bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Sierra Nevada serpentinites: the serpentinites most used in Spanish heritage buildings
Authors: Navarro Rafael , Pereira Dolores , Rodríguez-Navarro Carlos , Sebastián-Pardo Eduardo 
Published: June 2014

Abstract
Serpentinites from Sierra Nevada (Granada, south of Spain) have traditionally been used as ornamental elements in historical buildings, both indoors and outdoors. The cathedral, the Palace of Charles V, the Royal Chancellery in Granada and some others are good examples of their use. Outside Granada, the serpentinites are seen at the monastery of El Escorial, The Royal Palace and the convent of Las Salesas Reales, all of them part of Madrid's architectural heritage, although there are much more examples to be found across the country. There are two quarries located in Sierra Nevada that supplied all the material to make the different elements in the above buildings. In this work, we report a thorough characterization of the main characteristics of the serpentinites from Sierra Nevada in order to propose this stone as a possible candidate as a ‘Global Heritage Stone Resource’. This work is important for duly recognizing a natural stone that has been profusely used in the past in the construction of a magnificent heritage of important cities, and historical quarries should be protected so that they can provide original material if required to do so in the future.
Inflammatory Biomarker C-Reactive Protein and Radiotherapy-Induced Early Adverse Skin Reactions in Patients with Breast Cancer
Authors: Rodriguez-Gil Jorge L. , Takita Cristiane , Wright Jean , Reis Isildinha M. , Zhao Wei , Lally Brian E. , Hu Jennifer J. 
Published: June 2014

Abstract
Background: Breast cancer is the most frequently diagnosed cancer and the second leading cause of cancer death in American women. Postsurgery adjuvant radiotherapy (RT) significantly reduced the local recurrence rate. However, many patients develop early adverse skin reactions (EASR) that impact quality of life and treatment outcomes.
Methods: We evaluated an inflammatory biomarker, C-reactive protein (CRP), in predicting RT-induced EASRs in 159 patients with breast cancer undergoing RT. In each patient, we measured pre- and post-RT plasma CRP levels using a highly sensitive ELISA CRP assay. RT-induced EASRs were assessed at weeks 3 and 6 using the National Cancer Institute Common Toxicity Criteria (v3.0). Associations between EASRs and CRP levels were assessed using logistic regression models after adjusting for potential confounders.
Results: RT-induced grade 2+ EASRs were observed in 8 (5%) and 80 (50%) patients at weeks 3 and 6 (end of RT), respectively. At the end of RT, a significantly higher proportion of African Americans developed grade 3 EASRs (13.8% vs. 2.3% in others); grade 2+ EASRs were significantly associated with: change of CRP &gt; 1 mg/L [odds ratio (OR), 2.51; 95% confidence interval (CI), 1.06–5.95; P = 0.04], obesity (OR, 2.08; 95% CI, 1.03–4.21; P = 0.04), or combined both factors (OR, 5.21; 95% CI, 1.77–15.38; P = 0.003).
Conclusion: This is the first study to demonstrate that an inflammatory biomarker CRP is associated with RT-induced EASRs, particularly combined with obesity.
Impact: Future larger studies are warranted to validate our findings and facilitate the discovery and development of anti-inflammatory agents to protect normal tissue from RT-induced adverse effects and improve quality of life in patients with breast cancer undergoing RT. Cancer Epidemiol Biomarkers Prev; 23(9); 1873–83. ©2014 AACR.
Differences in the Transcriptional Response to Fulvestrant and Estrogen Deprivation in ER-Positive Breast Cancer
Authors: Patani Neill , Dunbier Anita K. , Anderson Helen , Ghazoui Zara , Ribas Ricardo , Anderson Elizabeth , Gao Qiong , A'hern Roger , Mackay Alan , Lindemann Justin , Wellings Robert , Walker Jill , Kuter Irene , Martin Lesley-Ann , Dowsett Mitch 
Published: June 2014

AbstractPurpose: Endocrine therapies include aromatase inhibitors and the selective estrogen receptor (ER) downregulator fulvestrant. This study aimed to determine whether the reported efficacy of fulvestrant over anastrozole, and high- over low-dose fulvestrant, reflect distinct transcriptional responses.Experimental Design: Global gene expression profiles from ERα-positive breast carcinomas before and during presurgical treatment with fulvestrant (n = 22) or anastrozole (n = 81), and corresponding in vitro models, were compared. Transcripts responding differently to fulvestrant and estrogen deprivation were identified and integrated using Gene Ontology, pathway and network analyses to evaluate their potential significance.Results: The overall transcriptional response to fulvestrant and estrogen deprivation was correlated (r = 0.61 in presurgical studies, r = 0.87 in vitro), involving downregulation of estrogen-regulated and proliferation-associated genes. The transcriptional response to fulvestrant was of greater magnitude than estrogen deprivation (slope = 0.62 in presurgical studies, slope = 0.63 in vitro). Comparative analyses identified 28 genes and 40 Gene Ontology categories affected differentially by fulvestrant. Seventeen fulvestrant-specific genes, including CAV1/2, SNAI2, and NRP1, associated with ERα, androgen receptor (AR), and TP53, in a network regulating cell cycle, death, survival, and tumor morphology. Eighteen genes responding differently to fulvestrant specifically predicted antiproliferative response to fulvestrant, but not anastrozole. Transcriptional effects of low-dose fulvestrant correlated with high-dose treatment, but were of lower magnitude (ratio = 0.29).Conclusions: The transcriptional response to fulvestrant has much in common with estrogen deprivation, but is stronger with distinctions potentially attributable to arrest of estrogen-independent ERα activity and involvement of AR signaling. Genes responding differently to fulvestrant may have predictive utility. These data are consistent with the clinical efficacy of fulvestrant versus anastrozole and higher dosing regimens. Clin Cancer Res; 20(15); 3962–73. ©2014 AACR.
TP53 Mutations and Lung Cancer: Not All Mutations Are Created Equal
Authors: Govindan Ramaswamy , Weber Jason 
Published: June 2014

Abstract
Mutations in TP53 are common in non–small cell lung cancer. Apart from the loss of tumor-suppressor functions, TP53 mutations may result in gain of function favoring cellular proliferation, inhibition of apoptosis, and genomic instability. Some TP53 mutations are more likely to affect the course of the disease than others. Clin Cancer Res; 20(17); 4419–21. ©2014 AACR.
EZH2 Represses Target Genes through H3K27-Dependent and H3K27-Independent Mechanisms in Hepatocellular Carcinoma
Authors: Gao Shu-Bin , Zheng Qi-Fan , Xu Bin , Pan Chang-Bao , Li Kang-Li , Zhao Yue , Zheng Qi-Lin , Lin Xiao , Xue Li-Xiang , Jin Guang-Hui 
Published: June 2014

Abstract
Alterations of polycomb group (PcG) genes directly modulate the trimethylation of histone H3 lysine 27 (H3K27me3) and may thus affect the epigenome of hepatocellular carcinoma (HCC), which is crucial for controlling the HCC cell phenotype. However, the extent of downstream regulation by PcGs in HCC is not well defined. Using cDNA microarray analysis, we found that the target gene network of PcGs contains well-established genes, such as cyclin-dependent kinase inhibitors (CDKN2A), and genes that were previously undescribed for their regulation by PcG, including E2F1, NOTCH2, and TP53. Using chromatin immunoprecipitation assays, we demonstrated that EZH2 occupancy coincides with H3K27me3 at E2F1 and NOTCH2 promoters. Interestingly, PcG repress the expression of the typical tumor suppressor TP53 in human HCC cells, and an increased level of PcG was correlated with the downregulation of TP53 in certain HCC specimens. Unexpectedly, we did not find obvious H3K27me3 modification or an EZH2 binding signal at the TP53 promoters, suggesting that PcG regulates TP53 expression in an H3K27me3-independent manner. Finally, the reduced expression of PcGs effectively blocked the aggressive signature of liver cancer cells in vitro and in vivo.
Implications: Taken together, our results establish the functional and mechanistic significance of certain gene regulatory networks that are regulated by PcGs in HCC.
Visual Overview: http://mcr.aacrjournals.org/content/12/10/1388/F1.large.jpg.
Mol Cancer Res; 12(10); 1388–97. ©2014 AACR.
Effect of Bilateral Internal Mammary Artery Grafts on Long-Term Survival
Authors: Yi Gijong , Shine Brian , Rehman Syed M. , Altman Douglas G. , Taggart David P. 
Published: June 2014

Background—
Although the potential survival benefit of bilateral internal mammary artery (BIMA) grafting in comparison with single internal mammary artery (SIMA) grafting has been emphasized by many investigators, the use of BIMA is still low in clinical practice in the absence of randomized trials and long-term results. In the current study, we aimed to assess if there is a long-term survival benefit of BIMA up to 10 years after coronary bypass surgery.

Methods and Results—
We selected published articles comparing survival between SIMA and BIMA patients with follow-up duration of more than a mean of 9 years. We evaluated the log hazard ratio with 95% confidence interval for included studies by using a random-effects meta-analysis. Nine eligible observational studies provided 15 583 patients (8270 SIMA and 7313 BIMA) for meta-analysis. Five studies used propensity score methods for statistical adjustment, 2 with a propensity score–based patient-matching method and 3 with quintile-based stratification. A significant reduction in mortality by using BIMA was observed (hazard ratio, 0.79; 95% confidence interval, 0.75–0.84); no study showed any significantly harmful effect of BIMA on survival. Subgroups of studies using different statistical approaches—unmatched, quintile-based propensity score analysis, and propensity score–based exact patient matching—all showed the survival benefit of BIMA grafting.

Conclusions—
BIMA grafting appears to have better survival with up to 10 years follow-up in comparison with SIMA grafting. Long-term survival benefit of BIMA seems to continue in the second decade after surgery. An ongoing randomized trial comparing SIMA and BIMA groups will add evidence on this issue.
Hospital Variation in Survival Trends for In‐hospital Cardiac Arrest
Authors: Girotra Saket , Cram Peter , Spertus John A. , Nallamothu Brahmajee K. , Li Yan , Jones Philip G. , Chan Paul S. ,   The American Heart Association's Get With the Guidelines‐Resuscitation Investigators
Published: June 2014

Background
During the past decade, survival after in‐hospital cardiac arrest has improved markedly. It remains unknown whether the improvement in survival has occurred uniformly at all hospitals or was driven by large improvements at only a few hospitals.

Methods and Results

We identified 93 342 adults with an in‐hospital cardiac arrest at 231 hospitals in the Get With The Guidelines
®
‐Resuscitation registry during 2000–2010. Using hierarchical regression models, we evaluated hospital‐level trends in survival to discharge. Mean age was 66 years, 59% were men, and 21% were black. Between 2000 and 2010, there was a significant
decrease
in age, prevalence of heart failure and myocardial infarction, and cardiac arrests due to shockable rhythms (
P
<0.001 for all) and an
increase
in prevalence of sepsis, respiratory insufficiency, renal insufficiency, intensive care unit location, and mechanical ventilation before arrest
(P
<0.001 for all). After adjustment for temporal trends in baseline characteristics, hospital rates of in‐hospital cardiac arrest survival improved by 7% per year (
odds ratio [OR]
1.07, 95%
CI
1.06 to 1.08,
P
<0.001). Improvement in survival varied markedly and ranged from 3% in the bottom hospital quartile to 11% in the top hospital quartile. Compared with minor teaching hospitals (
OR
1.04, 95%
CI
1.02 to 1.06), hospital rate of survival improvement was greater at major teaching (
OR
1.08, 95%
CI
1.06 to 1.10) and nonteaching hospitals (
OR
1.07, 95%
CI
1.05 to 1.09,
P
value for interaction=0.03).

Conclusion
Although in‐hospital cardiac arrest survival has improved during the past decade, the magnitude of improvement varied across hospitals. Future studies are needed to identify hospital processes that have led to the largest improvement in survival.
Six-Minute Magnetic Resonance Imaging Protocol for Evaluation of Acute Ischemic Stroke
Authors: Nael Kambiz , Khan Rihan , Choudhary Gagandeep , Meshksar Arash , Villablanca Pablo , Tay Jennifer , Drake Kendra , Coull Bruce M. , Kidwell Chelsea S. 
Published: June 2014

Background and Purpose—
If magnetic resonance imaging (MRI) is to compete with computed tomography for evaluation of patients with acute ischemic stroke, there is a need for further improvements in acquisition speed.

Methods—
Inclusion criteria for this prospective, single institutional study were symptoms of acute ischemic stroke within 24 hours onset, National Institutes of Health Stroke Scale ≥3, and absence of MRI contraindications. A combination of echo-planar imaging (EPI) and a parallel acquisition technique were used on a 3T magnetic resonance (MR) scanner to accelerate the acquisition time. Image analysis was performed independently by 2 neuroradiologists.

Results—

A total of 62 patients met inclusion criteria. A repeat MRI scan was performed in 22 patients resulting in a total of 84 MRIs available for analysis. Diagnostic image quality was achieved in 100% of diffusion-weighted imaging, 100% EPI-fluid attenuation inversion recovery imaging, 98% EPI-gradient recalled echo, 90% neck MR angiography and 96% of brain MR angiography, and 94% of dynamic susceptibility contrast perfusion scans with interobserver agreements (
k
) ranging from 0.64 to 0.84. Fifty-nine patients (95%) had acute infarction. There was good interobserver agreement for EPI-fluid attenuation inversion recovery imaging findings (
k
=0.78; 95% confidence interval, 0.66–0.87) and for detection of mismatch classification using dynamic susceptibility contrast-Tmax (
k
=0.92; 95% confidence interval, 0.87–0.94). Thirteen acute intracranial hemorrhages were detected on EPI-gradient recalled echo by both observers. A total of 68 and 72 segmental arterial stenoses were detected on contrast-enhanced MR angiography of the neck and brain with
k
=0.93, 95% confidence interval, 0.84 to 0.96 and 0.87, 95% confidence interval, 0.80 to 0.90, respectively.

Conclusions—
A 6-minute multimodal MR protocol with good diagnostic quality is feasible for the evaluation of patients with acute ischemic stroke and can result in significant reduction in scan time rivaling that of the multimodal computed tomographic protocol.
Neuronal Production of Lipocalin-2 as a Help-Me Signal for Glial Activation
Authors: Xing Changhong , Wang Xiaoshu , Cheng Chongjie , Montaner Joan , Mandeville Emiri , Leung Wendy , van Leyen Klaus , Lok Josephine , Wang Xiaoying , Lo Eng H. 
Published: June 2014

Background and Purpose—
We explored the hypothesis that injured neurons release lipocalin-2 as a help me signal.

Methods—
In vivo lipocalin-2 responses were assessed in rat focal cerebral ischemia and human stroke brain samples using a combination of ELISA and immunostaining. In vitro, microglia and astrocytes were exposed to lipocalin-2, and various markers and assays of glial activation were quantified. Functional relevance of neuron-to-glia lipocalin-2 signaling was examined by transferring conditioned media from lipocalin-2–activated microglia and astrocytes onto neurons to see whether activated glia could protect neurons against oxygen–glucose deprivation and promote neuroplasticity.

Results—
In human stroke samples and rat cerebral ischemia, neuronal expression of lipocalin-2 was significantly increased. In primary cell cultures, exposing microglia and astrocytes to lipocalin-2 resulted in glial activation. In microglia, lipocalin-2 converted resting ramified shapes into a long-rod morphology with reduced branching, increased interleukin-10 release, and enhanced phagocytosis. In astrocytes, lipocalin-2 upregulated glial fibrillary acid protein, brain-derived neurotropic factor, and thrombospondin-1. Conditioned media from lipocalin-2–treated astrocytes upregulated synaptotagmin, and conditioned media from lipocalin-2–treated microglia upregulated synaptophysin and post-synaptic density 95 (PSD95) and protected neurons against oxygen–glucose deprivation.

Conclusions—
These findings provide proof of concept that lipocalin-2 is released by injured neurons as a help me distress signal that activates microglia and astrocytes into potentially prorecovery phenotypes.
Modification of Outcomes With Aspirin or Apixaban in Relation to Female and Male Sex in Patients With Atrial Fibrillation
Authors: Lip Gregory Y.H. , Eikelboom John , Yusuf Salim , Shestakovska Olga , Hart Robert G. , Connolly Stuart 
Published: June 2014

Background and Purpose—
The main objective of the present analysis was to assess the effect of treatment with aspirin compared with apixaban on ischemic stroke and major bleeding in women compared with men. Female patients with atrial fibrillation are at increased stroke risk compared with male patients, and the underlying reasons for higher risk are uncertain.

Methods—
Ancillary analysis of the Apixaban Versus Acetylsalicylic Acid [ASA] to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin K Antagonist Treatment (AVERROES) trial, comparing aspirin and apixaban, focused on sex differences. Mean follow-up was 1.1 years.

Results—

Women compared with men tended to be older (aspirin, 71.8 versus 68.8 years; apixaban, 71.4 versus 68.6 years), with a higher proportion of those aged ≥75 years. Also, women had less peripheral artery disease (aspirin, 2.4% versus 3.7%; apixaban, 1.4% versus 3.0%), more heart failure, and higher mean CHADS
2
(congestive heart failure, hypertension, age of 75 years or older, diabetes [1 point each], stroke or transient ischemic attack [2 points]) scores (aspirin, 2.2 versus 2.0; apixaban, 2.1 versus 2.0). Women compared with men had higher ischemic stroke rates (aspirin, 3.99% versus 2.28%; apixaban, 1.55% versus 0.82%) but similar bleeding rates (aspirin, 1.29% versus 1.22%; apixaban, 1.15% versus 1.36%). The relative effect of apixaban compared with aspirin was similar in men and women for both ischemic stroke (women, 3.99% versus 1.55%; hazard ratio, 0.39; 95% confidence interval, 0.23–0.64; men, 2.28% versus 0.82%; hazard ratio, 0.36; 95% confidence interval, 0.19–0.63;
P
int
=0.84) and major bleeding (women, 1.29% versus 1.15%; hazard ratio, 1.15; 95% confidence interval, 0.59–2.23; men, 1.36% versus 1.22%; hazard ratio, 1.13; 95% confidence interval, 0.64–2.02;
P
int
=0.96).

Conclusions—
Female patients with atrial fibrillation had higher ischemic stroke rates compared with male patients, but the relative effects of apixaban compared with aspirin on both ischemic stroke and bleeding were similar in men and women.
Synoptic-Scale Dual Structure of Precipitable Water along the Eastern Pacific ITCZ
Authors: Chen Guanghua , Takayabu Yukari N. , Yokoyama Chie 
Published: June 2014

Abstract
Using 10-yr high-resolution satellite and reanalysis data, the synoptic-scale dual structure of precipitable water (PW), in which the southern and northern bands straddled at the ITCZ produce zonally propagating meridional dipoles, is observed over the eastern Pacific (EP) during boreal summer and fall. Composites indicate that the PW dipole, concurrent with the dipole-like filtered divergence, has a shift to the west of the anomalously cyclonic circulation. The vertical structure of filtered meridional wind is characterized by a wavenumber-1 baroclinic mode, and the vertical motion has two peaks situated at 850 and 300 hPa, respectively. To the east of the PW dipole, the shallow convection is embedded within the deep convection, forming a multilevel structure of meridional wind on the ITCZ equatorward side. To the west of the PW dipole, the deep convection tends to be suppressed because of the invasion of midlevel dry air advected by northerly flows. The generation and propagation of the dual PW band can be attributed to the divergence and advection terms related to specific humidity and three-dimensional wind. By comparison, the PW anomalies over the western North Pacific, only exhibiting a single band, coincide with the centers of synoptic disturbances with a barotropic vertical structure. Because of the weakening of lower-level divergence, the vertical motion, and the horizontal gradient of PW, the synoptic-scale PW signal is reduced significantly. The typical cases and statistics confirm that the strong meridional dipoles and westward-propagating disturbances are closely associated with the distortion and breakdown of ITCZ over the EP.
The Intraseasonal Variability of African Easterly Wave Energetics
Authors: Alaka Ghassan J. , Maloney Eric D. 
Published: June 2014

Abstract
African easterly waves (AEWs) and associated perturbation kinetic energy (PKE) exhibit significant intraseasonal variability in tropical North Africa during boreal summer. Consistent with East Africa (e.g., east of Lake Chad) being an initiation region for AEWs, previous studies have shown that increased East African PKE precedes and leads to increased West African AEW activity on intraseasonal time scales. In this study, reanalysis budgets of PKE and perturbation available potential energy (PAPE) are used to understand this behavior. The variability of PKE and PAPE sources is analyzed as a function of Madden–Julian oscillation (MJO) phase and a local 30–90-day West African PKE index to diagnose when and where eddy energy conversions terms are important to periods of increased or decreased intraseasonal AEW activity. In East Africa, an increased meridional temperature gradient locally enhances baroclinic energy conversion anomalies to initiate periods of increased intraseasonal AEW activity. Downstream barotropic and baroclinic energy conversions associated with strong AEWs are important for the maintenance of intraseasonal AEW activity in West Africa. Barotropic energy conversions dominate south of the African easterly jet (AEJ), while baroclinic energy conversions are most important north of the AEJ. In both East and West Africa, diabatic heating does not appear to aid intraseasonal PKE creation. Instead, negative PAPE tendency anomalies due to the diabatic heating–temperature covariance act as a negative feedback to increased baroclinic energy conversion downstream in the AEJ.