bluuebunny/crossref_metadata_2025_split huggingface dataset:
Venous thromboembolism in cancer patients – Risk scores and recent randomised controlled trials
Authors: Ay Cihan , Pabinger Ingrid , Thaler Johannes 
Published: July 2012

SummaryCancer patients are at increased risk of developing venous thromboembolism (VTE). Guidelines recommend routine thromboprophylaxis in hospitalised acutely ill cancer patients and in myeloma patients receiving combination treatments including thalidomide or lenalidomide. Currently, thromboprophylaxis is not recommended in cancer out-patients. It is the aim of this review to give an overview of studies that applied scores for the risk assessment of cancer-related VTE. We will also discuss randomised controlled trials (RCTs) that investigated primary thromboprophylaxis in cancer patients. Recently, Khorana et al. published a practical and reproducible risk assessment score that includes clinical and laboratory parameters for the stratification of cancer patients according to their propensity to develop VTE. Patients assigned to the high-risk group are likely to benefit most from primary thromboprophylaxis. This score was validated in prospective and retrospective observational studies. In the Vienna Cancer and Thrombosis Study (CATS) the score was expanded by adding two biomarkers, and the prediction of VTE was considerably improved. In recent RCTs including cancer patients with different malignancies it was shown that thromboprophylaxis is safe and effective. However, VTE incidence rates were low. To date, no data is available from interventional studies applying thromboprophylaxis in cancer patients categorised into high-risk groups on the basis of risk assessment with scores. From the available literature we conclude that risk assessment for VTE is feasible in cancer patients;however, interventional studies to investigate the safety and efficacy of thromboprophylaxis in a high risk cancer population have yet to be performed.
Erythrocytes, leukocytes and platelets as a source of oxidative stress in chronic vascular diseases: Detoxifying mechanisms and potential therapeutic options
Authors: Madrigal-Matute Julio , Martinez-Pinna Roxana , Ramos-Mozo Priscila , Blanco-Colio Luis , Moreno Juan , Tarin Carlos , Burillo Elena , Fernandez-Garcia Carlos , Egido Jesus , Meilhac Olivier , Michel Jean-Baptiste , Martin-Ventura Jose 
Published: July 2012

SummaryOxidative stress is involved in the chronic pathological vascular remodelling of both abdominal aortic aneurysm and occlusive atherosclerosis. Red blood cells (RBCs), leukocytes and platelets present in both, aneurysmal intraluminal thrombus and intraplaque haemorraghes, could be involved in the redox imbalance inside diseased arterial tissues. RBCs haemolysis may release the pro-oxidant haemoglobin (Hb), which transfers heme to tissue and low-density lipoproteins. Heme-iron potentiates molecular, cell and tissue toxicity mediated by leukocytes and other sources of reactive oxygen species (ROS). Polymorphonuclear neutrophils release myeloperoxidase and, along with activated platelets, produce superoxide mediated by NADPH oxidase, causing oxidative damage. In response to this pro-oxidant milieu, several anti-oxidant molecules of plasma or cell origin can prevent ROS production. Free Hb binds to haptoglobin (Hp) and once Hp-Hb complex is endocytosed by CD163, liberated heme is converted into less toxic compounds by heme oxygenase-1. Iron homeostasis is mainly regulated by transferrin, which transports ferric ions to other cells. Transferrin-bound iron is internalised via endocytosis mediated by transferrin receptor. Once inside the cell, iron is mainly stored by ferritin. Other non hemo-iron related antioxidant enzymes (e.g. superoxide dismutase, catalase, thioredoxin and peroxiredoxin) are also involved in redox modulation in vascular remodelling. Oxidative stress is a main determinant of chronic pathological remodelling of the arterial wall, partially linked to the presence of RBCs, leukocytes, platelets and oxidised fibrin within tissue and to the imbalance between pro-/anti-oxidant molecules. Understanding the complex mechanisms underlying redox imbalance could help to define novel potential targets to decrease atherothrombotic risk.
A novel regulatory element between the human FGA and FGG genes
Authors: Fish Richard J. , Neerman-Arbez Marguerite 
Published: July 2012

SummaryHigh circulating fibrinogen levels correlate with cardiovascular disease (CVD) risk. Fibrinogen levels vary between people and also change in response to physiological and environmental stimuli. A modest proportion of the variation in fibrinogen levels can be explained by genotype, inferring that variation in genomic sequences that regulate the fibri-nogen genes (FGA, FGB and FGG) may affect hepatic fibrinogen production and perhaps CVD risk. We previously identified a conserved liver enhancer in the fibrinogen gene cluster (CNC12), between FGB and FGA. Genome-wide Chromatin immunoprecipitation-sequencing (ChIP-seq) demonstrated that transcription factors which bind fibrinogen gene promoters also interact with CNC12, as well as two potential fibrinogen enhancers (PFE), between FGA and FGG. Here we show that one of the PFE sequences has potent hepatocyte enhancer activity. Using a luciferase reporter gene system, we found that PFE2 enhances minimal promoter- and FGA promoter-driven gene expression in hepatoma cells, regardless of its orientation with respect to the promoters. A region within PFE2 bears a short series of conserved nucleotides which maintain enhancer activity without flanking sequence. We also demonstrate that PFE2 is a liver enhancer in vivo, driving enhanced green fluorescent protein expression in transgenic zebrafish larval livers. Our study shows that combining public domain ChIP-seq data with in vitro and in vivo functional tests can identify novel fibrinogen gene cluster regulatory sequences. Variation in such elements could affect fibrinogen production and influence CVD risk.
Circulating microparticles in carriers of factor V Leiden with and without a history of venous thrombosis
Authors: Campello Elena , Spiezia Luca , Radu Claudia M. , Bon Maria , Gavasso Sabrina , Zerbinati Patrizia , Woodhams Barry , Tormene Daniela , Prandoni Paolo , Simioni Paolo 
Published: July 2012

SummaryAlthough factor V Leiden (FVL) is a major determinant of thrombotic risk, the reason why less than 10% of carriers eventually develop venous thromboembolic (VTE) events is unknown. Recent observations suggest that circulating levels of microparticles (MP) may contribute to the thrombogenic profile of FVL carriers. We measured the plasma level of annexin V-MP (AMP) platelet-MP (PMP), endothelial-MP (EMP), leukocyte-MP (LMP) and tissue factor-bearing MP (TF+MP), and the MP procoagulant activity (PPL) in 142 carriers of FVL (of these 30 homozygous and 49 with prior VTE), and in 142 age and gender-matched healthy individuals. The mean (± SD) level of AMP was 2,802 ± 853 MP/ μl in carriers and 1,682 ± 897 in controls (p<0.0001). A statistically significant difference between homozygous and heterozygous carriers of FVL was seen in the level of PMP, EMP and LMP, but not in that of the remaining parameters. When the analysis was confined to carriers with and without a VTE history, the mean level of AMP was 3,110 ± 791 MP/ μl in the former, and 2,615 ± 839 MP/μl in the latter (p<0.005). The mean level of all subtypes of circulating MP showed a similar pattern. The PPL clotting time was 39 ± 9 seconds (sec) in carriers, and 52 ± 15 sec in controls (p=0.003); and was 35 ± 8 sec in carriers with prior thrombosis, and 41 ± 10 sec in thrombosis-free carriers (p<0.005). Our study results suggest that circulating MP may contribute to the development of thrombosis in carriers of FVL mutation.
Atrial fibrillation in pigs induces left atrial endocardial transcriptional remodelling
Authors: Cerveró Jorge , Segura Víctor , Macías Alfonso , Gavira Juan , Montes Ramón , Hermida José 
Published: July 2012

SummaryThe leading cause of cardioembolic stroke is atrial fibrillation (AF), which predisposes to atrial thrombus formation. Although rheological alterations promote a hypercoagulable environment, as yet undefined factors contribute to thrombogenesis. The role of the endocardium has barely been explored. To approach this topic, rapid atrial pacing (RAP) was applied in four pigs to mimic A F. Left and right endocardial cells were isolated separately and their gene expression pattern was compared with that of four control pigs. The AF-characteristic rhythm disorders and endothelial nitric oxide synthase down-regulation were successfully reproduced, and validated RAP to mimic A F. A change was observed in the transcriptomic endocardial profile after RAP: the expression of 364 genes was significantly altered (p<0.01), 29 of them having passed the B>0 criteria. The left atrial endocardium [325 genes (7 genes, B>0)] was largely responsible for such alterations. Blood coagulation, blood vessel morphogenesis and inflammatory response are among the most significant altered functions, and help to explain the activation of coagulation observed after RAP: D-dimer, 0.49 (1.63) vs. 0.23 (0.24) mg/l [median (interquartile range)] in controls, p=0.02. Furthermore, three genes directly related to thrombotic processes were differentially expressed after RAP: FGL2 [fold change (FC)=0.85; p=0.007], APLP2 (FC=-0.47; p=0.005) and ADAMTS-18 (FC=-0.69; p=0.004). We demonstrate for the first time that AF induces a global expression change in the left atrial endocardium associated with an activation of blood coagulation. The nature of some of the altered functions and genes provides clues to identify new therapeutic targets.
Psychometric properties of the 8-item Morisky Medication Adherence Scale in patients taking warfarin
Authors: Wang Ye , Kong Ming , Ko Yu 
Published: July 2012

SummaryThere is no patient-reported medication adherence measure that has been validated in Singapore. This study aimed to validate the 8-item Morisky Medication Adherence Scale (MMAS) in patients taking warfarin in Singapore. A cross-sectional survey was conducted in a convenience sample of 151 patients taking warfarin at an anticoagulation clinic in 2011. Respondents completed the MMAS in English or Chinese depending on their preference. The MMAS had a Cronbach′s alpha of 0.56 and good criterion-related validity as the scale scores were associated with warfarin refill rates (p = 0.04). Respondents with higher MMAS scores were found to have a higher percentage of International Normalised Ratios (INRs) within the therapeutic range (p = 0.01), higher adherence to diet recommendations (p = 0.02), and less perceived difficulty in taking all medications (p < 0.001); they were also more likely to take warfarin at the same time every day (p < 0.001). Confirmatory factor analysis showed that the eight items loaded onto one factor (RMSEA = 0.03). The sensitivity, specificity, positive predictive value and negative predictive value of the MMAS for identifying patients with poor INR control were 73.0%, 35.6%, 49.5% and 60.5%, respectively, using the time in the therapeutic INR range as the gold standard. This study shows that the 8-item MMAS has good validity and moderate reliability in patients taking warfarin. Future research is needed to investigate the scale′s psychometric properties in other patient populations and clinical settings.
Myocardial Notch Signaling Reprograms Cardiomyocytes to a Conduction-Like Phenotype
Authors: Rentschler Stacey , Yen Alberta H. , Lu Jia , Petrenko Nataliya B. , Lu Min Min , Manderfield Lauren J. , Patel Vickas V. , Fishman Glenn I. , Epstein Jonathan A. 
Published: July 2012

Background—

Notch signaling has previously been shown to play an essential role in regulating cell fate decisions and differentiation during cardiogenesis in many systems including
Drosophila
,
Xenopus
, and mammals. We hypothesized that Notch may also be involved in directing the progressive lineage restriction of cardiomyocytes into specialized conduction cells.

Methods and Results—
In hearts where Notch signaling is activated within the myocardium from early development onward, Notch promotes a conduction-like phenotype based on ectopic expression of conduction system–specific genes and cell autonomous changes in electrophysiology. With the use of an in vitro assay to activate Notch in newborn cardiomyocytes, we observed global changes in the transcriptome, and in action potential characteristics, consistent with reprogramming to a conduction-like phenotype.

Conclusions—
Notch can instruct the differentiation of chamber cardiac progenitors into specialized conduction-like cells. Plasticity remains in late-stage cardiomyocytes, which has potential implications for engineering of specialized cardiovascular tissues.
Statistics of Solar Cycle–La Niña Connection: Correlation of Two Autocorrelated Time Series
Authors: Haam Eddie , Tung Ka-Kit 
Published: July 2012

Abstract
Both the 11-yr solar cycle and the El Niño–Southern Oscillation (ENSO) phenomena are quasi periodic, with periods of 9–11 and 3–4 yr, respectively. There have been claims that the two are correlated, with the sun at its peak in sunspot number presumably forcing a cold event in the equatorial Pacific. However, both phenomena are also highly autocorrelated. Caution should be exercised when testing for the statistical significance of the correlation of two autocorrelated time series. The solar peak years can coincide with cold ENSO by chance, even if the two time series are independent, and the coincidence then persists for many cycles due to their autocorrelation, before drifting apart. This study demonstrates that this is indeed the case using the Quinn El Niño index (1525–1987), which is a chronicle of observations of El Niño–related events, and the sunspot number (SSN) series going back to 1750. Appropriate statistical tests are suggested that can test for correlation, taking into account autocorrelation applicable to the shorter instrumental records. There is so far no solar peak–La Niña connection found that is statistically significant.
The North Atlantic Oscillation and the North Atlantic Jet Variability: Precursors to NAO Regimes and Transitions
Authors: Luo Dehai , Cha Jing 
Published: July 2012

Abstract
In this paper, precursors to the North Atlantic Oscillation (NAO) and its transitions are investigated to understand the dynamical cause of the interdecadal NAO variability from dominant negative (NAO−) events during 1950–77 (P1) to dominant positive (NAO+) events during 1978–2010 (P2). It is found that the phase of the NAO event depends strongly on the latitudinal position of the North Atlantic jet (NAJ) prior to the NAO onset. The NAO− (NAO+) events occur frequently when the NAJ core prior to the NAO onset is displaced southward (northward), as the situation within P1 (P2). Thus, the northward (southward) shift of the NAJ from its mean position is a precursor to the NAO+ (NAO−) event.
This finding is further supported by results obtained from a weakly nonlinear model. Furthermore, the model results show that, when the Atlantic mean zonal wind exceeds a critical strength under which the dipole anomaly prior to the NAO onset is stationary, in situ NAO− (NAO+) events, which are events not preceded by opposite events, can occur frequently during P1 (P2) when the Atlantic storm track is not too strong. This mean zonal wind condition is easily satisfied during P1 and P2. However, when the Atlantic storm track (mean zonal wind) prior to the NAO onset is markedly intensified (weakened), the NAO event can undergo a transition from one phase to another, especially in a relatively strong background westerly wind, the Atlantic storm track has to be strong enough to produce a phase transition.
Robust Identification of Global Greening Phase Patterns from Remote Sensing Vegetation Products
Authors: Dahlke Carola , Loew Alexander , Reick Christian 
Published: July 2012

AbstractThe fraction of absorbed photosynthetically active radiation (fAPAR) is an essential diagnostic variable to investigate the temporal and spatial dynamics of the terrestrial biosphere. The present study provides a new method to assess global vegetation greening phase dynamics, derived from fAPAR time series from four different remote sensing products. A robust algorithm is developed to detect intra-annual greening phase patterns and derive seasonality patterns of vegetation dynamics at the global scale. The comparison of four independent remote sensing datasets shows significantly consistent global spatiotemporal patterns at the 95% confidence level. Regions where the remote sensing datasets show consistent results, as well as regions where at least one of the used remote sensing datasets deviates, can be identified. The derived global greening phase dataset and analysis method provides a solid framework for the evaluation of global vegetation models.
Comments on “Changes to the North Atlantic Subtropical High and Its Role in the Intensification of Summer Rainfall Variability in the Southeastern United States”
Authors: Diem Jeremy E. 
Published: July 2012

Abstract
In a recent article, Li et al. examined changes in the summer-season location of the western ridge of the North Atlantic subtropical high from 1948 to 2007 because there has been an increase in interannual summer rainfall variability in the southeastern United States. The following major conclusions by Li et al. are incorrect: the western ridge has undergone a significant westward trend since the late 1970s; the western ridge had increased meridional movement during 1978–2007 compared to 1948–1977; and global warming appears to be contributing to the westward expansion of the western ridge. Results presented in this paper reveal that the western ridge has been moving eastward over the past three decades, there was no change in latitudinal variance, and a westward movement of the western ridge should not be linked to global warming.
Importance of Ocean Dynamics for the Skewness of the Indian Ocean Dipole Mode
Authors: Ogata Tomomichi , Xie Shang-Ping , Lan Jian , Zheng Xiaotong 
Published: July 2012

AbstractInterannual anomalies of sea surface temperature (SST), wind, and cloudiness in the southeastern tropical Indian Ocean (SE-TIO) show negative skewness. In this research, asymmetry between warm and cold episodes in the SE-TIO and the importance of ocean dynamics are investigated. A coupled model simulation and observations show an asymmetric relationship between SST and the thermocline depth in the SE-TIO where SST is more sensitive to an anomalous shoaling than to deepening of the thermocline. This asymmetric thermocline feedback on SST is a result of a deep mean thermocline. Sensitivity experiments with an ocean general circulation model (OGCM) show that a negative SST skewness arises in response to sinusoidal zonal wind variations that are symmetric between the westerly and easterly phases. Heat budget analysis with an OGCM hindcast also supports the importance of ocean dynamics for SST skewness off Sumatra and Java.
AMO-Forced Regional Processes Affecting Summertime Precipitation Variations in the Central United States
Authors: Veres Michael C. , Hu Qi 
Published: July 2012

Abstract
Numerous previous studies have provided insight into the influence of the Atlantic multidecadal oscillation (AMO) on North American precipitation. However, these studies focused on large-scale processes, and additional studies are needed to gain understanding of local and regional processes that develop in different phases of the AMO and substantiate its influences on precipitation. In this study, the Weather Research and Forecasting (WRF) regional model is used to examine AMO-forced local and regional processes and how they have affected summertime precipitation variation in the central United States.
While moisture transport and convergence by the Great Plains low-level jet have been recognized as necessary conditions for summer precipitation, model simulations show similar low-level moisture flux convergence in the central United States between the cold and warm phases of the AMO. However, there was a strong moistening in the lower troposphere during the AMO cold phase, making the atmosphere more unstable for convection and precipitation. The source of the moisture was found to be a strong positive surface evaporation–precipitation feedback initiated and sustained by increased relative vorticity along a frontal zone. Along the frontal zone, isentropic stretching of the upper-level atmosphere and cyclonic circulation anomalies increased the relative vorticity during the AMO cold phase, providing the dynamic support needed to release the low-level moist instability and produce the increased precipitation. These results indicate that the dynamics of the circulation in the AMO cold phase played key roles to organize regional vorticity processes that further sustained a coupling of precipitation and the surface evaporation and perpetuated the precipitation.
Precursor Signals and Processes Associated with MJO Initiation over the Tropical Indian Ocean*
Authors: Zhao Chongbo , Li Tim , Zhou Tianjun 
Published: July 2012

Abstract
The precursor signals of convection initiation associated with the Madden–Julian oscillation (MJO) in boreal winter were investigated through the diagnosis of the 40-yr ECMWF Re-Analysis (ERA-40) data for the period 1982–2001. The western equatorial Indian Ocean (WIO) is a key region of the MJO initiation. A marked increase of specific humidity and temperature in the lower troposphere appears 5–10 days prior to the convection initiation. The increased moisture and temperature cause a convectively more unstable stratification, leading to the onset of convection.
A diagnosis of lower-tropospheric moisture (heat) budgets shows that the moisture (temperature) increase is caused primarily by the horizontal advection of the mean specific humidity (temperature) by the MJO flow. The anomalous flow is primarily determined by the downstream Rossby wave response to a preceding suppressed-phase MJO over the eastern Indian Ocean, whereas the upstream Kelvin wave response to the previous eastward-propagating convective-phase MJO is not critical. An idealized numerical experiment further supports this claim.
The Southern Hemisphere (SH) midlatitude Rossby wave train and associated wave activity flux prior to the MJO initiation were diagnosed. It is found that SH midlatitude Rossby waves may contribute to MJO initiation over the western Indian Ocean through wave energy accumulation. Idealized numerical experiments confirm that SH midlatitude perturbations play an important role in affecting the MJO variance in the tropics. A barotropic energy conversion diagnosis indicates that there is continuous energy transfer from the mean flow to intraseasonal disturbances over the initiation region, which may help trigger MJO development.