bluuebunny/crossref_metadata_2025_split huggingface dataset:
Blood Pressure Targets Recommended by Guidelines and Incidence of Cardiovascular and Renal Events in the Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial (ONTARGET)
Authors: Mancia Giuseppe , Schumacher Helmut , Redon Josep , Verdecchia Paolo , Schmieder Roland , Jennings Garry , Yusoff Khalid , Ryden Lars , Liu G. Lisheng , Teo Koon , Sleight Peter , Yusuf Salim 
Published: September 2011

Background—
Hypertension treatment guidelines recommend that blood pressure (BP) be lowered to <140/90 mm Hg, but that a reduction to <130/80 mm Hg be adopted in patients at high cardiovascular (CV) risk. We investigated the CV and renal benefits associated with these BP targets in the high-CV-risk population of the Ongoing Telmisartan Alone and in Combination With Ramipril Global End Point Trial (ONTARGET).

Methods and Results—
Patients were divided into 4 groups according to the proportion of in-treatment visits before the occurrence of an event (<25%–>75%) in which BP was reduced to <140/90 or <130/80 mm Hg. After adjustment for demographic and clinical variables, a progressive increase in the proportion of visits in which BP was reduced to <140/90 or <130/80 mm Hg was associated with a progressive reduction in the risk of stroke, new onset of microalbuminuria or macroalbuminuria, and return to normoalbuminuria in albuminuric patients. An increased frequency of BP control to either target did not have any consistent effect on the adjusted risk of myocardial infarction and heart failure. The adjusted risk of CV events was reduced by increasing the frequency of BP control to <140/90 mm Hg, but not to <130/80 mm Hg. Similar findings were obtained for the achievement of the BP target in the visit preceding a CV event.

Conclusion—
The more frequent achievement of the BP targets recommended by guidelines led to cerebrovascular and renal protection, but did not increase cardiac protection. Overall, CV protection was favorably affected by the less tight but not by the tighter BP target.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00153101.
Cardiomyocyte-Specific Deletion of the Vitamin D Receptor Gene Results in Cardiac Hypertrophy
Authors: Chen Songcang , Law Christopher S. , Grigsby Christopher L. , Olsen Keith , Hong Ting-Ting , Zhang Yan , Yeghiazarians Yerem , Gardner David G. 
Published: September 2011

Background—
A variety of studies carried out using either human subjects or laboratory animals suggest that vitamin D and its analogues possess important beneficial activity in the cardiovascular system. Using Cre-Lox technology we have selectively deleted the vitamin D receptor (VDR) gene in the cardiac myocyte in an effort to better understand the role of vitamin D in regulating myocyte structure and function.

Methods and Results—

Targeted deletion of the exon 4 coding sequence in the VDR gene resulted in an increase in myocyte size and left ventricular weight/body weight versus controls both at baseline and following a 7-day infusion of isoproterenol. There was no increase in interstitial fibrosis. These knockout mice demonstrated a reduction in end-diastolic and end-systolic volume by echocardiography, activation of the fetal gene program (ie, increased atrial natriuretic peptide and alpha skeletal actin gene expression), and increased expression of modulatory calcineurin inhibitory protein 1 (MCIP1), a direct downstream target of calcineurin/nuclear factor of activated
T
cell signaling. Treatment of neonatal cardiomyocytes with 1,25-dihydroxyvitamin D partially reduced isoproterenol-induced MCIP1 mRNA and protein levels and MCIP1 gene promoter activity.

Conclusions—
Collectively, these studies demonstrate that the vitamin D-VDR signaling system possesses direct, antihypertrophic activity in the heart. This appears to involve, at least in part, suppression of the prohypertrophic calcineurin/NFAT/MCIP1 pathway. These studies identify a potential mechanism to account for the reported beneficial effects of vitamin D in the cardiovascular system.
Peak Oxygen Uptake Correlates With Survival Without Clinical Deterioration in Ambulatory Children With Dilated Cardiomyopathy
Authors: Giardini Alessandro , Fenton Matthew , Andrews Rachel E. , Derrick Graham , Burch Michael 
Published: September 2011

Background—
Children stable at home with dilated cardiomyopathy remain at risk of death; there is evidence of survival benefit for transplantation out to 4 years postoperatively. The limited supply of donor organs makes risk stratification imperative, but although cardiopulmonary exercise test is well established as a powerful tool in adults with heart failure, no published studies have linked oxygen uptake to prognosis in children.

Methods and Results—

Between 2001 and 2009, using cardiopulmonary exercise test and echocardiography, we studied 82 children (mean age, 13.5±2.3 years) with dilated cardiomyopathy. All were ambulatory, outpatients, and >120 cm in height. All children completed a symptom-limited maximal exercise test. Resting left ventricular shortening fraction was 20±9%; peak heart rate was 87±13% of predicted; peak oxygen uptake (V̇
o
2
) was 67±22% of predicted; and ventilatory efficiency was 32±8. Follow-up was available for 100% of the children, and was a mean of 32.3±7.5 months. Eighteen patients reached the defined clinical end point of death or listing for urgent heart transplantation. On univariate analysis, left ventricular shortening fraction, peak heart rate, peak V̇
o
2
, peak systolic blood pressure, and ventilatory efficiency were all associated with adverse outcome. On multivariable Cox analysis, only peak V̇
o
2
(
P
=0.003) was associated with the study end point. Patients with a peak V̇
o
2
≤62% of predicted had a higher 24-month event rate (50.6% versus 4.4%; hazard ratio, 10.78).

Conclusions—

We have demonstrated that a cardiopulmonary exercise test is feasible in ambulatory children with dilated cardiomyopathy who are >120 cm height and for the first time have linked peak V̇
o
2
with outcome in children.
Analysis of the Atlantic Meridional Mode Using Linear Inverse Modeling: Seasonality and Regional Influences
Authors: Vimont Daniel J. 
Published: September 2011

Abstract
Predictability and variability of the tropical Atlantic Meridional Mode (AMM) is investigated using linear inverse modeling (LIM). Analysis of the LIM using an “energy” norm identifies two optimal structures that experience some transient growth, one related to El Niño–Southern Oscillation (ENSO) and the other to the Atlantic multidecadal oscillation (AMO)/AMM patterns. Analysis of the LIM using an AMM-norm identifies an “AMM optimal” with similar structure to the second energy optima (OPT2). Both the AMM-optimal and OPT2 exhibit two bands of SST anomalies in the mid- to high-latitude Atlantic. The AMM-optimal also contains some elements of the first energy optimal (ENSO), indicating that the LIM captures the well-known relationship between ENSO and the AMM.
Seasonal correlations of LIM predictions with the observed AMM show enhanced AMM predictability during boreal spring and for long-lead (around 11–15 months) forecasts initialized around September. Regional LIMs were constructed to determine the influence of tropical Pacific and mid- to high-latitude Atlantic SST on the AMM. Analysis of the regional LIMs indicates that the tropical Pacific is responsible for the AMM predictability during boreal spring. Mid- to high-latitude SST anomalies contribute to boreal summer and fall AMM predictability, and are responsible for the enhanced predictability from September initial conditions. Analysis of the empirical normal modes of the full LIM confirms these physical relationships. Results indicate a potentially important role for mid- to high-latitude Atlantic SST anomalies in generating AMM (and tropical Atlantic SST) variations, though it is not clear whether those anomalies provide any societally useful predictive skill.
A Remotely Operated Lidar for Aerosol, Temperature, and Water Vapor Profiling in the High Arctic
Authors: Nott G. J. , Duck T. J. , Doyle J. G. , Coffin M. E. W. , Perro C. , Thackray C. P. , Drummond J. R. , Fogal P. F. , McCullough E. , Sica R. J. 
Published: September 2011

Abstract
A Rayleigh–Mie–Raman lidar has been installed and is operating in the Polar Environment Atmospheric Research Laboratory at Eureka in the High Arctic (79°59′N, 85°56′W) as part of the Canadian Network for the Detection of Atmospheric Change. The lidar operates in both the visible and ultraviolet and measures aerosol backscatter and extinction coefficients, depolarization ratio, tropospheric temperature, and water vapor mixing ratio. Variable field of view, aperture, and filtering allow fine-tuning of the instrument for different atmospheric conditions. Because of the remote location, operations are carried out via a satellite link. The instrument is introduced along with the measurement techniques utilized and interference filter specifications. The temperature dependence of the water vapor signal depends on the filter specifications, and this is discussed in terms of minimizing the uncertainty of the water vapor mixing ratio product. Finally, an example measurement is presented to illustrate the potential of this instrument for studying the Arctic atmosphere.
Human Performance Consequences of Automated Decision Aids in States of Sleep Loss
Authors: Reichenbach Juliane , Onnasch Linda , Manzey Dietrich 
Published: September 2011

Objective: The authors investigated how human performance consequences of automated decision aids are affected by the degree of automation and the operator’s functional state. Background: As research has shown, decision aids may not only improve performance but also lead to new sorts of risks. Whereas knowledge exists about the impact of system characteristics (e.g., reliability) on human performance, little is known about how these performance consequences are moderated by the functional state of operators. Method: Participants performed a simulated supervisory process control task with one of two decision aids providing support for fault identification and management. One session took place during the day, and another one took place during the night after a prolonged waking phase of more than 20 hr. Results: Results showed that decision aids can support humans effectively in maintaining high levels of performance, even in states of sleep loss, with more highly automated aids being more effective than less automated ones. Furthermore, participants suffering from sleep loss were found to be more careful in interaction with the aids, that is, less prone to effects of complacency and automation bias. However, cost effects arose that included a decline in secondary-task performance and an increased risk of return-to-manual performance decrements. Conclusion: Automation support can help protect performance after a period of extended wakefulness. In addition, operators suffering from sleep loss seem to compensate for their impaired functional state by reallocating resources and showing a more attentive behavior toward possible automation failures. Application: Results of this research can inform the design of automation, especially decision aids.
Agreement in the Classification and Treatment of the Superior Labrum
Authors: Wolf Brian R. , Britton Carla L. , Vasconcellos David A. , Spencer Edwin E. ,   for the MOON Shoulder Group, Baumgarten Keith M. , Bishop Julie Y. , Brophy Robert H. , Carey James L. , Dunn Warren R. , Jones Grant L. , Kuhn John E. , Ma C. Benjamin , Marx Robert G. , McCarty Eric C. , Vidal Armando F. , Wright Rick W. 
Published: September 2011

Background: The Snyder classification scheme is the most commonly used system for classifying superior labral injuries. Although this scheme is intended to be used for arthroscopic visual classification only, it is thought that other nonarthroscopic historical variables also influence the classification. Purpose: This study was conducted to evaluate the intrasurgeon and intersurgeon agreement in classifying variable presentations of the superior labrum and to evaluate the influence of clinical variables on the classification and treatment choices of surgeons. Study Design: Cohort study (diagnosis); Level of evidence, 3. Methods: A group of arthroscopic shoulder surgeons were asked to rank in order of importance clinical variables considered in diagnosing and treating the superior labrum. The surgeons then watched 50 arthroscopic videos of the superior labrum, ranging from normal to pathologic, on 3 different occasions. The first and third viewings were accompanied by no clinical information. The second viewing was accompanied by a detailed clinical vignette for each video. The surgeons selected a classification and treatment for each video. Results: A patient’s job/sport, age, and physical examination findings were considered the most important clinical variables surgeons consider during management of the superior labrum. Comparing the 2 viewings without clinical information, surgeons selected a different classification 28.5% of the time from the first to the second time. A different classification was chosen 71.5% of the time when the surgeon was supplied a clinical vignette at the subsequent viewing. Similarly, the treatment selected changed in 36% and 69.1% of cases when viewed again without vignettes and with vignettes, respectively. Intersurgeon agreement was moderate without clinical vignettes and fair with vignettes. Historical, physical examination, and surgical observations were found to influence the odds of change of classification. Conclusion: There is significant intrasurgeon and intersurgeon variability in classification and treatment of the superior labrum. Clinical historical, examination, and surgical findings influence classification and treatment choices.
Pralatrexate: A novel synthetic antifolate for relapsed or refractory peripheral T-cell lymphoma and other potential uses
Authors: Hui John , Przespo Eugene , Elefante Anjana 
Published: September 2011

Purpose: The pharmacology, pharmacokinetics, clinical trials, adverse effects, dosage, and economic considerations of pralatrexate (PDX) are reviewed. Summary: Peripheral T-cell lymphoma (PTCL) comprises approximately 15–20% of all aggressive lymphomas and 5–10% of all non-Hodgkin’s lymphomas. Advanced PTCL is often refractory to traditional first-line chemotherapy regimens. PDX was developed as a synthetic folate analog antimetabolite that competitively inhibits dihydrofolate reductase (DHFR). This results in the depletion of thymidine, leading to interference with deoxyribonucleic acid synthesis and cancer cell death. PDX has a higher potency than methotrexate and edatrexate (EDX). The efficacy and safety of PDX have been demonstrated in the PROPEL trial, a prospective phase II trial in patients with relapsed or refractory PTCL. Patients with prior stem cell transplantation receiving PDX also had similar response rates (RRs). PDX was investigated on the treatment of relapsed or refractory cutaneous T-cell lymphoma, previously treated advanced non-small cell lung cancer and other solid malignancies. PDX has similar side effects to other DHFR inhibitors. The most common side effect of PDX is mucositis. The recommended dose of PDX is 30 mg/m2 weekly once for 6 weeks in 7-week cycle until disease progresses or unacceptable toxicity for PTCL and may require dose reduction or discontinuation. Patients should be supplemented with oral folic acid and intramuscular vitamin B12 injections. Conclusion: PDX provides clinical benefit to patients with relapsed or refractory PTCL with durable complete and partial responses in patients who had not responded to multiple prior treatment regimens.
Second induction with high-dose cytarabine and mitoxantrone: different impact on pediatric AML patients with t(8;21) and with inv(16)
Authors: Creutzig Ursula , Zimmermann Martin , Bourquin Jean-Pierre , Dworzak Michael N. , von Neuhoff Christine , Sander Annette , Schrauder André , Teigler-Schlegel Andrea , Starý Jan , Corbacioglu Selim , Reinhardt Dirk 
Published: September 2011

Abstract
Patients with core binding factor acute myeloid leukemia (CBF-AML) benefit from more intensive chemotherapy, but whether both the t(8;21) and inv(16)/t (16;16) subtypes requires intensification remained to be determined. In the 2 successive studies (AML-BFM-1998 and AML-BFM-2004), 220 CBF-AML patients were treated using the same chemotherapy backbone, whereby reinduction with high-dose cytarabine and mitoxantrone (HAM) was scheduled for these cohorts only in study AML-BFM-1998 but not in AML-BFM-2004 against the background to minimize overtreatment. Five-year overall survival (OS) and event-free survival (EFS) were significantly higher and the cumulative incidence of relapse (CIR) lower in t(8;21) patients treated with HAM (n = 78) compared with without HAM (n = 53): OS 92% ± 3% versus 80% ± 6%, plogrank0.047, EFS 84% ± 4% versus 59% ± 7%, plogrank0.001, and CIR 14% ± 4% versus 34% ± 7%, p(gray)0.006. These differences were not seen for inv(16) (n = 43 and 46, respectively): OS 93% ± 4% versus 94% ± 4%, EFS 75% ± 7% versus 71% ± 9% and CIR 15% ± 6% versus 23% ± 8% (not significant). The subtype t(8;21), but not inv(16), was an independent predictor of worse outcome without HAM reinduction. Based on our data, a 5-year OS of > 90% can be expected for CBF-AML, when stratifying t(8;21), but not inv(16), patients to high-risk chemotherapy, including HAM reinduction.
Association between copy number variation of complement component C4 and Graves' disease
Authors: Liu Yu-Huei , Wan Lei , Chang Chwen-Tzuei , Liao Wen-Ling , Chen Wen-Chi , Tsai Yuhsin , Tsai Chang-Hai , Tsai Fuu-Jen 
Published: September 2011

Abstract

Background
Gene copy number of complement component C4, which varies among individuals, may determine the intrinsic strength of the classical complement pathway. Presuming a major role of complement as an effecter in peptide-mediated inflammation and phagocytosis, we hypothesized that C4 genetic diversity may partially explain the development of Graves' disease (GD) and the variation in its outcomes.

Methods
A case-control study including 624 patients with GD and 160 healthy individuals were enrolled. CNV of C4 isotypes (C4A and C4B) genes were performed by quantitative real-time polymerase chain reaction analysis. Statistical comparison and identification of CNV of total C4, C4 isotypes (C4A and C4B) and C4 polymorphisms were estimated according to the occurrence of GD and its associated clinical features.

Results
Individuals with 4, 2, and 2 copies of C4, C4A and C4B genes, especially those with A2B2 polymorphism may associate with the development of GD (p = 0.001, OR = 10.994, 95% CI: 6.277-19.255; p = 0.008, OR = 1.732, 95% CI: 1.190-2.520; p = 2.420 × 10-5, OR = 2.621, 95% CI: 1.791-3.835; and p = 1.395 × 10-4, OR = 2.671, 95% CI: 1.761-4.052, respectively). Although the distribution of copy number for total C4, C4 isotypes as well as C4 polymorphisms did not associate with the occurrence of goiter, nodular hyperplasia, GO and myxedema, <2 copies of C4A may associate with high risk toward vitiligo in patients with GD (p = 0.001, OR = 5.579, 95% CI: 1.659-18.763).

Conclusions
These results may be further estimated for its clinical application on GD and the vitiligo in patients with GD.
A holistic phylogeny of the coronin gene family reveals an ancient origin of the tandem-coronin, defines a new subfamily, and predicts protein function
Authors: Eckert Christian , Hammesfahr Björn , Kollmar Martin 
Published: September 2011

Abstract

Background
Coronins belong to the superfamily of the eukaryotic-specific WD40-repeat proteins and play a role in several actin-dependent processes like cytokinesis, cell motility, phagocytosis, and vesicular trafficking. Two major types of coronins are known: First, the short coronins consisting of an N-terminal coronin domain, a unique region and a short coiled-coil region, and secondly the tandem coronins comprising two coronin domains.

Results
723 coronin proteins from 358 species have been identified by analyzing the whole-genome assemblies of all available sequenced eukaryotes (March 2011). The organisms analyzed represent most eukaryotic kingdoms but also cover every taxon several times to provide a better statistical sampling. The phylogenetic tree of the coronin domains based on the Bayesian method is in accordance with the most recent grouping of the major kingdoms of the eukaryotes and also with the grouping of more recently separated branches. Based on this "holistic" approach the coronins group into four classes: class-1 (Type I) and class-2 (Type II) are metazoan/choanoflagellate specific classes, class-3 contains the tandem-coronins (Type III), and the new class-4 represents the coronins fused to villin (Type IV). Short coronins from non-metazoans are equally related to class-1 and class-2 coronins and thus remain unclassified.

Conclusions
The coronin class distribution suggests that the last common eukaryotic ancestor possessed a single and a tandem-coronin, and most probably a class-4 coronin of which homologs have been identified in Excavata and Opisthokonts although most of these species subsequently lost the class-4 homolog. The most ancient short coronin already contained the trimerization motif in the coiled-coil domain.
Comparative Transcriptomes Profiling of Photoperiod-sensitive Male Sterile Rice Nongken 58S During the Male Sterility Transition between Short-day and Long-day
Authors: Wang Wei , Liu Zhenwei , Guo Zhibin , Song Gaoyuan , Cheng Qin , Jiang Daiming , Zhu Yingguo , Yang Daichang 
Published: September 2011

Abstract

Background
Photoperiod-sensitive genic male sterile (PGMS) rice, Nongken 58S, was discovered in 1973. It has been widely used for the production of hybrid rice, and great achievements have been made in improving rice yields. However, the mechanism of the male sterility transition in PGMS rice remains to be determined.

Results
To investigate the transcriptome during the male sterility transition in PGMS rice, the transcriptome of Nongken 58S under short-day (SD) and long-day (LD) at the glume primordium differentiation and pistil/stamen primordium forming stages was compared. Seventy-three and 128 differentially expressed genes (DEGs) were identified at the glume primordium differentiation and pistil/stamen primordium forming stages, respectively. Five and 22 genes were markedly up-regulated (≥ 5-fold), and two and five genes were considerably down-regulated (≥ 5-fold) under SD during the male sterility transition. Gene ontology annotation and pathway analysis revealed that four biological processes and the circadian rhythms and the flowering pathways coordinately regulated the male sterility transition. Further quantitative PCR analysis demonstrated that the circadian rhythms of OsPRR1, OsPRR37, OsGI, Hd1, OsLHY and OsDof in leaves were obviously different between Nongken 58S and Nongken 58 under LD conditions. Moreover, both OsPRR37 and Hd1 in the inflorescence displayed differences between Nongken 58S and Nongken 58 under both LD and SD conditions.

Conclusion
The results presented here indicate that the transcriptome in Nongken 58S was significantly suppressed under LD conditions. Among these DEGs, the circadian rhythm and the flowering pathway were involved in the male sterility transition. Furthermore, these pathways were coordinately involved in the male sterility transition in PGMS rice.