bluuebunny/crossref_metadata_2025_split huggingface dataset:
Everolimus Triggers Cytokine Release by Macrophages
Authors: Martinet Wim , Verheye Stefan , De Meyer Inge , Timmermans Jean-Pierre , Schrijvers Dorien M. , Van Brussel Ilse , Bult Hidde , De Meyer Guido R.Y. 
Published: February 2012

Objective—
Stent-based delivery of the mammalian target of rapamycin (mTOR) inhibitor everolimus is a promising strategy for the treatment of coronary artery disease. We studied potential adverse effects associated with mTOR inhibition.

Methods and Results—
Macrophages in culture were either treated with everolimus or starved to inhibit mTOR. Everolimus led to inhibition of protein translation, activation of p38 MAPK, and the release of proinflammatory cytokines (eg, IL-6, TNFα) and chemokines (eg, MCP1, Rantes) before induction of autophagic death. These effects were also observed with rapamycin, but not after starvation. Everolimus-induced cytokine release was similar in macrophages lacking the essential autophagy gene Atg7 but was inhibited when macrophages were cotreated with p38 MAPK inhibitor SB202190 or the glucocorticoid clobetasol. Combined stent-based delivery of clobetasol and everolimus in rabbit plaques downregulated TNFα expression as compared with everolimus-treated plaques but did not affect the ability of everolimus to induce macrophage clearance.

Conclusion—
mTOR inhibition by everolimus triggers cytokine release in macrophages through inhibition of protein translation and p38 activation. These findings provide a rationale for combined local treatment of atherosclerotic plaques with everolimus and an anti-inflammatory agent.
Asialoerythropoietin, a Nonerythropoietic Derivative of Erythropoietin, Displays Broad Anti-Heart Failure Activity
Authors: Takeyama Toshiaki , Takemura Genzou , Kanamori Hiromitsu , Kawaguchi Tomonori , Ogino Atsushi , Watanabe Takatomo , Morishita Kentaro , Tsujimoto Akiko , Goto Kazuko , Maruyama Rumi , Ushikoshi Hiroaki , Kawasaki Masanori , Yamada Kazunari , Nikami Hideki , Fujiwara Takako , Fujiwara Hisayoshi , Minatoguchi Shinya 
Published: February 2012

Background—
We investigated the effects of asialoerythropoietin (asialoEPO), a nonerythrogenic erythropoietin derivative, on 3 murine models of heart failure with different etiologies.

Methods and Results—
Doxorubicin (15 mg/kg) induced heart failure within 2 weeks (toxic cardiomyopathy). Treatment with asialoEPO (6.9 μg/kg) for 2 weeks thereafter attenuated the associated left ventricular dysfunction and dilatation. In addition, the asialoEPO-treated heart showed less myocardial fibrosis, inflammation, and oxidative damage, and diminished atrophic cardiomyocyte degeneration, which was accompanied by restored expression of GATA-4 and sarcomeric proteins. Mice with large 6-week-old myocardial infarctions exhibited marked left ventricular dysfunction with adverse remodeling (ischemic cardiomyopathy). AsialoEPO treatment for 4 weeks significantly mitigated progression of the dysfunction and remodeling and reduced myocardial fibrosis, inflammation, and oxidative damage. Finally, 25-week-old δ-sarcoglycan-deficient mice (genetic cardiomyopathy) were treated with asialoEPO for 5 weeks. AsialoEPO mitigated the progressive cardiac remodeling and dysfunction through cardiomyocyte hypertrophy, and upregulated expression of GATA-4 and sarcomeric proteins. AsialoEPO appears to act by altering the activity of the downstream erythropoietin receptor signals extracellular signal-regulated protein kinase, Akt, signal transducer, and activator of transcription 3 and 5 in a model-specific manner.

Conclusions—
The findings suggest that asialoEPO exerts broad cardioprotective effects through distinct mechanisms depending on the model, which are independent of the erythrogenic action. This compound may be promising for the treatment of heart failure of various etiologies.
Topographic Location of Acute Pontine Infarction Is Associated With the Development of Progressive Motor Deficits
Authors: Oh Semi , Bang Oh Young , Chung Chin-Sang , Lee Kwang Ho , Chang Won Hyuk , Kim Gyeong-Moon 
Published: February 2012

Background and Purpose—
Motor weakness progression is relatively common in acute pontine infarction and frequently associated with increased functional disability. We designed this study to identify the predictors of progression of motor weakness in patients with pontine infarction during the acute phase.

Methods—
We identified consecutive patients with acute ischemic stroke in the pons. Patients were defined as having progressive motor deficits (PMD) if their motor National Institutes of Health Stroke Scale scores increased by ≥1 unit between the maximal and initial neurological deficits. To define the predictors of PMD in patients with a pontine infarct, clinical, laboratory, diffusion-weighted imaging lesion location, and magnetic resonance angiographic variables were investigated.

Results—
A total of 190 patients (male:female=112:78, 66.4±10.6) were identified, and 49 (25.8%) patients were diagnosed with progressive motor deficits. Logistic multiple regression analysis identified lesion involvement of the lower pons (odds ratio, 3.768; 95% confidence interval, 1.696–8.371) as an independent risk factor contributing to motor progression. Although 34 patients (17.9%) had significant basilar artery stenosis, there was no relationship between PMD in pontine infarct patients and the presence of basilar artery stenosis. Additionally, female and previous hypertension were associated with PMD (odds ratio, 2.651, 95% confidence interval, 1.211–5.802; odds ratio, 3.051, 95% confidence interval, 1.087–9.673).

Conclusions—
Our results suggest that lower pons lesions may contribute to progressive motor deficits in patients with isolated acute pontine infarction. Infarct topography is therefore a potential prognostic factor of PMD, because the location of the infarct can affect the extent of ischemic degeneration of the corticospinal tract.
A Simple, Assumption-Free, and Clinically Interpretable Approach for Analysis of Modified Rankin Outcomes
Authors: Howard George , Waller Jennifer L. , Voeks Jenifer H. , Howard Virginia J. , Jauch Edward C. , Lees Kennedy R. , Nichols Fenwick T. , Rahlfs Volker W. , Hess David C. 
Published: February 2012

Background and Purpose—
There is debate regarding the approach for analysis of modified Rankin scale scores, the most common functional outcome scale used in acute stroke trials.

Methods—

We propose to use tests to assess treatment differences addressing the metric, “if a patient is chosen at random from each treatment group and if they have different outcomes, what is the chance the patient who received the investigational treatment will have a better outcome than will the patient receiving the standard treatment?” This approach has an associated statement of treatment efficacy easily understood by patients and clinicians, and leads to statistical testing of treatment differences by tests closely related to the Mann-Whitney
U
test (Wilcoxon Rank-Sum test), which can be tested precisely by permutation tests (randomization tests).

Results—
We show that a permutation test is as powerful as are other approaches assessing ordinal outcomes of the modified Rankin scores, and we provide data from several examples contrasting alternative approaches.

Discussion—
Whereas many approaches to analysis of modified Rankin scores outcomes have generally similar statistical performance, this proposed approach: captures information from the ordinal scale, provides a powerful clinical interpretation understood by both patients and clinicians, has power at least equivalent to other ordinal approaches, avoids assumptions in the parameterization, and provides an interpretable parameter based on the same foundation as the calculation of the probability value.
Microembolic Signals in Acute Posterior Circulation Cerebral Ischemia
Authors: Hwang Jaechun , Kim Suk Jae , Hong Ji Man , Bang Oh Young , Chung Chin-Sang , Lee Kwang Ho , Kim Gyeong-Moon 
Published: February 2012

Background and Purpose—
The clinical significance of microembolic signals (MES) in the posterior circulation remains unclear. The aim of this study was to investigate the sources and consequences of MES in acute posterior circulation cerebral ischemia.

Methods—
We evaluated a total of 140 consecutive patients (93 males, mean age 62.9 years) who had acute posterior circulation cerebral ischemia. The MES monitoring was conducted at the basilar artery through the suboccipital window for a 30-minute period.

Results—

MES were detected in 18 (12.9%) of the 140 patients. Clinical characteristics and laboratory data did not differ between the MES-positive and MES-negative groups. Intracranial vertebrobasilar artery (VBA) stenosis was independently associated with the presence of MES (odds ratio, 9.85; 95% confidence interval, 1.22–79.48;
P
=0.032), whereas the patients with vertebral artery stenosis that was limited to the extracranial portion did not show an association. Microembolic signals occurred significantly more frequently in patients with severe degree of VBA stenosis compared to those with nonsignificant stenosis (odds ratio, 9.88; 95% confidence interval, 1.23–79.07;
P
=0.031). In a subgroup analysis of the 79 patients who had lesions on diffusion-weighted images and relevant VBA stenosis, the MES-positive group showed more frequent embolic infarction (
P
=0.010) and multiple lesion patterns (
P
=0.007) than single perforating infarctions.

Conclusions—
In acute posterior circulation cerebral ischemia, intracranial and severe VBA stenosis is associated with MES and may be its root causes. The presence of MES in VBA stenosis suggests that multiple and embolic type infarctions are the mechanisms of stroke.
Using the Sensitivity of Large-Eddy Simulations to Evaluate Atmospheric Boundary Layer Models
Authors: Bellon Gilles , Stevens Bjorn 
Published: February 2012

Abstract
A simple framework to study the sensitivity of atmospheric boundary layer (ABL) models to the large-scale conditions and forcings is introduced. This framework minimizes the number of parameters necessary to describe the large-scale conditions, subsidence, and radiation. Using this framework, the sensitivity of the stationary ABL to the large-scale boundary conditions [underlying sea surface temperature (SST) and overlying humidity and temperature in the free troposphere] is investigated in large-eddy simulations (LESs). For increasing SST or decreasing free-tropospheric temperature, the LES exhibits a transition from a cloud-free, well-mixed ABL stationary state, through a cloudy, well-mixed stationary state and a stable shallow cumulus stationary state, to an unstable regime with a deepening shallow cumulus layer. For a warm SST, when increasing free-tropospheric humidity, the LES exhibits a transition from a stable shallow cumulus stationary state, through a stable cumulus-under-stratus stationary state, to an unstable regime with a deepening, cumulus-under-stratus layer. For a cool SST, when increasing the free-tropospheric humidity, the LES stationary state exhibits a transition from a cloud-free, well-mixed ABL regime, through a well-mixed cumulus-capped regime, to a stratus-capped regime with a decoupling between the subcloud and cloud layers.
This dataset can be used to evaluate other ABL models. As an example, the sensitivity of a bulk model based on the mixing-line model is presented. This bulk model reproduces the LES sensitivity to SST and free-tropospheric temperature for the stable and unstable shallow cumulus regimes, but it is less successful at reproducing the LES sensitivity to free-tropospheric humidity for both shallow cumulus and well-mixed regimes.
Auditory Perception of Motor Vehicle Travel Paths
Authors: Ashmead Daniel H. , Grantham D. Wesley , Maloff Erin S. , Hornsby Benjamin , Nakamura Takabun , Davis Timothy J. , Pampel Faith , Rushing Erin G. 
Published: February 2012

Objective: These experiments address concerns that motor vehicles in electric engine mode are so quiet that they pose a risk to pedestrians, especially those with visual impairments. Background: The “quiet car” issue has focused on hybrid and electric vehicles, although it also applies to internal combustion engine vehicles. Previous research has focused on detectability of vehicles, mostly in quiet settings. Instead, we focused on the functional ability to perceive vehicle motion paths. Method: Participants judged whether simulated vehicles were traveling straight or turning, with emphasis on the impact of background traffic sound. Results: In quiet, listeners made the straight-or-turn judgment soon enough in the vehicle’s path to be useful for deciding whether to start crossing the street. This judgment is based largely on sound level cues rather than the spatial direction of the vehicle. With even moderate background traffic sound, the ability to tell straight from turn paths is severely compromised. The signal-to-noise ratio needed for the straight-or-turn judgment is much higher than that needed to detect a vehicle. Conclusion: Although a requirement for a minimum vehicle sound level might enhance detection of vehicles in quiet settings, it is unlikely that this requirement would contribute to pedestrian awareness of vehicle movements in typical traffic settings with many vehicles present. Application: The findings are relevant to deliberations by government agencies and automobile manufacturers about standards for minimum automobile sounds and, more generally, for solutions to pedestrians’ needs for information about traffic, especially for pedestrians with sensory impairments.
The influence of multimodal behavioral treatment on the consumption of acute migraine drugs: a randomized, controlled study
Authors: Hedborg Kerstin , Muhr Carin 
Published: February 2012

Objectives: To characterize overall drug use in migraine in conjunction with multimodal behavioral treatment (MBT). Methods: Seventy-six adults reporting at least two monthly migraine attacks underwent a randomized, controlled, 24-week MBT intervention. Migraine drugs and symptoms were registered in an Internet-based diary. Results: During 4256 days of baseline registration, 859 drug doses were taken during 655 of the 856 days with migraine headache. Triptans and analgesics constituted 56.7 and 38.3% of all doses with efficacy ratios of 0.41 and 0.20, respectively. Men displayed significantly lower drug efficacy ( p = 0.001), and used triptans significantly less ( p < 0.001) and analgesics significantly more ( p < 0.001) than women. At the end of the MBT, total drug consumption decreased by 22% ( p = 0.029), corresponding to 27% fewer days with migraine headache. Drug efficacy increased during MBT from 0.30 to 0.52 ( p < 0.001), mainly explained by an increased proportion of mild attacks, which also was the attack category that displayed the largest increase in drug efficacy. Conclusions: Triptans were the most used and efficient drugs. MBT led to decreased and more efficient drug consumption. Men used triptans less frequently.
Elevated serum angiotensin converting enzyme levels as a reflection of bone marrow renin–angiotensin system activation in multiple myeloma
Authors: Albayrak Murat , Celebi Harika , Albayrak Aynur , Sayilir Abdurrahim , Yesil Yusuf , Balcik Ozlem Sahin , Yokus Osman , Celik Tugrul 
Published: February 2012

Introduction: Angiotensin converting enzyme (ACE) is a circulating enzyme that participates in the body’s renin–angiotensin system (RAS) and is localized on the endothelial cell surface in the lung and other vascular beds. It catalyses the conversion of decapeptide angiotensin I to octapeptide angiotensin II. In the present study, we aimed to analyse the possible relationship between the levels of ACE in the context of RAS in multiple myeloma (MM) pathogenesis. Materials and methods: The study was conducted on 25 MM patients (13 males, 12 females; median age 66 years, range 47–88) and 20 healthy controls. The clinical features of MM patients including demographics and laboratory findings were summarized. Serum ACE levels were measured by using commercially available kits. Results: The serum ACE levels of MM patients and controls were 32.60±20.26 and 15.35±6.47 respectively. Serum ACE levels were significantly higher in MM patients compared with control groups ( p<0.001). Conclusions: Being an important component of RAS, circulating ACE might be associated with clonal proliferation of malignant plasma cells in the bone marrow microenvironment. Identification of the pathobiological activity of the local RAS in MM would enlighten the biologic basis and clinical management of haematologic disorders.
The Midterm Experience of Tapered Stent Grafts in the Endovascular Management of Iliac Artery Aneurysms With Unfavorable Anatomy
Authors: Aldin Zaid , Kashef Elika , Jenkins Michael , Gibbs Richard , Wolfe John , Hamady Mohamad 
Published: February 2012

We report our experience and the midterm results of a modern technique for endovascular management of isolated iliac artery aneurysms (IAAs) with unfavorable neck anatomy, which involves the inversion of an iliac leg of a Zenith stent graft. Patients who underwent endovascular IAA repair from 2002 to 2010 were reviewed. A total of 12 patients, with a mean age of 77.6 years, underwent endovascular repair of 13 IAAs. Mean size of the aneurysms was 54.6 mm (range 34-133 mm). Mean proximal neck diameter was 18 mm (range 15-22 mm). In 7 patients, the length of the proximal neck was <15 mm (10-14 mm). Only 1 patient developed thrombosis of the stent graft immediately after the operation. Patients were followed up for a mean of 31.5 months (range 18-72 months). Our midterm results demonstrate the durability of this technique in the management of iliac aneurysms with unfavorable anatomy.
Microsatellite allele dose and configuration establishment (MADCE): an integrated approach for genetic studies in allopolyploids
Authors: van Dijk Thijs , Noordijk Yolanda , Dubos Tiphaine , Bink Marco CAM , Meulenbroek Bert J , Visser Richard GF , van de Weg Eric 
Published: February 2012

Abstract

Background
Genetic studies in allopolyploid plants are challenging because of the presence of similar sub-genomes, which leads to multiple alleles and complex segregation ratios. In this study, we describe a novel method for establishing the exact dose and configuration of microsatellite alleles for any accession of an allopolyploid plant species. The method, named Microsatellite Allele Dose and Configuration Establishment (MADCE), can be applied to mapping populations and pedigreed (breeding) germplasm in allopolyploids.

Results
Two case studies are presented to demonstrate the power and robustness of the MADCE method. In the mapping case, five microsatellites were analysed. These microsatellites amplified 35 different alleles based on size. Using MADCE, we uncovered 30 highly informative segregating alleles. A conventional approach would have yielded only 19 fully informative and six partially informative alleles. Of the ten alleles that were present in all progeny (and thereby ignored or considered homozygous when using conventional approaches), six were found to segregate by dosage when analysed with MADCE. Moreover, the full allelic configuration of the mapping parents could be established, including null alleles, homozygous loci, and alleles that were present on multiple homoeologues. In the second case, 21 pedigreed cultivars were analysed using MADCE, resulting in the establishment of the full allelic configuration for all 21 cultivars and a tracing of allele flow over multiple generations.

Conclusions
The procedure described in this study (MADCE) enhances the efficiency and information content of mapping studies in allopolyploids. More importantly, it is the first technique to allow the determination of the full allelic configuration in pedigreed breeding germplasm from allopolyploid plants. This enables pedigree-based marker-trait association studies the use of algorithms developed for diploid crops, and it may increase the effectiveness of LD-based association studies. The MADCE method therefore enables researchers to tackle many of the genotyping problems that arise when performing mapping, pedigree, and association studies in allopolyploids. We discuss the merits of MADCE in comparison to other marker systems in polyploids, including SNPs, and how MADCE could aid in the development of SNP markers in allopolyploids.
Fostered and left behind alleles in peanut: interspecific QTL mapping reveals footprints of domestication and useful natural variation for breeding
Authors: Fonceka Daniel , Tossim Hodo-Abalo , Rivallan Ronan , Vignes Hélène , Faye Issa , Ndoye Ousmane , Moretzsohn Márcio C , Bertioli David J , Glaszmann Jean-Christophe , Courtois Brigitte , Rami Jean-François 
Published: February 2012

AbstractBackgroundPolyploidy can result in genetic bottlenecks, especially for species of monophyletic origin. Cultivated peanut is an allotetraploid harbouring limited genetic diversity, likely resulting from the combined effects of its single origin and domestication. Peanut wild relatives represent an important source of novel alleles that could be used to broaden the genetic basis of the cultigen. Using an advanced backcross population developed with a synthetic amphidiploid as donor of wild alleles, under two water regimes, we conducted a detailed QTL study for several traits involved in peanut productivity and adaptation as well as domestication.ResultsA total of 95 QTLs were mapped in the two water treatments. About half of the QTL positive effects were associated with alleles of the wild parent and several QTLs involved in yield components were specific to the water-limited treatment. QTLs detected for the same trait mapped to non-homeologous genomic regions, suggesting differential control in subgenomes as a consequence of polyploidization. The noteworthy clustering of QTLs for traits involved in seed and pod size and in plant and pod morphology suggests, as in many crops, that a small number of loci have contributed to peanut domestication.ConclusionIn our study, we have identified QTLs that differentiated cultivated peanut from its wild relatives as well as wild alleles that contributed positive variation to several traits involved in peanut productivity and adaptation. These findings offer novel opportunities for peanut improvement using wild relatives.