bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiac Magnetic Resonance Imaging for Noninvasive Assessment of Cardiovascular Disease During the Follow-Up of Patients With Kawasaki Disease
Authors: Tacke Carline E. , Kuipers Irene M. , Groenink Maarten , Spijkerboer Anje M. , Kuijpers Taco W. 
Published: September 2011

Background—
Kawasaki disease (KD) is the most common cause of acquired coronary artery disease in childhood. In KD, the American Heart Association recommends echocardiography for routine coronary artery surveillance and nuclear perfusion scans and conventional coronary angiography in select patients. Cardiac MRI (CMRI) may be a noninvasive and radiation-free alternative. We applied CMRI during the follow-up of patients with KD and assessed the performance of CMRI compared with echocardiography.

Methods and Results—
Patients with KD aged ≥8 years were consecutively included. Sixty-three patients (median age, 14.6 years; 74.6% male sex) underwent a comprehensive CMRI protocol including adenosine stress testing to evaluate coronary artery anatomy, ischemia, and myocardial infarction. All patients underwent CMRI without significant complications. On CMRI, 23 coronary artery aneurysms (CAAs) were identified in 15 patients. CMRI detected thrombus formation in 6 CAAs in 4 patients, wall motion disturbances and ischemia in 4 patients, and delayed hyperenhancement indicating myocardial infarction in 5 patients. Wall motion and perfusion abnormalities were noted in territories supplied by affected coronary arteries. CMRI results were compared with recent echocardiography findings. In 6 of the 15 patients with CAAs on CMRI, CAAs were not detected by echocardiography.

Conclusions—
A comprehensive CMRI protocol including adenosine stress testing is feasible to identify coronary artery pathology, ischemia, and myocardial infarction in former patients with KD and compares favorably with echocardiography. CMRI may be used as a noninvasive and radiation-free imaging method for coronary artery surveillance during the long-term follow-up of patients with KD.
Decreased Nighttime Heart Rate Variability Is Associated With Increased Stroke Risk
Authors: Binici Zeynep , Mouridsen Mette Rauhe , Køber Lars , Sajadieh Ahmad 
Published: September 2011

Background and Purpose—
Prediction of stroke in healthy individuals is challenging and there is a diurnal variation of stroke onset. We hypothesized that heart rate variability with a focus on nighttime heart rate variability will predict the risk of stroke in apparently healthy middle-age and elderly subjects.

Methods—

The population-based cohort of the Copenhagen Holter Study, consisting of 678 healthy subjects between age 55 and 75 years with no history of cardiovascular disease or stroke, was evaluated. All underwent 48-hour ambulatory electrocardiogram monitoring. The SD of normal-to-normal RR intervals (SDNN) was selected as the method of measuring heart rate variability. Nighttime SDNN was measured between 02:00 and 02:15
am
and could be evaluated in 653 subjects. Median follow-up was 76 months.

Results—

Nighttime SDNN was lower in women than in men (
P
=0.0008), and in diabetics than nondiabetics (
P
=0.03). However, smoking, cholesterol, systolic blood pressure, and age were not associated with nighttime SDNN. The risk of stroke was significantly associated with nighttime SDNN in a univariate analysis (HR, 0.66; 95% CI, 0.50–0.88;
P
=0.004) and after adjustment for conventional risk factors (HR, 0.67; 95% CI, 0.51–0.89;
P
=0.005) per 10 ms increments of SDNN. Eighty-one percent of all strokes (21/26) occurred in 330 subjects with the lower half of nighttime SDNN (≤38 ms; HR, 4.31; 95% CI, 1.62–11.42;
P
=0.003).

Conclusions—
Nocturnal heart rate variability is a strong marker for the development of stroke in apparently healthy subjects. The mechanism is unknown, but reduced parasympathetic activity may increase the risk of stroke by increasing the risk of arrhythmias.
Stress Worsens Endothelial Function and Ischemic Stroke via Glucocorticoids
Authors: Balkaya Mustafa , Prinz Vincent , Custodis Florian , Gertz Karen , Kronenberg Golo , Kroeber Jan , Fink Klaus , Plehm Ralph , Gass Peter , Laufs Ulrich , Endres Matthias 
Published: September 2011

Background and Purpose—
Chronic stress is associated with increased stroke risk. However, the underlying pathophysiological mechanisms are poorly understood. We examined the effects of chronic stress on endothelial function and ischemic brain injury in a mouse model.

Methods—

129/SV mice were treated with glucocorticoid receptor antagonist mifepristone (25 mg kg
−1
/d) or vehicle and exposed to 28 days of chronic stress consisting of exposure to rat, restraint stress, and tail suspension. Heart rate and blood pressure were continuously recorded by telemetry. Endothelial nitric oxide synthase mRNA and protein expression as well as superoxide production and lipid hydroperoxides were quantified. Endothelium-dependent vasorelaxation was measured in aortic rings. Ischemic lesion volume was quantified after 30 minutes filamentous middle cerebral artery occlusion and 72 hours reperfusion.

Results—
Chronic stress caused a significant increase in heart rate, impaired endothelium-dependent vasorelaxation, increased superoxide production, and reduced aortic and brain endothelial nitric oxide synthase levels. Animals exposed to chronic stress showed major increases in ischemic lesion size. These deleterious effects of stress were completely reversed by treatment with mifepristone.

Conclusions—
Chronic stress increases stroke vulnerability likely through endothelial dysfunction, which can be reversed by a glucocorticoid receptor antagonist.
How I treat pregnancy-related venous thromboembolism
Authors: Middeldorp Saskia 
Published: September 2011

AbstractVenous thromboembolism (VTE) complicates ∼ 1 to 2 of 1000 pregnancies, with pulmonary embolism being a leading cause of maternal mortality and deep vein thrombosis an important cause of maternal morbidity, also on the long term. However, a strong evidence base for the management of pregnancy-related VTE is missing. Management is not standardized between physicians, centers, and countries. The management of pregnancy-related VTE is based on extrapolation from the nonpregnant population, and clinical trial data for the optimal treatment are not available. Low-molecular-weight heparin (LMWH) in therapeutic doses is the treatment of choice during pregnancy, and anticoagulation (LMWH or vitamin K antagonists postpartum) should be continued until 6 weeks after delivery with a minimum total duration of 3 months. Use of LMWH or vitamin K antagonists does not preclude breastfeeding. Whether dosing should be based on weight or anti-Xa levels is unknown, and practices differ between centers. Management of delivery, including the type of anesthesia if deemed necessary, requires a multidisciplinary approach, and several options are possible, depending on local preferences and patient-specific conditions.
Integrated genomic analysis of relapsed childhood acute lymphoblastic leukemia reveals therapeutic strategies
Authors: Hogan Laura E. , Meyer Julia A. , Yang Jun , Wang Jinhua , Wong Nicholas , Yang Wenjian , Condos Gregory , Hunger Stephen P. , Raetz Elizabeth , Saffery Richard , Relling Mary V. , Bhojwani Deepa , Morrison Debra J. , Carroll William L. 
Published: September 2011

Abstract
Despite an increase in survival for children with acute lymphoblastic leukemia (ALL), the outcome after relapse is poor. To understand the genetic events that contribute to relapse and chemoresistance and identify novel targets of therapy, 3 high-throughput assays were used to identify genetic and epigenetic changes at relapse. Using matched diagnosis/relapse bone marrow samples from children with relapsed B-precursor ALL, we evaluated gene expression, copy number abnormalities (CNAs), and DNA methylation. Gene expression analysis revealed a signature of differentially expressed genes from diagnosis to relapse that is different for early (< 36 months) and late (≥ 36 months) relapse. CNA analysis discovered CNAs that were shared at diagnosis and relapse and others that were new lesions acquired at relapse. DNA methylation analysis found increased promoter methylation at relapse. There were many genetic alterations that evolved from diagnosis to relapse, and in some cases these genes had previously been associated with chemoresistance. Integration of the results from all 3 platforms identified genes of potential interest, including CDKN2A, COL6A2, PTPRO, and CSMD1. Although our results indicate that a diversity of genetic changes are seen at relapse, integration of gene expression, CNA, and methylation data suggest a possible convergence on the WNT and mitogen-activated protein kinase pathways.
Haploidentical hematopoietic transplantation: current status and future perspectives
Authors: Reisner Yair , Hagin David , Martelli Massimo F. 
Published: September 2011

Abstract
For patients with hematologic malignancies at high risk of relapse who do not have matched donors, a suitable alternative stem cell source is the HLAhaploidentical 2 or 3-loci mismatched family donor who is readily available for nearly all patients. Transplantation across the major HLA barrier is associated with strong T-cell alloreactions, which were originally manifested as a high incidence of severe GVHD and graft rejection. The present review shows how these obstacles to successful transplantation were overcome in the last 15 years, making full haplotype-mismatched transplantation a clinical reality that provides similar outcomes to transplantation from matched unrelated donors. The review also discusses the advantages and drawbacks of current options for full haplotypemismatched transplantation and highlights innovative approaches for re-building immunity after transplantation and improving survival.
Exhaled nitric oxide and the risk of wheezing in infancy: the Generation R Study
Authors: Gabriele C. , Jaddoe V.W. , van Mastrigt E. , Arends L.R. , Hofman A. , Moll H.A. , de Jongste J.C. 
Published: September 2011

We assessed whether exhaled nitric oxide fraction (FeNO), a marker of eosinophilic airway inflammation, at 6 months was associated with the risk of wheezing during the first 2 yrs of life.In the Generation R birth cohort, pre- and post-natal risk factors for respiratory morbidity and respiratory symptoms were assessed by questionnaires at 6 and 24 months. In 428 infants, off-line mixed oral/nasalFeNOwas successfully measured during tidal breathing at 6 months. Complete data onFeNOand respiratory symptoms within the first 6 months of life were available for 294 infants.FeNOwas higher in males, was positively associated with age and was negatively associated with upper and lower respiratory symptoms within the first 6 months. Logistic regression analysis showed that for every ppb increase ofFeNOmeasured at 6 months, infants had a 1.06 (95% confidence interval 1.01–1.11)-fold increased risk of wheezing in the second year of life. HighFeNO(>17.5 ppb) showed a limited added value in predicting wheezing in the second year.We conclude thatFeNOat 6 months is positively associated with the risk of wheezing, but has limited added value in predicting wheezing in the second year of life in individual children.
Updated genome assembly and annotation of Paenibacillus larvae, the agent of American foulbrood disease of honey bees
Authors: Chan Queenie WT , Cornman R Scott , Birol Inanc , Liao Nancy Y , Chan Simon K , Docking T Roderick , Jackman Shaun D , Taylor Greg A , Jones Steven JM , de Graaf Dirk C , Evans Jay D , Foster Leonard J 
Published: September 2011

Abstract

Background
As scientists continue to pursue various 'omics-based research, there is a need for high quality data for the most fundamental 'omics of all: genomics. The bacterium Paenibacillus larvae is the causative agent of the honey bee disease American foulbrood. If untreated, it can lead to the demise of an entire hive; the highly social nature of bees also leads to easy disease spread, between both individuals and colonies. Biologists have studied this organism since the early 1900s, and a century later, the molecular mechanism of infection remains elusive. Transcriptomics and proteomics, because of their ability to analyze multiple genes and proteins in a high-throughput manner, may be very helpful to its study. However, the power of these methodologies is severely limited without a complete genome; we undertake to address that deficiency here.

Results
We used the Illumina GAIIx platform and conventional Sanger sequencing to generate a 182-fold sequence coverage of the P. larvae genome, and assembled the data using ABySS into a total of 388 contigs spanning 4.5 Mbp. Comparative genomics analysis against fully-sequenced soil bacteria P. JDR2 and P. vortex showed that regions of poor conservation may contain putative virulence factors. We used GLIMMER to predict 3568 gene models, and named them based on homology revealed by BLAST searches; proteases, hemolytic factors, toxins, and antibiotic resistance enzymes were identified in this way. Finally, mass spectrometry was used to provide experimental evidence that at least 35% of the genes are expressed at the protein level.

Conclusions
This update on the genome of P. larvae and annotation represents an immense advancement from what we had previously known about this species. We provide here a reliable resource that can be used to elucidate the mechanism of infection, and by extension, more effective methods to control and cure this widespread honey bee disease.
A new class of IMP dehydrogenase with a role in self-resistance of mycophenolic acid producing fungi
Authors: Hansen Bjarne G , Genee Hans J , Kaas Christian S , Nielsen Jakob B , Regueira Torsten B , Mortensen Uffe H , Frisvad Jens C , Patil Kiran R 
Published: September 2011

Abstract

Background
Many secondary metabolites produced by filamentous fungi have potent biological activities, to which the producer organism must be resistant. An example of pharmaceutical interest is mycophenolic acid (MPA), an immunosuppressant molecule produced by several Penicillium species. The target of MPA is inosine-5'-monophosphate dehydrogenase (IMPDH), which catalyses the rate limiting step in the synthesis of guanine nucleotides. The recent discovery of the MPA biosynthetic gene cluster from Penicillium brevicompactum revealed an extra copy of the IMPDH-encoding gene (mpaF) embedded within the cluster. This finding suggests that the key component of MPA self resistance is likely based on the IMPDH encoded by mpaF.

Results
In accordance with our hypothesis, heterologous expression of mpaF dramatically increased MPA resistance in a model fungus, Aspergillus nidulans, which does not produce MPA. The growth of an A. nidulans strain expressing mpaF was only marginally affected by MPA at concentrations as high as 200 μg/ml. To further substantiate the role of mpaF in MPA resistance, we searched for mpaF orthologs in six MPA producer/non-producer strains from Penicillium subgenus Penicillium. All six strains were found to hold two copies of IMPDH. A cladistic analysis based on the corresponding cDNA sequences revealed a novel group constituting mpaF homologs. Interestingly, a conserved tyrosine residue in the original class of IMPDHs is replaced by a phenylalanine residue in the new IMPDH class.

Conclusions
We identified a novel variant of the IMPDH-encoding gene in six different strains from Penicillium subgenus Penicillium. The novel IMPDH variant from MPA producer P. brevicompactum was shown to confer a high degree of MPA resistance when expressed in a non-producer fungus. Our study provides a basis for understanding the molecular mechanism of MPA resistance and has relevance for biotechnological and pharmaceutical applications.
Mechanisms of Melanocortin-2 Receptor (MC2R) Internalization and Recycling in Human Embryonic Kidney (HEK) Cells: Identification of Key Ser/Thr (S/T) Amino Acids
Authors: Roy Simon , Roy Sébastien Jean , Pinard Sandra , Taillefer Louis-Daniel , Rached Mohamed , Parent Jean-Luc , Gallo-Payet Nicole 
Published: September 2011

AbstractACTH is the most important stimulus of the adrenal cortex. The precise molecular mechanisms underlying the ACTH response are not yet clarified. The functional ACTH receptor includes melanocortin-2 receptor (MC2R) and MC2R accessory proteins (MRAP). In human embryonic kidney 293/Flp recombinase target cells expressing MC2R, MRAP1 isoforms, and MRAP2, we found that ACTH induced a concentration-dependent and arrestin-, clathrin-, and dynamin-dependent MC2R/MRAP1 internalization, followed by intracellular colocalization with Rab (Ras-like small guanosine triphosphate enzyme)4-, Rab5-, and Rab11-positive recycling endosomes. Preincubation of cells with monensin and brefeldin A revealed that 28% of the internalized receptors were recycled back to the plasma membrane and participated in total accumulation of cAMP. Moreover, certain intracellular Ser and Thr (S/T) residues of MC2R were found to play important roles not only in plasma membrane targeting and function but also in promoting receptor internalization. The S/T residues T131, S140, T204, and S280 were involved in MRAP1-independent cell-surface MC2R expression. Other mutants (S140A, S208A, and S202D) had lower cell-surface expressions in absence of MRAPβ. In addition, T143A and T147D drastically impaired cell-surface expression and function, whereas T131A, T131D, and S280D abrogated MC2R internalization. Thus, the modification of MC2R intracellular S/T residues may positively or negatively regulate its plasma membrane expression and the capacity of ACTH to induce cAMP accumulation. Mutations of T131, T143, T147, and S280 into either A or D had major repercussions on cell-surface expression, cAMP accumulation, and/or internalization parameters, pointing mostly to the second intracellular loop as being crucial for MC2R expression and functional regulation.
Image Analysis of Strains in Soils Subjected to Wetting and Drying
Authors: Rojas J. C. , Gallipoli D. , Wheeler S. J. 
Published: September 2011

Abstract
A novel image based technique has been developed to measure strains of soil specimens subjected to wetting-drying by using vapor equilibrium with closed-loop ventilation. A digital SLR camera, fitted with a macro telephoto lens, and an advanced photo system type-C (APS-C) sensor have been used to take images of specimens during wetting-drying. By using the simple radial model of optical distortion, it has been shown that macro fixed focal length lenses introduce extremely small strain errors, which can be neglected. It has also been shown that APS-C sensors are preferable to large Full Frame sensors when the specimen image does not fit the entire sensor area and pixel density, rather than pixel resolution, becomes the key parameter controlling measurement precision. Images of specimens have been acquired at different times during wetting-drying of the soil and processed by using the Adobe Photoshop software to assess evolution of strains. In particular, the planar strain field has been measured by means of a virtual “optical” strain gage rosette tracking the same three points on the specimen image throughout equalization. Multiple optical strain gage rosettes at different scales and positions have been employed to assess the uniformity of the strain field. The method was validated by imposing six different values of suction on six distinct specimens of the same isotropically compacted bentonite, with five values producing soil shrinkage (drying) and one value producing soil swelling (wetting). An excellent repeatability of results was observed in terms of both water content and strains. In addition, for each suction level, almost identical strain equalization curves are obtained from the analysis of multiple optical strain gage rosettes of different sizes placed at different locations over the specimen image. This confirms uniformity of the strain field and excludes the presence of friction at the specimen base.
Characterizing the Precision Uncertainty in Vibratory Roller Measurement Values
Authors: Facas Norman W. , Mooney Michael A. 
Published: September 2011

Abstract
Understanding precision uncertainty in roller measurement values (MV) from continuous compaction control and intelligent compaction vibratory soil and asphalt rollers is required for implementation of roller-based specifications for pavement construction quality control/quality assurance (QC/QA). Accordingly, MV uncertainty can have a significant influence on the acceptance criteria specified in QC/QA. Two pertinent uncertainties are examined within this context: (1) uncertainty in single roller MV data and (2) uncertainty in the difference between roller MVs at the same location from consecutive passes. The uncertainties were estimated from roller MV records using two experimental methods: (1) evaluation of consecutive pass MV records and (2) determination of a nugget variance from geostatistical variogram analysis of a single pass of MV data. The nugget method was found to be dependent on the reporting characteristics of the MV data. A procedure that uses uncertainty analysis to determine malfunctioning roller measurement systems and MVs insensitive to soil properties was demonstrated. The uncertainties from different MVs were found to be similar when evaluated on the same soil. However, MV uncertainty was found to vary between different soils using the same roller. The uncertainty estimated in this study has significant implications on acceptance criteria and nature of QC/QA specification.
Effects of MBE growth on the optical properties of AlGaN quantum wells
Authors: Feng W. , Rajanna G. , Sohal S. , Nikishin S. A. , Bernussi A. A. , Holtz M. 
Published: September 2011

ABSTRACTOptical studies are reported of multiple quantum wells, based on AlGaN for emission in the deep ultraviolet. The materials are grown using gas source molecular beam epitaxy in a growth regime which transitions from purely two-dimensional to mixed two- and three-dimensional well formation. Low temperature photoluminescence and absorption measurements are used to obtain the Stokes shift, and temperature dependence is used to estimate the thermal activation energy associated with photoluminescence intensity decrease. Variations in these energies are attributed to the well morphologies.
In the News
Authors: Nicogossian Arnauld 
Published: September 2011

AbstractIn the Editors' opinion, the materials summarized in this section have the potential for the development of health policies and standards, or for use in the daily practice and counseling of patients in preventative care. For additional information, readers might wish to visit Internet‐based medical news websites, some free of charge, such as PLoS Medicine, MedScape, Stone Heart, American College of Physicians, and the World Medical Association.