bluuebunny/crossref_metadata_2025_split huggingface dataset:
The New Kid on the Block: RET in Lung Cancer
Authors: Gainor Justin F. , Shaw Alice T. 
Published: June 2013

Abstract
Summary: RET has recently been identified as a potential new oncogenic driver in a subset of patients with non–small cell lung cancer (NSCLC). In this issue of Cancer Discovery, Drilon and colleagues report preliminary trial data with a RET inhibitor in RET fusion-positive NSCLC, validating RET as a therapeutic target in lung cancer. Cancer Discov; 3(6); 604–6. ©2013 AACR.
See related article by Drilon et al., p. 630
FGFR Fusions in the Driver's Seat
Authors: Sabnis Amit J. , Bivona Trever G. 
Published: June 2013

Abstract
Summary: Through a clinical deep sequencing protocol, Wu and colleagues have identified multiple FGFR fusion proteins in diverse cancers. Pharmacologic inhibition of FGFR suppressed the growth of FGFR fusion–positive tumor models, suggesting that these FGFR fusions are oncogenic drivers and highlighting the use of streamlined clinical sequencing efforts to identify novel, actionable driver oncoproteins in human tumors. Cancer Discov; 3(6); 607–9. ©2013 AACR.
See related article by Wu et al., p. 636
Rapid Estrogen Receptor Signaling Mediates Estrogen-Induced Inhibition of Vascular Smooth Muscle Cell Proliferation
Authors: Ueda Kazutaka , Lu Qing , Baur Wendy , Aronovitz Mark J. , Karas Richard H. 
Published: June 2013

Objective—
The proliferation of vascular smooth muscle cells (VSMCs) plays a crucial role in vascular diseases, such as atherosclerosis and restenosis, after percutaneous coronary intervention. Many studies have shown that estrogen inhibits VSMC proliferation in response to vascular injury in the mouse carotid injury model. However, the mechanisms that mediate these effects remain unclear. Here, we investigated the mechanisms by which estrogen inhibits VSMC proliferation.

Approach and Results—
We established a novel transgenic mouse line, referred to as the disrupting peptide mice, in which rapid estrogen receptor (ER)–mediated signaling is abolished by overexpression of a peptide that prevents the ER from forming a signaling complex necessary for rapid signaling. Carotid artery VSMCs from disrupting peptide mice or littermate wild-type female mice were obtained by the explant method. In VSMCs derived from wild-type mice, estrogen significantly inhibited VSMC proliferation. Phosphorylation levels of Akt and extracellular regulated kinase induced by platelet derived growth factor were significantly inhibited by estrogen pretreatment. Estrogen enhanced complex formation between ERα and protein phosphatase 2A (PP2), and enhanced PP2A activity. The blockade of PP2A activity abolished the estrogen-induced antiproliferative effect on VSMCs. In contrast, none of these effects of estrogen observed in the wild-type VSMCs were observed in VSMCs derived from disrupting peptide mice. These results support that rapid, non-nuclear ER signaling is required for estrogen-induced inhibition of VSMC proliferation, and further that PP2A activation by estrogen mediates estrogen-induced antiproliferative effects.

Conclusions—
These findings support that PP2A activation via rapid, non-nuclear ER signaling may be a novel target for therapeutic approaches to inhibit VSMC proliferation, which plays a central role in atherosclerosis and restenosis.
Adventitial Stem Cells in Vein Grafts Display Multilineage Potential That Contributes to Neointimal Formation
Authors: Chen Yikuan , Wong Mei Mei , Campagnolo Paola , Simpson Russell , Winkler Bernhard , Margariti Andriani , Hu Yanhua , Xu Qingbo 
Published: June 2013

Objective—
This study was designed to carry out the characterization of stem cells within the adventitia and to elucidate their functional role in the pathogenesis of vein graft atherosclerosis.

Approach and Results—
A mouse vein graft model was used to investigate the functional role of adventitial stem/progenitor cells on atherosclerosis. The adventitia of vein grafts underwent significant remodeling during early stages of vessel grafting and displayed markedly heterogeneous cell compositions. Immunofluorescence staining indicated a significant number of stem cell antigen-1–positive cells that were closely located to vasa vasorum. In vitro clonogenic assays demonstrated 1% to 11% of growing rates from adventitial cell cultures, most of which could be differentiated into smooth muscle cells (SMCs). These stem cell antigen-1–positive cells also displayed a potential to differentiate into adipogenic, osteogenic, or chondrogenic lineages in vitro. In light of the proatherogenic roles of SMCs in atherosclerosis, we focused on the functional roles of progenitor-SMC differentiation, in which we subsequently demonstrated that it was driven by direct interaction of the integrin/collagen IV axis. The ex vivo bioreactor system revealed the migratory capacity of stem cell antigen-1–positive progenitor cells into the vessel wall in response to stromal cell-derived factor-1. Stem cell antigen-1–positive cells that were applied to the outer layer of vein grafts showed enhanced atherosclerosis in apolipoprotein E–deficient mice, which contributed to ≈30% of neointimal SMCs.

Conclusions—
We demonstrate that during pathological conditions in vein grafting, the adventitia harbors stem/progenitor cells that can actively participate in the pathogenesis of vascular disease via differentiation into SMCs.
Flt-1 (Vascular Endothelial Growth Factor Receptor-1) Is Essential for the Vascular Endothelial Growth Factor–Notch Feedback Loop During Angiogenesis
Authors: Chappell John C. , Mouillesseaux Kevin P. , Bautch Victoria L. 
Published: June 2013

Objective—
Vascular endothelial growth factor (VEGF) signaling induces Notch signaling during angiogenesis. Flt-1/VEGF receptor-1 negatively modulates VEGF signaling. Therefore, we tested the hypothesis that disrupted Flt-1 regulation of VEGF signaling causes Notch pathway defects that contribute to dysmorphogenesis of Flt-1 mutant vessels.

Approach and Results—

Wild-type and
flt-1
−/−
mouse embryonic stem cell–derived vessels were exposed to pharmacological and protein-based Notch inhibitors with and without added VEGF. Vessel morphology, endothelial cell proliferation, and Notch target gene expression levels were assessed. Similar pathway manipulations were performed in developing vessels of zebrafish embryos. Notch inhibition reduced
flt-1
−/−
embryonic stem cell–derived vessel branching dysmorphogenesis and endothelial hyperproliferation, and rescue of
flt-1
−/−
vessels was accompanied by a reduction in elevated Notch targets. Surprisingly, wild-type vessel morphogenesis and proliferation were unaffected by Notch suppression, Notch targets in wild-type endothelium were unchanged, and Notch suppression perturbed zebrafish intersegmental vessels but not caudal vein plexuses. In contrast, exogenous VEGF caused wild-type embryonic stem cell–derived vessel and zebrafish intersegmental vessel dysmorphogenesis that was rescued by Notch blockade.

Conclusions—

Elevated Notch signaling downstream of perturbed VEGF signaling contributes to aberrant
flt-1
−/−
blood vessel formation. Notch signaling may be dispensable for blood vessel formation when VEGF signaling is below a critical threshold.
The Insufficiency of Left Anterior Oblique and the Usefulness of Right Anterior Oblique Projection for Correct Localization of a Computed Tomography–Verified Right Ventricular Lead Into the Midseptum
Authors: Osmancik Pavel , Stros Petr , Herman Dalibor , Curila Karol , Petr Robert 
Published: June 2013

Background—
The aim of the study was to verify the correct anchoring location for the tip of the right ventricular lead using cardiac computed tomography and to assess the best fluoroscopic and ECG criteria associated with the correct location of the electrode into the midseptum.

Methods and Results—

Patients indicated to pacemaker implantation were prospectively enrolled. The right ventricular lead was implanted into the midseptum according to standard criteria in left anterior oblique 40 view. The cardiac shadow on the right anterior oblique 30 was divided into 4 quadrants perpendicular to the lateral cardiac silhouette and the position of the lead tip was analyzed. The exact position of the lead tip was assessed using computed tomography. Of 51 patients, the right ventricular lead was anchored midseptum in 21 (41.2%; MS group). In 30 patients (58.8%; non-MS group), the lead was anchored in the adjacent anterior wall. The angle between the lead and horizontal axis on the left anterior oblique was similar in both groups. The non-MS group was associated with shorter distances between the tip and the cardiac contours in the right anterior oblique 30 (96.7% of leads in the non-MS group were in the outer quadrant versus 9.6% in the MS group;
P
<0.001). The presence of the lead in the middle or inferior quadrants was independently associated with correct midseptum placement with positive predictive value of 94.7%.

Conclusions—
Despite the optimal shape of the left anterior oblique, substantial numbers of leads were not anchored in the midseptum. Knowing the right anterior oblique 30 lead position can ensure proper midseptal placement.
Ultra-Sensitive Molecular MRI of Vascular Cell Adhesion Molecule-1 Reveals a Dynamic Inflammatory Penumbra After Strokes
Authors: Gauberti Maxime , Montagne Axel , Marcos-Contreras Oscar A. , Le Béhot Audrey , Maubert Eric , Vivien Denis 
Published: June 2013

Background and Purpose—
Our aim was to assess the spatiotemporal evolution of the cerebrovascular inflammation occurring after ischemic and hemorrhagic strokes using a recently developed, fast, and ultra-sensitive molecular MRI method.

Methods—
We first assessed longitudinally the cerebrovascular inflammation triggered by collagenase-induced hemorrhage and by permanent/transient middle cerebral artery occlusion in mice, using MRI after injection of microparticles of iron oxide targeted to vascular cell adhesion molecule-1 (MPIOs-αVCAM-1). Thereafter, we used this method to study the anti-inflammatory effects of celecoxib, atorvastatin, and dipyridamole after stroke.

Results—
Using multiparametric MRI, we demonstrated that the level and the kinetics of cerebrovascular VCAM-1 expression depend on several parameters, including stroke pathogenesis, the natural history of the disease, and the administration of inflammation-modulating drugs. Interestingly, in transient middle cerebral artery occlusion and intracranial hemorrhage models, VCAM-1 expression was maximal at 24 hours and almost returned to baseline 5 days after stroke onset. In contrast, after permanent middle cerebral artery occlusion, VCAM-1 overexpression was sustained between 24 hours and 5 days, and was particularly significant in the peri-infarct areas. Our results suggest that these perilesional areas expressing VCAM-1 constitute an inflammatory penumbra that is recruited by the ischemic core during the subacute phase. Using MPIOs-αVCAM-1–enhanced imaging, we also provided evidence that celecoxib and atorvastatin (but not dipyridamole) alleviate VCAM-1 overexpression after stroke and prevent formation of the inflammatory penumbra.

Conclusions—
MPIOs-αVCAM-1–enhanced imaging seems to be promising in the detection of individuals presenting with severe cerebrovascular responses after stroke, which could therefore benefit from anti-inflammatory treatments.
Dabigatran Versus Warfarin
Authors: Hori Masatsugu , Connolly Stuart J. , Zhu Jun , Liu Li Sheng , Lau Chu-Pak , Pais Prem , Xavier Denis , Kim Sung Soon , Omar Razali , Dans Antonio L. , Tan Ru San , Chen Jyh-Hong , Tanomsup Supachai , Watanabe Mitsunori , Koyanagi Masahide , Ezekowitz Michael D. , Reilly Paul A. , Wallentin Lars , Yusuf Salim 
Published: June 2013

Background and Purpose—
Intracranial hemorrhage rates are higher in Asians than non-Asians, especially in patients receiving warfarin. This randomized evaluation of long-term anticoagulation therapy subgroup analysis assessed dabigatran etexilate (DE) and warfarin effects on stroke and bleeding rates in patients from Asian and non-Asian countries.

Methods—
There were 2782 patients (15%) from 10 Asian countries and 15 331 patients from 34 non-Asian countries. A Cox regression model, with terms for treatment, region, and their interaction was used.

Results—

Rates of stroke or systemic embolism in Asians were 3.06% per year on warfarin, 2.50% per year on DE 110 mg BID (DE 110), and 1.39% per year on DE 150 mg BID (DE 150); in non-Asians, the rates were 1.48%, 1.37%, and 1.06% per year with no significant treatment-by-region interactions. Hemorrhagic stroke on warfarin occurred more often in Asians than non-Asians (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.3–4.7;
P
=0.007), with significant reductions for DE compared with warfarin in both Asian (DE 110 versus warfarin HR, 0.15; 95% CI, 0.03–0.66 and DE 150 versus warfarin HR, 0.22; 95% CI, 0.06–0.77) and non-Asian (DE 110 versus warfarin HR, 0.37; 95% CI, 0.19–0.72 and DE 150 versus warfarin HR, 0.28; 95% CI, 0.13–0.58) patients. Major bleeding rates in Asians were significantly lower on DE (both doses) than warfarin (warfarin 3.82% per year, DE 110 2.22% per year, and DE 150 2.17% per year).

Conclusions—
Hemorrhagic stroke rates were higher on warfarin in Asians versus non-Asians, despite similar blood pressure, younger age, and lower international normalized ratio values. Hemorrhagic strokes were significantly reduced by DE in both Asians and non-Asians. DE benefits were consistent across Asian and non-Asian subgroups.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00262600.
Modulating the Motor System by Action Observation After Stroke
Authors: Garrison Kathleen Alice , Aziz-Zadeh Lisa , Wong Savio Waiho , Liew Sook-Lei , Winstein Carolee Joyce 
Published: June 2013

Background and Purpose—
Much recent interest surrounds the use of action observation, which is observing another individual performing a motor task, in stroke rehabilitation, to promote motor recovery by engaging similar brain regions to action execution. This may be especially useful in individuals with limited mobility. Here, we assess how cortical motor activity during action observation is affected by stroke and by stroke-related motor deficits.

Methods—
We used functional MRI to compare brain activity during right and left hand action observation in right-handed nondisabled participants and participants who were right-handed before left hemisphere stroke. All participants performed the same actions after their functional MRI.

Results—

Nondisabled participants show greater bilateral cortical motor activity when observing actions made using the left hand, whereas participants with stroke show greater ipsilesional cortical motor activity when observing actions made using the right (paretic) hand (
P
<0.05; corrected). For both groups, action processing is modulated by motor capability: cortical motor activity is greater when observing the hand with lower motor scores (
P
<0.05; corrected). Furthermore, for stroke, the extent of ipsilesional activity correlates with lesion volume (
P
=0.049), in a pattern that suggests adaptive plasticity.

Conclusions—
We found that action observation activates specific motor plans in damaged motor circuits after stroke, and this activity is related to motor capability to perform the same actions. Cortical motor activity during action observation may be relevant to motor learning, and to motor relearning in stroke rehabilitation.
Filtering Sensory Information with XCSF: Improving Learning Robustness and Robot Arm Control Performance
Authors: Kneissler Jan , Stalph Patrick O. , Drugowitsch Jan , Butz Martin V. 
Published: June 2013

It has been shown previously that the control of a robot arm can be efficiently learned using the XCSF learning classifier system, which is a nonlinear regression system based on evolutionary computation. So far, however, the predictive knowledge about how actual motor activity changes the state of the arm system has not been exploited. In this paper, we utilize the forward velocity kinematics knowledge of XCSF to alleviate the negative effect of noisy sensors for successful learning and control. We incorporate Kalman filtering for estimating successive arm positions, iteratively combining sensory readings with XCSF-based predictions of hand position changes over time. The filtered arm position is used to improve both trajectory planning and further learning of the forward velocity kinematics. We test the approach on a simulated kinematic robot arm model. The results show that the combination can improve learning and control performance significantly. However, it also shows that variance estimates of XCSF prediction may be underestimated, in which case self-delusional spiraling effects can hinder effective learning. Thus, we introduce a heuristic parameter, which can be motivated by theory, and which limits the influence of XCSF's predictions on its own further learning input. As a result, we obtain drastic improvements in noise tolerance, allowing the system to cope with more than 10 times higher noise levels.
Global Identification of Previously Undetected Pre-Satellite-Era Tropical Cyclone Candidates in NOAA/CIRES Twentieth-Century Reanalysis Data
Authors: Truchelut Ryan E. , Hart Robert E. , Luthman Briana 
Published: June 2013

AbstractPrior to the satellite era, limited synoptic observation networks led to an indefinite number of tropical cyclones (TCs) remaining undetected. This period of decreased confidence in the TC climatological record includes the first two-thirds of the twentieth century. While prior studies found that this undersampling exists, disagreement regarding its magnitude has caused difficulties in interpreting multidecadal changes in TC activity. Previous research also demonstrated that reanalyses can be used to extend TC climatology, utilizing the NOAA/Cooperative Institute for Research in Environmental Sciences (CIRES) Twentieth-Century Reanalysis to manually identify previously unknown Atlantic Ocean basin potential TCs. This study expands the spatiotemporal scope of the earlier work by presenting a filtering algorithm that dramatically improves the efficiency with which candidate events are identified in the reanalysis. This algorithm was applied to all tropical basins for the years 1871–1979, resulting in the first quantitative and objective global TC candidate event counts for the decades prior to formal recordkeeping. Observational verification performed on a subset of these events indicates that the algorithm identifies potential missing TCs at a success rate approximating that of earlier work with a significant decrease in the amount of time required. Extrapolating these proportions to all of the candidate events identified suggests that this method may help to locate hundreds of previously unknown TCs worldwide for future study and cataloging. As such, the dataset produced by this research is a source of independent guidance for use in ongoing and future TC climatology revision efforts to produce a more complete historical record more quickly than with current methods.
Atmospheric Forcing of Debris Flows in the Southern Swiss Alps
Authors: Toreti Andrea , Schneuwly-Bollschweiler Michelle , Stoffel Markus , Luterbacher Jürg 
Published: June 2013

AbstractThis article addresses the role of large-scale circulation and thermodynamical features in the release of past debris flows in the Swiss Alps by using classification algorithms, potential instability, and convective time scale. The study is based on a uniquely dense dendrogeomorphic time series of debris flows covering the period 1872–2008, reanalysis data, instrumental time series, and gridded hourly precipitation series (1992–2006) over the area. Results highlight the crucial role of synoptic and mesoscale forcing as well as of convective equilibrium on triggering rainfalls. Two midtropospheric synoptic patterns favor anomalous southwesterly flow toward the area and high potential instability. These findings imply a certain degree of predictability of debris-flow events and can therefore be used to improve existing alert systems.
Applications of Bivariate Fourier Series for Solving the Poisson Equation in Limited-Area Modeling of the Atmosphere: Higher Accuracy with a Boundary Buffer Strip Discarded and an Improved Order-Raising Procedure
Authors: Boyd John P. , Deng Difei , Chen Qiu-Shi , Gao Shouting 
Published: June 2013

Abstract
Bivariate Fourier series have many benefits in limited-area modeling (LAM), weather forecasting, and meteorological data analysis. However, atmospheric data are not spatially periodic on the LAM domain (“window”), which can be normalized to the unit square (x, y) ∈ [0, 1] ⊗ [0, 1] by rescaling the coordinates. Most Fourier LAM meteorology has employed rather low-order methods that have been quite successful in spite of Gibbs phenomenon at the boundaries of the artificial periodicity window. In this article, the authors explain why. Because data near the boundary between the high-resolution LAM window and the low-resolution global model are necessarily suspect, corrupted by the discontinuity in resolution, meteorologists routinely ignore LAM results in a buffer strip of nondimensional width D, and analyze only the Fourier sums in the smaller domain (x, y) ∈ [D, 1 − D] ⊗ [D, 1 − D]. It is shown that the error in a one-dimensional Fourier series with N terms or in a two-dimensional series with N2 terms, is smaller by a factor of N on a boundary-buffer-discarded domain than on the full unit square. A variety of procedures for raising the order of Fourier series convergence are described, and it is explained how the deletion of the boundary strip greatly simplifies and improves these enhancements. The prime exemplar is solving the Poisson equation with homogeneous boundary conditions by sine series, but the authors also discuss the Laplace equation with inhomogeneous boundary conditions.
Emergent Regularities of Interpersonal Victimization
Authors: Birks Daniel , Townsley Michael , Stewart Anna 
Published: June 2013

Objectives: Apply computational agent-based modeling to explore the generative sufficiency of several mechanisms derived from the field of environmental criminology in explaining commonly observed patterns of interpersonal victimization. Method: Controlled simulation experiments compared patterns of simulated interpersonal victimization to three empirically derived regularities of crime using established statistical techniques: (1) spatial clustering (nearest neighbor index), (2) repeat victimization (Gini coefficient), and (3) journeys to crime (Pearson’s coefficient of skewness). Results: Large, statistically significant increases in spatial clustering, repeat victimization, and journey to crime skewness are observed when virtual offenders operate according to mechanisms proposed by the routine activity approach, rational choice perspective, and geometry/pattern theories of crime. Conclusion: This research provides support for several propositions of environmental criminology in explaining why interpersonal victimization tends to be spatially concentrated, experienced by a small number of repeat victims, and why aggregate journey to crime curves tend to follow a distance decay relationship. By extending previous work in agent-based modeling of property victimization, it also demonstrates that the same core mechanisms are sufficient to generate plausible patterns of crime when examining fundamentally different types of offending.