bluuebunny/crossref_metadata_2025_split huggingface dataset:
A national survey of the management of atrial fibrillation with antithrombotic drugs in Italian primary care
Authors: Filippi Alessandro , Alacqua Marianna , Cowell Warren , Shakespeare Annabelle , Mantovani Lorenzo , Bianchi Cosetta , Cricelli Claudio , Mazzaglia Giampiero 
Published: March 2010

SummaryThe aims of this study were to investigate trends in the incidence of diagnosed atrial fibrillation (AF), and to identify factors associated with the prescription of antithrombotics (ATs) and to identify the persistence of patients with oral anticoagulant (OAC) treatment in primary care. Data were obtained from 400 Italian primary care physicians providing information to the Health Search/Thales Database from 2001 to 2004. The age-standardised incidence of AF was: 3.9–3.0 cases, and 3.6–3.0 cases per 1,000 person-years in males and females, respectively. During the study period, 2,016 (37.2%) patients had no prescription, 1,663 (30.7%) were prescribed an antiplatelet (AP) agent, 1,440 (26.6%) were prescribed an OAC and 301 (5.5%) had both prescriptions. The date of diagnosis (p = 0.0001) affected the likelihood of receiving an OAC. AP, but not OAC, use significantly increased with a worsening stroke risk profile using the CHADS2 risk score. Older age increased the probability (p < 0.0001) of receiving an AP, but not an OAC. Approximately 42% and 24% of patients persisted with OAC treatment at one and two years, respectively, the remainder interrupted or discontinued their treatment. Underuse and discontinuation of OAC treatment is common in incident AF patients. Risk stratification only partially influences AT management.
Association between the Thr325Ile polymorphism of the thrombinactivatable fibrinolysis inhibitor and stroke in the Ludwigshafen Risk and Cardiovascular Health Study
Authors: Lorenz Martin , März Winfried , Cousin Emmanuelle , Mace Sandrine , Deleuze Jean-Francois , Kozian Detlef 
Published: March 2010

SummaryThe thrombin-activatable fibrinolysis inhibitor (TAFI) is a key mediator in the regulation of endogenous fibrinolysis, down-regulating clot lysis by degrading the C-terminal lysine residues from fibrin, which are important for binding and activating plasminogen. Elevated TAFI antigen levels have been suggested to be associated with promoter variants and the Ala147Thr polymorphism; increased TAFI stability and antifibrinolytic potential instead have been associated with the Thr325Ile polymorphism. We investigated the influence of these two polymorphisms on cardiovascular and thrombotic events in patients of the Ludwig-shafen Risk and Cardiovascular Health (LURIC) study. The LURIC study is a prospective cohort study comprising more than 3,300 patients aimed at identifying biochemical and genetic markers for metabolic and cardiovascular diseases. We demonstrate that the Ile/Ile genotype at position 325 of TAFI associates with the incidence of stroke and the age at onset of first stroke in patients of the LURIC cohort. Both the incidence of stroke and the risk of a premature event are higher in TAFI Ile325Ile patients with predisposing risk factors for thrombotic events such as diabetes mellitus, myocardial infarction or hypertension, alone or in combination. In contrast, no significant association was identified for the TAFI Ala147Thr polymorphism. The robust association of the TAFI Thr325Ile polymorphism with the incidence and the age at onset of first stroke strongly suggests a key role for TAFI in the pathogenetic mechanism of stroke.
External quality assessment (EQA) for CoaguChek monitors
Authors: Jespersen Joergen , van den Besselaar A. M. H. P. , van der Meer Felix , Palareti Gualtiero , Tripodi Armando , Shiach Caroline , Keown Michelle , Ibrahim Saied , Poller Leon 
Published: March 2010

SummaryAnticoagulant control facilities are being overwhelmed by requests for monitoring and large numbers of patients are not therefore receiving treatment. Procedures designed for point-of-care testing have therefore been developed, the most popular being the CoaguChek. The need for external quality assessment (EQA) of monitors used by patients in self-management has been stressed in a European Commission (EC) Directive. It would not however be feasible for all CoaguChek monitors to be enrolled in national or regional EQA schemes which take time to organise and analyse. The European Concerted Action on Anticoagulation (ECAA) has therefore evolved a simpler system. Its value has been assessed in collaboration with the European Concerted Action on Thrombosis (ECAT). 523 monitors were tested at nine clinics which asked patients to bring their CoaguChek instruments to be assessed with the ECAA/ECAT procedure based on a set of 5 plasma samples with certified international normalised ratios (INR). 15% or more deviation from the certified INR on a single certified plasma sample from the set was defined by the ECAA as the limit of acceptable performance. One hundred and six (20.3%) of the monitors tested showed significant deviation and higher than average incidence of significant INR deviations reported with one specific numbered lot of test strips. Recent ECAA/ECAT, Danish and Italian studies report regular EQA of CoaguChek monitors is essential. There is general agreement that this should be performed at reasonably frequent intervals, at six months or whenever there is a change of the manufacturer’s test strips.
Assessing the Short-Term Forecast Capability of Nonstandardized Surface Observations Using the National Digital Forecast Database (NDFD)
Authors: Hilliker Joby L. , Akasapu Girish , Young George S. 
Published: March 2010

Abstract
The number of surface observations from nonstandardized networks across the United States has appreciably increased the last several years. Automated Weather Services, Inc. (AWS), maintains one example of this type of network offering nonstandardized observations for ∼8000 sites. The present study assesses the utility of such a network to improve short-term (i.e., lead times &lt;12 h) National Digital Forecast Database (NDFD) forecasts for three parameters most relevant to the energy industry—temperature, dewpoint, and wind speed. A 1-yr sample of 13 AWS sites is chosen to evaluate the magnitude of forecast improvement (skill) and influence of physical location (siting) on such improvements. Hourly predictions are generated using generalized additive modeling (GAM)—a nonlinear statistical equation incorporating a predetermined set of the most significant AWS and NDFD predictors. Two references are used for comparison: (i) persistence climatology (PC) forecasts and (ii) NDFD forecasts calibrated to the AWS sites (CNDFD). The skill, measured via the percent improvement (reduction) in the mean absolute error (MAE), of forecasts generated by the study’s technique (CNDFD+) is comparable (&lt;5%) to PC for lead times of 1–3 h for dewpoint and wind speed. Skill relative to PC slowly increases with lead time, with temperature exhibiting the greatest relative-to-PC skill (∼30% at 12 h). When compared to baseline CNDFD forecasts, the MAE of the generated CNDFD+ forecasts is reduced 65% for temperature and dewpoint at the 1-h lead time. An exponential drop in improvement occurs for longer lead times. Wind speed improvements are notably less, with little skill (&lt;5%) demonstrated for forecasts beyond 4 h. Overall, CNDFD+ forecasts have the greatest accuracy relative to CNDFD and PC for the middle (3–7 h) lead times tested in the study. Variations in CNDFD+ skill exist with respect to AWS location. Tested stations located in complex terrain generally exhibit greater skill relative to CNDFD than the 13-station average for temperature (and, to a lesser degree, dewpoint). Relative to PC, however, the same subset of stations exhibits skill below the 13-station average. No conclusive relationship can be made between CNDFD+ skill and the sample stations located near water.
Energetics Responses to Increases in Greenhouse Gas Concentration
Authors: Hernández-Deckers Daniel , von Storch Jin-Song 
Published: March 2010

Abstract
Increasing greenhouse gas concentrations warm the troposphere. However, it is not clear whether this implies changes in the energetics. To study the energetics responses to CO2 increases, changes in the Lorenz energy cycle (LEC) are evaluated using output from the atmosphere–ocean ECHAM5/Max Planck Institute Ocean Model (MPI-OM). Equilibrium 2 × CO2 experiments and 10-yr transient experiments with 3% increase per year are analyzed.
Globally, doubling of CO2 results in a decrease in the LEC strength—defined as the total conversion of available potential energy P into kinetic energy K—but also in an increase in the zonal-mean K. These global changes are a consequence of the strengthening of the LEC in the upper troposphere and the weakening of the cycle below. The two opposite responses result from the simulated warming pattern that shows the strongest warming in the upper tropical troposphere and in the lower troposphere at high latitudes. This warming structure causes changes in the horizontal temperature variance and in mean static stability, which increase zonal-mean P in the upper troposphere and decrease it below, triggering the two opposite responses via changes in baroclinic activity. In general, the lower-region weakening is stronger in the Northern Hemisphere, while the upper-region strengthening, and the increase of zonal-mean P and K, is stronger in the Southern Hemisphere. The former is more pronounced in the transient experiments but decreases in the stabilized 2 × CO2 climate.
Clinico-pathological evidence that axonal loss underlies disability in progressive multiple sclerosis
Authors: Tallantyre Emma C , Bø Lars , Al-Rawashdeh Omar , Owens Trudy , Polman Chris H , Lowe James S , Evangelou Nikos 
Published: March 2010

Growing evidence suggests that axonal degeneration rather than demyelination is the pathological substrate underlying chronic, irreversible disability in multiple sclerosis. However, direct evidence linking clinical disability measured in vivo with corresponding post-mortem measures of axonal pathology is lacking. Our objective in this study was to investigate the relationship between motor disability accumulated by patients with multiple sclerosis during life and the degree of axonal loss observed in their descending motor tracts after death. Human spinal cord derived at autopsy from 45 patients with multiple sclerosis was investigated. The medical records of each patient were reviewed by a multiple sclerosis neurologist to determine the degree of motor disability reached before death. Spinal cord sections were stained immunohistochemically. The degree of demyelination and the number of surviving corticospinal tract axons were measured in each patient. Patients who had accumulated higher levels of motor disability prior to death demonstrated fewer surviving corticospinal axons. Motor disability did not correlate with degree of demyelination. This study provides for the first time, direct clinico-pathological evidence that axonal loss is the pathological substrate of established disability in multiple sclerosis.
Promoter hypermethylation in MLL-r infant acute lymphoblastic leukemia: biology and therapeutic targeting
Authors: Schafer Eric , Irizarry Rafael , Negi Sandeep , McIntyre Emily , Small Donald , Figueroa Maria E. , Melnick Ari , Brown Patrick 
Published: March 2010

Abstract
Cooperating leukemogenic events in MLL-rearranged (MLL-r) infant acute lymphoblastic leukemia (ALL) are largely unknown. We explored the role of promoter CpG island hypermethylation in the biology and therapeutic targeting of MLL-r infant ALL. The HELP (HpaII tiny fragment enrichment by ligation-mediated polymerase chain reaction [PCR]) assay was used to examine genome-wide methylation of a cohort of MLL-r infant leukemia samples (n = 5), other common childhood ALLs (n = 5), and normals (n = 5). Unsupervised analysis showed tight clustering of samples into their known biologic groups, indicating large differences in methylation patterns. Global hypermethylation was seen in the MLL-r cohort compared with both the normals and the others, with ratios of significantly (P < .001) hypermethylated to hypomethylated CpGs of 1.7 and 2.9, respectively. A subset of 7 differentially hypermethylated genes was assayed by quantitative reverse-transcription (qRT)–PCR, confirming relative silencing in 5 of 7. In cell line treatment assays with the DNA methyltransferase inhibitor (DNMTi) decitabine, MLL-r (but not MLL wild-type cell lines) showed dose- and time-dependent cytotoxicity and re-expression of 4 of the 5 silenced genes. Methylation-specific PCR (MSP) confirmed promoter hypermethylation at baseline, and a relative decrease in methylation after treatment. DNMTi may represent a novel molecularly targeted therapy for MLL-r infant ALL.
Early detrimental T-cell effects in experimental cerebral ischemia are neither related to adaptive immunity nor thrombus formation
Authors: Kleinschnitz Christoph , Schwab Nicholas , Kraft Peter , Hagedorn Ina , Dreykluft Angela , Schwarz Tobias , Austinat Madeleine , Nieswandt Bernhard , Wiendl Heinz , Stoll Guido 
Published: March 2010

Abstract
T cells contribute to the pathophysiology of ischemic stroke by yet unknown mechanisms. Mice with transgenic T-cell receptors (TCRs) and mutations in costimulatory molecules were used to define the minimal immunologic requirements for T cell–mediated ischemic brain damage. Stroke was induced in recombination activating gene 1–deficient (RAG1−/−) mice devoid of T and B cells, RAG1−/− mice reconstituted with B cells or T cells, TCR-transgenic mice bearing 1 single CD8+ (2C/RAG2, OTI/RAG1 mice) or CD4+ (OTII/RAG1, 2D2/RAG1 mice) TCR, mice lacking accessory molecules of TCR stimulation (CD28−/−, PD1−/−, B7-H1−/− mice), or mice deficient in nonclassical T cells (natural killer T [NKT] and γδ T cells) by transient middle cerebral artery occlusion (tMCAO). Stroke outcome was assessed at day 1. RAG1−/− mice and RAG1−/− mice reconstituted with B cells developed significantly smaller brain infarctions compared with controls, but thrombus formation after FeCl3-induced vessel injury was unimpaired. In contrast, TCR-transgenic mice and mice lacking costimulatory TCR signals were fully susceptible to tMCAO similar to mice lacking NKT and γδ T cells. These findings were corroborated by adoptive transfer experiments. Our data demonstrate that T cells critically contribute to cerebral ischemia, but their detrimental effect neither depends on antigen recognition nor TCR costimulation or thrombus formation.
Endothelial lumen signaling complexes control 3D matrix–specific tubulogenesis through interdependent Cdc42- and MT1-MMP–mediated events
Authors: Sacharidou Anastasia , Koh Wonshill , Stratman Amber N. , Mayo Anne M. , Fisher Kevin E. , Davis George E. 
Published: March 2010

AbstractHere, we define an endothelial cell (EC) lumen signaling complex involving Cdc42, Par6b, Par3, junction adhesion molecule (Jam)–B and Jam-C, membrane type 1–matrix metalloproteinase (MT1-MMP), and integrin α2β1, which coassociate to control human EC tubulogenesis in 3D collagen matrices. Blockade of both Jam-B and Jam-C using antibodies, siRNA, or dominant-negative mutants completely interferes with lumen and tube formation resulting from a lack of Cdc42 activation, inhibition of Cdc42-GTP–dependent signal transduction, and blockade of MT1-MMP–dependent proteolysis. This process requires interdependent Cdc42 and MT1-MMP signaling, which involves Par3 binding to the Jam-B and Jam-C cytoplasmic tails, an interaction that is necessary to physically couple the components of the lumen signaling complex. MT1-MMP proteolytic activity is necessary for Cdc42 activation during EC tube formation in 3D collagen matrices but not on 2D collagen surfaces, whereas Cdc42 activation is necessary for MT1-MMP to create vascular guidance tunnels and tube networks in 3D matrices through proteolytic events. This work reveals a novel interdependent role for Cdc42-dependent signaling and MT1-MMP–dependent proteolysis, a process that occurs selectively in 3D collagen matrices and that requires EC lumen signaling complexes, to control human EC tubulogenesis during vascular morphogenesis.
Sodium valproate-induced congenital cardiac abnormalities in mice are associated with the inhibition of histone deacetylase
Authors: Wu Gang , Nan Changlong , Rollo Johnathon C , Huang Xupei , Tian Jie 
Published: March 2010

Abstract

Background
Valproic acid, a widely used anticonvulsant drug, is a potent teratogen resulting in various congenital abnormalities. However, the mechanisms underlying valproic acid induced teratogenesis are nor clear. Recent studies indicate that histone deacetylase is a direct target of valproic acid.

Methods
In the present study, we have used histological analysis and RT-PCR assays to examine the cardiac abnormalities in mice treated with sodium valproate (NaVP) and determined the effects of NaVP on histone deacetylase activity and the expression of heart development-related genes in mouse myocardial cells.

Results
The experimental data show that NaVP can induce cardiac abnormalities in fetal mice in a dose-dependent manner. NaVP causes a dose-dependent inhibition of hitone deacetylase (HDAC) activity in mouse myocardial cells. However, the expression levels of HDAC (both HDAC1 and HDAC2) are not significantly changed in fetal mouse hearts after administration of NaVP in pregnant mice. The transcriptional levels of other heart development-related genes, such as CHF1, Tbx5 and MEF2, are significantly increased in fetal mouse hearts treated with NaVP.

Conclusions
The study indicates that administration of NaVP in pregnant mice can result in various cardiac abnormalities in fetal hearts, which is associated with an inhibition of histone deacetylase without altering the transcription of this enzyme.
Mechanical strain modulates age-related changes in the proliferation and differentiation of mouse adipose-derived stromal cells
Authors: Huang See-Chang , Wu Tzu-Chin , Yu Hsiao-Chi , Chen Mei-Ru , Liu Chun-Min , Chiang Wen-Sheng , Lin Kurt M 
Published: March 2010

Abstract

Background
Previous studies on the effects of aging in human and mouse mesenchymal stem cells suggest that a decline in the number and differentiation potential of stem cells may contribute to aging and aging-related diseases. In this report, we used stromal cells isolated from adipose tissue (ADSCs) of young (8-10 weeks), adult (5 months), and old (21 months) mice to test the hypothesis that mechanical loading modifies aging-related changes in the self-renewal and osteogenic and adipogenic differentiation potential of these cells.

Results
We show that aging significantly reduced the proliferation and increased the adipogenesis of ADSCs, while the osteogenic potential is not significantly reduced by aging. Mechanical loading (10% cyclic stretching, 0.5 Hz, 48 h) increased the subsequent proliferation of ADSCs from mice of all ages. Although the number of osteogenic colonies with calcium deposition was increased in ADSCs subjected to pre-strain, it resulted from an increase in colony number rather than from an increase in osteogenic potential after strain. Pre-strain significantly reduced the number of oil droplets and the expression of adipogenic marker genes in adult and old ADSCs. Simultaneously subjecting ADSCs to mechanical loading and adipogenic induction resulted in a stronger inhibition of adipogenesis than that caused by pre-strain. The reduction of adipogenesis by mechanical strain was loading-magnitude dependent: loading with 2% strain only resulted in a partial inhibition, and loading with 0.5% strain could not inhibit adipogenesis in ADSCs.

Conclusions
We demonstrate that mechanical stretching counteracts the loss of self-renewal in aging ADSCs by enhancing their proliferation and, at the same time, reduces the heightened adipogenesis of old cells. These findings are important for the further study of stem cell control and treatment for a variety of aging related diseases.
Transcriptional and pathway analysis in the hypothalamus of newly hatched chicks during fasting and delayed feeding
Authors: Higgins Stacy E , Ellestad Laura E , Trakooljul Nares , McCarthy Fiona , Saliba Jason , Cogburn Larry A , Porter Tom E 
Published: March 2010

Abstract

Background
The hypothalamus plays a central role in regulating appetite and metabolism. However, the gene networks within the hypothalamus that regulate feed intake and metabolism, and the effects of fasting on those pathways are not completely understood in any species. The present experiment evaluated global hypothalamic gene expression in newly hatched chicks using microarray analysis to elucidate genes and pathways regulated by feeding, fasting, and delayed feeding. Ten groups of chicks were sampled over four days post-hatch, including fed, fasted, and 48 h fasted followed by access to feed for 4 h, 24 h, and 48 h. Hypothalamic samples were collected for microarray analysis (n = 4). Expression patterns of selected genes were confirmed by quantitative real-time PCR. Pathway analysis of the microarray results predicted a network of genes involved in neuropeptide or neurotransmitter signaling. To confirm the functionality of this predicted gene network, hypothalamic neurons from fed and fasted chicks were isolated and cultured in the presence of neuropeptide Y, somatostatin, α-melanocyte stimulating hormone, norepinephrine, and L-phospho-serine. Results confirmed functional relationships among members of the predicted gene network. Moreover, the effects observed were dependant upon the nutritional state of the animals (fed vs. fasted).

Results
Differences in gene expression (≥ 1.6 fold) were detected in 1,272 genes between treatments, and of those, 119 genes were significantly (P < 0.05) different. Pathway Miner analysis revealed that six genes (SSTR5, NPY5R, POMC, ADRB2, GRM8, and RLN3) were associated within a gene network. In vitro experiments with primary hypothalamic neurons confirmed that receptor agonists involved in this network regulated expression of other genes in the predicted network, and this regulation within the network was influenced by the nutritional status and age of the chick.

Conclusions
Microarray analysis of the hypothalamus during different nutritional states revealed that many genes are differentially regulated. We found that functional interactions exist among six differentially regulated genes associated within a putative gene network from this experiment. Considering that POMC, an important gene in controlling metabolism, was central to this network, this gene network may play an important role in regulation of feeding and metabolism in birds.