bluuebunny/crossref_metadata_2025_split huggingface dataset:
PTEN Loss Is Associated with Worse Outcome in HER2-Amplified Breast Cancer Patients but Is Not Associated with Trastuzumab Resistance
Authors: Stern Howard M. , Gardner Humphrey , Burzykowski Tomasz , Elatre Wafaa , O'Brien Carol , Lackner Mark R. , Pestano Gary A. , Santiago Angela , Villalobos Ivonne , Eiermann Wolfgang , Pienkowski Tadeusz , Martin Miguel , Robert Nicholas , Crown John , Nuciforo Paolo , Bee Valerie , Mackey John , Slamon Dennis J. , Press Michael F. 
Published: February 2015

Abstract
Purpose: To investigate the clinical relevance of PTEN in HER2-amplified and HER2-nonamplified disease.
Experimental Design: We assessed PTEN status in two large adjuvant breast cancer trials (BCIRG-006 and BCIRG-005) using a PTEN immunohistochemical (IHC) assay that was previously validated in a panel of 33 breast cancer cell lines and prostate cancer tissues with known PTEN gene deletion.
Results: In the HER2-positive patient population, absence of tumor cell PTEN staining occurred at a rate of 5.4% and was independent of ER/PR status. In contrast, 15.9% of HER2-negative patients exhibited absence of PTEN staining with the highest frequency seen in triple-negative breast cancer (TNBC) subgroup versus ER/PR-positive patients (35.1% vs. 10.9%). Complete absence of PTEN staining in tumor cells was associated with poor clinical outcome in HER2-positive disease. Those patients whose cancers demonstrated absent PTEN staining had a significant decrease in disease-free survival (DFS) and overall survival (OS) compared with patients with tumors exhibiting any PTEN staining patterns (low, moderate, or high). Trastuzumab appeared to provide clinical benefit even for patients lacking PTEN staining. In the HER2-negative population, there were no statistically significant differences in clinical outcome based on PTEN status.
Conclusions: This study is the largest to date examining PTEN status in breast cancer and the data suggest that the rate and significance of PTEN status differ between HER2-positive and HER2-negative disease. Furthermore, the data clearly suggest that HER2-positive patients with PTEN loss still benefit from trastuzumab. Clin Cancer Res; 21(9); 2065–74. ©2015 AACR.
Role of Mutation and Pharmacologic Block of Human KCNH2 in Vasculogenesis and Fetal Mortality
Authors: Teng Guoqi , Zhao Xiang , Lees-Miller James P. , Belke Darrell , Shi Chunhua , Chen Yongxiang , O’Brien Edward R. , Fedak Paul W. , Bracey Nathan , Cross James C. , Duff Henry J. 
Published: February 2015

Background—

N629D
KCNH2
is a human missense long-QT2 mutation. Previously, we reported that the N629D/N629D mutation embryos disrupted cardiac looping, right ventricle development, and ablated I
Kr
activity at E9.5. The present study evaluates the role of KCNH2 in vasculogenesis.

Methods and Results—
N629D/N629D yolk sac vessels and aorta consist of sinusoids without normal arborization. Isolated E9.5 +/+ first branchial arches showed normal outgrowth of mouse ERG–positive/α-smooth muscle actin coimmunolocalized cells; however, outgrowth was grossly reduced in N629D/N629D. N629D/N629D aortas showed fewer α-smooth muscle actin positive cells that were not coimmunolocalized with mouse ERG cells. Transforming growth factor-β treatment of isolated N629D/N629D embryoid bodies partially rescued this phenotype. Cultured N629D/N629D embryos recapitulate the same cardiovascular phenotypes as seen in vivo. Transforming growth factor-β treatment significantly rescued these embryonic phenotypes. Both in vivo and in vitro, dofetilide treatment, over a narrow window of time, entirely recapitulated the N629D/N629D fetal phenotypes. Exogenous transforming growth factor-β treatment also rescued the dofetilide-induced phenotype toward normal.

Conclusions—
Loss of function of KCNH2 mutations results in defects in cardiogenesis and vasculogenesis. Because many medications inadvertently block the KCNH2 potassium current, these novel findings seem to have clinical relevance.
The Cardiovascular Health in Ambulatory Care Research Team (CANHEART)
Authors: Tu Jack V. , Chu Anna , Donovan Linda R. , Ko Dennis T. , Booth Gillian L. , Tu Karen , Maclagan Laura C. , Guo Helen , Austin Peter C. , Hogg William , Kapral Moira K. , Wijeysundera Harindra C. , Atzema Clare L. , Gershon Andrea S. , Alter David A. , Lee Douglas S. , Jackevicius Cynthia A. , Bhatia R. Sacha , Udell Jacob A. , Rezai Mohammad R. , Stukel Thérèse A. 
Published: February 2015

Background—
The CArdiovascular HEalth in Ambulatory care Research Team (CANHEART) is conducting a unique, population-based observational research initiative aimed at measuring and improving cardiovascular health and the quality of ambulatory cardiovascular care provided in Ontario, Canada. A particular focus will be on identifying opportunities to improve the primary and secondary prevention of cardiovascular events in Ontario’s diverse multiethnic population.

Methods and Results—
A population-based cohort comprising 9.8 million Ontario adults ≥20 years in 2008 was assembled by linking multiple electronic survey, health administrative, clinical, laboratory, drug, and electronic medical record databases using encoded personal identifiers. The cohort includes ≈9.4 million primary prevention patients and ≈400 000 secondary prevention patients. Follow-up on clinical events is achieved through record linkage to comprehensive hospitalization, emergency department, and vital statistics administrative databases. Profiles of cardiovascular health and preventive care will be developed at the health region level, and the cohort will be used to study the causes of regional variation in the incidence of major cardiovascular events and other important research questions.

Conclusions—
Linkage of multiple databases will enable the CANHEART study cohort to serve as a powerful big data resource for scientific research aimed at improving cardiovascular health and health services delivery. Study findings will be shared with clinicians, policy makers, and the public to facilitate population health interventions and quality improvement initiatives.
Interleukin 23 Levels Are Increased in Carotid Atherosclerosis
Authors: Abbas Azhar , Gregersen Ida , Holm Sverre , Daissormont Isabelle , Bjerkeli Vigdis , Krohg-Sørensen Kirsten , Skagen Karolina R. , Dahl Tuva B. , Russell David , Almås Trine , Bundgaard Dorte , Alteheld Lars Holger , Rashidi Azita , Dahl Christen P. , Michelsen Annika E. , Biessen Erik A. , Aukrust Pål , Halvorsen Bente , Skjelland Mona 
Published: February 2015

Background and Purpose—
Interleukin (IL)-23 is a cytokine in the IL-12 family, mainly produced by antigen-presenting cells with a central role in inflammation. We hypothesize that IL-23 is also important in atherogenesis and investigate this in a population with carotid atherosclerosis.

Methods—
Plasma levels of IL-23 were measured in patients with carotid artery stenosis and in healthy controls. The mRNA levels of IL-23 and its receptor, IL-23R, were measured in atherosclerotic plaques, nonatherosclerotic vessels, peripheral blood mononuclear cells, and plasmacytoid dendritic cells.

Results—
Our findings were as follows: (1) patients with carotid atherosclerosis (n=177) had significantly raised plasma levels of IL-23 when compared with healthy controls (n=24) with particularly high levels in those with the most recent symptoms. (2) mRNA levels of IL-23 and IL-23R were markedly increased in carotid plaques (n=68) when compared with nonatherosclerotic vessels (n=8–10). Immunostaining showed colocalization to plaque macrophages. (3) Patients with carotid atherosclerosis had increased mRNA levels of both IL-23 and IL-23R in plasmacytoid dendritic cells, but not in peripheral blood mononuclear cells. (4) IL-23 increased IL-17 release in monocytes and particularly in peripheral blood mononuclear cells from patients with carotid atherosclerosis, but not in cells from healthy controls. (5) IL-23 gave a prominent tumor necrosis factor release in monocytes from patients with carotid atherosclerosis but not in cells from healthy controls. (6) High plasma levels of IL-23 were associated with increased mortality during follow-up.

Conclusions—
We have shown an association between IL-23 and disease progression in patients with carotid atherosclerosis, potentially involving IL-17-related mechanisms.
Genetic Study of Intracranial Aneurysms
Authors: Yan Junxia , Hitomi Toshiaki , Takenaka Katsunobu , Kato Masayasu , Kobayashi Hatasu , Okuda Hiroko , Harada Kouji H. , Koizumi Akio 
Published: February 2015

Background and Purpose—
Rupture of intracranial aneurysms (IAs) causes subarachnoid hemorrhage, leading to immediate death or severe disability. Identification of the genetic factors involved is critical for disease prevention and treatment. We aimed to identify the susceptibility genes for IAs.

Methods—
Exome sequencing was performed in 12 families with histories of multiple cases of IA (number of cases per family ≥3), with a total of 42 cases. Various filtering strategies were used to select the candidate variants. Replicate association studies of several candidate variants were performed in probands of 24 additional IA families and 426 sporadic IA cases. Functional analysis for the mutations was conducted.

Results—

After sequencing and filtering, 78 variants were selected for the following reasons: allele frequencies of variants in 42 patients was significantly (
P
<0.05) larger than expected; variants were completely shared by all patients with IA within ≥1 family; variants predicted damage to the structure or function of the protein by PolyPhen-2 (Polymorphism Phenotyping V2) and SIFT (Sorting Intolerance From Tolerant). We selected 10 variants from 9 genes (
GPR63
,
ADAMST15
,
MLL2
,
IL10RA
,
PAFAH2
,
THBD
,
IL11RA
,
FILIP1L
, and
ZNF222
) to form 78 candidate variants by considering commonness in families, known disease genes, or ontology association with angiogenesis. Replicate association studies revealed that only p.E133Q in
ADAMTS15
was aggregated in the familial IA cases (odds ratio, 5.96; 95% confidence interval, 2.40–14.82;
P
=0.0001; significant after the Bonferroni correction [
P
=0.05/78=0.0006]). Silencing
ADAMTS15
and overexpression of
ADAMTS15
p.E133Q accelerated endothelial cell migration, suggesting that
ADAMTS15
may have antiangiogenic activity.

Conclusions—

ADAMTS15
is a candidate gene for IAs.
An Analysis of a Barotropically Unstable, High–Rossby Number Vortex in Shear
Authors: Ryglicki David R. 
Published: February 2015

Abstract
The interactions of the barotropic instability found at low levels in tropical cyclones and a shear forcing are presented. Previous works have indicated that at low levels of tropical cyclones, the inner edge of the core may be barotropically unstable and thereby able to support counterpropagating vortex Rossby wave interactions. It has also been demonstrated that hurricanes and other barotropic vortices possess innate, dry abilities to maintain themselves when under the duress of vertical wind shear. This work will address how these two separate processes interact with each other.
In this study, the barotropic ring is given additional vorticity in the outer regions to mimic observations more closely. This allows for the outward propagation of energy and simultaneous reduction of the radius of maximum wind. When this vortex is sheared, it is found that the shear forcing, which acts as a de facto wavenumber-1 forcing, does not noticeably alter the growth of the most unstable mode, wavenumber 3. The tilt precession of the vortex is altered greatly, as the tilt becomes both larger and slower. Palinstrophy and deformation analysis indicates that overall peak mixing is also reduced, owing to changes in the axisymmetrization process. Energetics analyses show that the radial component of the shear forcing acts to generate eddies while the tangential component of the shear tends to destroy eddies. The calculations are carried out a second time with another center-finding method, which shows the tilt to be much smaller and more variable while imparting a large wavenumber-1 signal in Fourier analyses.
Stochastic and Perturbed Parameter Representations of Model Uncertainty in Convection Parameterization*
Authors: Christensen H. M. , Moroz I. M. , Palmer T. N. 
Published: February 2015

Abstract
It is now acknowledged that representing model uncertainty in atmospheric simulators is essential for the production of reliable probabilistic forecasts, and a number of different techniques have been proposed for this purpose. This paper presents new perturbed parameter schemes for use in the European Centre for Medium-Range Weather Forecasts (ECMWF) convection scheme. Two types of scheme are developed and implemented. Both schemes represent the joint uncertainty in four of the parameters in the convection parameterization scheme, which was estimated using the Ensemble Prediction and Parameter Estimation System (EPPES). The first scheme developed is a fixed perturbed parameter scheme, where the values of uncertain parameters are varied between ensemble members, but held constant over the duration of the forecast. The second is a stochastically varying perturbed parameter scheme. The performance of these schemes was compared to the ECMWF operational stochastic scheme, stochastically perturbed parameterization tendencies (SPPT), and to a model that does not represent uncertainty in convection. The skill of probabilistic forecasts made using the different models was evaluated. While the perturbed parameter schemes improve on the stochastic parameterization in some regards, the SPPT scheme outperforms the perturbed parameter approaches when considering forecast variables that are particularly sensitive to convection. Overall, SPPT schemes are the most skillful representations of model uncertainty owing to convection parameterization.
Marine Boundary Layer Heights and Their Longitudinal, Diurnal, and Interseasonal Variability in the Southeastern Pacific Using COSMIC, CALIOP, and Radiosonde Data
Authors: Ho Shu-peng , Peng Liang , Anthes Richard A. , Kuo Ying-Hwa , Lin Hsiao-Chun 
Published: February 2015

Abstract
The spatial and temporal variability of the marine boundary layer (MBL) over the southeastern Pacific is studied using high-resolution radiosonde data from the VAMOS Ocean–Cloud–Atmosphere–Land Study Regional Experiment (VOCALS-REx), lidar cloud measurements from the CALIOP instrument on the CALIPSO satellite, radio occultation (RO) data from the COSMIC satellites, and the ERA-Interim. The height of the MBL (MBLH) is estimated using three RO-derived parameters: the bending angle, refractivity, and water vapor pressure computed from the refractivity derived from a one-dimensional variational data inversion (1D-VAR) procedure. Two different diagnostic methods (minimum gradient and break point method) are compared. The results show that, although a negative bias in the refractivity exists as a result of superrefraction, the spatial and temporal variations of the MBLH determined from the RO observations are consistent with those from CALIOP and the radiosondes. The authors find that the minimum gradient in the RO bending angle gives the most accurate estimation of the MBL height.
Dominating Controls for Wetter South Asian Summer Monsoon in the Twenty-First Century
Authors: Mei Rui , Ashfaq Moetasim , Rastogi Deeksha , Leung L. Ruby , Dominguez Francina 
Published: February 2015

AbstractThis paper analyzes a suite of global climate models from phase 5 of the Coupled Model Intercomparison Project (CMIP5) archives to understand the mechanisms behind a net increase in the South Asian summer monsoon precipitation in response to enhanced radiative forcing during the twenty-first century. An increase in radiative forcing fuels an increase in the atmospheric moisture content through warmer temperatures, which overwhelms the weakening of monsoon circulation and results in an increase of moisture convergence and therefore summer monsoon precipitation over South Asia. Moisture source analysis suggests that both regional (local recycling, the Arabian Sea, the Bay of Bengal) and remote (including the south Indian Ocean) sources contribute to the moisture supply for precipitation over South Asia during the summer season that is facilitated by the monsoon dynamics. For regional moisture sources, the effect of excessive atmospheric moisture is offset by weaker monsoon circulation and uncertainty in the response of the evapotranspiration over land, so anomalies in their contribution to the total moisture supply are either mixed or muted. In contrast, weakening of the monsoon dynamics has less influence on the moisture supply from remote sources that not only is a dominant moisture contributor in the historical period but is also the net driver of the positive summer monsoon precipitation response in the twenty-first century. The results also indicate that historic measures of the monsoon dynamics may not be well suited to predict the nonstationary moisture-driven South Asian summer monsoon precipitation response in the twenty-first century.
Seasonal Analysis of Return Periods for Maximum Daily Precipitation in the Brazilian Amazon
Authors: Santos Eliane Barbosa , Lucio Paulo Sérgio , Santos e Silva Cláudio Moisés 
Published: February 2015

AbstractThe aim of this study is to estimate the return period of maximum daily precipitation for each season of the year in different subregions of the Brazilian Amazon. For this, the extreme value theory was used, through the generalized extreme value (GEV) distribution and the generalized Pareto distribution (GPD). The GEV distribution and GPD were applied in precipitation series from homogeneous regions of the Brazilian Amazon. The GEV and GPD goodness of fit were evaluated by the application of the Kolmogorov–Smirnov (KS) test, which compares the cumulative empirical distributions with theoretical ones. The KS test results indicate that the tested distributions have a good fit, particularly the GEV distribution. Thus, they are adequate to study the seasonal maximum daily precipitation. The results indicate that extremes of more intense rainfall are expected during the rainy or transition seasons of each subregion. Using the GEV distribution (GPD), a daily total of 146.1 (201.6), 143.1 (209.5), and 109.4 (152.4) mm is expected at least once a year in the south, at the Atlantic coast in the Amazon catchment, and in the northwest of the Brazilian Amazon, respectively.
Relationship Between Knee Mechanics and Time Since Injury in ACL-Deficient Knees Without Signs of Osteoarthritis
Authors: Zabala Michael E. , Favre Julien , Andriacchi Thomas P. 
Published: February 2015

Background: There is increasing evidence that kinematic changes after anterior cruciate ligament (ACL) injury can influence the risk for premature osteoarthritis. However, kinematics can change over time, and the factors influencing those changes remain unknown but potentially important. Hypothesis/Purpose: The purpose of this study was to perform gait analysis on a population of ACL-deficient (ACLD) subjects without knee osteoarthritis after considerable time had elapsed since their injuries. The following hypotheses were tested: (1) ACLD knees will have greater anterior femoral translation, external femoral rotation, and flexion moment as compared with healthy contralateral knees with increased time since injury; (2) side-to-side differences in anterior femoral translation and external femoral rotation are positively associated with side-to-side differences in knee flexion moment. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Nineteen subjects with unilateral ACLD (time since injury, 1-384 months) underwent gait testing. Linear regression testing was performed for significant relationships between side-to-side differences in tibial translation and rotation during stance and the amount of time since injury, as well as the relationship between differences in peak flexion moment and differences in translation and rotation. Results: There was a time dependency in side-to-side differences. Subjects with shorter times since injury had the femur of the ACLD knee more posteriorly translated and internally rotated than the femur of the contralateral knee, and subjects with longer times since injury had the femur of the ACLD knee more anteriorly translated ( R2 = 0.33) and externally rotated ( R2 = 0.53) than the femur of the contralateral knee. Additionally, when the population was stratified into 2 subgroups based on time after injury (short-term: 1.4-18.7 months; long-term: 58-383.5 months), a relationship between side-to-side differences in knee flexion moment and side-to-side differences in knee translation and rotation was found for the long-term subgroup. Conclusion: The results of this study provide an understanding of the relationship between kinematics and kinetics of the ACLD knee and the amount of time since injury. They suggest that elapsed time since injury might be an important factor when the function of ACL-injured knees is interpreted as it relates to osteoarthritis.
Influence of tacrolimus on podocyte injury inducted by angiotensin II
Authors: Shengyou Yu , Li Yu , Zhihong Hao , Yuanyuan Ma 
Published: February 2015

Objective: This study investigated the protective effect of FK506 in podocytes and the correlation of TRPC6 with podocyte injury repair. Methods: MPC5 were cultured in vitro, parallel with the control group, an Ang II stimulation group, and an FK506 intervention group. The apoptosis rate with flow cytometry also detected TRPC6 mRNA and protein expression by RT-PCR and Western blot, and then observed the distribution of TRPC6 with indirect immunofluorescence labeling under confocal microscope. Results: The activities of podocytes significantly increased after FK506 intervention for 24 hours and 48 hours when compared with the Ang II stimulation group, and the apoptosis rate was markedly lower than that of the Ang II stimulation group, while in contrast to TRPC6 mRNA and protein expression. Conclusion: FK506 can directly act on the podocytes to inhibit Ang II-induced damage on podocyte structures and reduce the apoptosis rate of podocytes, which may be related to stabilizing TRPC6 expression and distribution in podocytes by FK506, thus maintaining the structure and function integrity of the slit diaphragm and playing a role in protecting podocytes and antiproteinuria.
Meeting the online educational needs of international health promoters: an evaluation of a comprehensive, multilingual global training program in tobacco control
Authors: Spires Mark , Cohen Joanna 
Published: February 2015

Introduction: An evaluation of a global online training program in tobacco control offered in multiple languages was conducted to identify ways in which the varied online educational needs of its international participants could be more effectively met. Methods: An online survey was administered to a sample of training participants to solicit feedback regarding course content and delivery. In addition, participants’ training site usage patterns were examined. Results: Findings showed high levels of satisfaction with training content and delivery, as well as of knowledge acquisition and utilization. Respondents indicated that it was important that course content be current and relevant to their practice. Conclusions: Although findings are consistent with best practices for online continuing education, in practice it is challenging to keep material updated, incorporate examples and case studies from the participants’ countries, and integrate adequate opportunities for interactivity when a course has geographically and linguistically diverse participants. Low-cost, technologically appropriate solutions should be developed to maximize the effectiveness of similar continuing education programs for health promoters worldwide.