bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protein S Is a Cofactor for Platelet and Endothelial Tissue Factor Pathway Inhibitor-α but Not for Cell Surface–Associated Tissue Factor Pathway Inhibitor
Authors: Wood Jeremy P. , Ellery Paul E. R. , Maroney Susan A. , Mast Alan E. 
Published: November 2013

Objective—
Tissue factor pathway inhibitor (TFPI) is produced in 2 isoforms: TFPIα, a soluble protein in plasma, platelets, and endothelial cells, and TFPIβ, a glycosylphosphatidylinositol-anchored protein on endothelium. Protein S (PS) functions as a cofactor for TFPIα, enhancing the inhibition of factor Xa. However, PS does not alter the inhibition of prothrombinase by TFPIα, and PS interactions with TFPIβ are undescribed. Thus, the physiological role and scope of the PS–TFPI system remain unclear.

Approach and Results—
Here, the cofactor activity of PS toward platelet and endothelial TFPIα and endothelial TFPIβ was quantified. PS enhanced the inhibition of factor Xa by TFPIα from platelets and endothelial cells and stabilized the TFPIα/factor Xa inhibitory complex, delaying thrombin generation by prothrombinase. By contrast, PS did not enhance the inhibitory activity of TFPIβ or a membrane-anchored form of TFPI containing the PS-binding third Kunitz domain (K1K2K3) although PS did function as a cofactor for K1K2K3 enzymatically released from the cell surface.

Conclusions—
The PS–TFPI anticoagulant system is limited to plasma TFPIα and TFPIα released from platelets and endothelial cells. PS likely functions to localize solution-phase TFPIα to the cell surface, where factor Xa is bound. PS does not alter the activity of membrane-associated TFPI. Because activated platelets release TFPIα and PS, the PS–TFPIα anticoagulant system may act physiologically to dampen thrombin generation at the platelet surface.
Preliminary Biomarkers for Identification of Human Ascending Thoracic Aortic Aneurysm
Authors: Black Kendra M. , Masuzawa Akihiro , Hagberg Robert C. , Khabbaz Kamal R. , Trovato Mary E. , Rettagliati Verna M. , Bhasin Manoj K. , Dillon Simon T. , Libermann Towia A. , Toumpoulis Ioannis K. , Levitsky Sidney , McCully James D. 
Published: November 2013

Background

Human ascending thoracic aortic aneurysms (
ATAAs
) are life threatening and constitute a leading cause of mortality in the
United States
. Previously, we demonstrated that collagens α2(V) and α1(XI)
mRNA
and protein expression levels are significantly increased in
ATAAs
.

Methods and Results

In this report, the authors extended these preliminary studies using high‐throughput proteomic analysis to identify additional biomarkers for use in whole blood real‐time
RT
‐
PCR
analysis to allow for the identification of
ATAAs
before dissection or rupture. Human
ATAA
samples were obtained from male and female patients aged 65±14 years. Both bicuspid and tricuspid aortic valve patients were included and compared with nonaneurysmal aortas (mean diameter 2.3 cm). Five biomarkers were identified as being suitable for detection and identification of
ATAAs
using q
RT
‐
PCR
analysis of whole blood. Analysis of 41 samples (19 small, 13 medium‐sized, and 9 large
ATAAs
) demonstrated the overexpression of 3 of these transcript biomarkers correctly identified 79.4% of patients with
ATAA
of ≥4.0 cm (
P
<0.001, sensitivity 0.79,
CI
=0.62 to 0.91; specificity 1.00, 95%
CI
=0.42 to 1.00).

Conclusion

A preliminary transcript biomarker panel for the identification of
ATAAs
using whole blood q
RT
‐
PCR
analysis in men and women is presented.
Protective Effect of Time Spent Walking on Risk of Stroke in Older Men
Authors: Jefferis Barbara J. , Whincup Peter H. , Papacosta Olia , Wannamethee S. Goya 
Published: November 2013

Background and Purpose—
Older adults have the highest risks of stroke and the lowest physical activity levels. It is important to quantify how walking (the predominant form of physical activity in older age) is associated with stroke.

Methods—
A total of 4252 men from a UK population-based cohort reported usual physical activity (regular walking, cycling, recreational activity, and sport) in 1998 to 2000. Nurses took fasting blood samples and made anthropometric measurements.

Results—

Among 3435 ambulatory men free from cardiovascular disease and heart failure in 1998 to 2000, 195 first strokes occurred during 11-year follow-up. Men walked a median of 7 (interquartile range, 3–12) hours/wk; walking more hours was associated with lower heart rate, D-dimer, and higher forced expiratory volume in 1 second. Compared with men walking 0 to 3 hours/wk, men walking 4 to 7, 8 to 14, 15 to 21, and >22 hours had age- and region-adjusted hazard ratios (95% confidence intervals) for stroke of 0.89 (0.60–1.31), 0.63 (0.40–1.00), 0.68 (0.35–1.32), and 0.36 (0.14–0.91), respectively,
P
(trend)=0.006. Hazard ratios were somewhat attenuated by adjustment for established and novel risk markers (inflammatory and hemostatic markers and cardiac function [N-terminal pro-brain natriuretic peptide]) and walking pace, but linear trends remained. There was little evidence for a dose–response relationship between walking pace and stroke; comparing average pace or faster to a baseline of slow pace, the hazard ratio for stroke was 0.65 (95% confidence interval, 0.44–0.97), which was fully mediated by time spent walking.

Conclusions—
Time spent walking was associated with reduced risk of onset of stroke in dose–response fashion, independent of walking pace. Walking could form an important part of stroke-prevention strategies in older people.
Time to Brain Imaging in Acute Stroke Is Improving
Authors: Sauser Kori , Burke James F. , Levine Deborah A. , Scott Phillip A. , Meurer William J. 
Published: November 2013

Background and Purpose—
Patients with acute ischemic stroke benefit from rapid evaluation and treatment, and timely brain imaging is a necessary component. We determined the effect of a targeted behavioral intervention on door-to-imaging time (DIT) among patients with ischemic stroke treated with tissue-type plasminogen activator. Second, we examined the variation in DIT accounted for by patient-level and hospital-level factors.

Methods—
The Increasing Stroke Treatment through Interventional behavioral Change Tactics (INSTINCT) trial was a cluster-randomized, controlled trial involving 24 Michigan hospitals. The intervention aimed to increase tissue-type plasminogen activator utilization. Detailed chart abstractions collected data for 557 patients with ischemic stroke. We used a series of hierarchical linear mixed-effects models to evaluate the effect of the intervention on DIT (difference-in-differences analysis) and used patient-level and hospital-level explanatory variables to decompose variation in DIT.

Results—

DIT improved over time, without a difference between intervention and control hospitals (intervention: 23.7–19.3 minutes, control: 28.9–19.2 minutes;
P
=0.56). Adjusted DIT was faster in patients who arrived by ambulance (7.2 minutes; 95% confidence interval, 4.1–10.2), had severe strokes (1.0 minute per +5-point National Institutes of Health Stroke Scale; 95% confidence interval, 0.1–2.0), and presented in the postintervention period (4.9 minutes; 95% confidence interval, 2.3–7.4). After accounting for these factors, 13.8% of variation in DIT was attributable to hospital. Neither hospital stroke volume nor stroke center status was associated with DIT.

Conclusions—
Performance on DIT improved similarly in intervention and control hospitals, suggesting that nonintervention factors explain the improvement. Hospital-level factors explain a modest proportion of variation in DIT, but further research is needed to identify the hospital-level factors responsible.
Zonal Gradients in the Lower Atmosphere and Upper Ocean across the Windward Antilles during Midsummer 2012
Authors: Jury Mark R. 
Published: November 2013

AbstractThis observational study examines zonal gradients in the lower atmosphere and upper ocean across the windward Antilles during midsummer 2012. While earlier work reported on meridional confluence, here the focus is on the zonal enrichment of trade winds by upstream shallow seas and islands. Intercomparisons along 18.2°N are made between modern reanalysis and satellite estimates, and coastal station, moored buoy, aircraft, and radiosonde observations for one case and as a June–July 2012 average. Mean gradients per 100 km east of Puerto Rico were 0.2 g kg−1 for 925-hPa specific humidity, 0.16°C for SST, 0.01 m for sea level, and 2.0 × 10−3 g kg−1 for cloud water. Zonal changes in the lower atmosphere occur in three stages: 1) Atlantic, where westward ocean currents, strong trade winds, and subsidence prevail; 2) Antilles, where ocean currents diminish and sea temperatures increase; and 3) island, where trade winds abate [−1 m s−1 (100 km)−1] and diurnal evapotranspiration greater than 10 mm day−1 offsets large-scale subsidence producing a localized convection.
Probability of Convectively Induced Turbulence Associated with Geostationary Satellite–Inferred Cloud-Top Cooling
Authors: Monette Sarah A. , Sieglaff Justin M. 
Published: November 2013

AbstractThe probability of turbulence in the region of identified cloud-top cooling (CTC) from a satellite-based algorithm is calculated. It is found that the overall turbulence probability is low, with only 3.93% of 738 Boeing 737s and 757s experiencing light or greater turbulence. Predicting the probability of turbulence is done using a Bayesian scheme. This prediction scheme relies on the CTC magnitude as well as the relationship between the CTC and aircraft. At higher CTC magnitudes [≤−16 K (15 min)−1], turbulence is more common, with the conditional probability of turbulence exceeding the conditional probability of no turbulence. Aircraft with flight levels that are less than 8000 ft (~2440 m) above the cloud height also have a higher conditional probability of turbulence than no turbulence. Overall, the Bayesian scheme is found to be more skillful when compared with use of climatological information alone.
Inconclusive Evidence for Allergic Rhinitis to Predict a Prolonged or Chronic Course of Acute Rhinosinusitis
Authors: Frerichs Kristine A. , Nigten Gea , Romeijn Kalynda , Kaper Nina M. , Grolman Wilko , van der Heijden Geert J. M. G. 
Published: November 2013

ObjectiveTo systematically review the evidence on allergic rhinitis as a predictor for a prolonged or chronic course in adult patients with acute rhinosinusitis.Data SourcesPubmed, EMBASE, and the Cochrane library.Review MethodsA systematic literature search was performed on March 15, 2013. During screening of title and abstract, 3 authors independently selected studies on allergic rhinitis as a predictor for the course of acute rhinosinusitis in adults. The reported study design was assessed for directness of evidence and risk of bias. We aimed to extract prior and posterior probabilities for a prolonged or chronic course of acute rhinosinusitis.ResultsOf 13,202 retrieved articles, 2 articles were eligible for study assessment. They provided a high directness of evidence but carried a high risk of bias. The studies showed an incidence of a prolonged and chronic course of, respectively,. 19 (95% confidence interval [CI]. 16‐.23) and. 05 (95% CI,. 02‐.13). In patients with allergic rhinitis, the incidence was. 25 (95% CI,. 18‐.35) and. 14 (95% CI,. 04‐.34), so the added value of allergic rhinitis to predict a prolonged course is 6% and to predict a chronic course 8%.Conclusion and RecommendationWhile the 2 included studies suggest that allergic rhinitis adds little to the prediction of a prolonged or chronic course in patients with acute rhinosinusitis, they carry a high risk of bias. As the available evidence does not provide grounds for different management of patients with and without allergic rhinitis, namely, according to clinical practice guidelines, both can be managed with expectant observation and symptomatic treatment.
Dexamethasone Otoprotection in a Multidose Cisplatin Ototoxicity Mouse Model
Authors: Hughes Amy Lawrason , Hussain Nighat , Pafford Ryan , Parham Kourosh 
Published: November 2013

ObjectiveTo develop a murine model for multidose administration of cisplatin that produces significant hearing threshold elevations and to use this model to assess the protective properties of intratympanic (IT) dexamethasone against cisplatin ototoxicity.Study DesignControlled repeated measures design.SettingTranslational research laboratory.Subjects and MethodsIntraperitoneal (IP) cisplatin, 2 or 3 mg/kg/day, was administered for a total of 5 or 10 days in young CBA/J mice. Pure‐tone evoked auditory brainstem response (ABR) thresholds were performed on days 7, 14, 21, and 28 to evaluate hearing threshold shifts. After development of the optimal dosing regimen, 15 mice received IT dexamethasone (24 mg/ml) in one ear and IT saline in the contralateral ear.ResultsSignificant threshold elevations were obtained for the 2 and 3 mg/kg/day 10 day groups, but both had high mortality rates and were excluded as potential multidose murine models. The 3 mg/kg/day 5 day group had a lower mortality rate and significant ABR threshold elevations for all frequencies on days 7, 14, 21, and 28. Using this dosing model, no statistically significant difference between IT dexamethasone and saline treated ears was found.ConclusionsUnlike previous single dose models, IT dexamethasone did not have an otoprotective effect in a multidose murine model of cisplatin ototoxicity.
Toll-like receptor 4 gene polymorphism 1196 C/T does not influence the risk of neuropsychiatric systemic lupus erythematosus in Polish population – a preliminary report
Authors: Bogaczewicz A , Sobow T , Bogaczewicz J , Kaleta B , Sysa-Jedrzejowska A , Robak E , Lukaszkiewicz J , Dariusz S , Wozniacka A 
Published: November 2013

Objective Recent data indicate that Toll-like receptors (TLRs) participate in various neuropathologic conditions, including ictogenesis, myelin disruptions associated with chronic alcohol abuse, behavioral and cognitive dysfunctions associated with alcohol-induced neuroinflammatory damage, and activation of microglia to reduce amyloid β deposits. As seizures and depression are well known neuropsychiatric syndromes in systemic lupus erythematosus (SLE) the aim of the study was to investigate whether TLR4 gene polymorphism 1196C/T (rs4986791, Thr399Ile) was a candidate for susceptibility of development of neuropsychiatric systemic lupus erythematosus (NPSLE). Methods The study covered 60 patients with SLE and 100 healthy individuals. TLR4 1196C/T genotyping was performed by real-time polymerase chain reaction with the SimpleProbe. Results The SLE group comprised 86.7% of patients with wild-type homozygotes CC and 13.3% heterozygotes CT and no homozygotes TT. The control group consisted of 85% wild-type homozygotes CC, 15% heterozygotes CT and no homozygotes TT. The frequencies of genotype and allele distribution in SLE patients did not differ significantly from those of the control subjects. The probability of describing the possible risk of SLE imputed to genotype did not significantly differ in comparison with the healthy individuals ( p = 0.77, odds ratio = 0.87, 95% confidence interval 0.34–2.19). A significant genotype association of genotype CC with arthritis was found in SLE patients ( p = 0.02). It was further confirmed by a significant association of a dominant allele C with arthritis ( p = 0.02). No association between CC and CT genotypes of TLR4 1196C/T and NPSLE was found. Allele distribution of TLR4 1196C/T also was not associated with NPSLE. No other significant differences were found in genotype and allele frequencies regarding clinical manifestation of SLE patients. Conclusion In the Polish population of SLE patients, 1196C/T polymorphism of TLR4 gene does not increase the risk of development of NPSLE; however, genotype CC and a dominant allele C is associated with arthritis in the course of SLE.
Multidimensional approach to non-cystic fibrosis bronchiectasis: the FACED score
Authors: Martínez-García Miguel Á. , de Gracia Javier , Vendrell Relat Monserrat , Girón Rosa-Maria , Máiz Carro Luis , de la Rosa Carrillo David , Olveira Casilda 
Published: November 2013

Bronchiectasis is a multidimensional disease and, therefore, its severity or prognosis cannot be adequately quantified by analysing one single variable. The objective of the present study was to develop a multidimensional score that classifies the severity of bronchiectasis according to its prognosis.This is an observational multicentre study including 819 patients diagnosed with non-cystic fibrosis bronchiectasis using high-resolution computed tomography. 397 subjects were selected at random to construct the score while the remaining 422 were used for its validation. The outcome was 5-year all-cause mortality after radiological diagnosis. A logistic regression analysis was used to select the variables included in the final score.The final seven-point score incorporated five dichotomised variables: forced expiratory volume in 1 s % predicted (F, cut-off 50%, maximum value 2 points); age (A, cut-off 70 years, maximum value 2 points); presence of chronic colonisation byPseudomonas aeruginosa(C, dichotomic, maximum value 1 point); radiological extension (E, number of lobes affected, cut-off two lobes, maximum value 1 point); and dyspnoea (D, cut-off grade II on the Medical Research Council scale, maximum value 1 point) to construct the FACED score. The validation cohort confirmed the score’s validity.We conclude that this easy-to-use multidimensional grading system proved capable of accurately classifying the severity of bronchiectasis according to its prognosis.
emPHasis-10: development of a health-related quality of life measure in pulmonary hypertension
Authors: Yorke Janelle , Corris Paul , Gaine Sean , Gibbs J. Simon R. , Kiely David G. , Harries Carl , Pollock Val , Armstrong Iain 
Published: November 2013

The aim of this study was to develop a measure of the impact of pulmonary hypertension (PH) on health-related quality of life (HRQoL) as there is a need for a short, validated instrument that can be used in routine clinical practice.Interviews were conducted with 30 PH patients to derive 32 statements, which were presented as a semantic differential six-point scale (0–5), with contrasting adjectives at each end. This item list was completed by patients attending PH clinics across the UK and Ireland. Rasch analysis was applied to identify items fitting a uni-dimensional model.226 patients (mean age 55.6±14 years; 70% female) with PH (82% had pulmonary arterial hypertension) completed the study questionnaires. 10 of the 32 items demonstrated fit to the Rasch model (Chi-squared 16; p>0.05) and generated the emPHasis-10 questionnaire. Test–retest (intraclass correlation coefficient 0.95, n=33) and internal consistency (Chronbach’s α=0.9) were strong. emPHasis-10 scores correlated consistently with other relevant measures and discriminated subgroups of patients stratified by World Health Organization functional class (ANOVA F=1.73; p<0.001).The emPHasis-10 is a short questionnaire for assessing HRQoL in pulmonary arterial hypertension. It has excellent measurement properties and is sensitive to differences in relevant clinical parameters. It is freely available for clinical and academic use.
Molecular adaptation of telomere associated genes in mammals
Authors: Morgan Claire C , Mc Cartney Ann M , Donoghue Mark TA , Loughran Noeleen B , Spillane Charles , Teeling Emma C , O’Connell Mary J 
Published: November 2013

AbstractBackgroundPlacental mammals display a huge range of life history traits, including size, longevity, metabolic rate and germ line generation time. Although a number of general trends have been proposed between these traits, there are exceptions that warrant further investigation. Species such as naked mole rat, human and certain bat species all exhibit extreme longevity with respect to body size. It has long been established that telomeres and telomere maintenance have a clear role in ageing but it has not yet been established whether there is evidence for adaptation in telomere maintenance proteins that could account for increased longevity in these species.ResultsHere we carry out a molecular investigation of selective pressure variation, specifically focusing on telomere associated genes across placental mammals. In general we observe a large number of instances of positive selection acting on telomere genes. Although these signatures of selection overall are not significantly correlated with either longevity or body size we do identify positive selection in the microbat speciesMyotis lucifugusin functionally important regions of the telomere maintenance genesDKC1andTERT, and in naked mole rat in the DNA repair geneBRCA1.ConclusionThese results demonstrate the multifarious selective pressures acting across the mammal phylogeny driving lineage-specific adaptations of telomere associated genes. Our results show that regardless of the longevity of a species, these proteins have evolved under positive selection thereby removing increased longevity as the single selective force driving this rapid rate of evolution. However, evidence of molecular adaptations specific to naked mole rat andMyotis lucifugushighlight functionally significant regions in genes that may alter the way in which telomeres are regulated and maintained in these longer-lived species.
Cross-over study of influence of oral vitamin C supplementation on inflammatory status in maintenance hemodialysis patients
Authors: Zhang KunYing , Li YinHui , Cheng XuYang , Liu Li , Bai WenYing , Guo WeiYa , Wu LeiYun , Zuo Li 
Published: November 2013

Abstract

Background
Both vitamin C deficiency and inflammation are prevalent in maintenance hemodialysis (MHD) patients. In this study, we aimed to elucidate the effect of oral vitamin C supplementation on inflammatory status in MHD patients with low vitamin C level and high hypersensitive C-reactive protein (hs-CRP) level.

Methods
A total of 128 patients were recruited in our present study. Patients were divided into two groups. In group 1 (n = 67), patients were orally administered with 200 mg/day vitamin C in the first 3 months, and then the vitamin C supplementation was withdrawn in the next 3 months. In group 2 (n = 61), patients were not given vitamin C in the first 3 months, and then they were orally administered with 200 mg/day in the next 3 months. Levels of hs-CRP, prealbumin, albumin and hemoglobin as well as the EPO resistance index (ERI) were determined at the baseline and every 3 months throughout the study. Plasma vitamin C level was determined by high-performance liquid chromatography with UV detection.

Results
Among the 128 patients, 28 of them dropped out of the study before completion. Consequently, a total of 100 patients (group 1: n = 48; group 2: n = 52) were included in the final analysis. At the baseline, the plasma vitamin C level of all patients was less than 4 μg/mL. However, this proportion was decreased to 20% after the vitamin C supplementation for 3 months. Compared with patients without the vitamin C supplementation, a decreased level of hs-CRP and an increased level of prealbumin were induced by the vitamin C supplementation for 3 months in both groups. However, levels of these biomarkers returned to their original state after the supplementation was withdrawn. Same beneficial effects on plasma albumin, hemoglobin and ERI response to vitamin C supplementation were observed in the two groups without statistical significance.

Conclusions
The inflammatory status in MHD patients with plasma vitamin C deficiency and high levels of inflammatory markers could be partially improved by long-term oral administration of small doses of vitamin C.

Trial registration
The clinical trial number: NCT01356433.