bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stone heritage in Southeast Slovenia
Authors: Golež M. , Mirtič B. 
Published: August 2014

Abstract
The landscape of southeast Slovenia and its heritage in stone is, in terms of geology, primarily identified through the application of various types of sandstone of Miocene age, from those of Lower Miocene found in the wider areas of Celje and Ptuj to those of Middle Miocene found in and around Šmarje pri Jelšah and Rogaška Slatina. The inactive quarries in this region reveal traces of stonemasonry, while the outcrops of clastic sedimentary rocks reveal their diverse geological heritage. Hence, the wealth of natural and cultural heritage of a place is intertwined in one spot, offering an opportunity to make stonemasonry, stonemasons’ products, the traditional technological know-how, as well as arts and sciences, popular. With the stone heritage of southeast Slovenia gravely threatened, the abandoned quarries identified represent potential sites for obtaining natural stone for the purposes of renovating architectural heritage structures in the Slovenian countryside and more widely, like in the case of the revitalization of the abandoned quarry in Strtenica.
MYCN-Dependent Expression of Sulfatase-2 Regulates Neuroblastoma Cell Survival
Authors: Solari Valeria , Borriello Lucia , Turcatel Gianluca , Shimada Hiroyuki , Sposto Richard , Fernandez G. Esteban , Asgharzadeh Shahab , Yates Edwin A. , Turnbull Jeremy E. , DeClerck Yves A. 
Published: August 2014

Abstract
Heparan sulfate proteoglycans (HSPG) play a critical role in the interaction of tumor cells and their microenvironment. HSPG activity is dictated by sulfation patterns controlled by sulfotransferases, which add sulfate groups, and sulfatases (Sulf), which remove 6-O-sulfates. Here, we report altered expression of these enzymes in human neuroblastoma cells with higher levels of Sulf-2 expression, a specific feature of MYCN-amplified cells (MYCN-A cells) that represent a particularly aggressive subclass. Sulf-2 overexpression in neuroblastoma cells lacking MYCN amplification (MYCN-NA cells) increased their in vitro survival. Mechanistic investigations revealed evidence of a link between Sulf-2 expression and MYCN pathogenicity in vitro and in vivo. Analysis of Sulf-2 protein expression in 65 human neuroblastoma tumors demonstrated a higher level of Sulf-2 expression in MYCN-A tumors than in MYCN-NA tumors. In two different patient cohorts, we confirmed the association in expression patterns of Sulf-2 and MYCN and determined that Sulf-2 overexpression predicted poor outcomes in a nonindependent manner with MYCN. Our findings define Sulf-2 as a novel positive regulator of neuroblastoma pathogenicity that contributes to MYCN oncogenicity. Cancer Res; 74(21); 5999–6009. ©2014 AACR.
Metastatic Consequences of Immune Escape from NK Cell Cytotoxicity by Human Breast Cancer Stem Cells
Authors: Wang Bin , Wang Qiang , Wang Zhe , Jiang Jun , Yu Shi-Cang , Ping Yi-Fang , Yang Jing , Xu Sen-Lin , Ye Xian-Zong , Xu Chuan , Yang Lang , Qian Cheng , Wang Ji Ming , Cui You-Hong , Zhang Xia , Bian Xiu-Wu 
Published: August 2014

Abstract
Breast cancer stem-like cells (BCSC) are crucial for metastasis but the underlying mechanisms remain elusive. Here, we report that tumor-infiltrating natural killer (NK) cells failed to limit metastasis and were not associated with improved therapeutic outcome of BCSC-rich breast cancer. Primary BCSCs were resistant to cytotoxicity mediated by autologous/allogeneic NK cells due to reduced expression of MICA and MICB, two ligands for the stimulatory NK cell receptor NKG2D. Furthermore, the downregulation of MICA/MICB in BCSCs was mediated by aberrantly expressed oncogenic miR20a, which promoted the resistance of BCSC to NK cell cytotoxicity and resultant lung metastasis. The breast cancer cell differentiation–inducing agent, all-trans retinoic acid, restored the miR20a–MICA/MICB axis and sensitized BCSC to NK cell–mediated killing, thereby reducing immune escape–associated BCSC metastasis. Together, our findings reveal a novel mechanism for immune escape of human BCSC and identify the miR20a–MICA/MICB signaling axis as a therapeutic target to limit metastatic breast cancer. Cancer Res; 74(20); 5746–57. ©2014 AACR.
β-Catenin Contributes to Lung Tumor Development Induced by EGFR Mutations
Authors: Nakayama Sohei , Sng Natasha , Carretero Julian , Welner Robert , Hayashi Yuichiro , Yamamoto Mihoko , Tan Alistair J. , Yamaguchi Norihiro , Yasuda Hiroyuki , Li Danan , Soejima Kenzo , Soo Ross A. , Costa Daniel B. , Wong Kwok-Kin , Kobayashi Susumu S. 
Published: August 2014

Abstract
The discovery of somatic mutations in EGFR and development of EGFR tyrosine kinase inhibitors (TKI) have revolutionized treatment for lung cancer. However, resistance to TKIs emerges in almost all patients and currently no effective treatment is available. Here, we show that β-catenin is essential for development of EGFR-mutated lung cancers. β-Catenin was upregulated and activated in EGFR-mutated cells. Mutant EGFR preferentially bound to and tyrosine phosphorylated β-catenin, leading to an increase in β-catenin–mediated transactivation, particularly in cells harboring the gefitinib/erlotinib-resistant gatekeeper EGFR-T790M mutation. Pharmacologic inhibition of β-catenin suppressed EGFR-L858R-T790M mutated lung tumor growth, and genetic deletion of the β-catenin gene dramatically reduced lung tumor formation in EGFR-L858R-T790M transgenic mice. These data suggest that β-catenin plays an essential role in lung tumorigenesis and that targeting the β-catenin pathway may provide novel strategies to prevent lung cancer development or overcome resistance to EGFR TKIs. Cancer Res; 74(20); 5891–902. ©2014 AACR.
Activated d16HER2 Homodimers and SRC Kinase Mediate Optimal Efficacy for Trastuzumab
Authors: Castagnoli Lorenzo , Iezzi Manuela , Ghedini Gaia C. , Ciravolo Valentina , Marzano Giulia , Lamolinara Alessia , Zappasodi Roberta , Gasparini Patrizia , Campiglio Manuela , Amici Augusto , Chiodoni Claudia , Palladini Arianna , Lollini Pier Luigi , Triulzi Tiziana , Menard Sylvie , Nanni Patrizia , Tagliabue Elda , Pupa Serenella M. 
Published: August 2014

AbstractA splice isoform of the HER2 receptor that lacks exon 16 (d16HER2) is expressed in many HER2-positive breast tumors, where it has been linked with resistance to the HER2-targeting antibody trastuzumab, but the impact of d16HER2 on tumor pathobiology and therapeutic response remains uncertain. Here, we provide genetic evidence in transgenic mice that expression of d16HER2 is sufficient to accelerate mammary tumorigenesis and improve the response to trastuzumab. A comparative analysis of effector signaling pathways activated by d16HER2 and wild-type HER2 revealed that d16HER2 was optimally functional through a link to SRC activation (pSRC). Clinically, HER2-positive breast cancers from patients who received trastuzumab exhibited a positive correlation in d16HER2 and pSRC abundance, consistent with the mouse genetic results. Moreover, patients expressing high pSRC or an activated “d16HER2 metagene” were found to derive the greatest benefit from trastuzumab treatment. Overall, our results establish the d16HER2 signaling axis as a signature for decreased risk of relapse after trastuzumab treatment. Cancer Res; 74(21); 6248–59. ©2014 AACR.
Molecular Pathways: Autophagy in Cancer—A Matter of Timing and Context
Authors: Cicchini Michelle , Karantza Vassiliki , Xia Bing 
Published: August 2014

Abstract
Autophagy is an intracellular self-digestion mechanism, by which cellular components are sorted into double-membrane autophagosomes and delivered to lysosomes for degradation. Cells use autophagy to dispose of wastes and eliminate hazards, while recycling nutrients and tuning metabolism in the process. Through these functions, autophagy promotes cell fitness, genome integrity, tissue homeostasis, and cell survival and growth under stress. Both autophagy upregulation and downregulation have been found in human cancers, suggesting a complex role in tumor development. Accumulating results from autophagy-deficient mice and mouse models of human cancers have demonstrated that autophagy generally suppresses tumor initiation, but promotes tumor progression, in a manner that is dependent on timing and context and modified by specific tumorigenic events. Given the role of autophagy in facilitating tumor growth, autophagy inhibition has gained wide attention as a potential anticancer therapy. Here, we summarize relevant genetic, preclinical, and clinical studies and discuss the multifaceted role of autophagy in cancer, as well as the prospects of autophagy inhibition for cancer therapy. Clin Cancer Res; 21(3); 498–504. ©2014 AACR.
Complete Loss of PTEN Protein Expression Correlates with Shorter Time to Brain Metastasis and Survival in Stage IIIB/C Melanoma Patients withBRAFV600 Mutations
Authors: Bucheit Amanda D. , Chen Guo , Siroy Alan , Tetzlaff Michael , Broaddus Russell , Milton Denai , Fox Patricia , Bassett Roland , Hwu Patrick , Gershenwald Jeffrey E. , Lazar Alexander J. , Davies Michael A. 
Published: August 2014

AbstractPurpose: Loss of function of PTEN is a frequent event in melanoma, particularly in tumors with BRAFV600 mutations. The prevalence, pathologic features, and clinical outcomes associated with PTEN loss in patients with stage IIIB/C melanoma were interrogated to improve our understanding of the clinical significance of this molecular event.Experimental Design: Archival tissue from lymphadenectomy specimens among patients (n = 136) with stage IIIB or IIIC melanoma was assessed by DNA sequencing for activating BRAF and NRAS mutations, and by immunohistochemistry for the expression of PTEN protein. Associations of these molecular aberrations with demographics, tumor characteristics, and clinical outcomes were determined.Results: The prevalence of BRAFV600 mutations (40% overall), NRAS mutations (10%), and PTEN loss (25%) did not vary by pathologic substage. BRAF/NRAS mutation status did not correlate with distant disease-free survival (DDFS) or overall survival (OS). Complete loss of PTEN expression correlated with shorter OS but not DDFS. When stratified by specific sites of distant metastasis, PTEN loss was associated with significantly shorter time to melanoma brain metastasis (MBM), but not to liver, lung, or bone metastasis. Analysis of PTEN in mutationally defined subsets showed that PTEN loss was significantly associated with OS and time to MBM in patients with BRAFV600 mutations.Conclusions: Loss of PTEN protein expression correlates significantly with decreased OS and time to MBM in stage IIIB/C melanoma patients with BRAFV600 mutations. The findings add to evidence supporting a significant role for PTEN loss and the PI3K–AKT pathway in melanoma. Clin Cancer Res; 20(21); 5527–36. ©2014 AACR.
Ubiquitin-Like Protein ISG15 (Interferon-Stimulated Gene of 15 kDa) in Host Defense Against Heart Failure in a Mouse Model of Virus-Induced Cardiomyopathy
Authors: Rahnefeld Anna , Klingel Karin , Schuermann Anett , Diny Nicola L. , Althof Nadine , Lindner Anika , Bleienheuft Philipp , Savvatis Konstantinos , Respondek Dorota , Opitz Elisa , Ketscher Lars , Sauter Martina , Seifert Ulrike , Tschöpe Carsten , Poller Wolfgang , Knobeloch Klaus-Peter , Voigt Antje 
Published: August 2014

Background—
Common causative agents in the development of inflammatory cardiomyopathy include cardiotropic viruses such as coxsackievirus B3 (CVB3). Here, we investigated the role of the ubiquitin-like modifier interferon-stimulated gene of 15 kDa (ISG15) in the pathogenesis of viral cardiomyopathy.

Methods and Results—

In CVB3-infected mice, the absence of protein modification with ISG15 was accompanied by a profound exacerbation of myocarditis and by a significant increase in mortality and heart failure. We found that ISG15 in cardiomyocytes contributed significantly to the suppression of viral replication. In the absence of an intact ISG15 system, virus titers were markedly elevated by postinfection day 8, and viral RNA persisted in ISG15
−/−
mice at postinfection day 28. Ablation of the ISG15 protein modification system in CVB3 infection predisposed mice to long-term disease with deposition of collagen fibers, all leading to inflammatory cardiomyopathy. We found that ISG15 acts as part of the intrinsic immunity in cardiomyocytes and detected no significant effects of ISG15 modification on the cellular immune response. ISG15 modification of CVB3 2A protease counterbalanced CVB3-induced cleavage of the host cell eukaryotic initiation factor of translation eIF4G in cardiomyocytes, thereby counterbalancing the shutoff of host cell translation in CVB3 infection. We demonstrate that ISG15 suppressed infectious virus yield in human cardiac myocytes and the induction of ISG15 in patients with viral cardiomyopathy.

Conclusions—
The ISG15 conjugation system represents a critical innate response mechanism in cardiomyocytes to fight the battle against invading pathogens, limiting inflammatory cardiomyopathy, heart failure, and death. Interference with the ISG15 system might be a novel therapeutic approach in viral cardiomyopathy.
Numerical Simulations of Bow Echo Formation Following a Squall Line–Supercell Merger
Authors: French Adam J. , Parker Matthew D. 
Published: August 2014

Abstract
Output from idealized numerical simulations is used to investigate the storm-scale processes responsible for squall-line evolution following a merger with an isolated supercell. A simulation including a squall line–supercell merger is compared to one using the same initial squall line and background environment without the merger. These simulations reveal that while bow echo formation is favored by the strongly sheared background environment, the merger produces a more compact bowing structure owing to a locally enhanced rear-inflow jet. The merger also represents a favored location for severe weather production relative to other portions of the squall line, with surface winds, vertical vorticity, and rainfall all being maximized in the vicinity of the merger.
An analysis of storm-scale processes reveals that the premerger squall line weakens as it encounters outflow from the preline supercell, and the supercell becomes the leading edge of the merged system. Subsequent localized strengthening of the cold pool and rear-inflow jet produce a compact, intense bow echo local to the merger, with a descending rear-inflow jet creating a broad swath of damaging surface winds. These features, common to severe bow echoes, are shown to be a direct result of the merger in the present simulations, and are diminished or absent in the no-merger simulation. Sensitivity tests reveal that mergers in a weaker vertical wind shear environment do not produce an enhanced bow echo structure, and only produce a localized region of marginally enhanced surface winds. Additional tests demonstrate that the details of postmerger evolution vary with merger location along the line.
Assessing the alcohol–BMI relationship in a US national sample of college students
Authors: Barry Adam E , Piazza-Gardner Anna K , Holton M Kim 
Published: August 2014

Objective: This study sought to assess the body mass index (BMI)–alcohol relationship among a US national sample of college students. Design: Secondary data analysis using the Fall 2011 National College Health Assessment (NCHA). Setting: A total of 44 US higher education institutions. Methods: Participants included a national sample of college students ( N = 27,774). BMI, frequency of alcohol consumption and binge drinking were measured based on responses to items in the NCHA. T-tests and two-way analysis of variance (ANOVA) identified differences in BMI based on drinking status and sex. Results: Drinkers exhibited significantly lower BMIs than non-drinkers, t(26,968) = 5.55, p < .001. Binge drinkers exhibited significantly lower BMIs than non-binge-drinkers, t(27,094) = 2.64, p < .001. A significant interaction for drinking frequency and sex existed, F(5, 20,434) = 4.121, p = .001, but no interaction effect was present for sex and binge drinking frequency. Respondents drinking 1–20 days/month had lower BMIs compared to non-drinkers. Furthermore, frequency of past month drinking (β = −.08, p < .001) made a unique contribution to explaining BMI, such that BMI decreased as the days one consumed alcohol increased. Conclusion: Non-drinkers exhibited significantly higher BMIs than drinkers, regardless of whether consumption was measured as drinking status, frequency of past 30 day use, or binge drinking frequency. Findings build on previous literature which has produced mixed results depending on the operationalisation of alcohol use. Future research into why differences exist in BMI among drinkers versus non-drinkers is warranted.
Why can't Jamal Read?
Authors: Husband Terry 
Published: August 2014

There's no simple answer why black males struggle with reading, but part of the problem stems from correctable factors that tend to lead to an early disconnect. Black boys are unique in that they're in two groups that have historically underachieved in reading — boys and blacks. Although black boys are not a homogenous group, understanding what underlies gaps in both arenas can help educators develop responses to reduce the disparities.
Double-Dipping for Course Credit
Authors: Zimmermann Scott 
Published: August 2014

Are dual-credit courses living up to the hype that they will help prepare students for college, reduce college costs, and make U.S. students more competitive? Programs that let high school students attend college classes have been around for 25 years and frequently are considered among the solutions to raising college graduation rates, adding rigor to high school curricula, and taking a chunk out of college costs. They've become popular, too. A 2005 report by the National Center for Education Statistics (NCES) found that 70% of public high schools offered courses for dual credit. The Bill & Melinda Gates Foundation began its Early College High School Initiative in 2002 and has since grown to include partnerships with over 130 schools in 24 states.
Queens College: A Program for Math Teachers Requires a Complex Formula
Authors: Artzt Alice F. , Curcio Frances R. , Sultan Alan 
Published: August 2014

Teacher educators have not been sitting quietly by the side as others have demanded changes in teacher preparation programs. Across the nation, scores of efforts are underway to recruit, train, induct, and retain a highly skilled class of professionals for American schools. These stories cover just a fraction of the initiatives, projects, and programs launched by school districts, universities, foundations, and others, all aimed at advancing student learning by improving teaching. A program that produces math teachers and a healthy retention rate does so by wrapping itself around students and giving them time to learn and grow into the profession.
Development of persistent headache following stroke: A 3-year follow-up
Authors: Hansen Anne P , Marcussen Ninna S , Klit Henriette , Kasch Helge , Jensen Troels S , Finnerup Nanna B 
Published: August 2014

Background Headache following stroke has been described in previous studies with an incidence of 23%–54%, but a clear description of headache developing after stroke onset is still lacking. The aim of this study was to determine the incidence and characteristics of persistent novel headache after stroke and to describe the use of medication, including dipyridamole. Methods As a follow-up to a prospective study, a standardized questionnaire about characteristics of novel headache and medication use was sent out to surviving patients three years after their stroke. Results The questionnaire was sent to 256 patients and returned by 222, of whom 12% (26/222) of patients reported persistent novel headache. Dipyridamole had no significant influence on the incidence. Stroke-attributed headache according to predefined criteria was reported in 7.2% (16/222) of patients, with tension-type-like headache in 50.0%, migraine-like in 31.3% and medication overuse in 6.25% of patients. More than half of patients experienced moderate to severe pain and had a score of 55 or above on the Headache Impact Test-6 scale. Conclusion Novel headache after stroke affects one in 10 patients and seems to be unrelated to dipyridamole use. Persistent headache attributed to stroke is similar to tension-type headache for half of patients.
Risk of Anterior Cruciate Ligament Injury in Athletes on Synthetic Playing Surfaces
Authors: Balazs George C. , Pavey Gabriel J. , Brelin Alaina M. , Pickett Adam , Keblish David J. , Rue John-Paul H. 
Published: August 2014

Background: The effect of synthetic playing surfaces on the risk of injury in athletes is frequently debated in the orthopaedic literature. Biomechanical studies have identified increased frictional force at the shoe-surface interface, theoretically increasing the risk of injury relative to natural grass. This increase in frictional force is potentially relevant for the risk of anterior cruciate ligament (ACL) rupture, where noncontact mechanisms are frequent. However, clinical studies examining this issue have shown mixed results. Hypothesis/Purpose: The purpose of this study was to systematically review the available literature on risk of ACL rupture on natural grass versus artificial turf. We hypothesized that the risk of ACL rupture on synthetic playing surfaces would not be higher than that of natural grass playing surfaces. Study Design: Systematic review. Methods: A systematic keyword search was performed of OVID, EMBASE, the Cochrane Library of Systematic Reviews, and the PROSPERO International Prospective Register of Systematic Reviews. Candidate articles were included if they reported the risk ratio of ACL rupture on natural grass versus synthetic playing surfaces, were of level 3 evidence or better, and included only ACL injuries sustained during organized athletic events. Exclusion criteria included a study with non-field-related sports and the use of historical cohorts for calculating risk ratios. Results: A total of 10 studies with 963 ACL injuries met criteria for inclusion, all of which reported on soccer and football cohorts. Among these, 4 studies (753 ACL injuries) found an increased risk of ACL injury on artificial playing surfaces. All 4 of these articles were conducted using American football cohorts, and they included both earlier-generation surfaces (AstroTurf) and modern, 3rd-generation surfaces. Only 1 study in football players found a reduced risk of ACL injury on synthetic playing surfaces. No soccer cohort found an increased risk of ACL injury on synthetic surfaces. Conclusion: High-quality studies support an increased rate of ACL injury on synthetic playing surfaces in football, but there is no apparent increased risk in soccer. Further study is needed to clarify the reason for this apparent discrepancy.