bluuebunny/crossref_metadata_2025_split huggingface dataset:
Progression Rate and Ipsilateral Neurological Events in Asymptomatic Carotid Stenosis
Authors: Hirt Liam S. 
Published: July 2011

Background and Purpose—
Progression of asymptomatic carotid stenoses with >50% luminal narrowing is associated with an increased risk of stroke. The significance of the progression rate in these patients is unknown. The main aim of this study was to evaluate the rate of change of carotid luminal narrowing over 1 year, as a risk factor for ipsilateral ischemic events, in patients with a >50% asymptomatic carotid stenosis. Secondary aims were to establish the incidence of changes in carotid luminal narrowing and establish additional risk factors for ipsilateral neurological events.

Methods—
A retrospective analysis was conducted of data derived from the deferred endarterectomy arm of the Asymptomatic Carotid Surgery Trial. Patients were followed up for ≥5 years with serial carotid duplex examinations. Data were derived from information obtained at randomization and annual follow-up visits with carotid duplex examination. Potential risk factors for ipsilateral neurological events were analyzed in Poisson regression models.

Results—
Data from 1469 patients were included. Two hundred forty-four had ipsilateral events; 240 had ipsilateral carotid surgery; 370 died from nonstroke causes; and 82 had an asymptomatic carotid occlusion. The annual incidence of progression in the cohort as a whole was 5.2%. Ipsilateral events occurred in 17% of patients. Diabetes and previous contralateral symptoms showed a significant independent association with ipsilateral neurological events. Ipsilateral events were associated with high rates of progression over 1 year but not with low progression rates or regression.

Conclusions—
Fast rates of progression of carotid luminal narrowing should be interpreted as a sign of significantly increased risk of future ipsilateral neurological events.
Arterial Spin-Labeling MRI Can Identify the Presence and Intensity of Collateral Perfusion in Patients With Moyamoya Disease
Authors: Zaharchuk Greg , Do Huy M. , Marks Michael P. , Rosenberg Jarrett , Moseley Michael E. , Steinberg Gary K. 
Published: July 2011

Background and Purpose—
Determining the presence and adequacy of collateral blood flow is important in cerebrovascular disease. Therefore, we explored whether a noninvasive imaging modality, arterial spin labeling (ASL) MRI, could be used to detect the presence and intensity of collateral flow using digital subtraction angiography (DSA) and stable xenon CT cerebral blood flow as gold standards for collaterals and cerebral blood flow, respectively.

Methods—
ASL and DSA were obtained within 4 days of each other in 18 patients with Moyamoya disease. Two neurointerventionalists scored DSA images using a collateral grading scale in regions of interest corresponding to ASPECTS methodology. Two neuroradiologists similarly scored ASL images based on the presence of arterial transit artifact. Agreement of ASL and DSA consensus scores was determined, including kappa statistics. In 15 patients, additional quantitative xenon CT cerebral blood flow measurements were performed and compared with collateral grades.

Results—

The agreement between ASL and DSA consensus readings was moderate to strong, with a weighted kappa value of 0.58 (95% confidence interval, 0.52–0.64), but there was better agreement between readers for ASL compared with DSA. Sensitivity and specificity for identifying collaterals with ASL were 0.83 (95% confidence interval, 0.77–0.88) and 0.82 (95% confidence interval, 0.76–0.87), respectively. Xenon CT cerebral blood flow increased with increasing DSA and ASL collateral grade (
P
<0.05).

Conclusions—
ASL can noninvasively predict the presence and intensity of collateral flow in patients with Moyamoya disease using DSA as a gold standard. Further study of other cerebrovascular diseases, including acute ischemic stroke, is warranted.
Charlson Comorbidity Index Adjustment in Intracerebral Hemorrhage
Authors: Bar Barak , Hemphill J. Claude 
Published: July 2011

Background and Purpose—
Previous studies of intracerebral hemorrhage (ICH) outcome prediction models have not systematically included adjustment for comorbid conditions. The purpose of this study was to assess whether the Charlson Comorbidity Index (CCI) was associated with early mortality and long-term functional outcome in patients with intracerebral hemorrhage.

Methods—
We performed a retrospective analysis on a prospective observational cohort of patients with ICH admitted to 2 University of California San Francisco hospitals from June 1, 2001 to May 31, 2004. Components of the ICH score and use of early care limitations were recorded. Outcome was assessed using the modified Rankin Scale to 12 months. The CCI was derived using hospital discharge International Classification of Diseases, revision 9 codes and patient history obtained from standardized case report forms.

Results—

In this cohort of 243 ICH patients, comorbid conditions were common, with CCI scores ranging from 0 to 12. Only 29% of patients with high CCI scores (≥3) achieved a 12-month modified Rankin Scale score of ≥3 compared with 48% of patients with CCI scores of 0 (
P
=0.02). CCI score was independently predictive of 12-month functional outcome, with higher CCI having a greater impact (CCI=2: odds ratio, 2.3;
P
=0.06; CCI=≥3: odds ratio, 3.5;
P
=0.001).

Conclusions—
Comorbid medical conditions as measured by the CCI independently influence outcome after ICH. Future ICH outcome studies should account for the impact of comorbidities on patient outcome.
Autoimmune Responses to the Brain After Stroke Are Associated With Worse Outcome
Authors: Becker Kyra J. , Kalil Angela J. , Tanzi Pat , Zierath Dannielle K. , Savos Anna V. , Gee J. Michael , Hadwin Jessica , Carter Kelly T. , Shibata Dean , Cain Kevin C. 
Published: July 2011

Background and Purpose—
Immune responses to brain antigens occur after stroke, and experimental studies show that the likelihood of developing a detrimental autoimmune response to these antigens is increased by systemic inflammation at the time of stroke. The aim of this study was to determine if patients who developed infection in the poststroke period would be similarly predisposed to develop autoimmune responses to central nervous system antigens.

Methods—
We enrolled 114 patients within 72 hours of ischemic stroke. Clinical and demographic data were obtained, and cellular immune responses to a panel of central nervous system antigens were assessed during the initial week and again at Day 90. Outcome was assessed using the modified Rankin Scale.

Results—

Patients who developed an infection, especially pneumonia, in the 15 days after stroke were more likely to evidence a Th1(+) response to myelin basic protein and glial fibrillary acidic protein (
P
=0.019 and
P
=0.039, respectively) at 90 days after stroke. Further, more robust Th1 responses to myelin basic protein at 90 days were associated with a decreased likelihood of good outcome, even after adjusting for baseline stroke severity and patient age (OR, 0.477; 95% CI, 0.244 to 0.935;
P
=0.031).

Conclusions—
This study demonstrates that immune responses to brain antigens occur after stroke. Although these responses are likely to be an epiphenomenon of ischemic brain injury, the response to myelin basic protein appears to have clinical consequences. The potential role of postischemic autoimmune-mediated brain injury deserves further investigation.
Patients With Traumatic Brain Injury
Authors: Chen Yi-Hua , Kang Jiunn-Horng , Lin Herng-Ching 
Published: July 2011

Background and Purpose—
Previous studies have identified an array of morbidities following traumatic brain injury (TBI), including certain neurological disorders. However, no direct evidence has been reported on the link between TBI and stroke. This population-based study was designed to estimate the risk of stroke during a period of 5 years following a TBI, compared with individuals who did not suffer TBI during the same period.

Methods—
Data were obtained from the Longitudinal Health Insurance Database 2000 (LHID 2000). A total of 23 199 patients receiving ambulatory or hospitalization care with a diagnosis of TBI were included, together with 69 597 non-TBI patients as our comparison group, matched by sex, age, and year of index use of health care. Each individual was followed for 5 years to identify subsequent occurrence of stroke. Cox proportional hazard regressions were performed for analysis.

Results—
During the 3-month follow-up period, 675 strokes (2.91%) occurred in TBI patients and in 207 patients (0.30%) in the non-TBI comparison cohort. A diagnosis of TBI was independently associated with a 10.21 (95% CI, 8.71–11.96), 4.61 (95% CI, 4.16–5.11), and 2.32 (95% CI, 2.17–2.47) times greater risk of stroke during 3-month, 1-year, and 5-year follow-up, respectively, after adjusting for sociodemographic characteristics and selected comorbidities. The risk of intracerebral hemorrhage was more noticeable among patients with TBI compared with those without a TBI.

Conclusions—
This is the first report showing an increased risk of stroke among individuals who have sustained a TBI. We suggest a need for more intensive medical monitoring and health education following TBI, especially during the first few months and years.
Endothelial progenitor cell–dependent angiogenesis requires localization of the full-length form of uPAR in caveolae
Authors: Margheri Francesca , Chillà Anastasia , Laurenzana Anna , Serratì Simona , Mazzanti Benedetta , Saccardi Riccardo , Santosuosso Michela , Danza Giovanna , Sturli Niccolò , Rosati Fabiana , Magnelli Lucia , Papucci Laura , Calorini Lido , Bianchini Francesca , Del Rosso Mario , Fibbi Gabriella 
Published: July 2011

Abstract
Endothelial urokinase-type plasminogen activator receptor (uPAR) is thought to provide a regulatory mechanism in angiogenesis. Here we studied the proangiogenic role of uPAR in endothelial colony-forming cells (ECFCs), a cell population identified in human umbilical blood that embodies all of the properties of an endothelial progenitor cell matched with a high proliferative rate. By using caveolae-disrupting agents and by caveolin-1 silencing, we have shown that the angiogenic properties of ECFCs depend on caveolae integrity and on the presence of full-length uPAR in such specialized membrane invaginations. Inhibition of uPAR expression by antisense oligonucleotides promoted caveolae disruption, suggesting that uPAR is an inducer of caveolae organization. Vascular endothelial growth factor (VEGF) promoted accumulation of uPAR in ECFC caveolae in its undegraded form. We also demonstrated that VEGF-dependent ERK phosphorylation required integrity of caveolae as well as caveolar uPAR expression. VEGF activity depends on inhibition of ECFC MMP12 production, which results in impairment of MMP12-dependent uPAR truncation. Further, MMP12 overexpression in ECFC inhibited vascularization in vitro and in vivo. Our data suggest that intratumor homing of ECFCs suitably engineered to overexpress MMP12 could have the chance to control uPAR-dependent activities required for tumor angiogenesis and malignant cells spreading.
PMLRARα binds to Fas and suppresses Fas-mediated apoptosis through recruiting c-FLIP in vivo
Authors: Tao Rong-Hua , Berkova Zuzana , Wise Jillian F. , Rezaeian Abdol-Hossein , Daniluk Urszula , Ao Xue , Hawke David H. , Karp Judith E. , Lin Hui-Kuan , Molldrem Jeffrey J. , Samaniego Felipe 
Published: July 2011

Abstract
Defective Fas signaling leads to resistance to various anticancer therapies. Presence of potential inhibitors of Fas which could block Fas signaling can explain cancer cells resistance to apoptosis. We identified promyelocytic leukemia protein (PML) as a Fas-interacting protein using mass spectrometry analysis. The function of PML is blocked by its dominant-negative form PML–retinoic acid receptor α (PMLRARα). We found PMLRARα interaction with Fas in acute promyelocytic leukemia (APL)–derived cells and APL primary cells, and PML-Fas complexes in normal tissues. Binding of PMLRARα to Fas was mapped to the B-box domain of PML moiety and death domain of Fas. PMLRARα blockage of Fas apoptosis was demonstrated in U937/PR9 cells, human APL cells and transgenic mouse APL cells, in which PMLRARα recruited c-FLIPL/S and excluded procaspase 8 from Fas death signaling complex. PMLRARα expression in mice protected the mice against a lethal dose of agonistic anti-Fas antibody (P < .001) and the protected tissues contained Fas-PMLRARα-cFLIP complexes. Taken together, PMLRARα binds to Fas and blocks Fas-mediated apoptosis in APL by forming an apoptotic inhibitory complex with c-FLIP. The presence of PML-Fas complexes across different tissues implicates that PML functions in apoptosis regulation and tumor suppression are mediated by direct interaction with Fas.
Genetic polymorphisms in glutathione S-transferase (GST) superfamily and risk of arsenic-induced urothelial carcinoma in residents of southwestern Taiwan
Authors: Hsu Ling-I , Chen Wu-Ping , Yang Tse-Yen , Chen Yu-Hsin , Lo Wann-Cheng , Wang Yuan-Hung , Liao Ya-Tang , Hsueh Yu-Mei , Chiou Hung-Yi , Wu Meei-Maan , Chen Chien-Jen 
Published: July 2011

Abstract

Background
Arsenic exposure is an important public health issue worldwide. Dose-response relationship between arsenic exposure and risk of urothelial carcinoma (UC) is consistently observed. Inorganic arsenic is methylated to form the metabolites monomethylarsonic acid and dimethylarsinic acid while ingested. Variations in capacity of xenobiotic detoxification and arsenic methylation might explain individual variation in susceptibility to arsenic-induced cancers.

Methods
To estimate individual susceptibility to arsenic-induced UC, 764 DNA specimens from our long-term follow-up cohort in Southwestern Taiwan were used and the genetic polymorphisms in GSTM1, GSTT1, GSTP1 and arsenic methylation enzymes including GSTO1 and GSTO2 were genotyped.

Results
The GSTT1 null was marginally associated with increased urothelial carcinoma (UC) risk (HR, 1.91, 95% CI, 1.00-3.65), while the association was not observed for other GSTs. Among the subjects with cumulative arsenic exposure (CAE) ≥ 20 mg/L*year, the GSTT1 null genotype conferred a significantly increased cancer risk (RR, 3.25, 95% CI, 1.20-8.80). The gene-environment interaction between the GSTT1 and high arsenic exposure with respect to cancer risk was statistically significant (multiplicative model, p = 0.0151) and etiologic fraction was as high as 0.86 (95% CI, 0.51-1.22). The genetic effects of GSTO1/GSTO2 were largely confined to high arsenic level (CAE ≥ 20). Diplotype analysis showed that among subjects exposed to high levels of arsenic, the AGG/AGG variant of GSTO1 Ala140Asp, GSTO2 5'UTR (-183)A/G, and GSTO2 Asn142Asp was associated with an increased cancer risk (HRs, 4.91, 95% CI, 1.02-23.74) when compared to the all-wildtype reference, respectively.

Conclusions
The GSTs do not play a critical role in arsenic-induced urothelial carcinogenesis. The genetic effects of GSTT1 and GSTO1 on arsenic-induced urothelial carcinogenesis are largely confined to very high exposure level.
MAVENs: Motion analysis and visualization of elastic networks and structural ensembles
Authors: Zimmermann Michael T , Kloczkowski Andrzej , Jernigan Robert L 
Published: July 2011

Abstract

Background
The ability to generate, visualize, and analyze motions of biomolecules has made a significant impact upon modern biology. Molecular Dynamics has gained substantial use, but remains computationally demanding and difficult to setup for many biologists. Elastic network models (ENMs) are an alternative and have been shown to generate the dominant equilibrium motions of biomolecules quickly and efficiently. These dominant motions have been shown to be functionally relevant and also to indicate the likely direction of conformational changes. Most structures have a small number of dominant motions. Comparing computed motions to the structure's conformational ensemble derived from a collection of static structures or frames from an MD trajectory is an important way to understand functional motions as well as evaluate the models. Modes of motion computed from ENMs can be visualized to gain functional and mechanistic understanding and to compute useful quantities such as average positional fluctuations, internal distance changes, collectiveness of motions, and directional correlations within the structure.

Results
Our new software, MAVEN, aims to bring ENMs and their analysis to a broader audience by integrating methods for their generation and analysis into a user friendly environment that automates many of the steps. Models can be constructed from raw PDB files or density maps, using all available atomic coordinates or by employing various coarse-graining procedures. Visualization can be performed either with our software or exported to molecular viewers. Mixed resolution models allow one to study atomic effects on the system while retaining much of the computational speed of the coarse-grained ENMs. Analysis options are available to further aid the user in understanding the computed motions and their importance for its function.

Conclusion
MAVEN has been developed to simplify ENM generation, allow for diverse models to be used, and facilitate useful analyses, all on the same platform. This represents an integrated approach that incorporates all four levels of the modeling process - generation, evaluation, analysis, visualization - and also brings to bear multiple ENM types. The intension is to provide a versatile modular suite of programs to a broader audience. MAVEN is available for download at http://maven.sourceforge.net.
Consistent metagenes from cancer expression profiles yield agent specific predictors of chemotherapy response
Authors: Li Qiyuan , Eklund Aron C , Birkbak Nicolai J , Desmedt Christine , Haibe-Kains Benjamin , Sotiriou Christos , Symmans W Fraser , Pusztai Lajos , Brunak Søren , Richardson Andrea L , Szallasi Zoltan 
Published: July 2011

Abstract

Background
Genome scale expression profiling of human tumor samples is likely to yield improved cancer treatment decisions. However, identification of clinically predictive or prognostic classifiers can be challenging when a large number of genes are measured in a small number of tumors.

Results
We describe an unsupervised method to extract robust, consistent metagenes from multiple analogous data sets. We applied this method to expression profiles from five "double negative breast cancer" (DNBC) (not expressing ESR1 or HER2) cohorts and derived four metagenes. We assessed these metagenes in four similar but independent cohorts and found strong associations between three of the metagenes and agent-specific response to neoadjuvant therapy. Furthermore, we applied the method to ovarian and early stage lung cancer, two tumor types that lack reliable predictors of outcome, and found that the metagenes yield predictors of survival for both.

Conclusions
These results suggest that the use of multiple data sets to derive potential biomarkers can filter out data set-specific noise and can increase the efficiency in identifying clinically accurate biomarkers.
Analysis of the dynamics of limb transcriptomes during mouse development
Authors: Gyurján Istvan , Sonderegger Bernhard , Naef Felix , Duboule Denis 
Published: July 2011

Abstract

Background
The development of vertebrate limbs has been a traditional system to study fundamental processes at work during ontogenesis, such as the establishment of spatial cellular coordinates, the effect of diffusible morphogenetic molecules or the translation between gene activity and morphogenesis. In addition, limbs are amongst the first targets of malformations in human and they display a huge realm of evolutionary variations within tetrapods, which make them a paradigm to study the regulatory genome.

Results
As a reference resource for future biochemical and genetic analyses, we used genome-wide tiling arrays to establish the transcriptomes of mouse limb buds at three different stages, during which major developmental events take place. We compare the three time-points and discuss some aspects of these datasets, for instance related to transcriptome dynamics or to the potential association between active genes and the distribution of intergenic transcriptional activity.

Conclusions
These datasets provide a valuable resource, either for research projects involving gene expression and regulation in developing mouse limbs, or as examples of tissue-specific, genome-wide transcriptional activities.
Stops making sense: translational trade-offs and stop codon reassignment
Authors: Johnson Louise J , Cotton James A , Lichtenstein Conrad P , Elgar Greg S , Nichols Richard A , Polly p David , Le Comber Steven C 
Published: July 2011

Abstract

Background
Efficient gene expression involves a trade-off between (i) premature termination of protein synthesis; and (ii) readthrough, where the ribosome fails to dissociate at the terminal stop. Sense codons that are similar in sequence to stop codons are more susceptible to nonsense mutation, and are also likely to be more susceptible to transcriptional or translational errors causing premature termination. We therefore expect this trade-off to be influenced by the number of stop codons in the genetic code. Although genetic codes are highly constrained, stop codon number appears to be their most volatile feature.

Results
In the human genome, codons readily mutable to stops are underrepresented in coding sequences. We construct a simple mathematical model based on the relative likelihoods of premature termination and readthrough. When readthrough occurs, the resultant protein has a tail of amino acid residues incorrectly added to the C-terminus. Our results depend strongly on the number of stop codons in the genetic code. When the code has more stop codons, premature termination is relatively more likely, particularly for longer genes. When the code has fewer stop codons, the length of the tail added by readthrough will, on average, be longer, and thus more deleterious. Comparative analysis of taxa with a range of stop codon numbers suggests that genomes whose code includes more stop codons have shorter coding sequences.

Conclusions
We suggest that the differing trade-offs presented by alternative genetic codes may result in differences in genome structure. More speculatively, multiple stop codons may mitigate readthrough, counteracting the disadvantage of a higher rate of nonsense mutation. This could help explain the puzzling overrepresentation of stop codons in the canonical genetic code and most variants.