bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacogenetics role in the safety of acenocoumarol therapy
Authors: Jiménez-Varo Enrique , Cañadas-Garre Marisa , Gutiérrez-Pimentel María José , Henriques Cristina Isabel , Pinheiro Ana Margarida , Calleja-Hernández Miguel Ángel 
Published: June 2014

SummaryVitamin K antagonists (VKAs) remain as the most prescribed drug for treatment and prevention of thrombotic disorders in many countries, despite the recent approval of the new oral anticoagulants (NOACs). Although effectiveness and safety of VKAs are tightly associated to maintaining the patient within the international normalised ratio (INR) therapeutic range (TWR), they have been likened to NOACs when patients are in good INR control (≥66% of TWR). Therefore, assessing the safety of patients should be a priority in the selection of the anticoagulation therapy. The aim of this study was to evaluate the association between CYP2C9*2, CYP2C9*3, VKORC1, CYP4F2*3, ABCB1 C3435T, APOE, CYP2C19*2 and CYP2C19*17 gene polymorphisms and treatment safety in 128 patients diagnosed with atrial fibrillation or venous thromboembolism during the initial first seven months of acenocoumarol therapy. After the first month, VKORC1-Tallele and APOE-E3/E3 genotype were independently associated to higher time above therapeutic range (TAR) and lower time below the therapeutic range (TBR). After seven months, VKORC1 T-allele predicted higher TAR, and was also associated to increased INR>4, particularly the TT-genotype (odds ratio [OR]: 32; 95% confidence interval [CI95%]: 6–175; p=810–5). C-alleles for CYP2C9*3 (OR: 5.5; CI95%: 1.8–17; p=0.003) and ABCB1 (OR: 8.9;CI95%: 1.1–70; p=0.039) independently influenced on INR>6 . Patients VKORC1-TT/ABCB1-C remained 26.8% [19.7–38.9] TAR, with associated relative risk (RR) for INR>4 1.8 higher (CI95%: 1.2–2.5; p=0.015). Patients VKORC1-TT also presented the highest risk of bleeding events (RR: 3.5;CI95%: 1.4–8.4; p=0,010). In conclusion, VKORC1, CYP2C9*3, APOE and ABCB1 genotypes should be considered in prevention of overanticoagulation and bleeding events in the initiation of acenocoumarol therapy.
A barbárie moderna do agronegócio-latifundiário-exportador e suas implicações socioambientais
Authors: Camacho Rodrigo Simão 
Published: June 2014

O modelo agrário/agrícola nacional, dominado pelo capital nacional e internacional, baseado no latifúndio, na monocultura e na exportação, traz conseqüências negativas sociais e ambientais. Por isso, esse modelo representa, contraditoriamente, ao mesmo tempo a Barbárie e a Modernidade. Neste sentido, a alternativa contrária a esse modelo está na construção de uma reforma agrária que permita a produção da agricultura camponesa e de todos os povos do campo de maneira plena, pois estes mantêm uma relação equilibrada com a natureza, produzem cultura no campo e cumprem um papel importante na produção de alimentos saudáveis para toda a população.
Dietary Intake of Calcium and Phosphorus and Serum Concentration in Relation to the Risk of Coronary Artery Calcification in Asymptomatic Adults
Authors: Kwak Sang Mi , Kim Jong Sung , Choi Yuni , Chang Yoosoo , Kwon Min-Jung , Jung Jin-Gyu , Jeong Chul , Ahn Jiin , Kim Hyun Soo , Shin Hocheol , Ryu Seungho 
Published: June 2014

Objective—
The current data regarding the association between calcium and phosphorus and cardiovascular disease are lacking. The aim of this study was to explore whether dietary calcium and phosphorus intake and their serum levels are associated with the prevalence of coronary artery calcification (CAC) using cardiac computed tomography in asymptomatic participants without a history of chronic kidney disease or cardiovascular disease.

Approach and Results—

A cross-sectional study was performed in 23 652 Korean participants (40.8±7.3 years, male 83.5%) without chronic kidney disease (estimated glomerular filtration rate≥60 mL/min per 1.73 m
2
) or clinically overt cardiovascular disease, who underwent cardiac computed tomographic estimation of CAC scores as part of a general health checkup in addition to completing a self-administered food frequency questionnaire. We assessed the relationship of dietary calcium and phosphorus intake and serum levels with CAC scores using both multivariate-adjusted Tobit models and multinomial logistic regression models. Neither dietary calcium nor phosphorus intake was consistently associated with CAC scores. However, the serum calcium, phosphorus, and calcium–phosphorus product levels were significantly associated with the CAC score ratios. In multivariable-adjusted models, the CAC score ratios (95% confidence intervals) comparing the highest quartiles of serum calcium, phosphorus, and calcium–phosphorus product levels to the lowest quartiles were 1.89 (1.36–2.64), 3.33 (2.55–4.35), and 3.98 (3.00–5.28), respectively (
P
for trend <0.001).

Conclusions—
Elevated serum levels of calcium, phosphorus, and calcium–phosphorus product, but not dietary consumption, are associated with increased CAC scores. Our findings should be explored in further research.
Nitric Oxide Prevents Aortic Neointimal Hyperplasia by Controlling Macrophage Polarization
Authors: Lavin Begoña , Gómez Monica , Pello Oscar M. , Castejon Borja , Piedras Maria J. , Saura Marta , Zaragoza Carlos 
Published: June 2014

Objective—
Nitric oxide synthase 3 (NOS3) prevents neointima hyperplasia by still unknown mechanisms. To demonstrate the significance of endothelial nitric oxide in the polarization of infiltrated macrophages through the expression of matrix metalloproteinase (MMP)-13 in neointima formation.

Approach and Results—
After aortic endothelial denudation, NOS3 null mice show elevated neointima formation, detecting increased mobilization of LSK (lineage-negative [Lin]-stem-cell antigen 1 [SCA1]+KIT+) progenitor cells, and high ratios of M1 (proinflammatory) to M2 (resolving) macrophages, accompanied by high expression of interleukin-5, interleukin-6, MCP-1 (monocyte chemoattractant protein), VEGF (vascular endothelial growth factor), GM-CSF (granulocyte-macrophage colony stimulating factor), interleukin-1β, and interferon-γ. In conditional c-Myc knockout mice, in which M2 polarization is defective, denuded aortas showed extensive wall thickening as well. Conditioned medium from NOS3-deficient endothelium induced extensive repolarization of M2 macrophages to an M1 phenotype, and vascular smooth muscle cells proliferated and migrated faster in conditioned medium from M1 macrophages. Among the different proteins participating in cell migration, MMP-13 was preferentially expressed by M1 macrophages. M1-mediated vascular smooth muscle cell migration was inhibited when macrophages were isolated from MMP-13–deficient mice, whereas exogenous administration of MMP-13 to vascular smooth muscle cell fully restored migration. Excess vessel wall thickening in mice lacking NOS3 was partially reversed by simultaneous deletion of MMP-13, indicating that NOS3 prevents neointimal hyperplasia by preventing MMP-13 activity. An excess of M1-polarized macrophages that coexpress MMP-13 was also detected in human carotid samples from endarterectomized patients.

Conclusions—
These findings indicate that at least M1 macrophage-mediated expression of MMP-13 in NOS3 null mice induces neointima formation after vascular injury, suggesting that MMP-13 may represent a new promising target in vascular disease.
Epigenome-Wide Association Study of Fasting Blood Lipids in the Genetics of Lipid-Lowering Drugs and Diet Network Study
Authors: Irvin Marguerite R. , Zhi Degui , Joehanes Roby , Mendelson Michael , Aslibekyan Stella , Claas Steven A. , Thibeault Krista S. , Patel Nikita , Day Kenneth , Jones Lindsay Waite , Liang Liming , Chen Brian H. , Yao Chen , Tiwari Hemant K. , Ordovas Jose M. , Levy Daniel , Absher Devin , Arnett Donna K. 
Published: June 2014

Background—
Genetic research regarding blood lipids has largely focused on DNA sequence variation; few studies have explored epigenetic effects. Genome-wide surveys of DNA methylation may uncover epigenetic factors influencing lipid metabolism.

Methods and Results—

To identify whether differential methylation of cytosine-(phosphate)-guanine dinucleotides (CpGs) correlated with lipid phenotypes, we isolated DNA from CD4+ T cells and quantified the proportion of sample methylation at >450 000 CpGs by using the Illumina Infinium HumanMethylation450 Beadchip in 991 participants of the Genetics of Lipid Lowering Drugs and Diet Network. We modeled the percentage of methylation at individual CpGs as a function of fasting very-low-density lipoprotein cholesterol and triglycerides (TGs) by using mixed linear regression adjusted for age, sex, study site, cell purity, and family structure. Four CpGs (cg00574958, cg17058475, cg01082498, and cg09737197) in intron 1 of carnitine palmitoyltransferase 1A (
CPT1A
) were strongly associated with very-low low-density lipoprotein cholesterol (
P
=1.8×10
–21
to 1.6×10
–8
) and TG (
P
=1.6×10
–26
to 1.5×10
–9
). Array findings were validated by bisulfite sequencing. We performed quantitative polymerase chain reaction experiments demonstrating that methylation of the top CpG (cg00574958) was correlated with
CPT1A
expression. The association of cg00574958 with TG and
CPT1A
expression were replicated in the Framingham Heart Study (
P
=4.1×10
–14
and 3.1×10
–13
, respectively). DNA methylation at
CPT1A
cg00574958 explained 11.6% and 5.5% of the variation in TG in the discovery and replication cohorts, respectively.

Conclusions—

This genome-wide epigenomic study identified
CPT1A
methylation as strongly and robustly associated with fasting very-low low-density lipoprotein cholesterol and TG. Identifying novel epigenetic contributions to lipid traits may inform future efforts to identify new treatment targets and biomarkers of disease risk.
The American Heart Association Life's Simple 7 and Incident Cognitive Impairment: The REasons for Geographic And Racial Differences in Stroke (REGARDS) Study
Authors: Thacker Evan L. , Gillett Sarah R. , Wadley Virginia G. , Unverzagt Frederick W. , Judd Suzanne E. , McClure Leslie A. , Howard Virginia J. , Cushman Mary 
Published: June 2014

Background

Life's Simple 7 is a new metric based on modifiable health behaviors and factors that the American Heart Association uses to promote improvements to cardiovascular health (
CVH
). We hypothesized that better Life's Simple 7 scores are associated with lower incidence of cognitive impairment.

Methods and Results

For this prospective cohort study, we included
RE
asons for Geographic And Racial Differences in Stroke (
REGARDS
) participants aged 45+ who had normal global cognitive status at baseline and no history of stroke (N=17 761). We calculated baseline Life's Simple 7 score (range, 0 to 14) based on smoking, diet, physical activity, body mass index, blood pressure, total cholesterol, and fasting glucose. We identified incident cognitive impairment using a 3‐test measure of verbal learning, memory, and fluency obtained a mean of 4 years after baseline. Relative to the lowest tertile of Life's Simple 7 score (0 to 6 points), odds ratios of incident cognitive impairment were 0.65 (0.52, 0.81) in the middle tertile (7 to 8 points) and 0.63 (0.51, 0.79) in the highest tertile (9 to 14 points). The association was similar in blacks and whites, as well as outside and within the Southeastern stroke belt region of the United States.

Conclusions

Compared with low
CVH
, intermediate and high
CVH
were both associated with substantially lower incidence of cognitive impairment. We did not observe a dose‐response pattern; people with intermediate and high levels of
CVH
had similar incidence of cognitive impairment. This suggests that even when high
CVH
is not achieved, intermediate levels of
CVH
are preferable to low
CVH
.
A Critical Role for the Vascular Endothelium in Functional Neurovascular Coupling in the Brain
Authors: Chen Brenda R. , Kozberg Mariel G. , Bouchard Matthew B. , Shaik Mohammed A. , Hillman Elizabeth M. C. 
Published: June 2014

Background
The functional modulation of blood flow in the brain is critical for brain health and is the basis of contrast in functional magnetic resonance imaging. There is evident coupling between increases in neuronal activity and increases in local blood flow; however, many aspects of this neurovascular coupling remain unexplained by current models. Based on the rapid dilation of distant pial arteries during cortical functional hyperemia, we hypothesized that endothelial signaling may play a key role in the long‐range propagation of vasodilation during functional hyperemia in the brain. Although well characterized in the peripheral vasculature, endothelial involvement in functional neurovascular coupling has not been demonstrated.

Methods and Results

We combined in vivo exposed‐cortex multispectral optical intrinsic signal imaging (
MS
‐
OISI
) with a novel in vivo implementation of the light‐dye technique to record the cortical hemodynamic response to somatosensory stimulus in rats before and after spatially selective endothelial disruption. We demonstrate that discrete interruption of endothelial signaling halts propagation of stimulus‐evoked vasodilation in pial arteries, and that wide‐field endothelial disruption in pial arteries significantly attenuates the hemodynamic response to stimulus, particularly the early, rapid increase and peak in hyperemia.

Conclusions
Involvement of endothelial pathways in functional neurovascular coupling provides new explanations for the spatial and temporal features of the hemodynamic response to stimulus and could explain previous results that were interpreted as evidence for astrocyte‐mediated control of functional hyperemia. Our results unify many aspects of blood flow regulation in the brain and body and prompt new investigation of direct links between systemic cardiovascular disease and neural deficits.
Precipitation Estimation from the ARM Distributed Radar Network during the MC3E Campaign
Authors: Giangrande Scott E. , Collis Scott , Theisen Adam K. , Tokay Ali 
Published: June 2014

AbstractThis study presents radar-based precipitation estimates collected during the 2-month U.S. Department of Energy Atmospheric Radiation Measurement Program (ARM)–NASA Midlatitude Continental Convective Clouds Experiment (MC3E). Emphasis is on the usefulness of radar observations from the C-band and X-band scanning ARM precipitation radars (CSAPR and XSAPR, respectively) for rainfall estimation products to distances within 100 km of the Lamont, Oklahoma, ARM facility. The study utilizes a dense collection of collocated ARM, NASA Global Precipitation Measurement, and nearby surface Oklahoma Mesonet gauge records to evaluate radar-based hourly rainfall products and campaign-optimized methods over individual gauges and for areal rainfall characterizations. Rainfall products are also evaluated against the performance of a regional NWS Weather Surveillance Radar-1988 Doppler (WSR-88D) S-band dual-polarization radar product. Results indicate that the CSAPR system may achieve similar point– and areal–gauge bias and root-mean-square (RMS) error performance to a WSR-88D reference for the variety of MC3E deep convective events sampled. The best campaign rainfall performance was achieved when using radar relations capitalizing on estimates of the specific attenuation from the CSAPR system. The XSAPRs demonstrate limited capabilities, having modest success in comparison with the WSR-88D reference for hourly rainfall accumulations that are under 10 mm. All rainfall estimation methods exhibit a reduction by a factor of 1.5–2.5 in RMS errors for areal accumulations over a 15-km2 NASA dense gauge network, with the smallest errors typically associated with dual-polarization radar methods.
Impacts of Projected Climate Change over the Lake Champlain Basin in Vermont
Authors: Guilbert Justin , Beckage Brian , Winter Jonathan M. , Horton Radley M. , Perkins Timothy , Bomblies Arne 
Published: June 2014

AbstractThe Lake Champlain basin is a critical ecological and socioeconomic resource of the northeastern United States and southern Quebec, Canada. While general circulation models (GCMs) provide an overview of climate change in the region, they lack the spatial and temporal resolution necessary to fully anticipate the effects of rising global temperatures associated with increasing greenhouse gas concentrations. Observed trends in precipitation and temperature were assessed across the Lake Champlain basin to bridge the gap between global climate change and local impacts. Future shifts in precipitation and temperature were evaluated as well as derived indices, including maple syrup production, days above 32.2°C (90°F), and snowfall, relevant to managing the natural and human environments in the region. Four statistically downscaled, bias-corrected GCM simulations were evaluated from the Coupled Model Intercomparison Project phase 5 (CMIP5) forced by two representative concentration pathways (RCPs) to sample the uncertainty in future climate simulations. Precipitation is projected to increase by between 9.1 and 12.8 mm yr−1 decade−1 during the twenty-first century while daily temperatures are projected to increase between 0.43° and 0.49°C decade−1. Annual snowfall at six major ski resorts in the region is projected to decrease between 46.9% and 52.4% by the late twenty-first century. In the month of July, the number of days above 32.2°C in Burlington, Vermont, is projected to increase by over 10 days during the twenty-first century.
Impact of Soil Moisture–Atmosphere Interactions on Surface Temperature Distribution
Authors: Berg Alexis , Lintner Benjamin R. , Findell Kirsten L. , Malyshev Sergey , Loikith Paul C. , Gentine Pierre 
Published: June 2014

Abstract
Understanding how different physical processes can shape the probability distribution function (PDF) of surface temperature, in particular the tails of the distribution, is essential for the attribution and projection of future extreme temperature events. In this study, the contribution of soil moisture–atmosphere interactions to surface temperature PDFs is investigated. Soil moisture represents a key variable in the coupling of the land and atmosphere, since it controls the partitioning of available energy between sensible and latent heat flux at the surface. Consequently, soil moisture variability driven by the atmosphere may feed back onto the near-surface climate—in particular, temperature. In this study, two simulations of the current-generation Geophysical Fluid Dynamics Laboratory (GFDL) Earth System Model, with and without interactive soil moisture, are analyzed in order to assess how soil moisture dynamics impact the simulated climate. Comparison of these simulations shows that soil moisture dynamics enhance both temperature mean and variance over regional “hotspots” of land–atmosphere coupling. Moreover, higher-order distribution moments, such as skewness and kurtosis, are also significantly impacted, suggesting an asymmetric impact on the positive and negative extremes of the temperature PDF. Such changes are interpreted in the context of altered distributions of the surface turbulent and radiative fluxes. That the moments of the temperature distribution may respond differentially to soil moisture dynamics underscores the importance of analyzing moments beyond the mean and variance to characterize fully the interplay of soil moisture and near-surface temperature. In addition, it is shown that soil moisture dynamics impacts daily temperature variability at different time scales over different regions in the model.
A Description of Local and Nonlocal Eddy–Mean Flow Interaction in a Global Eddy-Permitting State Estimate
Authors: Chen Ru , Flierl Glenn R. , Wunsch Carl 
Published: June 2014

AbstractThe assumption that local baroclinic instability dominates eddy–mean flow interactions is tested on a global scale using a dynamically consistent eddy-permitting state estimate. Interactions are divided into local and nonlocal. If all the energy released from the mean flow through eddy–mean flow interaction is used to support eddy growth in the same region, or if all the energy released from eddies through eddy–mean flow interaction is used to feed back to the mean flow in the same region, eddy–mean flow interaction is local; otherwise, it is nonlocal. Different regions have different characters: in the subtropical region studied in detail, interactions are dominantly local. In the Southern Ocean and Kuroshio and Gulf Stream Extension regions, they are mainly nonlocal. Geographical variability of dominant eddy–eddy and eddy–mean flow processes is a dominant factor in understanding ocean energetics.
Weather, Climate, and Resource Information Should Meet the Needs of Sahelian Pastoralists
Authors: Rasmussen Laura Vang , Mertz Ole , Rasmussen Kjeld , Nieto Hector , Ali Abdou , Maiga Idrissa 
Published: June 2014

Abstract
There has been an increasing focus on providing better weather, climate, and resource information for decision making in drylands. This study explores what kind of information pastoralists in the Sahel received in 2013 and how they responded to this information. Moreover, the study assesses whether the disseminated information corresponds to the actual needs of pastoralists. The overall objective is thus to identify the outcome of providing weather, climate, and resource information to pastoralists and thereby to explore whether and how various products may guide their mobility and decision-making patterns. The results show that few of the interviewed pastoralists receive the seasonal rainfall forecasts, which have been produced since 1998 by the Climate Outlook Forum for West Africa. The pastoralists who did receive the forecasts used the information to adjust their crop cultivation strategies rather than to support livestock management decisions. To do the latter, pastoralists need information pertaining to the availability of grazing resources in various areas, the onset date of the rains, flooding events, and finescale information on rainfall amount during the first weeks of the rainy season. Such information could be used to adjust the purchase of supplementary fodder, to make qualified choices on transhumance destinations, and to make changes in herd composition. As pastoralists primarily acquire this information by calling friends and family in nearby areas, the results point to a strong disconnect between the parameters and scale of information that pastoralists need and those currently provided.
Standard and trace-dose lithium: A systematic review of dementia prevention and other behavioral benefits
Authors: Mauer Sivan , Vergne Derick , Ghaemi S Nassir 
Published: June 2014

Objective: Dementia is a major public health issue, with notably high rates in persons with mood illnesses. Lithium has been shown to have considerable neuroprotective effects, even in trace or low doses. The aim of this review is to summarize the current understanding of lithium benefits in trace or low doses in dementia prevention and for other behavioral or medical benefits. Methods: A systematic review identified 24 clinical, epidemiological, and biological reports that met inclusion criteria of assessing lithium in standard or low doses for dementia or other behavioral or medical benefits. Results: Five out of seven epidemiological studies found an association between standard-dose lithium and low dementia rates. Nine out of 11 epidemiological studies, usually of drinking water sources, found an association between trace-dose lithium and low suicide/homicide/mortality and crime rates. All four small randomized clinical trials of lithium for Alzheimer’s dementia have found at least some clinical or biological benefits versus placebo. Only one small randomized clinical trial (RCT) of trace lithium has been conducted, assessing mood symptoms in former substance abusers, and found benefit with lithium versus placebo. Conclusions: Lithium, in both standard and trace doses, appears to have biological benefits for dementia, suicide, and other behavioral outcomes. Further RCT research of trace lithium in dementia is warranted.