bluuebunny/crossref_metadata_2025_split huggingface dataset:
Myocardial Infarction After Carotid Stenting and Endarterectomy
Authors: Blackshear Joseph L. , Cutlip Donald E. , Roubin Gary S. , Hill Michael D. , Leimgruber Pierre P. , Begg Richard J. , Cohen David J. , Eidt John F. , Narins Craig R. , Prineas Ronald J. , Glasser Stephen P. , Voeks Jenifer H. , Brott Thomas G. ,   for the CREST Investigators
Published: May 2011

Background—
The Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST) found a higher risk of stroke after carotid artery stenting and a higher risk of myocardial infarction (MI) after carotid endarterectomy.

Methods and Results—

Cardiac biomarkers and ECGs were performed before and 6 to 8 hours after either procedure and if there was clinical evidence of ischemia. In CREST, MI was defined as biomarker elevation plus either chest pain or ECG evidence of ischemia. An additional category of biomarker elevation with neither chest pain nor ECG abnormality was prespecified (biomarker+ only). Crude mortality and risk-adjusted mortality for MI and biomarker+ only were assessed during follow-up. Among 2502 patients, 14 MIs occurred in carotid artery stenting and 28 MIs in carotid endarterectomy (hazard ratio, 0.50; 95% confidence interval, 0.26 to 0.94;
P
=0.032) with a median biomarker ratio of 40 times the upper limit of normal. An additional 8 carotid artery stenting and 12 carotid endarterectomy patients had biomarker+ only (hazard ratio, 0.66; 95% confidence interval, 0.27 to 1.61;
P
=0.36), and their median biomarker ratio was 14 times the upper limit of normal. Compared with patients without biomarker elevation, mortality was higher over 4 years for those with MI (hazard ratio, 3.40; 95% confidence interval, 1.67 to 6.92) or biomarker+ only (hazard ratio, 3.57; 95% confidence interval, 1.46 to 8.68). After adjustment for baseline risk factors, both MI and biomarker+ only remained independently associated with increased mortality.

Conclusions—
In patients randomized to carotid endarterectomy versus carotid artery stenting, both MI and biomarker+ only were more common with carotid endarterectomy. Although the levels of biomarker elevation were modest, both events were independently associated with increased future mortality and remain an important consideration in choosing the mode of carotid revascularization or medical therapy.

Clinical Trial Registration—

URL:
http://www.ClinicalTrials.gov
. Unique identifier: NCT00004732.
Role of Pyruvate Dehydrogenase Inhibition in the Development of Hypertrophy in the Hyperthyroid Rat Heart
Authors: Atherton Helen J. , Dodd Michael S. , Heather Lisa C. , Schroeder Marie A. , Griffin Julian L. , Radda George K. , Clarke Kieran , Tyler Damian J. 
Published: May 2011

Background—
Hyperthyroidism increases heart rate, contractility, cardiac output, and metabolic rate. It is also accompanied by alterations in the regulation of cardiac substrate use. Specifically, hyperthyroidism increases the ex vivo activity of pyruvate dehydrogenase kinase, thereby inhibiting glucose oxidation via pyruvate dehydrogenase. Cardiac hypertrophy is another effect of hyperthyroidism, with an increase in the abundance of mitochondria. Although the hypertrophy is initially beneficial, it can eventually lead to heart failure. The aim of this study was to use hyperpolarized magnetic resonance spectroscopy to investigate the rate and regulation of in vivo pyruvate dehydrogenase flux in the hyperthyroid heart and to establish whether modulation of flux through pyruvate dehydrogenase would alter cardiac hypertrophy.

Methods and Results—

Hyperthyroidism was induced in 18 male Wistar rats with 7 daily intraperitoneal injections of freshly prepared triiodothyronine (0.2 mg · kg
−1
· d
−1
). In vivo pyruvate dehydrogenase flux, assessed with hyperpolarized magnetic resonance spectroscopy, was reduced by 59% in hyperthyroid animals (0.0022±0.0002 versus 0.0055±0.0005 second
−1
;
P
=0.0003), and this reduction was completely reversed by both short- and long-term delivery of dichloroacetic acid, a pyruvate dehydrogenase kinase inhibitor. Hyperpolarized [2-
13
C]pyruvate was also used to evaluate Krebs cycle metabolism and demonstrated a unique marker of anaplerosis, the level of which was significantly increased in the hyperthyroid heart. Cine magnetic resonance imaging showed that long-term dichloroacetic acid treatment significantly reduced the hypertrophy observed in hyperthyroid animals (100±20 versus 200±30 mg;
P
=0.04) despite no change in the increase observed in cardiac output.

Conclusions—
This work has demonstrated that inhibition of glucose oxidation in the hyperthyroid heart in vivo is mediated by pyruvate dehydrogenase kinase. Relieving this inhibition can increase the metabolic flexibility of the hyperthyroid heart and reduce the level of hypertrophy that develops while maintaining the increased cardiac output required to meet the higher systemic metabolic demand.
Familial Evaluation in Arrhythmogenic Right Ventricular Cardiomyopathy
Authors: Quarta Giovanni , Muir Alison , Pantazis Antonios , Syrris Petros , Gehmlich Katja , Garcia-Pavia Pablo , Ward Deirdre , Sen-Chowdhry Srijita , Elliott Perry M. , McKenna William J. 
Published: May 2011

Background—
With recognition of disease-causing genes in arrhythmogenic right ventricular cardiomyopathy, mutation analysis is being applied.

Methods and Results—

The role of genotyping in familial assessment for arrhythmogenic right ventricular cardiomyopathy was investigated, including the prevalence of mutations in known causal genes, the penetrance and expressivity in genotyped families, and the utility of the 2010 Task Force criteria in clinical diagnosis. Clinical and molecular genetic evaluation was performed in 210 first-degree and 45 second-degree relatives from 100 families. In 51 families, the proband was deceased. The living probands had a high prevalence of ECG abnormalities (89%) and ventricular arrhythmia (78%) and evidence of more severe disease than relatives. Definite or probable causal mutations were found in 58% of families and 73% of living probands, of whom 28% had an additional desmosomal variant (ie, mutation or polymorphism). Ninety-three relatives had a causal mutation; 33% fulfilled the 2010 criteria, whereas only 19% satisfied the 1994 version (
P
=0.03). An additional desmosomal gene variant was found in 10% and was associated with a 5-fold increased risk of developing penetrant disease (odds ratio, 4.7; 95% confidence interval, 1.1 to 20.4;
P
=0.04).

Conclusions—
Arrhythmogenic right ventricular cardiomyopathy is a genetically complex disease characterized by marked intrafamilial phenotype diversity. Penetrance is definition dependent and is greater with the 2010 criteria compared with the 1994 criteria. Relatives harboring >1 genetic variant had significantly increased risk of developing clinical disease, potentially an important determinant of the phenotypic heterogeneity seen within families with arrhythmogenic right ventricular cardiomyopathy.
Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy
Authors: Cox Moniek G.P.J. , van der Zwaag Paul A. , van der Werf Christian , van der Smagt Jasper J. , Noorman Maartje , Bhuiyan Zahir A. , Wiesfeld Ans C.P. , Volders Paul G.A. , van Langen Irene M. , Atsma Douwe E. , Dooijes Dennis , van den Wijngaard Arthur , Houweling Arjan C. , Jongbloed Jan D.H. , Jordaens Luc , Cramer Maarten J. , Doevendans Pieter A. , de Bakker Jacques M.T. , Wilde Arthur A.M. , van Tintelen J. Peter , Hauer Richard N.W. 
Published: May 2011

Background—
Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is an autosomal dominant inherited disease with incomplete penetrance and variable expression. Causative mutations in genes encoding 5 desmosomal proteins are found in ≈50% of ARVD/C index patients. Previous genotype-phenotype relation studies involved mainly overt ARVD/C index patients, so follow-up data on relatives are scarce.

Methods and Results—

One hundred forty-nine ARVD/C index patients (111 male patients; age, 49±13 years) according to 2010 Task Force criteria and 302 relatives from 93 families (282 asymptomatic; 135 male patients; age, 44±13 years) were clinically and genetically characterized. DNA analysis comprised sequencing of plakophilin-2 (
PKP2
), desmocollin-2, desmoglein-2, desmoplakin, and plakoglobin and multiplex ligation-dependent probe amplification to identify large deletions in
PKP2.
Pathogenic mutations were found in 87 index patients (58%), mainly truncating
PKP2
mutations, including 3 cases with multiple mutations. Multiplex ligation-dependent probe amplification revealed 3
PKP2
exon deletions. ARVD/C was diagnosed in 31% of initially asymptomatic mutation-carrying relatives and 5% of initially asymptomatic relatives of index patients without mutation. Prolonged terminal activation duration was observed more than negative T waves in V
1
to V
3
, especially in mutation-carrying relatives <20 years of age. In 45% of screened families, ≥1 affected relatives were identified (90% with mutations).

Conclusions—

Pathogenic desmosomal gene mutations, mainly truncating
PKP2
mutations, underlie ARVD/C in the majority (58%) of Dutch index patients and even 90% of familial cases. Additional multiplex ligation-dependent probe amplification analysis contributed to discovering pathogenic mutations underlying ARVD/C. Discovering pathogenic mutations in index patients enables those relatives who have a 6-fold increased risk of ARVD/C diagnosis to be identified. Prolonged terminal activation duration seems to be a first sign of ARVD/C in young asymptomatic relatives.
Interannual to Interdecadal Variabilities of the Indonesian Throughflow Source Water Pathways in the Pacific Ocean
Authors: Valsala Vinu , Maksyutov Shamil , Murtugudde Raghu 
Published: May 2011

Abstract
Some of the possible interannual to interdecadal variabilities of the Indonesian Throughflow (ITF) source water pathways in the Pacific Ocean are identified from an ocean reanalysis product provided by the European Centre for Medium-Range Weather Forecasts (ECMWF) under the name Ocean Reanalysis, version S3 (ORA-S3). The data were used in an offline mode to evolve adjoint pathways of a passive tracer, which is injected from the key channels of the Indonesian straits where the ITF enters into the Indian Ocean. The adjoint pathways are simulated using interannually varying circulations for 41 yr starting from December 2000 to January 1960 with reversed currents and other physical parameters (control run). A climatological run for the 41 yr is produced with the reversed currents and other physical parameters as a monthly climatology. The adjoint pathway variability is found by subtracting the climatological run from the control run. The empirical orthogonal function (EOF) analysis carried out over the monthly differences between the tracer concentrations of the control run and the climatological run shows that the ITF is largely supplied from the northwestern tropical Pacific during a normal year, whereas the supply from the south equatorial Pacific is dominant during El Niño–Southern Oscillation (ENSO) years at a lag of 6 months. The interannual variability of the ITF source water pathways in the Pacific is largely determined by the ENSO variability and they are confined to the tropical Pacific, whereas the corresponding interdecadal variability is controlled by the meridional overturning circulations in the tropical and subtropical Pacific. The adjoint pathways hint that the ITF volume transport may have interdecadal variability; they are closely related to the variability of the subtropical cells (STCs) in the Pacific Ocean and can be quantified using the tropical convergence changes. The ITF is just an active member of the recharge–discharge of tropical warm waters at all time scales, and its role in the coupled climate variability of the Indo-Pacific needs to be assessed in that context.
Rossby Wave Scales, Propagation, and the Variability of Eddy-Driven Jets
Authors: Barnes Elizabeth A. , Hartmann Dennis L. 
Published: May 2011

Abstract
The eddy-driven jet is located in the midlatitudes, bounded on one side by the pole and often bounded on the opposite side by a strong Hadley-driven jet. This work explores how the eddy-driven jet and its variability persist within these limits. It is demonstrated in a barotropic model that as the jet is located at higher latitudes, the eddy length scale increases as predicted by spherical Rossby wave theory, and the leading mode of variability of the jet changes from a meridional shift to a pulse. Looking equatorward, a similar change in eddy-driven jet variability is observed when it is moved equatorward toward a constant subtropical jet. In both the poleward and equatorward limits, the change in variability from a shift to a pulse is due to the modulation of eddy propagation and momentum flux. Near the pole, the small value of beta (the meridional gradient of absolute vorticity) and subsequent lack of wave breaking near the pole account for the change in variability, whereas on the equatorward side of the jet the strong subtropical winds can affect eddy propagation and restrict the movement of the eddy-driven jet or cause bimodal behavior of the jet latitude. Barotropic quasilinear theory thus suggests that the leading mode of zonal-wind variability will transition from a shift to a pulse as the eddy-driven jets move poleward with climate change, and that the eddy length scale will increase as the jet moves poleward.
The Global Characteristics of the Wavenumber Spectrum of Ocean Surface Wind
Authors: Xu Yongsheng , Fu Lee-Lueng , Tulloch Ross 
Published: May 2011

Abstract
The wavenumber spectra of wind kinetic energy over the ocean from Quick Scatterometer (QuikSCAT) observations have revealed complex spatial variability in the wavelength range of 1000–3000 km, with spectral slopes varying from −1.6 to −2.9. Here the authors performed a spectral analysis of QuikSCAT winds over the global ocean and found that (i) the spectral slopes become steeper toward the Poles in the Pacific and in the South Atlantic, and the slopes exhibit minimal longitudinal dependence in the South Pacific; (ii) the steepest slopes are in the tropical Indian Ocean and the shallowest slopes are in the tropical Pacific and Atlantic; and (iii) the spectra are steeper in winter than summer in most regions of the midlatitude Northern Hemisphere. The new findings reported in the paper provide a test bed for theoretical studies and atmospheric general circulation models.
Extending the role of computational fluid dynamics in screw machines
Authors: Kovacevic A , Stosic N , Mujic E , Smith I K , Guerrato D 
Published: May 2011

Previous publications show that computational fluid dynamics (CFD) can be readily used for the flow prediction and analysis of screw compressors. Several case studies are presented in this article to show the scope and applicability of such methods. These include solid–fluid interaction in screw compressors, prediction of flow generated noise in screw machines, cavitation modelling in gear pumps, and flow in multiphase pumps for oil and gas industry. Numerical grids for all these cases were generated by the authors using an in-house grid generator, while the CFD calculations were performed with a variety of commercially available CFD codes. In order to validate the accuracy of the CFD calculations, an extended test programme was carried out using laser Doppler velocimetry to measure the mean and fluctuating velocity distribution in screw compressor flow domains. The measurement results are then compared with the CFD simulations. The results confirm the viability of the developed techniques. It is shown in this publication that the flexibility of the developed method creates further opportunities for a broader use of CFD for analysis of twin screw machines in a range of new applications.
RAC2, AEP, and ICAM1 expression are associated with CNS disease in a mouse model of pre-B childhood acute lymphoblastic leukemia
Authors: Holland Mark , Castro Fernanda V. , Alexander Seema , Smith Duncan , Liu Jizhong , Walker Michael , Bitton Danny , Mulryan Kate , Ashton Garry , Blaylock Morgan , Bagley Steve , Connolly Yvonne , Bridgeman John , Miller Crispin , Krishnan Shekhar , Dempsey Clare , Masurekar Ashish , Stern Peter , Whetton Anthony , Saha Vaskar 
Published: May 2011

AbstractWe developed a murine model of CNS disease to obtain a better understanding of the pathogenesis of CNS involvement in pre-B-cell acute lymphoblastic leukemia (ALL). Semiquantitative proteomic discovery–based approaches identified unique expression of asparaginyl endopeptidase (AEP), intercellular adhesion molecule 1 (ICAM1), and ras-related C3 botulinum toxin substrate 2 (RAC2), among others, in an invasive pre-B-cell line that produced CNS leukemia in NOD-SCID mice. Targeting RAC2 significantly inhibited in vitro invasion and delayed disease onset in mice. Induced expression of RAC2 in cell lines with low/absent expression of AEP and ICAM1 did not result in an invasive phenotype or murine CNS disease. Flow cytometric analysis identified an enriched population of blast cells expressing ICAM1/lymphocyte function associated antigen-1 (LFA-1)/CD70 in the CD10+/CD19+ fraction of bone marrow aspirates obtained from relapsed compared with normal controls and those with primary disease. CD10+/CD19+ fractions obtained from relapsed patients also express RAC2 and give rise to CNS disease in mice. Our data suggest that combinations of processes are involved in the pathogenesis of CNS disease in pre-B-cell ALL, support a model in which CNS disease occurs as a result of external invasion, and suggest that targeting the processes of adhesion and invasion unique to pre-B cells may prevent recurrences within the CNS.
Perforin is a critical physiologic regulator of T-cell activation
Authors: Lykens Jennifer E. , Terrell Catherine E. , Zoller Erin E. , Risma Kimberly , Jordan Michael B. 
Published: May 2011

AbstractIndividuals with impaired perforin-dependent cytotoxic function (Ctx−) develop a fatal inflammatory disorder called hemophagocytic lymphohistiocytosis (HLH). It has been hypothesized that immune hyperactivation during HLH is caused by heightened infection, defective apoptosis/responsiveness of Ctx− lymphocytes, or enhanced antigen presentation. Whereas clinical and experimental data suggest that increased T-cell activation drives HLH, potential abnormalities of T-cell activation have not been well characterized in Ctx− hosts. To define such abnormalities and to test these hypotheses, we assessed in vivo T-cell activation kinetics and viral loads after lymphocytic choriomeningitis virus (LCMV) infection of Ctx− mice. We found that increased T-cell activation occurred early during infection of Ctx− mice, while they had viral burdens that were identical to those of WT animals, demonstrating that T-cell hyperactivation was independent of viral load. Furthermore, cell transfer and signaling studies indicated that increased antigenic stimulation, not a cell-intrinsic defect of responsiveness, underlay heightened T-cell activation in vivo. Finally, direct measurement of viral antigen presentation demonstrated an increase in Ctx− mice that was proportional to abnormal T-cell activation. We conclude that perforin-dependent cytotoxicity has an immunoregulatory role that is distinguishable from its pathogen clearance function and limits T-cell activation in the physiologic context by suppressing antigen presentation.
Administration of probiotics influences F4 (K88)-positive enterotoxigenic Escherichia coli attachment and intestinal cytokine expression in weaned pigs
Authors: Daudelin Jean-François , Lessard Martin , Beaudoin Frédéric , Nadeau Éric , Bissonnette Nathalie , Boutin Yvan , Brousseau Jean-Philippe , Lauzon Karoline , Fairbrother John Morris 
Published: May 2011

Abstract
This study evaluated the effect of the probiotics Pediococcus acidilactici and Saccharomyces cerevisiae boulardii on the intestinal colonization of O149 enterotoxigenic Escherichia coli harbouring the F4 (K88) fimbriae (ETEC F4) and on the expression of ileal cytokines in weaned pigs. At birth, different litters of pigs were randomly assigned to one of the following treatments: 1) control without antibiotics or probiotics (CTRL); 2) reference group in which chlortetracycline and tiamulin were added to weanling feed (ATB); 3) P. acidilactici; 4) S. cerevisiae boulardii; or 5) P. acidilactici + S. cerevisiae boulardii. Probiotics were administered daily (1 × 109 CFU per pig) during the lactation period and after weaning (day 21). At 28 days of age, all pigs were orally challenged with an ETEC F4 strain, and a necropsy was performed 24 h later. Intestinal segments were collected to evaluate bacterial colonization in the small intestine and ileal cytokine expressions. Attachment of ETEC F4 to the intestinal mucosa was significantly reduced in pigs treated with P. acidilactici or S. cerevisiae boulardii in comparison with the ATB group (P = 0.01 and P = 0.03, respectively). In addition, proinflammatory cytokines, such as IL-6, were upregulated in ETEC F4 challenged pigs treated with P. acidilactici alone or in combination with S. cerevisiae boulardii compared with the CTRL group. In conclusion, the administration of P. acidilactici or S. cerevisiae boulardii was effective in reducing ETEC F4 attachment to the ileal mucosa, whereas the presence of P. acidilactici was required to modulate the expression of intestinal inflammatory cytokines in pigs challenged with ETEC F4.
Role of redox environment on the oligomerization of higher molecular weight adiponectin
Authors: Briggs David B , Giron Rebecca M , Malinowski Pamela R , Nuñez Martha , Tsao Tsu-Shuen 
Published: May 2011

Abstract

Background
Adiponectin is an adipocyte-secreted hormone with insulin-sensitizing and anti-inflammatory actions. The assembly of trimeric, hexameric, and higher molecular weight (HMW) species of adiponectin is a topic of significant interest because physiological actions of adiponectin are oligomer-specific. In addition, adiponectin assembly is an example of oxidative oligomerization of multi-subunit protein complexes in endoplasmic reticulum (ER).

Results
We previously reported that trimers assemble into HMW adiponectin via intermediates stabilized by disulfide bonds, and complete oxidation of available cysteines locks adiponectin in hexameric conformation. In this study, we examined the effects of redox environment on the rate of oligomer formation and the distribution of oligomers. Reassembly of adiponectin under oxidizing conditions accelerated disulfide bonding but favored formation of hexamers over the HMW species. Increased ratios of HMW to hexameric adiponectin could be achieved rapidly under oxidizing conditions by promoting disulfide rearrangement.

Conclusions
Based upon these observations, we propose oxidative assembly of multi-subunit adiponectin complexes in a defined and stable redox environment is favored under oxidizing conditions coupled with high rates of disulfide rearrangement.