bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Androgen Receptor Induces Integrin α6β1 to Promote Prostate Tumor Cell Survival via NF-κB and Bcl-xL Independently of PI3K Signaling
Authors: Lamb Laura E. , Zarif Jelani C. , Miranti Cindy K. 
Published: February 2011

Abstract
Recent studies indicate that androgen receptor (AR) signaling is critical for prostate cancer cell survival, even in castration-resistant disease wherein AR continues to function independently of exogenous androgens. Integrin-mediated adhesion to the extracellular matrix is also important for prostate cell survival. AR-positive prostate cancer cells express primarily integrin α6β1 and adhere to a laminin-rich matrix. In this study, we show that active nuclear-localized AR protects prostate cancer cells from death induced by phosphoinositide 3-kinase (PI3K) inhibition when cells adhere to laminin. Resistance to PI3K inhibition is mediated directly by an AR-dependent increase in integrin α6β1 mRNA transcription and protein expression. Subsequent signaling by integrin α6β1 in AR-expressing cells increased NF-κB activation and Bcl-xL expression. Blocking AR, integrin α6, NF-κB, or Bcl-xL concurrent with inhibition of PI3K was sufficient and necessary to trigger death of laminin-adherent AR-expressing cells. Taken together, these results define a novel integrin-dependent survival pathway in prostate cancer cells that is regulated by AR, independent of and parallel to the PI3K pathway. Our findings suggest that combined targeting of both the AR/α6β1 and PI3K pathways may effectively trigger prostate cancer cell death, enhancing the potential therapeutic value of PI3K inhibitors being evaluated in this setting. Cancer Res; 71(7); 2739–49. ©2011 AACR.
STAT3 Expression, Molecular Features, Inflammation Patterns, and Prognosis in a Database of 724 Colorectal Cancers
Authors: Morikawa Teppei , Baba Yoshifumi , Yamauchi Mai , Kuchiba Aya , Nosho Katsuhiko , Shima Kaori , Tanaka Noriko , Huttenhower Curtis , Frank David A. , Fuchs Charles S. , Ogino Shuji 
Published: February 2011

AbstractPurpose: STAT3 is a transcription factor that is constitutively activated in some cancers. It seems to play crucial roles in cell proliferation and survival, angiogenesis, tumor-promoting inflammation, and suppression of antitumor host immune response in the tumor microenvironment. Although the STAT3 signaling pathway is a potential drug target, clinical, pathologic, molecular, or prognostic features of STAT3-activated colorectal cancer remain uncertain.Experimental Design: Utilizing a database of 724 colon and rectal cancer cases, we evaluated phosphorylated STAT3 (p-STAT3) expression by immunohistochemistry. The Cox proportional hazards model was used to compute mortality HR, adjusting for clinical, pathologic, and molecular features, including microsatellite instability (MSI), the CpG island methylator phenotype (CIMP), LINE-1 methylation, 18q LOH, TP53 (p53), CTNNB1 (β-catenin), JC virus T-antigen, and KRAS, BRAF, and PIK3CA mutations.Results: Among the 724 tumors, 131 (18%) showed high-level p-STAT3 expression (p-STAT3-high), 244 (34%) showed low-level expression (p-STAT3-low), and the remaining 349 (48%) were negative for p-STAT3. p-STAT3 overexpression was associated with significantly higher colorectal cancer–specific mortality [log-rank P = 0.0020; univariate HR (p-STAT3-high vs. p-STAT3-negative): 1.85, 95% CI: 1.30–2.63, Ptrend = 0.0005; multivariate HR: 1.61, 95% CI: 1.11–2.34, Ptrend = 0.015]. p-STAT3 expression was positively associated with peritumoral lymphocytic reaction (multivariate OR: 3.23; 95% CI: 1.89–5.53, P &lt; 0.0001). p-STAT3 expression was not associated with MSI, CIMP, or LINE-1 hypomethylation.Conclusions: STAT3 activation in colorectal cancer is associated with adverse clinical outcome, supporting its potential roles as a prognostic biomarker and a chemoprevention and/or therapeutic target. Clin Cancer Res; 17(6); 1452–62. ©2011 AACR.
Emergency Department Crowding and Time to Care in Patients With Acute Stroke
Authors: Chatterjee Pia , Cucchiara Brett L. , Lazarciuc Nicole , Shofer Frances S. , Pines Jesse M. 
Published: February 2011

Background and Purpose—
Emergency department (ED) crowding occurs when demands for ED care exceed the supply of available resources. Prior studies have shown that ED crowding is associated with a delay in provision of critical ED services, but the impact of ED crowding on acute stroke care has not been extensively studied.

Methods—
We conducted a retrospective study of patients who presented to the ED with acute stroke symptoms (ischemic stroke, transient ischemic attack, intracerebral hemorrhage) at 2 hospitals. All patients with active stroke symptoms who presented within 3 hours were included and a random sample of patients with symptoms >3 hours was used for comparison. The association between ED crowding measures (waiting room number, ED occupancy, number of admitted patients, and total patient hours) and time to head CT order, completion, and interpretation, and time to administration of thrombolysis was determined.

Results—
Of 253 patients presenting with acute stroke symptoms ≤3 hours from symptom onset, 52 (21%) received thrombolysis. A random comparison group of 253 patients with symptoms >3 hours was identified. There was no significant association between ED crowding and delays in CT timing or thrombolysis in patients with symptoms ≤3 hours. Several measures of ED crowding were associated with prolonged times to CT order and completion in patients with symptoms >3 hours.

Conclusions—
ED crowding was not associated with care delays in thrombolysis-eligible patients with stroke. However, those with symptoms >3 hours do experience CT delays at higher levels of ED crowding.
Restenosis Is More Frequent After Carotid Stenting Than After Endarterectomy
Authors: Arquizan Caroline , Trinquart Ludovic , Touboul Pierre-Jean , Long Anne , Feasson Séverine , Terriat Béatrice , Gobin-Metteil Marie-Pierre , Guidolin Brigitte , Cohen Serge , Mas Jean-Louis 
Published: February 2011

Background and Purpose—
Carotid angioplasty and stenting (CAS) may be more often associated with residual or recurrent stenosis than carotid endarterectomy (CEA). We compared the rates of restenosis in patients treated with CAS or CEA in the EVA-3S trial.

Methods—
Five hundred seven patients (242 treated by CAS and 265 by CEA) had carotid ultrasound follow-up (mean carotid ultrasound follow-up, 2.1 years) according to a predefined protocol. Carotid restenosis of 50% to 69% was diagnosed on planimetry, whereas carotid restenosis of ≥70% or occlusion was diagnosed using either planimetry or velocity criteria.

Results—

The rate of carotid restenosis of ≥50% or occlusion was significantly higher after CAS (12.5%) than after CEA (5.0%; time ratio, 0.16; 95% CI, 0.03–0.76;
P
=0.02). The rates of severe restenosis of ≥70% or occlusion were low and did not differ significantly between the 2 groups (3-year rates are 3.3% in the CAS group and 2.8% in the CEA group). Age at baseline was the only vascular risk factor significantly associated with carotid restenosis. Our study could not detect any effect of carotid restenosis on ipsilateral stroke.

Conclusions—
The short-term rate of carotid restenosis of ≥50% or occlusion is ≈2.5-times more common after CAS than after CEA, a difference accounted for by an excess risk in moderate restenosis. More data with longer follow-up are needed to assess the rates of late severe restenosis and to determine the relation between restenosis and recurrent stroke over time.
Carotid Plaque Area and Intima-Media Thickness in Prediction of First-Ever Ischemic Stroke
Authors: Mathiesen Ellisiv B. , Johnsen Stein Harald , Wilsgaard Tom , Bønaa Kaare H. , Løchen Maja-Lisa , Njølstad Inger 
Published: February 2011

Background and Purpose—
Carotid plaque and intima-media thickness (IMT) are recognized as risk factors for ischemic stroke, but their predictive value has been debated and varies between studies. The purpose of this longitudinal population-based study was to assess the risk of ischemic stroke associated with plaque area and IMT in the carotid artery.

Methods—
IMT and total plaque area in the right carotid artery were measured with ultrasound in 3240 men and 3344 women aged 25 to 84 years who participated in a population health study in 1994 to 1995. First-ever ischemic strokes were identified through linkage to hospital and national diagnosis registries, with follow-up until December 31, 2005.

Results—

Incident ischemic strokes occurred in 7.3% (n=235) of men and 4.8% (n=162) of women. The hazard ratio for 1 SD increase in square-root-transformed plaque area was 1.23 (95% CI, 1.09–1.38;
P
=0.0009) in men and 1.19 (95% CI, 1.01–1.41;
P
=0.04) in women when adjusted for other cardiovascular risk factors. The multivariable-adjusted hazard ratio in the highest quartile of plaque area versus no plaque was 1.73 (95% CI, 1.19–2.52;
P
=0.004) in men and 1.62 (95% CI, 1.04–2.53;
P
=0.03) in women. The multivariable-adjusted hazard ratio for 1 SD increase in IMT was 1.08 (95% CI, 0.95–1.22;
P
=0.2) in men and 1.24 (95% CI, 1.05–1.48;
P
=0.01) in women. There were no differences in stroke risk across quartiles of IMT in multivariable analysis.

Conclusions—
In the present study, total plaque area appears to be a stronger predictor than IMT for first-ever ischemic stroke.
Cognitive Context Determines Dorsal Premotor Cortical Activity During Hand Movement in Patients After Stroke
Authors: Dennis Andrea , Bosnell Rose , Dawes Helen , Howells Ken , Cockburn Janet , Kischka Udo , Matthews Paul , Johansen-Berg Heidi 
Published: February 2011

Background and Purpose—
Stroke patients often have difficulties in simultaneously performing a motor and cognitive task. Functional imaging studies have shown that movement of an affected hand after stroke is associated with increased activity in multiple cortical areas, particularly in the contralesional hemisphere. We hypothesized patients for whom executing simple movements demands greater selective attention will show greater brain activity during movement.

Methods—
Eight chronic stroke patients performed a behavioral interference test using a visuo-motor tracking with and without a simultaneous cognitive task. The magnitude of behavioral task decrement under cognitive motor interference (CMI) conditions was calculated for each subject. Functional MRI was used to assess brain activity in the same patients during performance of a visuo-motor tracking task alone; correlations between CMI score and movement-related brain activation were then explored.

Results—

Movement-related activation in the dorsal precentral gyrus of the contralesional hemisphere correlated strongly and positively with CMI score (
r
2
at peak voxel=0.92;
P
<0.05). Similar but weaker relationships were observed in the ventral precentral and middle frontal gyrus. There was no independent relationship between hand motor impairment and CMI.

Conclusions—
Results suggest that variations in the degree to which a cognitive task interferes with performance of a concurrent motor task explains a substantial proportion of the variations in movement-related brain activity in patients after stroke. The results emphasize the importance of considering cognitive context when interpreting brain activity patterns and provide a rationale for further evaluation of integrated cognitive and movement interventions for rehabilitation in stroke.
Altered Expression of PIWI RNA in the Rat Brain After Transient Focal Ischemia
Authors: Dharap Ashutosh , Nakka Venkata Prasuja , Vemuganti Raghu 
Published: February 2011

Background and Purpose—
The PIWI-interacting RNA (piRNA) is the most predominant RNA species in eukaryotes. The piRNA are a class of noncoding RNAs that bind and degrade the RNA formed by the transposons to control the transposon-induced gene mutations. The role of piRNA after focal ischemia is not yet evaluated.

Methods—
We profiled 39 727 piRNAs in the cerebral cortex of adult rats subjected to transient focal ischemia using microarrays. The RT targets of stroke-responsive piRNAs were identified with bioinformatics. To understand how piRNAs are controlled, we analyzed the transcription factor binding sites in the putative promoters of 10 representative stroke-responsive piRNAs.

Results—
In the ipsilateral cortex of ischemic rats, 105 piRNAs showed altered expression (54 up- and 51 downregulated; >2.5-fold) compared with shams. Twenty-five of those showed a >5-fold change. A bioinformatics search showed that the transposon targets of the highly stroke-responsive piRNAs are distributed among the 20 autosomal chromosomes and there is a redundancy in the targets between the piRNAs. Furthermore, the transposon targets were observed to be highly repetitious for each piRNA across the chromosome length. Of the 159 transcription factors observed to have binding sites in the piRNA gene promoters, 59% belonged to 20 major families indicating that transcription factors control stroke-responsive piRNAs in a redundant manner.

Conclusions—
The present study is the first to show that many piRNAs are expressed in adult rodent brain and several of them respond to focal ischemia.
An Analysis of Inflation Times During Balloon-Assisted Aneurysm Coil Embolization and Ischemic Complications
Authors: Spiotta Alejandro M. , Bhalla Tarun , Hussain Muhammad S. , Sivapatham Thinesh , Batra Ayush , Hui Ferdinand , Rasmussen Peter A. , Moskowitz Shaye I. 
Published: February 2011

Background and Purpose—
The introduction of balloon remodeling has revolutionized the approach to coiling of wide-neck aneurysms. We studied the effects of balloon inflation during coil embolization on ischemic complications.

Methods—
A retrospective review was undertaken of the most recent 147 patients undergoing balloon remodeling for unruptured intracranial aneurysm coil embolization at a single institution (81 balloon, 66 unassisted). All underwent postprocedural MRI.

Results—
Among patients in the “balloon” group, the mean total inflation time was 18 minutes (range, 1–43), a mean number of inflations of 4 (range, 1–9), a mean maximum single inflation time of 7 minutes (range, 1–19), a mean reperfusion time of 2.2 minutes between inflations, and an average procedure time of 2 hours and 10 minutes. Asymptomatic diffusion-weighted imaging abnormalities were detected on postprocedural MRI in 21.5% of patients and symptomatic lesions were identified in 3.8%. Both silent and symptomatic ischemic rates were similar in the internal control group. Patients with ischemic findings were older and more likely have diabetes; no differences were found with respect to total balloon inflation time, number of inflations, maximum inflation time, or reperfusion times.

Conclusions—
We found no significant relationship between balloon inflation practices and ischemic events. Older and diabetic patients were more likely to have ischemic events develop.
Visual Perfusion–Diffusion Mismatch Is Equivalent to Quantitative Mismatch
Authors: Luby Marie , Ku Katherine D. , Latour Lawrence L. , Merino José G. , Hsia Amie W. , Lynch John K. , Warach Steven 
Published: February 2011

Background and Purpose—
The concept of stroke MRI mismatch based on qualitative evaluation of diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) has been applied in clinical practice for several years. The benefit of MRI in providing pathological evidence of ischemia before thrombolytic treatment has been demonstrated. The purpose of this study is to determine the reliability of the qualitative method and compare it with quantitative mismatch measurement in thrombolytic-treated patients.

Methods—
Patients (n=70) were selected from the Lesion Evolution of Stroke and Ischemic On Neuroimaging (LESION) database if they: (1) were treated with intravenous recombinant tissue plasminogen activator; (2) had a pretreatment MRI with evaluable DWI and PWI; and (3) had acute ischemic lesion volume >10 mL on DWI as determined by core imaging laboratory measurements. Quantitative mismatch was defined as a difference of >50 mL between abnormal mean transit time and DWI volumes. Sample characteristics and postdischarge modified Rankin Scale for the positive mismatch patients were compared between the subgroups identified by qualitative versus quantitative methods.

Results—
Patient characteristics and thrombolytic outcomes (sex, age, National Institutes of Health Stroke Scale, mismatch volume, and modified Rankin Scale) did not differ for mismatch patients identified by qualitative versus quantitative methods. Qualitative mismatch selection among neurologists had a high sensitivity (0.82), specificity (0.80), accuracy (0.81), and positive predictive value (0.88) compared with quantitative measurements.

Conclusions—
We observed that qualitative evaluation of mismatch identified the same thrombolytic-treated patients compared with retrospective quantitative mismatch measurements.
Traditional Risk Factors for Incident Cardiovascular Events Have Limited Importance in Later Life Compared With the Health in Men Study Cardiovascular Risk Score
Authors: Beer Christopher , Alfonso Helman , Flicker Leon , Norman Paul E. , Hankey Graeme J. , Almeida Osvaldo P. 
Published: February 2011

Background and Purpose—
This study aimed to determine, among older men, the risk and independent significant baseline prognostic factors for first-ever stroke and MI.

Methods—
We performed a prospective cohort study of 4382 community-dwelling older men (mean age, 75.4±4.2 years) with no history of stroke or MI. Baseline data comprised questionnaire responses, clinical measurements, and comorbidity.

Results—

After a median of 6 years (interquartile range, 5.2–7.2) of follow-up, the overall rate of stroke/MI was 2.61 (95% CI, 2.42–2.81) per 100 person-years. Among major traditional risk prediction variables, only age and smoking were significantly associated with stroke/MI. In our final multivariate model, the independent significant predictors of stroke/MI were age (HR for age older than 85, 3.18; 95% CI, 2.05–4.93), diastolic blood pressure <70 mm Hg (Hazard ratio [HR], 1.45; 95% CI, 1.18–1.78), high-sensitivity C-reactive protein >3 mg/L (HR, 1.29; 95% CI, 1.05–1.59), homocysteine >15 umol/L (HR, 1.35; 95% CI, 1.09–1.67), waist-to-hip ratio >1 (HR, 1.47; 95% CI, 1.20–1.18), and fair or poor self-reported health (HR, 1.52; 95% CI, 1.19–1.94). A new risk model incorporating these variables performed well compared with the Framingham risk equation (Harrell C of 0.660 versus C of 0.620; integrated discrimination improvement of 1.85%; z=4.95;
P
<0.001; net reclassification index of 0.08; z=2.0;
P
=0.023). The model was used to develop an 8- point clinical risk score comprising the independent predictors of stroke/MI among this population.

Conclusions—
Traditional vascular risk factors did not optimally predict stroke/MI among this cohort of community-dwelling older men. We have constructed a new risk score that requires validation in other data sets.
Bone Marrow Stromal Cells Promote Skilled Motor Recovery and Enhance Contralesional Axonal Connections After Ischemic Stroke in Adult Mice
Authors: Liu Zhongwu , Li Yi , Zhang Rui Lan , Cui Yisheng , Chopp Michael 
Published: February 2011

Background and Purpose—
We tested the effect of bone marrow stromal cells (BMSCs) on neuronal remodeling of the corticospinal tract originating from the contralesional cortex in mice subjected to unilateral pyramidotomy (PT) followed by middle cerebral artery occlusion (MCAO).

Methods—
Adult mice with transgenic yellow fluorescent protein labeling in the corticospinal tract were subjected to right hemispheric PT and right permanent or sham MCAO. One day later, the mice were treated intravenously with BMSCs or phosphate-buffered saline. A Foot-Fault test and a single pellet-reaching test were performed before surgery, 3 days after MCAO, and weekly thereafter. Pseudorabies virus-614-monomeric red fluorescent protein was injected into the left forelimb flexor muscles 28 days after surgery (4 days before euthanasia). The brain and cervical cord were processed for fluorescent microscopy to detect red fluorescent protein and yellow fluorescent protein labeling, respectively.

Results—

Significant functional improvements were evident in PT-MCAO mice treated with BMSCs (n=9) compared with phosphate-buffered saline-treated mice (n=9,
P
<0.05), but not in mice with PT-sham MCAO treated with either phosphate-buffered saline (n=9) or BMSCs (n=10). Furthermore, in PT-MCAO mice, both corticospinal tract axonal density in the denervated side of the cervical gray matter and red fluorescent protein-labeled pyramidal neurons in the left intact cortex were significantly increased compared with PT-sham MCAO mice (
P
<0.05). BMSCs significantly enhanced both corticospinal tract density and red fluorescent protein labeling in PT-MCAO mice (
P
<0.05) only. The behavioral outcome was highly correlated with corticospinal tract density and red fluorescent protein labeling.

Conclusions—
BMSCs amplify stroke-induced contralesional neuronal remodeling, which contributes to motor recovery after stroke.
Perceiving Opponent Hues in Color Induction Displays
Authors: Mingolla Ennio , Livitz Gennady , Eskew, Jr. Rhea , Yazdanbakhsh Arash 
Published: February 2011

AbstractAccording to Hering's color theory, certain hues (red vs green and blue vs yellow) are mutually exclusive as components of a single color; consequently a color cannot be perceived as reddish-green or bluish-yellow. The goal of our study is to test this key postulate of the opponent color theory. Using the method of adjustment, our observers determine the boundaries of chromatic zones in a red–green continuum. We demonstrate on two distinct stimulus sets, one formed using a chromatic grid and neon spreading and the other based on solid colored regions, that the chromatic contrast of a purple surround over a red figure results in perception of 'forbidden' reddish-green colors. The observed phenomenon can be understood as resulting from the construction of a virtual filter, a process that bypasses photoreceptor summation and permits forbidden color combinations. Showing that opponent hue combinations, previously reported only under artificial image stabilization, can be present in normal viewing conditions offers new approaches for the experimental study of the dimensionality and structure of perceptual color space.
The Effect of Set Size on the Dynamics of Binocular Rivalry
Authors: Paffen Chris , Hooge Ignace 
Published: February 2011

AbstractDuring binocular rivalry, the percept alternates between dissimilar images presented dichoptically. A central question in studies on binocular rivalry is whether its dynamics are affected by attention. Here we approach this question by studying how set size affects the number of alternations reported from a rivalry-inducing display. The results show that the number of alternations reported increased only slightly with increasing set size. In follow-up experiments we show that neither (1) limitations in response speed nor (2) grouping cues are responsible for this result, and that (3) increasing set size decreases the number of alternations reported per rivalry-inducing element. Our results show that the spatial distribution of attention affects the number of alternations reported in a rivalry-inducing display.