɛe (16.2 ± 4.1% vs 22.5 ± 5.5%), and Ɛa (14.5 ± 4.1% vs 19.9 ± 5.0%, all P < .001) strain. All LA phasic strain correlated with LV GLS at rest, at low‐dose dobutamine, and LV CR. There was no correlation between LA strain and LVEF or LV CR assessed by LVEF. LV GLS and LAVImax were the strongest independent determinants for LA Ɛs/Ɛe and LA Ɛa, respectively.ConclusionCompared to controls, hypertensive patients had impaired LA strain, which correlated with LV GLS and CR. LV GLS and LAVImax were the strongest independent determinants for LA Ɛs/Ɛe and LA Ɛa, respectively, independent of BP and LVMi.
Accumulation of NO2− during periods of drying stimulates soil N2O emissions during subsequent rewetting
Authors: Liu S. , Schloter M. , Brüggemann N. 
Published: June 2018

SummaryRewetting of soil might contribute considerably to the annual production of nitrous oxide (N2O) in ecosystems subjected to long dry periods. Therefore, it is crucial to elucidate the most important factors responsible for large pulses of N2O with rewetting. In this study, we carried out a series of rewetting experiments with soil samples collected from upland and riparian forest, grassland and arable land. We analysed the dynamics of ammonium (NH4+), nitrite (NO2−), nitrate (NO3−) and dissolved organic matter (DOM) of air‐dried soil samples after rewetting. We also analysed the effects of sterilization of soil samples by γ‐irradiation on N2O production with rewetting. Furthermore, we explored the effects of rewetting and sterilization on the isotopic composition of N2O in the different soil samples. The grassland soil produced the largest amount of N2O (64.1 μg N kg−1) in 1 hour on rewetting, followed by upland forest soil, whereas it was least for soils from riparian forest and arable land. Gamma irradiation, however, decreased soil N2O production from forest soil samples by 30–90% after rewetting, but increased N2O production in grassland and arable land soils three‐fold and two‐fold, respectively. Correlation analysis revealed that NO2− concentration in the soil samples at the time of rewetting was the most relevant factor that explained soil N2O production after rewetting. Furthermore, the addition of NO2− before rewetting increased N2O production during rewetting more than with additions of NO3− and NH4+ in all soil samples. The 15N site preference values of N2O produced after rewetting were close to 0‰, indicating a denitrification‐related production process according to the classical view. However, additional abiotic processes responsible for soil N2O production during rewetting cannot be excluded.Highlights
Mechanisms responsible for large N2O production during rewetting of soil are not well understood.
Nitrite content in dry soil was strongly correlated with N2O production after rewetting.
The 15N site preference of the N2O produced was close to 0‰ after rewetting.
Additional abiotic processes could have contributed to N2O formation from NO2−.
Digital ITEMS Module 1: Reliability in Classical Test Theory
Authors: Lewis Charlie , Chajewski Michael , Rupp André A. 
Published: June 2018

AbstractIn this ITEMS module, we provide a two‐part introduction to the topic of reliability from the perspective of classical test theory (CTT). In the first part, which is directed primarily at beginning learners, we review and build on the content presented in the original didactic ITEMS article by Traub and Rowley (1991). Specifically, we discuss the notion of reliability as an intuitive everyday concept to lay the foundation for its formalization as a reliability coefficient via the basic CTT model. We then walk through the step‐by‐step computation of key reliability indices and discuss the data collection conditions under which each is most suitable. In the second part, which is directed primarily at intermediary learners, we present a distribution‐centered perspective on the same content. We discuss the associated assumptions of various CTT models ranging from parallel to congeneric, and review how these affect the choice of reliability statistics. Throughout the module, we use a customized Excel workbook with sample data and basic data manipulation functionalities to illustrate the computation of individual statistics and to allow for structured independent exploration. In addition, we provide quiz questions with diagnostic feedback as well as short videos that walk through sample exercises within the workbook.
Use of brivaracetam in genetic generalized epilepsies and for acute, intravenous treatment of absence status epilepticus
Authors: Strzelczyk Adam , Kay Lara , Bauer Sebastian , Immisch Ilka , Klein Karl Martin , Knake Susanne , Kowski Alexander , Kunz Rhina , Kurlemann Gerhard , Langenbruch Lisa , Möddel Gabriel , Müller‐Schlüter Karen , Reif Philipp S. , Schubert‐Bast Susanne , Steinhoff Bernhard J. , Steinig Isabel , Willems Laurent M. , von Podewils Felix , Rosenow Felix 
Published: June 2018

SummaryObjectiveThe objective of this study was to evaluate effectiveness, retention, and tolerability of brivaracetam (BRV) in genetic generalized epilepsies (GGE) in clinical practice.MethodsA multicenter, retrospective cohort study recruiting all patients that started BRV in 2016 and 2017.ResultsA total of 61 patients (mean age = 29.8, range = 9‐90 years, 41 female [67%]) were treated with BRV. They were difficult to control, with 2.4 failed antiepileptic drugs (AEDs) in the past, taking 1.9 AEDs on average at baseline. The length of exposure to BRV ranged from 7 days to 24 months, with a mean retention time of 7.9 months, resulting in a total exposure time to BRV of 483 months. The retention rate was 82% at 3 months and 69% at 6 months. Efficacy at 3 months was 36% (50% responder rate), with 25% seizure‐free for 3 months. Patients with juvenile myoclonic epilepsy showed a responder rate of 60%, with 40% being free of any seizures. Long‐term 50% responder rate was present in 17 patients (28%; 11 seizure‐free [18%]) for >6 months and in 14 patients (23%; 10 seizure‐free [16%]) for >12 months. Treatment‐emergent adverse events were observed in 26% of the patients, with the most common being somnolence, ataxia, and psychobehavioral adverse events. Use of intravenous BRV with bolus injection of 200‐300 mg in two females with absence status epilepticus was well tolerated, but did not result in cessation of status epilepticus.SignificanceUse of BRV in GGE is well tolerated, and 50% responder rates are similar to those observed in the regulatory trials for focal epilepsies. An immediate switch from levetiracetam (LEV) to BRV at a ratio of 15:1 is feasible. The occurrence of psychobehavioral adverse events seems less prominent than under LEV, and a switch to BRV can be considered in patients with LEV‐induced adverse events.
Why are female color polymorphisms rare in territorial damselflies?
Authors: Cabezas Castillo María Beatriz , Grether Gregory F. 
Published: June 2018

AbstractIn nonterritorial damselflies, females often come in multiple color morphs, perhaps because females with rare colors experience reduced sexual harassment, and thus have a frequency‐dependent fitness advantage, compared to females of the most common color morph, but such polymorphisms are rare in territorial species. We consider three hypotheses to explain the rarity of female color polymorphisms in territorial species: (a) misdirected male aggression, (b) poor male mate recognition, and (c) low mating harassment rates. The first hypothesis has some empirical support, and can account for the absence of andromorphs (i.e., females that resemble males), but does not explain the absence of multiple heteromorphs. We tested the second hypothesis by presenting females of two novel color morphs (green‐ or red‐banded abdomens) to territorial male Hetaerina capitalis. Females of both novel color morphs elicited fewer sexual responses than control females, and the red morph occasionally elicited aggressive responses. These results indicate that novel female color morphs would experience reduced mating harassment in this species, contradicting the hypothesis that male mate recognition is too poorly developed to reduce harassment of novel female morphs. By process of elimination, the third hypothesis, that harassment rates are too low in territorial species to provide rare female morphs a fitness advantage, is favored, but remains untested. Our findings also suggest that the common practice of color‐marking odonates for behavioral research is likely to interfere with mate choice, as has long been known to be the case in birds.
The catalytic effect of internationalization on innovation
Authors: Chang Ching‐Hsing , Chang Ching‐Hung , Hsu Pi‐Kun , Yang Sheng‐Yung 
Published: June 2018

AbstractThis paper examines how internationalization spurs corporate innovation. Internationalization heightens the competitive environment of firms, while increasing financial flexibility. The increased competition reduces agency problems and motivates innovation projects which are supported by improved financial flexibility. We obtain robust evidence with the difference‐in‐differences and instrumental variable approaches. The passage of antitakeover laws and the 1989 Loma Prieta earthquake are treated as exogenous variations to corporate governance; shocks on firm capital supply measured by mutual fund redemptions are also considered. A less positive finding is that internationalization motivates firms to focus on the appropriability of innovation rather than on basic research.
Strength in diversity: Phenotypic, functional, and molecular heterogeneity within the memory B cell repertoire
Authors: Good‐Jacobson Kim L. 
Published: June 2018

SummaryThe vast majority of vaccines exploit antibody memory to induce lasting immunity. Memory B cells are generated during the initial response to infection, but persist long after the infection has cleared. Immune memory success relies on its adaptability: in response to different pathogens, variants of a single pathogen, and in balancing persistence with reactivation and plasma cell differentiation. This is likely achieved by producing a B cell memory population that is highly diverse, and recent work has highlighted the importance of memory B cell subsets in mediating the dichotomous roles of the population. This review will detail the characterization, function and both intrinsic and extrinsic regulation of different memory B cell subsets: memory B cell precursors within the germinal center, phenotypic, and functional heterogeneity of the memory B cell population, and memory B cell subsets that reside in tissues. In particular, understanding the genetic and epigenetic regulation of memory B diversity may be critical for gaining insight into B cell memory responses to pathogens that have evaded effective vaccine design. Therefore, there is a vital need to understand the mechanisms underlying the origin, function and translational potential of the heterogeneity within the memory B cell population.