bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transforming Growth Factor-β Signaling in Myogenic Cells Regulates Vascular Morphogenesis, Differentiation, and Matrix Synthesis
Authors: Jaffe Mia , Sesti Casilde , Washington Ida M. , Du Liang , Dronadula Nagadhara , Chin Michael T. , Stolz Donna B. , Davis Elaine C. , Dichek David A. 
Published: October 2011

Objective—
Transforming growth factor-β (TGF-β) signaling is required for normal vascular development. We aimed to discover the role of TGF-β signaling in embryonic smooth muscle cells (SMCs).

Methods and Results—

We bred mice with smooth muscle (SM) 22α-Cre and
Tgfbr2
flox
alleles to generate embryos in which the type II TGF-β receptor (TGFBR2; required for TGF-β signaling) was deleted in SMCs. Embryos were harvested between embryonic day (E) 9.5 and E18.5 and examined grossly, microscopically, and by histochemical and RNA analyses. SM22α-Cre
+/0
Tgfbr2
flox/flox
(knockout [KO]) embryos died before E15.5 with defects that included cardiac outflow tract abnormalities, persistence of the right dorsal aorta, and dilation of the distal aorta. Histological analyses suggested normal expression of SMC differentiation markers in KO aortas; however, RNA analyses showed that SMC differentiation markers were increased in KO cardiac outflow vessels but decreased in the descending aorta. KO aortas had only rare mature elastin deposits and contained abnormal aggregates of extracellular matrix proteins. Expression of several matrix proteins was significantly decreased in KO descending aortas but not in cardiac outflow vessels.

Conclusion—
TGF-β signaling in SMCs controls differentiation, matrix synthesis, and vascular morphogenesis. Effects of TGF-β on SMC gene expression appear to differ depending on the location of SMCs in the aorta.
Intracranial Hemorrhage, Outcome, and Mortality After Intra-Arterial Therapy for Acute Ischemic Stroke in Patients Under Oral Anticoagulants
Authors: De Marchis Gian Marco , Jung Simon , Colucci Giuseppe , Meier Niklaus , Fischer Urs , Weck Anja , Mono Marie-Luise , Galimanis Aekaterini , Mattle Heinrich P. , Schroth Gerhard , Gralla Jan , Arnold Marcel , Brekenfeld Caspar 
Published: October 2011

Background and Purpose—
Use of intravenous tissue-type plasminogen activator (IV tPA) for acute ischemic stroke is restricted to patients with an international normalized ratio (INR) less than 1.7. However, a recent study showed increased risk of symptomatic intracranial hemorrhage after IV tPA use in patients with oral anticoagulants (OAC) even with an INR less than 1.7. The present study assessed the risk of symptomatic intracranial hemorrhage, clinical outcome, and mortality after intra-arterial therapy (IAT) in patients with and without previous use of OAC.

Methods—
Consecutive patients treated with IAT from December 1992 to October 2010 were included. Clinical outcome and mortality were assessed 90 days after stroke onset. Patients with and without previous use of OAC were compared.

Results—

Overall, 714 patients were treated with IAT. Twenty-eight patients (3.9%) were under OAC at time of symptom onset. Median INR in the OAC group was 1.79 (interquartile range [IQR], 1.41–2.3) and 1.01 (IQR, 1.0–1.09;
P
<0.0001) in the group without OAC. Patients treated with OAC at admission underwent more often mechanical-only IAT than did patients without OAC (46.4% versus 12.8%;
P
<0.0001). Comparing patients with and without previous use of OAC, we did not find any statistical difference in the rate of symptomatic intracranial hemorrhage (7.1% versus 6.0%;
P
=0.80), unfavorable outcome (modified Rankin Scale score, 3–6; 67.9% versus 50.9%;
P
=0.11), and mortality (17.9% versus 21.6%;
P
=0.58).

Conclusions—
Previous use of OAC did not significantly increase the risk of symptomatic intracranial hemorrhage after IAT or the risk of unfavorable outcome and mortality 90 days after IAT.
Cerebral Blood Flow Is the Optimal CT Perfusion Parameter for Assessing Infarct Core
Authors: Campbell Bruce C.V. , Christensen Søren , Levi Christopher R. , Desmond Patricia M. , Donnan Geoffrey A. , Davis Stephen M. , Parsons Mark W. 
Published: October 2011

Background and Purpose—
CT perfusion (CTP) is widely and rapidly accessible for imaging acute ischemic stroke but has limited validation. Cerebral blood volume (CBV) has been proposed as the best predictor of infarct core. We tested CBV against other common CTP parameters using contemporaneous diffusion MRI.

Methods—
Patients with acute ischemic stroke <6 hours after onset had CTP and diffusion MRI <1 hour apart, before any reperfusion therapies. CTP maps of time to peak (TTP), absolute and relative CBV, cerebral blood flow (CBF), mean transit time (MTT), and time to peak of the deconvolved tissue residue function (Tmax) were generated. The diffusion lesion was manually outlined to its maximal visual extent. Receiver operating characteristic (ROC) analysis area under the curve (AUC) was used to quantify the correspondence of each perfusion parameter to the coregistered diffusion-weighted imaging lesion. Optimal thresholds were determined (Youden index).

Results—
In analysis of 98 CTP slabs (54 patients, median onset to CT 190 minutes, median CT to MR 30 minutes), relative CBF performed best (AUC, 0.79; 95% CI, 0.77–81), significantly better than absolute CBV (AUC, 0.74; 95% CI, 0.73–0.76). The optimal threshold was <31% of mean contralateral CBF. Specificity was reduced by low CBF/CBV in noninfarcted white matter in cases with reduced contrast bolus intensity and leukoaraiosis.

Conclusions—
In contrast to previous reports, CBF corresponded with the acute diffusion-weighted imaging lesion better than CBV, although no single threshold avoids detection of false-positive regions in unaffected white matter. This relates to low signal-to-noise ratio in CTP maps and emphasizes the need for optimized acquisition and postprocessing.
Hospitalization Costs for Patients With Acute Ischemic Stroke Treated With Endovascular Embolectomy in the United States
Authors: Brinjikji Waleed , Kallmes David F. , Rabinstein Alejandro A. , Lanzino Giuseppe , Cloft Harry J. 
Published: October 2011

Background and Purpose—
It is important to know the costs of hospitalization for patients undergoing endovascular embolectomy so that comparisons can be made with payments to hospitals.

Methods—
Using the National Inpatient Sample, we evaluated the costs of hospitalization for patients treated with endovascular embolectomy in the United States from 2006 to 2008. The primary end point examined in this study was total hospital costs, and these were correlated with clinical outcome.

Results—
A total of 3864 patients received endovascular embolectomy. A total of 1649 patients were <65 years old and 2205 patients were ≥65 years old. Median hospital costs in 2008 dollars were $36 999 (interquartile range, $26 662–$56 405) for patients with good outcome, $50 628 (interquartile range, $33 135–$76 063) for patients with severe disability, and $35 109 (interquartile range, $25 053–$62 621) for patients with mortality.

Conclusions—
Hospitalization costs for patients treated with endovascular embolectomy are rather high, probably due to the serious nature of their illness. Medicare payments have not been adequate reimbursement for these hospitalizations.
Aspirin as a Promising Agent for Decreasing Incidence of Cerebral Aneurysm Rupture
Authors: Hasan David M. , Mahaney Kelly B. , Brown Robert D. , Meissner Irene , Piepgras David G. , Huston John , Capuano Ana W. , Torner James C. ,   for the International Study of Unruptured Intracranial Aneurysms Investigators
Published: October 2011

Background and Purpose—
Chronic inflammation is postulated as an important phenomenon in intracranial aneurysm wall pathophysiology. This study was conducted to determine if aspirin use impacts the occurrence of intracranial aneurysm rupture.

Methods—
Subjects enrolled in the International Study of Unruptured Intracranial Aneurysms (ISUIA) were selected from the prospective untreated cohort (n=1691) in a nested case–control study. Cases were subjects who subsequently had a proven aneurysmal subarachnoid hemorrhage during a 5-year follow-up period. Four control subjects were matched to each case by site and size of aneurysm (58 cases, 213 control subjects). Frequency of aspirin use was determined at baseline interview. Aspirin frequency groups were analyzed for risk of aneurysmal hemorrhage. Bivariable and multivariable analyses were performed using conditional logistic regression.

Results—

A trend of a protective effect for risk of unruptured intracranial aneurysm rupture was observed. Patients who used aspirin 3× weekly to daily had an OR for hemorrhage of 0.40 (95% CI, 0.18–0.87); reference group, no use of aspirin), patients in the “< once a month” group had an OR of 0.80 (95% CI, 0.31–2.05), and patients in the “> once a month to 2×/week” group had an OR of 0.87 (95% CI, 0.27–2.81;
P
=0.025). In multivariable risk factor analyses, patients who used aspirin 3 times weekly to daily had a significantly lower odds of hemorrhage (adjusted OR, 0.27; 95% CI, 0.11–0.67;
P
=0.03) compared with those who never take aspirin.

Conclusions—
Frequent aspirin use may confer a protective effect for risk of intracranial aneurysm rupture. Future investigation in animal models and clinical studies is needed.
Sphingosine Kinase 2 Mediates Cerebral Preconditioning and Protects the Mouse Brain Against Ischemic Injury
Authors: Yung Lai Ming , Wei Ying , Qin Tao , Wang Yumei , Smith Charles D. , Waeber Christian 
Published: October 2011

Background and Purpose—
Cerebral preconditioning provides insights into endogenous mechanisms that protect the brain from ischemic injury. Hypoxia and the anesthetic isoflurane are powerful preconditioning agents. Recent data show that sphingosine 1-phosphate receptor stimulation improves outcome in rodent models of stroke. Endogenous sphingosine 1-phosphate levels are controlled by the expression and activity of sphingosine kinases (SPK). We hypothesize that SPK upregulation mediates preconditioning induced by isoflurane and hypoxia and reduces ischemic injury.

Methods—

Male wild-type C57BL/J, SPK1
−/−
and SPK2
−/−
mice were exposed to isoflurane or hypoxia preconditioning before transient middle cerebral artery occlusion. Infarct volume and neurological outcome were measured 24 hours later. SPK inhibitors (SKI-II and ABC294640) were used to test the involvement of SPK2. Expressions of SPK1, SPK2, and hypoxia-inducible factor 1α were determined. Primary cultures of mouse cortical neurons were exposed to isoflurane before glutamate- or hydrogen peroxide-induced cell death.

Results—

Isoflurane preconditioning and hypoxia preconditioning significantly reduced infarct volume and improved neurological outcome in wild-type and SPK1
−/−
mice but not in SPK2
−/−
mice. Pretreatment with SKI-II or ABC294640 abolished the isoflurane preconditioning-induced tolerance. Western blot showed a rapid and sustained increase in SPK2 level, whereas SPK1 level was similar between preconditioned mice and controls. Hypoxia-inducible factor 1α was upregulated in wild-type isoflurane-preconditioned mice but not in SPK2
−/−
. Isoflurane preconditioning protected primary neurons against cell death, which was abolished in ABC294640-treated cells.

Conclusions—
Applying genetic and pharmacological approaches, we demonstrate that neuronal SPK2 isoform plays an important role in cerebral preconditioning.
Blood Pressure Reduction, Decreased Diffusion on MRI, and Outcomes After Intracerebral Hemorrhage
Authors: Garg Rajeev K. , Liebling Storm M. , Maas Matthew B. , Nemeth Alexander J. , Russell Eric J. , Naidech Andrew M. 
Published: October 2011

Background and Purpose—
Decreased diffusion (DD) consistent with acute ischemia may be detected on MRI after acute intracerebral hemorrhage (ICH), but its risk factors and impact on functional outcomes are not well-defined. We tested the hypotheses that DD after ICH is related to acute blood pressure (BP) reduction and lower hemoglobin and presages worse functional outcomes.

Methods—
Patients who underwent MRI were prospectively evaluated for DD by certified neuroradiologists blinded to outcomes. Hemoglobin and BP data were obtained via electronic queries. Outcomes were obtained at 14 days and 3 months with the modified Rankin Scale, a functional scale scored from 0 (no symptoms) to 6 (dead). We used logistic regression for dependence or death (modified Rankin Scale score 4–6).

Results—

DD distinct from the hematoma was found on MRI in 39 of 95 patients (41%). DD was associated with greater BP reductions from baseline and a higher risk of dependence or death at 3 months (odds ratio, 4.8; 95% confidence interval, 1.7–13.9;
P
=0.004) after correction for ICH score (1.8 per point; 95% confidence interval, 1.2–3.1;
P
=0.01). Lower hemoglobin was associated with worse ICH score, larger hematoma volume, and worse outcomes, but not DD.

Conclusions—
DD is common after ICH, associated with greater acute BP reductions, and associated with disability and death at 3 months in multivariate analysis. The potential benefits of acute BP reduction to reduce hematoma growth may be limited by DD. The prevention and treatment of cerebral ischemia manifested as DD are potential methods to improve outcomes.
Cerebral Mast Cells Mediate Blood-Brain Barrier Disruption in Acute Experimental Ischemic Stroke Through Perivascular Gelatinase Activation
Authors: Mattila Olli S. , Strbian Daniel , Saksi Jani , Pikkarainen Tero O. , Rantanen Ville , Tatlisumak Turgut , Lindsberg Perttu J. 
Published: October 2011

Background and Purpose—
Perivascularly positioned cerebral mast cells (MC) have been shown to participate in acute blood-brain barrier disruption and expansive brain edema following experimental transient cerebral ischemia. However, the underlying molecular mechanisms remain unknown. Because proteolytic gelatinase enzymes, matrix metalloproteinases (MMP)-2 and MMP-9, are thought to have a central role in compromising the integrity of the blood-brain barrier following ischemia, we examined whether cerebral MCs influence gelatinase activity in ischemic cerebral microvasculature.

Methods—

Rats underwent 60 minutes of middle cerebral artery occlusion followed by 3-hour reperfusion, and were treated with a MC-stabilizing (cromoglycate), or MC-degranulating (compound 48/80) agent, or vehicle. Genetically manipulated, MC-deficient WsRc
Ws/Ws
rats and their wild-type littermates (WT) underwent the same procedures. Cerebral edema and extravasation of Evans blue albumin were measured. Gelatinase activity was visualized by in situ zymography and was quantified with computerized high-throughput image and data analysis.

Results—

Activated MCs showed secretion of gelatinase-positive granules. Genetic MC deficiency decreased global gelatinase-active area (−69%, compared with WT;
P
<0.001) and the mean gelatinase activity of the ischemic microvasculature (−57% compared with WT;
P
=0.002). MC stabilization with cromoglycate decreased the percentage of microvessels with high gelatinase activity (−36% compared with saline;
P
<0.05). Compound 48/80 showed increased area of in situ zymography activity in the ischemic lesion (+55% compared with saline;
P
<0.001). Microvascular gelatinase activity correlated with brain swelling (
r
=0.84;
P
<0.001; and
r
=0.61;
P
=0.02).

Conclusions—
Our data demonstrate that cerebral MCs participate in regulation of acute microvascular gelatinase activation and consequent blood-brain barrier disruption following transient cerebral ischemia.
Stroke Quality Metrics
Authors: Parker Carol , Schwamm Lee H. , Fonarow Gregg C. , Smith Eric E. , Reeves Mathew J. 
Published: October 2011

Background and Purpose—
Stroke quality metrics play an increasingly important role in quality improvement and policies related to provider reimbursement, accreditation, and public reporting. We conducted 2 systematic reviews examining the relationships between compliance with stroke quality metrics and patient-centered outcomes, and public reporting of stroke metrics and quality improvement, quality of care, or outcomes.

Methods—
MEDLINE and EMBASE databases were searched to identify studies that evaluated the relationship between stroke quality metric compliance and patient-centered outcomes in acute hospital settings and public reporting of stroke quality metrics and quality improvement activities, quality of care, or patient outcomes. We specifically excluded studies that evaluated the effect of stroke units or hospital certification.

Results—
Fourteen studies met eligibility criteria for the review of stroke quality metric compliance and patient-centered outcomes; 9 found mostly positive associations, whereas 5 found no or very limited associations. Only 2 eligible studies were found that directly addressed the public reporting of stroke quality metrics.

Conclusions—
Some studies have found positive associations between stroke metric compliance and improved patient-centered outcomes. However, high-quality studies are lacking and several methodological difficulties make the interpretation of the reported associations challenging. Information on the impact of public reporting of stroke quality metric data is extremely limited. Legitimate questions remain as to whether public reporting of stroke metrics is accurate, effective, or has the potential for unintended consequences. The generation of high-quality data examining quality metrics and stroke outcomes as well as the impact of public reporting should be given priority.
Feedback-related Brain Potential Activity Complies with Basic Assumptions of Associative Learning Theory
Authors: Luque David , López Francisco J. , Marco-Pallares Josep , Càmara Estela , Rodríguez-Fornells Antoni 
Published: October 2011

Abstract
Feedback-related negativity (FRN) is an ERP component that distinguishes positive from negative feedback. FRN has been hypothesized to be the product of an error signal that may be used to adjust future behavior. In addition, associative learning models assume that the trial-to-trial learning of cue–outcome mappings involves the minimization of an error term. This study evaluated whether FRN is a possible electrophysiological correlate of this error term in a predictive learning task where human subjects were asked to learn different cue–outcome relationships. Specifically, we evaluated the sensitivity of the FRN to the course of learning when different stimuli interact or compete to become a predictor of certain outcomes. Importantly, some of these cues were blocked by more informative or predictive cues (i.e., the blocking effect). Interestingly, the present results show that both learning and blocking affect the amplitude of the FRN component. Furthermore, independent analyses of positive and negative feedback event-related signals showed that the learning effect was restricted to the ERP component elicited by positive feedback. The blocking test showed differences in the FRN magnitude between a predictive and a blocked cue. Overall, the present results show that ERPs that are related to feedback processing correspond to the main predictions of associative learning models.
Temporal Dynamics of Cognitive–Emotional Interplay in Moral Decision-making
Authors: Sarlo Michela , Lotto Lorella , Manfrinati Andrea , Rumiati Rino , Gallicchio Germano , Palomba Daniela 
Published: October 2011

Abstract
This study investigated the temporal dynamics of emotional and cognitive processing underlying decision-making in moral judgment. Thirty-seven participants were presented with a set of 60 dilemmas varying in whether killing one individual was an intended means to save others (instrumental dilemmas) or a foreseen but unintended consequence (incidental dilemmas). Participants were required to decide between Options A (letting a specific number of people die) and B (killing one person to save a specific number of people). ERPs were recorded to a slide displaying the letters A and B while subjects were deciding between the options, and movement-related potentials were recorded time-locked to the behavioral response, thus allowing the investigation of both stimulus- and response-related processes during decision-making. Ratings of emotional valence and arousal experienced during decision-making were collected after each decision. Compared with incidental dilemmas, instrumental dilemmas prompted a lower number of B choices and significantly more unpleasant decisions. A larger P260 component was found in the frontopolar and frontal areas when subjects were deciding on instrumental than incidental dilemmas, possibly reflecting an immediate affective reaction during the early stage of assessment and formation of preferences between available options. On the other hand, decisions on incidental dilemmas required greater attentional resources during the fairly controlled later processing, as reflected in the larger slow wave amplitudes. In addition, facilitation of action selection and implementation was found for incidental dilemmas during the second stage of decision-making, as supported by the larger amplitudes of both components of the Bereitschaftspotential.
On the Automaticity of Semantic Processing during Task Switching
Authors: Vachon François , Jolicœur Pierre 
Published: October 2011

Abstract
There is growing evidence that processes formerly believed to be automatic are, in fact, strongly modulated by top–down influences. The purpose of the present work was to investigate how cognitive control can affect the purported automaticity of word processing by examining the impact of task switching on semantic processing using the ERP technique. In the context of the psychological refractory period dual-task paradigm, two experiments contrasted the context-sensitive N400 ERP elicited by the second of two target words under conditions that involved either a task switch or no-task switch. Although the N400 was not affected by SOA in the absence of switching, it was strongly attenuated at short SOAs when the psychological refractory period procedure involved a switch from a perceptual to a semantic task (Experiment 1) or a switch between two different semantic tasks (Experiment 2). These findings suggest that semantic processing cannot be performed in parallel with task switching and illustrate limitations in the ability of the cognitive system to adapt flexibly to the dynamically changing challenges of the environment according to task demands and behavioral goals.
Noninvasively Decoding the Contents of Visual Working Memory in the Human Prefrontal Cortex within High-gamma Oscillatory Patterns
Authors: Polanía Rafael , Paulus Walter , Nitsche Michael A. 
Published: October 2011

Abstract
The temporal maintenance and subsequent retrieval of information that no longer exists in the environment is called working memory. It is believed that this type of memory is controlled by the persistent activity of neuronal populations, including the prefrontal, temporal, and parietal cortex. For a long time, it has been controversially discussed whether, in working memory, the PFC stores past sensory events or, instead, its activation is an extramnemonic source of top–down control over posterior regions. Recent animal studies suggest that specific information about the contents of working memory can be decoded from population activity in prefrontal areas. However, it has not been shown whether the contents of working memory during the delay periods can be decoded from EEG recordings in the human brain. We show that by analyzing the nonlinear dynamics of EEG oscillatory patterns it is possible to noninvasively decode with high accuracy, during encoding and maintenance periods, the contents of visual working memory information within high-gamma oscillations in the human PFC. These results are thus in favor of an active storage function of the human PFC in working memory; this, without ruling out the role of PFC in top–down processes. The ability to noninvasively decode the contents of working memory is promising in applications such as brain computer interfaces, together with computation of value function during planning and decision making processes.