bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect modification ofFADS2polymorphisms on the association between breastfeeding and intelligence: protocol for a collaborative meta-analysis
Authors: Hartwig Fernando Pires , Davies Neil Martin , Horta Bernardo Lessa , Victora Cesar Gomes , Davey Smith George 
Published: June 2016

IntroductionEvidence from observational studies and randomised controlled trials suggests that breastfeeding is positively associated with IQ, possibly because breast milk is a source of long-chain polyunsaturated fatty acids. Different studies have detected gene-breastfeeding interactions involvingFADS2variants and intelligence. However, findings are inconsistent regarding the direction of such effect modification.Methods/designTo clarify howFADS2and breastfeeding interact in their association with IQ, we are conducting a consortium-based meta-analysis of independent studies. Results produced by each individual study using standardised analysis scripts and harmonised data will be used.Inclusion criteria: breastfeeding, IQ and either rs174575 or rs1535 polymorphisms available; and being of European ancestry.Exclusion criteria: twin studies; only poorly imputed genetic data available; or unavailability of proper ethics approval. Studies will be invited based on being known to have at least some of the required data, or suggested by participating studies as potentially eligible. This inclusive approach will favour achieving a larger sample size and be less prone to publication bias.DiscussionImproving current understanding ofFADS2-breastfeeding interaction may provide important biological insights regarding the importance of long-chain polyunsaturated fatty acids for the breastfeeding-IQ association. This meta-analysis will help to improve such knowledge by replicating earlier studies, conducting additional analysis and evaluating different sources of heterogeneity. Publishing this protocol will minimise the possibility of bias due to post hoc changes to the analysis protocol.
Effectiveness of β-blockers in physically active patients with hypertension: protocol of a systematic review
Authors: Tučková Dagmar , Klugar Miloslav , Sovová Eliška , Sovová Markéta , Štégnerová Lenka 
Published: June 2016

IntroductionBased on more than 5 decades of epidemiological studies, it is now widely accepted that higher physical activity patterns and levels of cardiorespiratory fitness are associated with better health outcomes. Therefore, it is necessary to consider how treatment methods affect these two components. Clinically, one very important question concerns the influence of aerobic performance on patients being treated for hypertension. The administration of β-blockers can significantly reduce maximal—and especially submaximal—aerobic exercise capacity. The objective of this review is to determine, by comparison of existing mono and combination therapy, which β-blockers are less physically limiting for patients with hypertension who are physically active.MethodsA three-step strategy will be adopted in the review, following the methods used by the Joanna Briggs Institute (JBI). The initial search will be conducted using the MEDLINE and EMBASE databases. The second search will involve the listed databases for the published literature (MEDLINE, Biomedica Czechoslovaca, Tripdatabase, Pedro, EMBASE, the Cochrane Central Register of Controlled Trials, Cinahl, WoS) and the unpublished literature (Open Grey, Current Controlled Trials, MedNar, ClinicalTrials.gov, Cos Conference Papers Index, the International Clinical Trials Registry Platform of the WHO). Following the JBI methodology, analysis of title/abstracts and full texts, critical appraisal and data extraction will be carried out on selected studies using the JBI tool, MAStARI. This will be performed by two independent reviewers. If possible, statistical meta-analysis will be pooled. Statistical heterogeneity will be assessed. Subgroup analysis will be used for different age and gender characteristics. Funnel plots, Begg's rank correlation and Egger's regression test will be used to detect or correct publication bias.Ethics and disseminationThe results will be disseminated by publishing in a peer-reviewed journal. Ethical assessment is not needed—we will search/evaluate the existing sources of literature.Trial registration numberCRD42015026914.
Medical consumption compared for TIMI and HEART score in chest pain patients at the emergency department: a retrospective cost analysis
Authors: Nieuwets A , Poldervaart J M , Reitsma J B , Buitendijk S , Six A J , Backus B E , Hoes A W , Doevendans P A 
Published: June 2016

ObjectiveTo investigate which risk score (TIMI score or HEART score) identifies the largest population of low-risk patients at the emergency department (ED). Furthermore, we retrospectively calculated the corresponding expected decrease in medical consumption if these patients would have been discharged from the ED.MethodsWe performed analyses in two hospitals of the multicentre prospective validation study of the HEART score, executed in 2008 and 2009. Patients with chest pain presenting to the ED were included and information was collected on major adverse cardiac events (MACEs) and on hospital admissions and diagnostic procedures within 6 weeks. The TIMI and HEART score were calculated for each patient.ResultsWe analysed 640 patients (59% male, mean age of 60, cumulative incidence of MACE 17%). An estimated total of €763 468 was spent during follow-up on hospital admission and diagnostic procedures. In total, 256 (40%) patients had a HEART score of 0–3 and were considered low risk (miss rate 1.6%), a total of €64 107 was spent on diagnostic procedures and hospital admission after initial presentation in this group. In comparison, 105 (16%) patients with TIMI score of 0 were considered low risk (miss rate 0%), with a total of €14 670 spent on diagnostic procedures and initial hospital admission costs. With different cut-offs for low risk, HEART 0–2 (miss rate 0.7%), would have resulted in a total of €25 365 in savings, compared with €71 905 when an alternative low risk cut-off for TIMI of TIMI≤1 would be used (miss rate 3.0%).ConclusionsThe HEART score identifies more patients as low risk compared with the TIMI score, which may lead to a larger reduction in diagnostic procedures and costs in this low-risk group. Future studies should prospectively investigate whether adhering to the HEART score in clinical practice and early discharge of low-risk patients is safe and leads to a reduction in medical consumption.
Effectiveness of a pharmacist-led educational intervention to reduce the use of high-risk abbreviations in an acute care setting in Saudi Arabia: a quasi-experimental study
Authors: Haseeb Abdul , Winit-Watjana Win , Bakhsh Abdul-Rahman R , Elrggal Mahmoud E , Hadi Muhammad Abdul , Mously Alaa A , Gadibalban Asmaa Z , Al-Ibraheem Bashayir F , Almubark Rasha A , Ekram Rawan A , Khan Tahir Mehmood 
Published: June 2016

ObjectivesTo evaluate the effectiveness of a pharmacist-led educational intervention to reduce the use of high-risk abbreviations (HRAs) by healthcare professionals.DesignQuasi-experimental study consisting of a single group before-and-after study design.SettingA public emergency hospital in Mecca, Saudi Arabia.Participants660 (preintervention) and then 498 (postintervention) handwritten physician orders, medication administration records (MRAs) and pharmacy dispensing sheets of 482 and 388 patients, respectively, from emergency wards, inpatient settings and the pharmacy department were reviewed.InterventionThe intervention consisted of a series of interactive lectures delivered by an experienced clinical pharmacist to all hospital staff members and dissemination of educational tools (flash cards, printed list of HRAs, awareness posters) designed in line with the recommendations of the Institute for Safe Medical Practices and the US Food and Drug Administration. The duration of intervention was from April to May 2011.Main outcomeReduction in the incidence of HRAs use from the preintervention to postintervention study period.FindingsThe five most common abbreviations recorded prior to the interventions were ‘IJ for injection’ (28.6%), ‘SC for subcutaneous’ (17.4%), drug name and dose running together (9.7%), ‘OD for once daily’ (5.8%) and ‘D/C for discharge’ (4.3%). The incidence of the use of HRAs was highest in discharge prescriptions and dispensing records (72.7%) followed by prescriptions from in-patient wards (47.3%). After the intervention, the overall incidence of HRA was significantly reduced by 52% (ie, 53.6% vs 25.5%; p=0.001). In addition, there was a statistically significant reduction in the incidence of HRAs across all three settings: the pharmacy department (72.7% vs 39.3%), inpatient settings (47.3% vs 23.3%) and emergency wards (40.9% vs 10.7%).ConclusionsPharmacist-led educational interventions can significantly reduce the use of HRAs by healthcare providers. Future research should investigate the long-term effectiveness of such educational interventions through a randomised controlled trial.
Screening of (–SEA) α-thalassaemia using an immunochromatographic strip assay for the ζ-globin chain in a population with a high prevalence and heterogeneity of haemoglobinopathies
Authors: Jomoui Wittaya , Fucharoen Goonnapa , Sanchaisuriya Kanokwan , Fucharoen Supan 
Published: June 2016

AimsThe presence of the ζ-globin chain is a good marker of (--SEA) α0-thalassaemia. We evaluated an immunochromatographic (IC) strip assay for ζ-globin in screening for (--SEA) α0-thalassaemia in a population with a high prevalence and heterogeneity of haemoglobinopathies.MethodsThe study was carried out on 300 screen positive blood samples of Thai individuals. The IC strip assay for the ζ-globin chain was performed on all samples. The results were interpreted with thalassaemia genotyping using standard haemoglobin and DNA analyses.ResultsSeveral thalassaemia genotypes were noted. Among the 300 subjects investigated, 79 had a positive IC strip assay for ζ-globin and (--SEA) α0-thalassaemia was identified in 40 of them. No (--SEA) α0-thalassaemia was detected in the remaining 39 samples with a positive IC strip test result or in the 221 samples with a negative IC strip test result. Further DNA analysis identified α+-thalassaemia in 25 of the 39 (--SEA) α0-thalassaemia negative samples. Using this IC strip assay in combination with a conventional screening protocol for (--SEA) α0-thalassaemia could provide sensitivity and specificity of 100% and 90.4%, respectively.ConclusionsIC strip assay for ζ-globin is simple, rapid and does not require sophisticated equipment. Use of this test in addition to the existing screening protocol could detect potential (--SEA) α0-thalassaemia leading to a significant reduction in the workload of DNA analysis. This could be used in areas where haemoglobinopathies are prevalent and heterogeneous but molecular testing is not available.
Dual antiplatelet therapy may increase the risk of non-intracranial haemorrhage in patients with minor strokes: a subgroup analysis of the CHANCE trial
Authors: Wang David , Gui Li , Dong Yi , Li Hao , Li Shujuan , Zheng Huaguang , Wang Anxin , Meng Xia , Liu Li-Ping , Wang Yi-Long , Wang Guangyao , Jing Jing , Li Zixiao , Zhao Xing-Quan , Wang Yong-Jun 
Published: June 2016

AimThe aim of this study was to explore the difference between haemorrhagic events among those patients on either aspirin or aspirin plus clopidogrel who were enrolled in the Clopidogrel in High-Risk Patients with Acute Non-disabling Ischemic Cerebrovascular Events (CHANCE) trial.MethodsThis was an ad hoc analysis of the CHANCE trial; data on all patients with any haemorrhagic event were reviewed and analysed. Cox proportional hazards regression was used to determine factors association with any bleeding.ResultsIn the CHANCE trial, there were a total of 101 (2%) haemorrhagic events reported from 50 different hospitals. The clopidogrel–aspirin group had 60 (2.3%) cases and the aspirin group had 41 (1.6%, p=0.09). Moderate or severe haemorrhagic events occurred in 7 patients (0.3%) in the clopidogrel–aspirin group and in 8 (0.3%) in the aspirin group (p=0.73). Of 36 (0.7%) cases of intracranial haemorrhages, 20 (0.4%) were in the clopidogrel–aspirin group and 16 (0.3%) in the aspirin group. Each group had 8 (0.3%) cases of symptomatic haemorrhagic strokes. Other common haemorrhagic events included 24 (0.5%) cases of skin bruises, 13 (0.3%) gastrointestinal haemorrhages, 9 (0.2%) gum haemorrhages and 8 (0.2%) intraocular haemorrhages.ConclusionsThere was no overall significant difference in haemorrhagic events (p=0.29), especially in the rate of intracranial haemorrhages between the 2 treatment groups. However, patients enrolled with minor strokes had an increased risk of haemorrhagic events regardless of treatment group, not seen in patients with high-risk transient ischaemic attacks. Being elderly, of male gender and with a history of aspirin or proton pump inhibitor usage were associated with increased risk of haemorrhage. Patients with higher body mass index had lower risk of haemorrhagic events.Trial registration numberNCT00979589.
Biochar as soil amendment: Impact on chemical properties and corn nutrient uptake in a Podzol
Authors: Syuhada A.B. , Shamshuddin J. , Fauziah C.I. , Rosenani A.B. , Arifin A. 
Published: June 2016

A study was conducted to investigate the impact of biochar amendment on chemical properties and corn nutrient uptake in a sandy Podzol soil. Four rates of biochar (0, 5, 10, and 15 g kg−1) and two rates of inorganic fertilizer (0 and local recommendation rate for corn) were randomly applied to a completely randomized design with four replicates. Corn was grown for 45 d in a glasshouse using sandy Podzol. The increase in pH of the soil was concomitant with a decrease of exchangeable Al. The fertilized soil significantly increased total N, with a concomitant decrease in soil pH due to a N nitrification. Positive changes did occur in the soil due to biochar application, leading to a significant increase in dry matter yield and corn height. Corn N and K uptakes were significantly increased by the addition of biochar, but the same was not true for Ca and Mg. However, it was found that the concentrations of N, Ca, and Mg in the corn tissue were still lower than their critical level. Our results demonstrate that application of biochar alone is not able to supply enough nutrients for the healthy growth of corn.
Comparison of models for predicting pore space indices and their relationships with CO2 and N2O fluxes in a corn–soybean field
Authors: Panday Dinesh , Nkongolo Nsalambi V. 
Published: June 2016

Several models predict soil pore space indices (the relative gas diffusion coefficient, Ds/Do and the pore tortuosity, τ), but information is lacking on which models predicted indices better relate to soil processes. We compared pore space indices’ predictive models based on air-filled porosity (fa) alone vs. models using air-filled porosity and total pore space (Φ) (fa + Φ). We also assessed the relationships between these indices and CO2 and N2O. The study was conducted from 2011 to 2014 on a silt loam soil at Lincoln University. Soil samples were collected at 0–10 and 10–20 cm depth and oven dried at 105 °C for 72 h. After drying, fa and Φ were calculated and later used in models for predicting Ds/Do and τ. CO2 and N2O were measured with a Shimadzu gas chromatograph (GC) and a photoacoustic gas analyzer (PSA). Results showed that Ds/Do predicted using fa alone (Marshall and Buckingham) was higher as compared with values predicted with models based on fa + Φ (Sallam et al., Millington, and Jin and Jury) (P < 0.001). However, values of τ predicted with models based on fa alone were lowest (P < 0.001). CO2 and N2O measured with GC better related with Ds/Do and τ.
Interval-Valued Belief Rule Inference Methodology Based on Evidential Reasoning-IRIMER
Authors: Zhu Hua , Zhao Jianbin , Xu Yang , Du Limin 
Published: June 2016

In this paper, an interval-valued belief rule inference methodology based on evidential reasoning (IRIMER) is proposed, which includes the interval-valued belief rule representation scheme and its inference methodology. This interval-valued belief rule base is designed with interval-valued belief degrees embedded in both the consequents and the antecedents of each rule, which can represent uncertain information or knowledge more flexible and reasonable than the previous belief rule base. Then its inference methodology is developed on the interval-valued evidential reasoning (IER) approach. The IRIMER approach improves and extends the recently uncertainty inference methods from the rule representation scheme and the inference framework. Finally, a case is studied to demonstrate the concrete implementation process of the IRIMER approach, and comparison analysis shows that the IRIMER approach is more flexible and effective than the RIMER [J. B. Yang, J. Liu, J. Wang, H. S. Sii and H. W. Wang, Belief rule-base interference methodology using the evidential reasoning approach-RIMER, IEEE Transaction on Systems Man and Cybernetics Part A-Systems and Humans36 (2006) 266–285.] approach and the ERIMER [J. Liu, L. Martínez, A. Calzada and H. Wang, A novel belief rule base representation, generation and its inference methodology, Knowledge-Based Systems 53 (2013) 129–141.] approach.
Oncogenic Deregulation of EZH2 as an Opportunity for Targeted Therapy in Lung Cancer
Authors: Zhang Haikuo , Qi Jun , Reyes Jaime M. , Li Lewyn , Rao Prakash K. , Li Fugen , Lin Charles Y. , Perry Jennifer A. , Lawlor Matthew A. , Federation Alexander , De Raedt Thomas , Li Yvonne Y. , Liu Yan , Duarte Melissa A. , Zhang Yanxi , Herter-Sprie Grit S. , Kikuchi Eiki , Carretero Julian , Perou Charles M. , Reibel Jacob B. , Paulk Joshiawa , Bronson Roderick T. , Watanabe Hideo , Brainson Christine Fillmore , Kim Carla F. , Hammerman Peter S. , Brown Myles , Cichowski Karen , Long Henry , Bradner James E. , Wong Kwok-Kin 
Published: June 2016

Abstract
As a master regulator of chromatin function, the lysine methyltransferase EZH2 orchestrates transcriptional silencing of developmental gene networks. Overexpression of EZH2 is commonly observed in human epithelial cancers, such as non–small cell lung carcinoma (NSCLC), yet definitive demonstration of malignant transformation by deregulated EZH2 remains elusive. Here, we demonstrate the causal role of EZH2 overexpression in NSCLC with new genetically engineered mouse models of lung adenocarcinoma. Deregulated EZH2 silences normal developmental pathways, leading to epigenetic transformation independent of canonical growth factor pathway activation. As such, tumors feature a transcriptional program distinct from KRAS- and EGFR-mutant mouse lung cancers, but shared with human lung adenocarcinomas exhibiting high EZH2 expression. To target EZH2-dependent cancers, we developed a potent open-source EZH2 inhibitor, JQEZ5, that promoted the regression of EZH2-driven tumors in vivo, confirming oncogenic addiction to EZH2 in established tumors and providing the rationale for epigenetic therapy in a subset of lung cancer.
Significance: EZH2 overexpression induces murine lung cancers that are similar to human NSCLC with high EZH2 expression and low levels of phosphorylated AKT and ERK, implicating biomarkers for EZH2 inhibitor sensitivity. Our EZH2 inhibitor, JQEZ5, promotes regression of these tumors, revealing a potential role for anti-EZH2 therapy in lung cancer. Cancer Discov; 6(9); 1006–21. ©2016 AACR.
See related commentary by Frankel et al., p. 949.
This article is highlighted in the In This Issue feature, p. 932
Circulating Chemerin Is Associated With Carotid Plaque Instability, Whereas Resistin Is Related to Cerebrovascular Symptomatology
Authors: Gasbarrino Karina , Mantzoros Christos , Gorgui Jessica , Veinot John P. , Lai Chi , Daskalopoulou Stella S. 
Published: June 2016

Objective—
The rupture of unstable carotid atherosclerotic plaques is one of the main causes of cerebrovascular ischemic events. There is need for circulating markers that can predict plaque instability and risk of stroke. Proinflammatory chemerin, leptin, and resistin, along with anti-inflammatory adiponectin, are adipokines with direct influence on vascular function. We investigated the association of circulating adipokines with carotid plaque instability and cerebrovascular symptomatology.

Approach and Results—

Neurologically symptomatic and asymptomatic patients (n=165) scheduled for carotid endarterectomy were recruited. Fasting blood samples were collected preoperatively; adiponectin and leptin levels were determined by radioimmunoassay; and chemerin and resistin levels were measured by enzyme-linked immunosorbent assays. The instability of plaque specimens was assessed using gold-standard histological classifications. Chemerin was significantly associated with plaque instability. The fully adjusted model, accounting for age, sex, body mass index, high-sensitivity C-reactive protein, type 2 diabetes mellitus, and circulating adiponectin, leptin, and resistin, yielded an odds ratio of 0.991 (95% confidence interval 0.985–0.998) for plaque instability per unit increase in chemerin. High leptin levels were significantly associated with presence of specific features of plaque instability. In subjects with type 2 diabetes mellitus, resistin levels were significantly elevated in symptomatic when compared with asymptomatic subjects (
P
=0.001) and increased the risk of cerebrovascular symptomatology (adjusted odds ratio 1.264, 95% confidence interval 1.004–1.594).

Conclusions—
Low chemerin and high resistin levels were associated with carotid disease severity, suggesting that these adipokines may act as potential markers for plaque instability and stroke risk. Future studies are needed to assess causation between circulating adipokines and plaque instability.
Long-Term Mortality in Patients With Radiation-Associated Coronary Artery Disease Treated With Percutaneous Coronary Intervention
Authors: Reed Grant W. , Masri Ahmad , Griffin Brian P. , Kapadia Samir R. , Ellis Stephen G. , Desai Milind Y. 
Published: June 2016

Background—
The incidence and predictors of long-term mortality after percutaneous coronary intervention (PCI) for radiation-associated coronary artery disease are unknown.

Methods and Results—

In this observational study of 314 patients (age, 65.2±11.4 years; 233 [74%] women) treated with PCI, 157 patients with previous external beam radiation therapy (XRT) were matched 1:1 with 157 comparison patients with atherosclerotic coronary artery disease without previous XRT, based on age, sex, lesion artery, and PCI type. The primary end point was all-cause mortality, and the secondary end point was cardiovascular mortality. After follow-up of 6.6±5.5 years, there were 101 deaths; 59 in the XRT group and 42 in the comparison group (
P
=0.04). On Cox proportional hazards multivariable survival analysis, previous XRT remained an independent predictor of all-cause mortality (hazard ratio [HR] 1.85; 95% confidence interval [CI], 1.21–2.85;
P
=0.004) and cardiovascular mortality (HR, 1.70; 95% CI, 1.06–2.89;
P
=0.03). Additional independent predictors of increased all-cause mortality included balloon angioplasty or bare-metal stent placement compared with drug-eluting stent placement (HR, 2.50; 95% CI, 1.61–3.97;
P
<0.0001), SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) score of ≥11 (the sample median; HR, 1.99; 95% CI, 1.32–3.04;
P
<0.001), New York Heart Association functional class ≥3 (HR, 1.83; 95% CI, 1.15–2.91;
P
=0.012), history of smoking (HR, 1.88; 95% CI, 1.10–3.09;
P
=0.022), and age ≥65 years (HR, 1.70; 95% CI, 1.07–2.07;
P
=0.024).

Conclusions—
Compared with patients with typical atherosclerotic coronary artery disease, patients with radiation-associated coronary artery disease are at higher risk for mortality after PCI. Previous XRT exposure is independently associated with increased all-cause and cardiovascular mortality in patients treated with PCI.