bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Single Amino Acid in EBNA-2 Determines Superior B Lymphoblastoid Cell Line Growth Maintenance by Epstein-Barr Virus Type 1 EBNA-2
Authors: Tzellos Stelios , Correia Paulo B. , Karstegl Claudio Elgueta , Cancian Laila , Cano-Flanagan Julian , McClellan Michael J. , West Michelle J. , Farrell Paul J. 
Published: May 2014

ABSTRACTSequence differences in the EBNA-2 protein mediate the superior ability of type 1 Epstein-Barr virus (EBV) to transform human B cells into lymphoblastoid cell lines compared to that of type 2 EBV. Here we show that changing a single amino acid (S442D) from serine in type 2 EBNA-2 to the aspartate found in type 1 EBNA-2 confers a type 1 growth phenotype in a lymphoblastoid cell line growth maintenance assay. This amino acid lies in the transactivation domain of EBNA-2, and the S442D change increases activity in a transactivation domain assay. The superior growth properties of type 1 EBNA-2 correlate with the greater induction of EBV LMP-1 and about 10 cell genes, including CXCR7. In chromatin immunoprecipitation assays, type 1 EBNA-2 is shown to associate more strongly with EBNA-2 binding sites near the LMP-1 and CXCR7 genes. Unbiased motif searching of the EBNA-2 binding regions of the differentially regulated cell genes identified an ETS-interferon regulatory factor composite element motif that closely corresponds to the sequences known to mediate EBNA-2 regulation of the LMP-1 promoter. It appears that the superior induction by type 1 EBNA-2 of the cell genes contributing to cell growth is due to their being regulated in a manner different from that for most EBNA-2-responsive genes and in a way similar to that for the LMP-1 gene.IMPORTANCEThe EBNA-2 transcription factor plays a key role in B cell transformation by EBV and defines the two EBV types. Here we identify a single amino acid (Ser in type 1 EBV, Asp in type 2 EBV) of EBNA-2 that determines the superior ability of type 1 EBNA-2 to induce a key group of cell genes and the EBV LMP-1 gene, which mediate the growth advantage of B cells infected with type 1 EBV. The EBNA-2 binding sites in these cell genes have a sequence motif similar to the sequence known to mediate regulation of the EBV LMP-1 promoter. Further detailed analysis of transactivation and promoter binding provides new insight into the physiological regulation of cell genes by EBNA-2.
Rates of obstetric intervention and associated perinatal mortality and morbidity among low-risk women giving birth in private and public hospitals in NSW (2000–2008): a linked data population-based cohort study
Authors: Dahlen Hannah G , Tracy Sally , Tracy Mark , Bisits Andrew , Brown Chris , Thornton Charlene 
Published: May 2014

ObjectivesTo examine the rates of obstetric intervention and associated perinatal mortality and morbidity in the first 28 days among low-risk women giving birth in private and public hospitals in NSW (2000–2008).DesignLinked data population-based retrospective cohort study involving five data sets.SettingNew South Wales, Australia.Participants691 738 women giving birth to a singleton baby during the period 2000–2008.Main outcome measuresRates of neonatal resuscitation, perinatal mortality, neonatal admission following birth and readmission to hospital in the first 28 days of life in public and private obstetric units.ResultsRates of obstetric intervention among low-risk women were higher in private hospitals, with primiparous women 20% less likely to have a normal vaginal birth compared to the public sector. Neonates born in private hospitals were more likely to be less than 40 weeks; more likely to have some form of resuscitation; less likely to have an Apgar <7 at 5 min. Neonates born in private hospitals to low-risk mothers were more likely to have a morbidity attached to the birth admission and to be readmitted to hospital in the first 28 days for birth trauma (5% vs 3.6%); hypoxia (1.7% vs 1.2%); jaundice (4.8% vs 3%); feeding difficulties (4% vs 2.4%) ; sleep/behavioural issues (0.2% vs 0.1%); respiratory conditions (1.2% vs 0.8%) and circumcision (5.6 vs 0.3%) but they were less likely to be admitted for prophylactic antibiotics (0.2% vs 0.6%) and for socioeconomic circumstances (0.1% vs 0.7%). Rates of perinatal mortality were not statistically different between the two groups.ConclusionsFor low-risk women, care in a private hospital, which includes higher rates of intervention, appears to be associated with higher rates of morbidity seen in the neonate and no evidence of a reduction in perinatal mortality.
Do difficulties in accessing in-hours primary care predict higher use of out-of-hours GP services? Evidence from an English National Patient Survey
Authors: Zhou Yin , Abel Gary , Warren Fiona , Roland Martin , Campbell John , Lyratzopoulos Georgios 
Published: May 2014

IntroductionIt is believed that some patients are more likely to use out-of-hours primary care services because of difficulties in accessing in-hours care, but substantial evidence about any such association is missing.MethodsWe analysed data from 567 049 respondents to the 2011/2012 English General Practice Patient Survey who reported at least one in-hours primary care consultation in the preceding 6 months. Of those respondents, 7% also reported using out-of-hours primary care. We used logistic regression to explore associations between use of out-of-hours primary care and five measures of in-hours access (ease of getting through on the telephone, ability to see a preferred general practitioner, ability to get an urgent or routine appointment and convenience of opening hours). We illustrated the potential for reduction in use of out-of-hours primary care in a model where access to in-hours care was made optimal.ResultsWorse in-hours access was associated with greater use of out-of-hours primary care for each access factor. In multivariable analysis adjusting for access and patient characteristic variables, worse access was independently associated with increased out-of-hours use for all measures except ease of telephone access. Assuming these associations were causal, we estimated that an 11% relative reduction in use of out-of-hours primary care services in England could be achievable if access to in-hours care were optimal.ConclusionsThis secondary quantitative analysis provides evidence for an association between difficulty in accessing in-hours care and use of out-of-hours primary care services. The findings can motivate the development of interventions to improve in-hour access.
Association between resting heart rate across the life course and all-cause mortality: longitudinal findings from the Medical Research Council (MRC) National Survey of Health and Development (NSHD)
Authors: Ó Hartaigh Bríain , Gill Thomas M , Shah Imran , Hughes Alun D , Deanfield John E , Kuh Diana , Hardy Rebecca 
Published: May 2014

BackgroundResting heart rate (RHR) is an independent risk factor for mortality. Nevertheless, it is unclear whether elevations in childhood and mid-adulthood RHR, including changes over time, are associated with mortality later in life. We sought to evaluate the association between RHR across the life course, along with its changes and all-cause mortality.MethodsWe studied 4638 men and women from the Medical Research Council (MRC) National Survey of Health and Development (NSHD) cohort born during 1 week in 1946. RHR was obtained during childhood at ages 6, 7 and 11, and in mid-adulthood at ages 36 and 43. Using multivariable Cox regression, we calculated the HR for incident mortality according to RHR measured at each time point, along with changes in mid-adulthood RHR.ResultsAt age 11, those in the top fifth of the RHR distribution (≥97 bpm) had an increased adjusted hazard of 1.42 (95% CI 1.04 to 1.93) for all-cause mortality. A higher adjusted risk (HR, 95% CI 2.17, 1.40 to 3.36) of death was also observed for those in the highest fifth (≥81 bpm) at age 43. For a >25 bpm increased change in the RHR over the course of 7 years (age 36–43), the adjusted hazard was elevated more than threefold (HR, 95% CI 3.26, 1.54 to 6.90). After adjustment, RHR at ages 6, 7 and 36 were not associated with all-cause mortality.ConclusionsElevated RHR during childhood and midlife, along with greater changes in mid-adulthood RHR, are associated with an increased risk of all-cause mortality.
Volume and Aboveground Biomass Models for Dry Miombo Woodland in Tanzania
Authors: Mwakalukwa Ezekiel Edward , Meilby Henrik , Treue Thorsten 
Published: May 2014

Tools to accurately estimate tree volume and biomass are scarce for most forest types in East Africa, including Tanzania. Based on a sample of 142 trees and 57 shrubs from a 6,065 ha area of dry miombo woodland in Iringa rural district in Tanzania, regression models were developed for volume and biomass of three important species,Brachystegia spiciformisBenth. (n = 40),Combretum molleG. Don (n = 41), andDalbergia arbutifoliaBaker (n = 37) separately, and for broader samples of trees (28 species,n = 72), shrubs (16 species,n = 32), and trees and shrubs combined (44 species,n = 104). Applied independent variables were log-transformed diameter, height, and wood basic density, and in each case a range of different models were tested. The general tendency among the final models is that the fit improved when height and wood basic density were included. Also the precision and accuracy of the predictions tended to increase from general to species-specific models. Except for a few volume and biomass models developed for shrubs, all models hadR2values of 96–99%. Thus, the models appear robust and should be applicable to forests with similar site conditions, species, and diameter ranges.
VEGF/VEGFR-2 Upregulates EZH2 Expression in Lung Adenocarcinoma Cells and EZH2 Depletion Enhances the Response to Platinum-Based and VEGFR-2–Targeted Therapy
Authors: Riquelme Erick , Suraokar Milind , Behrens Carmen , Lin Heather Y. , Girard Luc , Nilsson Monique B. , Simon George , Wang Jing , Coombes Kevin R. , Lee J. Jack , Hong Waun Ki , Heymach John , Minna John D. , Wistuba Ignacio I. 
Published: May 2014

Abstract
Purpose: To investigate the mechanisms of regulation and role associated with enhancer of zeste homolog 2 (EZH2) expression in lung cancer cells.
Experimental Design: We investigated the mechanisms of EZH2 expression associated with the VEGF/VEGFR-2 pathway. Furthermore, we sought to determine the role of EZH2 in response of lung adenocarcinoma to platinum-based chemotherapy, as well as the effect of EZH2 depletion on VEGFR-2–targeted therapy in lung adenocarcinoma cell lines. In addition, we characterized EZH2 expression in lung adenocarcinoma specimens and correlated it with patients' clinical characteristics.
Results: In this study, we demonstrate that VEGF/VEGFR-2 activation induces expression of EZH2 through the upregulation of E2F3 and hypoxia-inducible factor-1α (HIF1α), and downregulated expression of miR-101. EZH2 depletion by treatment with 3-deazaneplanocin A and knockdown by siRNA decreased the expression of EZH2 and H3K27me3, increased PARP-C level, reduced cell proliferation and migration, and increased sensitivity of the cells to treatment with cisplatin and carboplatin. In addition, high EZH2 expression was associated with poor overall survival in patients who received platinum-based adjuvant therapy, but not in patients who did not receive this therapy. Furthermore, we demonstrated for the first time that the inhibition of EZH2 greatly increased the sensitivity of lung adenocarcinoma cells to the anti–VEGFR-2 drug AZD2171.
Conclusion: Our results suggest that the VEGF/VEGFR-2 pathway plays a role in regulation of EZH2 expression via E2F3, HIF1α, and miR-101. EZH2 depletion decreases the malignant potential of lung adenocarcinoma and sensitivity of the cells to both platinum-based and VEGFR-2–targeted therapy. Clin Cancer Res; 20(14); 3849–61. ©2014 AACR.
Genetic Determinants of P Wave Duration and PR Segment
Authors: Verweij Niek , Leach Irene Mateo , van den Boogaard Malou , van Veldhuisen Dirk J. , Christoffels Vincent M. ,   LifeLines Cohort Study, Hillege Hans L. , van Gilst Wiek H. , Barnett Phil , de Boer Rudolf A. , van der Harst Pim 
Published: May 2014

Background—
The PR interval on the ECG reflects atrial depolarization and atrioventricular nodal delay which can be partially differentiated by P wave duration and PR segment, respectively. Genome-wide association studies have identified several genetic loci for PR interval, but it remains to be determined whether this is driven by P wave duration, PR segment, or both.

Methods and Results—

We replicated 7 of the 9 known PR interval loci in 16 468 individuals of European ancestry. Four loci were unambiguously associated with PR segment, while the others were shared for P wave duration and PR segment. Next, we performed a genome-wide analysis on P wave duration and PR segment separately and identified 5 novel loci. Single-nucleotide polymorphisms in
KCND3
(
P
=8.3×10
–11
) and
FADS2
(
P
=2.7×10
–8
) were associated with P wave duration, whereas single-nucleotide polymorphisms near
IL17D (P
=2.3×10
–8
), in
EFHA1
(
P
=3.3×10
−10
), and in
LRCH1
(
P
=2.1×10
–8
) were associated with PR segment. Analysis on DNA elements indicated that genome-wide significant single-nucleotide polymorphisms were enriched at genomic regions suggesting active gene transcription in the human right atrium. Quantitative polymerase chain reaction showed that genes were significantly higher expressed in the right atrium and atrioventricular node compared with left ventricle (
P
=5.6×10
–6
).

Conclusions—
Genetic associations of PR interval seem to be mainly driven by genetic determinants of the PR segment. Some of the PR interval associations are strengthened by a directional consistent effect of genetic determinants of P wave duration. Through genome-wide association we also identified genetic variants specifically associated with P wave duration which might be relevant for cardiac biology.
Soluble Vascular Adhesion Protein-1 Predicts Incident Major Adverse Cardiovascular Events and Improves Reclassification in a Finnish Prospective Cohort Study
Authors: Aalto Kristiina , Havulinna Aki S. , Jalkanen Sirpa , Salomaa Veikko , Salmi Marko 
Published: May 2014

Background—
Vascular adhesion protein-1 (VAP-1) associates to subclinical atherosclerotic manifestations in young people, but its association to incident major adverse cardiovascular events (MACEs) and cardiovascular mortality in a general population is not known.

Methods and Results—

We used a newly developed ELISA to measure soluble VAP-1 (sVAP-1) levels in 2775 participants (mean age, 60 years) from a prospective cohort study (the FINRISK 2002). During a mean follow-up of 9 years, 265 participants underwent a MACE, and these participants had higher levels of sVAP-1 than those without MACE (868 ng/mL and 824 ng/mL, respectively,
P
<0.001). In multivariate-adjusted Cox proportional hazard model including traditional Framingham risk factors (age, sex, systolic blood pressure, cholesterol, high-density lipoprotein cholesterol, smoking, prevalent diabetes mellitus, and antihypertensive treatment), sVAP-1 independently predicted incident MACE (
P
=0.0046) and MACE mortality (
P
=0.026). The impact of sVAP-1 in predicting the 9-year absolute risk of MACE was analyzed using integrated discrimination improvement and net reclassification improvement with 10-fold cross-validation. Inclusion of sVAP-1 in the Framingham model improved integrated discrimination improvement (
P
=0.042), and the clinical net reclassification improvement by correctly reclassifying 9% (
P
=0.0019) of people in the intermediate risk (5%–20%) group.

Conclusions—
sVAP-1 associated with increased risk of MACE and MACE mortality in people aged >50 years without prior MACE, and inclusion of sVAP-1 in the risk prediction model improved the clinical net reclassification improvement of incident MACE. Thus, sVAP-1 may be a potential new biomarker for cardiovascular diseases.
Assessment of Censoring Using Coherency-Based Detectors on Dual-Polarized Weather Radar
Authors: Ivić Igor R. , Keränen Reino , Zrnić Dušan S. 
Published: May 2014

Abstract
In Doppler weather radars, signals may exhibit coherency in sample time, whereas noise does not. Additionally, in dual-polarized radars, samples of precipitation echo obtained in the two orthogonally polarized channels are substantially more correlated than samples of noise. Therefore, estimates of auto- and cross correlations can be used individually, collectively, and/or with power measurements to enhance detection of precipitation signals, compared to the approach that uses only power estimates from one channel. A possible advantage of using only estimates of coherency for signal detection is that the detector’s performance is less sensitive to errors in noise power measurements. Hence, censoring is more likely to produce desired false alarm rates even if nonnegligible uncertainties are present in the noise power estimates. In this work these aspects are considered using real data from weather radars. Three novel censoring approaches are evaluated and compared to the censoring approach that uses only estimates of signal and noise powers. The first approach uses only cross-correlation measurements, and the second approach combines these with the lag-1 autocorrelation estimates. The third approach utilizes all estimates as in the previous two approaches in combination with power measurements from the horizontal and the vertical channels. Herein, it is shown that, when more accurate measurements of noise powers are available, the third approach produces the highest detection rates followed by the second and the first approaches. Also, it is corroborated that the first and the second approaches exhibit less sensitivity to inaccurate system noise power measurements than the third one.
Dance therapy in patients with chronic heart failure: a systematic review and a meta-analysis
Authors: Gomes Neto Mansueto , Menezes Mayara Alves , Carvalho Vitor Oliveira 
Published: May 2014

Objective: To see whether dance therapy was more effective than conventional exercise in exercise capacity and health-related quality of life (HRQOL) in patients with chronic heart failure. Design and methods: Systematic review and meta-analysis. We searched MEDLINE, Cochrane Controlled Trials Register, EMBASE, SPORT Scielo, CINAHL (from the earliest date available to August 2013) for randomized controlled trials (RCTs), examining effects of dance therapy versus exercise and/or dance therapy versus control on exercise capacity (VO2peak), and quality-of-life (QOL) in chronic heart failure. Two reviewers selected studies independently. Weighted mean differences (WMDs) and 95% confidence intervals (CIs) were calculated, and heterogeneity was assessed using the I(2) test. Results: Two studies met the study criteria (62 dance therapy patients, 60 exercise patients and 61 controls patients). The results suggested that dance therapy compared with control had a positive impact on peak VO2 and HRQOL. Dance therapy resulted in improvement in: peak VO2 peak weighted mean difference (4.86 95% CI: 2.81 to 6.91) and global HRQOL standardized mean differences (2.09 95% CI: 1.65 to 2.54). Non-significant difference in VO2 peak and HRQOL for participants in the exercise group compared with dance therapy. No serious adverse events were reported. Conclusions: Dance therapy may improve peak VO2 and HRQOL in patients with chronic heart failure (CHF) and could be considered for inclusion in cardiac rehabilitation programmes.
The impact mechanism of social networks on Chinese rural–urban migrant workers’ behaviour and wages
Authors: Wang Chunchao , Lao Huahui , Zhou Xianbo 
Published: May 2014

AbstractChinese domestic rural–urban migrant workers have played a substantial role in economic development since the late 1970s. This article makes an attempt to establish a two-period hiring model interpreting the impact mechanism of social networks on migrant workers’ wages. The findings indicate that the extension of social networks of both firms and workers facilitates a decrease in the information gap between them and improves extra common benefits to both.
Biomechanical Comparison of an Open vs Arthroscopic Approach for Lateral Ankle Instability
Authors: Drakos Mark C. , Behrens Steve B. , Paller Dave , Murphy Conor , DiGiovanni Christopher W. 
Published: May 2014

Background: The current clinical standard for the surgical treatment of ankle instability remains the open modified Broström procedure. Modern advents in arthroscopic technology have allowed physicians to perform certain foot and ankle procedures arthroscopically as opposed to traditional open approaches. Methods: Twenty matched lower extremity cadaver specimens were obtained. Steinman pins were inserted into the tibia and talus with 6 sensors affixed to each pin. Specimens were placed in a Telos ankle stress apparatus in an anteroposterior and then lateral position, while a 1.7 N-m load was applied. For each of these tests, movement of the sensors was measured in 3 planes using the Optotrak Computer Navigation System. Changes in position were calculated and compared with the unloaded state. The anteriortalofibular ligament and the calcaneofibular ligament were thereafter sectioned from the fibula. The aforementioned measurements in the loaded and unloaded states were repeated on the specimens. The sectioned ligaments were then repaired using 2 corkscrew anchors. Ten specimens were repaired using a standard open Broström-type repair, while the matched pairs were repaired using an arthroscopic technique. Measurements were repeated and compared using a paired t test. Results: There was a statistically significant difference between the sectioned state and the other 3 states ( P < .05). There were no statistically significant differences between the intact state and either the open or arthroscopic state ( P > .05). There were no significant differences between the open and arthroscopic repairs with respect to translation and total combined motion during the talar tilt test ( P > .05). Statistically significant differences were demonstrated between the 2 methods in 3 specific axes of movement during talar tilt ( P = .04). Conclusion: Biomechanically effective ankle stabilization may be amenable to a minimally invasive approach. Clinical Relevance: A minimally invasive, arthroscopic approach can be considered for treating patients with lateral ankle instability who have failed conservative treatment.
CBFβ and RUNX1 are required at 2 different steps during the development of hematopoietic stem cells in zebrafish
Authors: Bresciani Erica , Carrington Blake , Wincovitch Stephen , Jones MaryPat , Gore Aniket V. , Weinstein Brant M. , Sood Raman , Liu P. Paul 
Published: May 2014

Key PointsCBFβ is not required for the emergence of nascent HSCs but is essential for a subsequent step before their release from the AGM. RUNX1 is able to drive the emergence of nascent HSCs in the AGM in the absence of its cofactor CBFβ.
miR-217 is an oncogene that enhances the germinal center reaction
Authors: de Yébenes Virginia G. , Bartolomé-Izquierdo Nahikari , Nogales-Cadenas Rubén , Pérez-Durán Pablo , Mur Sonia M. , Martínez Nerea , Di Lisio Lorena , Robbiani Davide F. , Pascual-Montano Alberto , Cañamero Marta , Piris Miguel A. , Ramiro Almudena R. 
Published: May 2014

Key Points
miR-217 enhances the GC reaction by dampening genotoxic-induced Bcl-6 degradation in GC B cells. miR-217 is an oncogene and its overexpression provides a model of miRNA-induced mature B-cell lymphomagenesis.
Fuzzy fixed point theorems in Hausdorff fuzzy metric spaces
Authors: Phiangsungnoen Supak , Sintunavarat Wutiphol , Kumam Poom 
Published: May 2014

Abstract
In this paper, we introduce the concept of fuzzy mappings in Hausdorff fuzzymetric spaces (in the sense of George and Veeramani (Fuzzy Sets Syst.64:395-399, 1994)). We establish the existence of α-fuzzyfixed point theorems for fuzzy mappings in Hausdorff fuzzy metric spaces, whichcan be utilized to derive fixed point theorems for multivalued mappings. We alsogive an illustrative example to support our main result.