bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alternation of histone and DNA methylation in human atherosclerotic carotid plaques
Authors: Napieralski Rudolf , Wagner Ernst , Gebhard Harry , Schmitt Manfred , Zimmermann Alexander , Eckstein Hans-Henning , Greißel Anna , Culmes Mihaela , Zernecke Alma , Pelisek Jaroslav 
Published: May 2015

SummaryLittle is known about epigenetics and its possible role in atherosclerosis. We here analysed histone and DNA methylation and the expression of corresponding methyltransferases in early and advanced human atherosclerotic carotid lesions in comparison to healthy carotid arteries. Western Blotting was performed on carotid plaques from our biobank with early (n=60) or advanced (n=60) stages of atherosclerosis and healthy carotid arteries (n=12) to analyse di-methylation patterns of histone H3 at positions K4, K9 and K27. In atherosclerotic lesions, di-methylation of H3K4 was unaltered and that of H3K9 and H3K27 significantly decreased compared to control arteries. Immunohistochemistry revealed an increased appearance of di-methylated H3K4 in smooth muscle cells (SMCs), a decreased expression of di-methylated H3K9 in SMCs and inflammatory cells, and reduced di-methylated H3K27 in inflammatory cells in advanced versus early atherosclerosis. Expression of corresponding histone methyltransferases MLL2 and G9a was increased in advanced versus early atherosclerosis. Genomic DNA hypomethylation, as determined by PCR for methylated LINE1 and SAT-alpha, was observed in early and advanced plaques compared to control arteries and in cell-free serum of patients with high-grade carotid stenosis compared to healthy volunteers. In contrast, no differences in DNA methylation were observed in blood cells. Expression of DNA-methyltransferase DNMT1 was reduced in atherosclerotic plaques versus controls, DNMT3A was undetectable, and DNMT3B not altered. DNA-demethylase TET1 was increased in atherosclerosisc plaques. The extent of histone and DNA methylation and expression of some corresponding methyltransferases are significantly altered in atherosclerosis, suggesting a possible contribution of epigenetics in disease development.
Microvesicles from platelets: novel drivers of vascular inflammation
Authors: Vajen Tanja , Mause Sebastian , Koenen Rory 
Published: May 2015

SummaryMicrovesicles are receiving increased attention not only as biomarkers but also as mediators of cell communication and as integral effectors of disease. Platelets present a major source of microvesicles and release these microvesicles either spontaneously or upon activation. Platelet-derived microvesicles retain many features of their parent cells and have been shown to exert modulatory effects on vascular and immune cells. Accordingly, microvesicles from platelets can be measured at increased levels in patients with cardiovascular disease or individuals at risk. In addition, isolated microvesicles from platelets were shown to exert immunomodulatory actions on various cell types. In this review the various aspects of platelet-derived microvesicles including release, clearance, measurement, occurrence during disease and relevance for the pathophysiology of vascular inflammation will be discussed.
The impact of selectins on mortality in stable carotid atherosclerosis
Authors: Hoke Matthias , Winter Max-Paul , Wagner Oswald , Exner Markus , Schillinger Martin , Arnold Zsuzsanna , Mlekusch Wolfgang , Maurer Gerald , Koppensteiner Renate , Minar Erich , Goliasch Georg 
Published: May 2015

SummaryCellular adhesion molecules also known as selectins promote recruitment of inflammatory cells into the arterial wall where they interact with lipid particles leading subsequently to plaque formation. The intercellular adhesion molecule-1 (ICAM-1), the vascular cell adhesion molecule-1 (VCAM-1) and the endothelial-leukocyte adhesion molecule 1 (ELAM-1) also known as E-selectin mediate the attachment of leukocytes and have been implicated in the destabilisation of atherosclerotic plaques. Therefore, we hypothesised that plasma selectin levels are associated with adverse clinical outcome. We prospectively studied 855 patients with sonographically confirmed carotid atherosclerosis. During a median follow-up of 6.2 years, corresponding to 5,551 overall person-years, 275 patients (26 %) died. We detected a significant association between cardiovascular mortality and ICAM-1 (adjusted hazard ratio [HR]: 3.43, 95 % confidence interval [CI] 2.00–5.88, p< 0.001) as well as VCAM-1 (adjusted HR: 2.51, 95 % CI 1.45–4.34, p=0.001) when comparing the fourth with the first quartile. Comparable results were obtained for all-cause mortality. In contrast, we could not detect a significant association between E-selectin and all-cause or cardiovascular mortality. We identified the selectins ICAM-1 and VCAM-1 as strong and independent predictors of all-cause and cardiovascular mortality in patients with stable carotid atherosclerosis. These molecules are elevated in states of endothelial activation and might assist to monitor anti-atherosclerotic therapy and select those patients with carotid atherosclerosis, who are at higher risk for cardiovascular events.
D-dimer for prediction of long-term outcome in cryptogenic stroke patients with patent foramen ovale
Authors: Kim Young Dae , Song Dongbeom , Nam Hyo Suk , Lee Kijeong , Yoo Joonsang , Hong Geu-Ru , Lee Hye Sun , Nam Chung Mo , Heo Ji Hoe 
Published: May 2015

SummaryPatent foramen ovale (PFO) is a potential cause of cryptogenic stroke, given the possibility of paradoxical embolism from venous to systemic circulation. D-dimer level is used to screen venous thrombosis. We investigated the risk of embolism and mortality according to the presence of PFO and D-dimer levels in cryptogenic stroke patients. A total of 570 first-ever cryptogenic stroke patients who underwent transesophageal echocardiography were included in this study. D-dimer was assessed using latex agglutination assay during admission. The association of long-term outcomes with the presence of PFO and D-dimer levels was investigated. PFO was detected in 241 patients (42.3 %). During a mean 34.0 ± 22.8 months of follow-up, all-cause death occurred in 58 (10.2 %) patients, ischaemic stroke in 33 (5.8 %), and pulmonary thromboembolism in 6 (1.1 %). Multivariate Cox regression analysis showed that a D-dimer level of > 1,000 ng/ml was an independent predictor for recurrent ischaemic stroke in patients with PFO (hazard ratio 5.341, 95 % confidence interval 1.648–17.309, p=0.005), but not in those without PFO. However, in patients without PFO, a D-dimer level of > 1,000 ng/ml was independently related with all-cause mortality. The risk of pulmonary thromboembolism tended to be high in patients with high D-dimer levels, regardless of PFO. Elevated D-dimer levels in cryptogenic stroke were predictive of the long-term outcome, which differed according to the presence of PFO. The coexistence of PFO and a high D-dimer level increased the risk of recurrent ischaemic stroke. The D-dimer test in cryptogenic stroke patients may be useful for predicting outcomes and deciding treatment strategy.
Anticoagulant therapy of cancer patients: Will patient selection increase overall survival?
Authors: Versteeg Henri , Borensztajn Keren , Spek C. Arnold 
Published: May 2015

SummaryAlready since the early 1800s, it has been recognised that malignancies may provoke thromboembolic complications, and indeed cancer patients are at increased risk of developing venous thrombosis. Interestingly, case control studies of deep-vein thrombosis suggested that low-molecular-weight heparin (LMWH) improved survival of cancer patients. This led to the hypothesis that cancer cells might ‘take advantage’ of a hypercoagulable state to more efficiently metastasise. Initial randomised placebo control trials showed that LMWH improve overall survival of cancer patients, especially in those patients with a relatively good prognosis. The failure of recent phase III trials, however, tempers enthusiasm for anticoagulant treatment in cancer patients despite an overwhelming body of literature showing beneficial effects of anticoagulants in preclinical models. Instead of discarding LMWH as potential (co)treatment modality in cancer patients, these disappointing recent trials should guide future preclinical research on anticoagulants in cancer biology. Most and for all, the underlying mechanisms by which coagulation drives tumour progression need to be elucidated. This could ultimately allow selection of cancer patients most likely to benefit from anticoagulant treatment and/or from targeted therapy downstream of coagulation factor signalling.
Fetal Mammalian Heart Generates a Robust Compensatory Response to Cell Loss
Authors: Sturzu Anthony C. , Rajarajan Kuppusamy , Passer Derek , Plonowska Karolina , Riley Alyssa , Tan Timothy C. , Sharma Arun , Xu Adele F. , Engels Marc C. , Feistritzer Rebecca , Li Guang , Selig Martin K. , Geissler Richard , Robertson Keston D. , Scherrer-Crosbie Marielle , Domian Ibrahim J. , Wu Sean M. 
Published: May 2015

Background—
Heart development is tightly regulated by signaling events acting on a defined number of progenitor and differentiated cardiac cells. Although loss of function of these signaling pathways leads to congenital malformation, the consequences of cardiac progenitor cell or embryonic cardiomyocyte loss are less clear. In this study, we tested the hypothesis that embryonic mouse hearts exhibit a robust mechanism for regeneration after extensive cell loss.

Methods and Results—
By combining a conditional cell ablation approach with a novel blastocyst complementation strategy, we generated murine embryos that exhibit a full spectrum of cardiac progenitor cell or cardiomyocyte ablation. Remarkably, ablation of up to 60% of cardiac progenitor cells at embryonic day 7.5 was well tolerated and permitted embryo survival. Ablation of embryonic cardiomyocytes to a similar degree (50% to 60%) at embryonic day 9.0 could be fully rescued by residual myocytes with no obvious adult cardiac functional deficit. In both ablation models, an increase in cardiomyocyte proliferation rate was detected and accounted for at least some of the rapid recovery of myocardial cellularity and heart size.

Conclusion—
Our study defines the threshold for cell loss in the embryonic mammalian heart and reveals a robust cardiomyocyte compensatory response that sustains normal fetal development.
Efficacy and Harms of Direct Oral Anticoagulants in the Elderly for Stroke Prevention in Atrial Fibrillation and Secondary Prevention of Venous Thromboembolism
Authors: Sharma Manuj , Cornelius Victoria R. , Patel Jignesh P. , Davies J. Graham , Molokhia Mariam 
Published: May 2015

Background—
Evidence regarding the use of direct oral anticoagulants (DOACs) in the elderly, particularly bleeding risks, is unclear despite the presence of greater comorbidities, polypharmacy, and altered pharmacokinetics in this age group.

Methods and Results—
We performed a systematic review and meta-analysis of randomized trials of DOACs (dabigatran, apixaban, rivaroxaban, and edoxaban) for efficacy and bleeding outcomes in comparison with vitamin K antagonists (VKA) in elderly participants (aged ≥75 years) treated for acute venous thromboembolism or stroke prevention in atrial fibrillation. Nineteen studies were eligible for inclusion, but only 11 reported data specifically for elderly participants. The efficacy in managing thrombotic risks for each DOAC was similar or superior to VKA in elderly patients. A nonsignificantly higher risk of major bleeding than with VKA was observed with dabigatran 150 mg (odds ratio, 1.18; 95% confidence interval, 0.97–1.44) but not with the 110-mg dose. Significantly higher gastrointestinal bleeding risks with dabigatran 150 mg (1.78, 1.35–2.35) and dabigatran 110 mg (1.40, 1.04–1.90) and lower intracranial bleeding risks than VKA for dabigatran 150 mg (0.43, 0.26–0.72) and dabigatran 110 mg (0.36, 0.22–0.61) were also observed. A significantly lower major bleeding risk in comparison with VKA was observed for apixaban (0.63, 0.51–0.77), edoxaban 60 mg (0.81, 0.67–0.98), and 30 mg (0.46, 0.38–0.57), whereas rivaroxaban showed similar risks.

Conclusions—
DOACs demonstrated at least equal efficacy to VKA in managing thrombotic risks in the elderly, but bleeding patterns were distinct. In particular, dabigatran was associated with a higher risk of gastrointestinal bleeding than VKA. Insufficient published data for apixaban, edoxaban, and rivaroxaban indicate that further work is needed to clarify the bleeding risks of these DOACs in the elderly.

Systematic Review Registration—

http://www.crd.york.ac.uk/PROSPERO
. Unique identifier: PROSPERO CRD42014007171/
Race and Ethnicity, Obesity, Metabolic Health, and Risk of Cardiovascular Disease in Postmenopausal Women
Authors: Schmiegelow Michelle D. , Hedlin Haley , Mackey Rachel H. , Martin Lisa W. , Vitolins Mara Z. , Stefanick Marcia L. , Perez Marco V. , Allison Matthew , Hlatky Mark A. 
Published: May 2015

Background
It is unclear whether obesity unaccompanied by metabolic abnormalities is associated with increased cardiovascular disease risk across racial and ethnic subgroups.

Methods and Results

We identified 14 364 postmenopausal women from the Women's Health Initiative who had data on fasting serum lipids and serum glucose and no history of
cardiovascular disease
or diabetes at baseline. We categorized women by body mass index (

in kg/m
2

) as normal weight (
body mass index
18.5 to <25), overweight (body mass index 25 to <30), or obese (
body mass index
≥30) and by metabolic health, defined first as the metabolic syndrome (metabolically unhealthy: ≥3 metabolic abnormalities) and second as the number of metabolic abnormalities. We used Cox proportional hazards regression to assess associations between baseline characteristics and cardiovascular risk. Over 13 years of follow‐up, 1101 women had a first
cardiovascular disease
event (coronary heart disease or ischemic stroke). Among black women without metabolic syndrome, overweight women had higher adjusted cardiovascular risk than normal weight women (hazard ratio [
HR
] 1.49), whereas among white women without metabolic syndrome, overweight women had similar risk to normal weight women (
HR
0.92, interaction
P
=0.05). Obese black women without metabolic syndrome had higher adjusted risk (
HR
1.95) than obese white women (
HR
1.07; interaction
P
=0.02). Among women with only 2 metabolic abnormalities, cardiovascular risk was increased in black women who were overweight (
HR
1.77) or obese (
HR
2.17) but not in white women who were overweight (
HR
0.98) or obese (
HR
1.06). Overweight and obese women with ≤1 metabolic abnormality did not have increased cardiovascular risk, regardless of race or ethnicity.

Conclusions
Metabolic abnormalities appeared to convey more cardiovascular risk among black women.
Joint Effect of Hypertension and Elevated Serum Phosphorus on the Risk of Mortality in National Health and Nutrition Examination Survey‐III
Authors: Vart Priya , Nigatu Yeshambel T. , Jaglan Ajay , van Zon Sander K. R. , Shafique Kashif 
Published: May 2015

Background
Elevated serum phosphorus might aggravate the effect of hypertension on mortality. The objective of this study was to examine the joint effect of hypertension and serum phosphorus on the risk of mortality.

Methods and Results

A large prospective (n=15 833), population‐based cohort of participants from the National Health and Nutritional Examination Survey
III
was examined to test potential synergism between hypertension, elevated serum phosphorus, and the risk of mortality. Interaction on additive scale and multiplicative scale was estimated. After a median follow‐up of 14.3 years, 1691 cases of cardiovascular mortality and 3875 cases of all‐cause mortality were identified. Interaction was observed between hypertension and elevated serum phosphorus on the additive scale for cardiovascular mortality (relative excess risk due to interaction, 0.99, 95%
CI
: 0.06; 1.92, adjusted for age, gender, race, and estimated glomerular filtration rate). No statistically significant interaction was found between hypertension and serum phosphorus for all‐cause mortality on the additive scale. No significant interaction was detected on the multiplicative scale. In sensitivity analysis, excluding participants who died in first 2 years and adjustment for additional confounders resulted in essentially similar findings.

Conclusions
The joint effect of hypertension and elevated serum phosphorus was larger than the sum of the independent effects on cardiovascular mortality but not on all‐cause mortality. Future studies should investigate whether controlling elevated serum phosphorus in hypertensive individuals helps in prevention of extra risk of cardiovascular mortality.
Cardiovascular Disease Performance Measures in the Outpatient Setting in India: Insights From the American College of Cardiology's PINNACLE India Quality Improvement Program (PIQIP)
Authors: Kalra Ankur , Pokharel Yashashwi , Hira Ravi S. , Risch Samantha , Vicera Veronique , Li Qiong , Kalra Ram N. , Kerkar Prafulla G. , Kumar Ganesh , Maddox Thomas M. , Oetgen William J. , Glusenkamp Nathan , Turakhia Mintu P. , Virani Salim S. 
Published: May 2015

Background

India has a growing burden of cardiovascular disease (
CVD
), yet data on the quality of outpatient care for patients with coronary artery disease, heart failure, and atrial fibrillation in India are very limited. We collected data on performance measures for 68 196 unique patients from 10 Indian cardiology outpatient departments from January 1, 2011, to February 5, 2014, in the American College of Cardiology's
PINNACLE
(Practice Innovation and Clinical Excellence) India Quality Improvement Program (
PIQIP
).
PIQIP
is India's first national outpatient
CVD
quality‐improvement program.

Methods and Results

In the
PIQIP
registry, we estimated the prevalence of
CVD
risk factors (hypertension, diabetes, dyslipidemia, and current tobacco use) and
CVD
among outpatients. We examined adherence with performance measures established by the American College of Cardiology, the American Heart Association, and the American Medical Association Physician Consortium for Performance Improvement for coronary artery disease, heart failure, and atrial fibrillation. There were a total of 68 196 patients (155 953 patient encounters), with a mean age of 50.6 years (
SD
18.2 years). Hypertension was present in 29.7% of patients, followed by diabetes (14.9%), current tobacco use (7.6%), and dyslipidemia (6.5%). Coronary artery disease was present in 14.8%, heart failure was noted in 4.0%, and atrial fibrillation was present in 0.5% of patients. Among eligible patients, the reported use of medications was as follows: aspirin in 48.6%, clopidogrel in 37.1%, and statin‐based lipid‐lowering therapy in 50.6% of patients with coronary artery disease;
RAAS
(renin–angiotensin–aldosterone system) antagonist in 61.9% and beta‐blockers in 58.1% of patients with heart failure; and oral anticoagulants in 37.0% of patients with atrial fibrillation.

Conclusions

This pilot study, initiated to improve outpatient
CVD
care in India, presents our preliminary results and barriers to data collection and demonstrates that such an initiative is feasible in a resource‐limited environment. In addition, we attempted to outline areas for further improvement in outpatient
CVD
care delivery in India.
Three-Dimensional Structure and Evolution of the Moisture Field in the MJO
Authors: Adames Ángel F. , Wallace John M. 
Published: May 2015

Abstract
The large-scale circulation features that determine the structure and evolution of MJO-related moisture and precipitation fields are examined using a linear analysis protocol based on daily 850- minus 150-hPa global velocity potential data. The analysis is augmented by a compositing procedure that emphasizes the structural features over the Indo-Pacific warm pool sector (60°E–180°) that give rise to the eastward propagation of the enhanced moisture and precipitation.
It is found that boundary layer (BL) convergence in the low-level easterlies to the east of the region of maximum ascent produces a deep but narrow plume of equatorial ascent that moistens the midtroposphere, while weakly diffluent flow above the BL spreads moisture away from the equator. Vertical advection of moisture from this plume of ascent accounts for the eastward propagation of the positive moisture anomalies across the Maritime Continent into the western Pacific. When the convection is first developing over the Indian Ocean, horizontal moisture advection contributes to both the eastward propagation and the amplification of the positive moisture anomalies along the equator to the east of the region of enhanced convection. Neither horizontal advection nor the net moistening from vertical advection and the apparent moisture sink exhibit significant westward tilt with height in the equatorial plane, but when they are superposed they explain the westward tilt of the moisture field. The strong spatial correlation between relative humidity and vertical velocity underscores the important role of equatorial wave dynamics in shaping the structure and evolution of the MJO.
LAPS–LOWICE: A Real-Time System for the Assessment of Low-Level Icing Conditions and Their Effect on Wind Power
Authors: Gregow E. , Bernstein B. , Wittmeyer I. , Hirvonen J. 
Published: May 2015

AbstractThe wind power industry is highly sensitive to weather, and there is a clear impact on turbine efficiency associated with icing, which can cause significant power losses and even result in the total shutdown of wind farms. Therefore, accurate analyses and forecasts of wind- and icing-related meteorological variables are of great importance. To this end, the Local Analysis and Prediction System (LAPS)–LOWICE system has been developed to produce real-time, hourly estimates of the presence, intensity, and impacts of icing on wind power production. As part of this development, it became clear that power losses did not correlate well with measured icing loads but correlated reasonably well with the time history of icing rate in combination with ice loss due to melting, sublimation, and shedding.
Massively Parallel DNA Sequencing Successfully Identified Seven Families With Deafness-Associated MYO6 Mutations
Authors: Miyagawa Maiko , Nishio Shin-ya , Kumakawa Kozo , Usami Shin-ichi 
Published: May 2015

Objectives: To elucidate the involvement of MYO6 mutations, known to be responsible for DFNA22/DFNB37, in Japanese hearing loss patients through the use of genetic analysis. Methods: Genomic variations responsible for hearing loss were identified by massively parallel DNA sequencing (MPS) of 63 target candidate genes in 1120 Japanese hearing loss patients, and the detailed clinical features for the patients with MYO6 mutations were collected and analyzed. Results: Four mutations were successfully found in 7 families exhibiting autosomal dominant inheritance. All of the patients showed progressive hearing loss, but hearing type and onset age varied. Further, none of the affected patients showed any associated symptoms, such as hypertrophic cardiomyopathy or retinitis pigmentosa. Conclusions: MPS is powerful tool for the identification of rare causative deafness gene mutations, such as MYO6. The clinical characteristics noted in the present study not only confirmed the findings of previous reports but provided important new clinical information.