bluuebunny/crossref_metadata_2025_split huggingface dataset:
CHAM: Improving Prefetch Efficiency Using a Composite Hierarchy-Aware Method
Authors: Qian Cheng , Huang Libo , Yu Qi , Wang Zhiying 
Published: November 2017

Hardware prefetching has always been a crucial mechanism to improve processor performance. However, an efficient prefetch operation requires a guarantee of high prefetch accuracy; otherwise, it may degrade system performance. Prior studies propose an adaptive priority controlling method to make better use of prefetch accesses, which improves performance in two-level cache systems. However, this method does not perform well in a more complex memory hierarchy, such as a three-level cache system. Thus, it is still necessary to explore the efficiency of prefetch, in particular, in complex hierarchical memory systems. In this paper, we propose a composite hierarchy-aware method called CHAM, which works at the middle level cache (MLC). By using prefetch accuracy as an evaluation criterion, CHAM improves the efficiency of prefetch accesses based on (1) a dynamic adaptive prefetch control mechanism to schedule the priority and data transfer of prefetch accesses across the cache hierarchical levels in the runtime and (2) a prefetch efficiency-oriented hybrid cache replacement policy to select the most suitable policy. To demonstrate its effectiveness, we have performed extensive experiments on 28 benchmarks from SPEC CPU2006 and two benchmarks from BioBench. Compared with a similar adaptive method, CHAM improves the MLC demand hit rate by 9.2% and an improvement of 1.4% in system performance on average in a single-core system. On a 4-core system, CHAM improves the demand hit rate by 33.06% and improves system performance by 10.1% on average.
The free fatty acid receptor 1 promotes airway smooth muscle cell proliferation through MEK/ERK and PI3K/Akt signaling pathways
Authors: Matoba Atsuko , Matsuyama Nao , Shibata Sumire , Masaki Eiji , Emala Charles W. , Mizuta Kentaro 
Published: November 2017

Obesity is a risk factor for asthma and influences airway hyperresponsiveness, which is in part modulated by airway smooth muscle proliferative remodeling. Plasma free fatty acids (FFAs) levels are elevated in obese individuals, and long-chain FFAs act as endogenous ligands for the free fatty acid receptor 1 (FFAR1), which couples to both Gq and Gi proteins. We examined whether stimulation of FFAR1 induces airway smooth muscle cell proliferation through classical MEK/ERK and/or phosphoinositide 3-kinase (PI3K)/Akt signaling pathways. The long-chain FFAs (oleic acid and linoleic acid) and a FFAR1 agonist (GW9508) induced human airway smooth muscle (HASM) cell proliferation, which was inhibited by the MEK inhibitor U0126 and the PI3K inhibitor LY294002 . The long-chain FFAs and GW9508 increased phosphorylation of ERK, Akt, and p70S6K in HASM cells and freshly isolated rat airway smooth muscle. Downregulation of FFAR1 in HASM cells by siRNA significantly attenuated oleic acid-induced phosphorylation of ERK and Akt. Oleic acid-induced ERK phosphorylation was blocked by either the Gαi-protein inhibitor pertussis toxin or U0126 and was partially inhibited by either the Gαq-specific inhibitor YM-254890 or the Gβγ signaling inhibitor gallein. Oleic acid significantly inhibited forskolin-stimulated cAMP activity, which was attenuated by pertussis toxin. Akt phosphorylation was inhibited by pertussis toxin, the ras inhibitor manumycin A, the Src inhibitor PP1, or LY294002 . Phosphorylation of p70S6K by oleic acid or GW9508 was significantly inhibited by LY294002 , U0126, and the mammalian target of rapamycin (mTOR) inhibitor rapamycin. In conclusion, the FFAR1 promoted airway smooth muscle cell proliferation and p70S6K phosphorylation through MEK/ERK and PI3K/Akt signaling pathways.
Effect of Time to Diagnostic Testing for Breast, Cervical, and Colorectal Cancer Screening Abnormalities on Screening Efficacy: A Modeling Study
Authors: Rutter Carolyn M. , Kim Jane J. , Meester Reinier G.S. , Sprague Brian L. , Burger Emily A. , Zauber Ann G. , Ergun Mehmet Ali , Campos Nicole G. , Doubeni Chyke A. , Trentham-Dietz Amy , Sy Stephen , Alagoz Oguzhan , Stout Natasha , Lansdorp-Vogelaar Iris , Corley Douglas A. , Tosteson Anna N.A. 
Published: November 2017

Abstract
Background: Patients who receive an abnormal cancer screening result require follow-up for diagnostic testing, but the time to follow-up varies across patients and practices.
Methods: We used a simulation study to estimate the change in lifetime screening benefits when time to follow-up for breast, cervical, and colorectal cancers was increased. Estimates were based on four independently developed microsimulation models that each simulated the life course of adults eligible for breast (women ages 50–74 years), cervical (women ages 21–65 years), or colorectal (adults ages 50–75 years) cancer screening. We assumed screening based on biennial mammography for breast cancer, triennial Papanicolaou testing for cervical cancer, and annual fecal immunochemical testing for colorectal cancer. For each cancer type, we simulated diagnostic testing immediately and at 3, 6, and 12 months after an abnormal screening exam.
Results: We found declines in screening benefit with longer times to diagnostic testing, particularly for breast cancer screening. Compared to immediate diagnostic testing, testing at 3 months resulted in reduced screening benefit, with fewer undiscounted life years gained per 1,000 screened (breast: 17.3%, cervical: 0.8%, colorectal: 2.0% and 2.7%, from two colorectal cancer models), fewer cancers prevented (cervical: 1.4% fewer, colorectal: 0.5% and 1.7% fewer, respectively), and, for breast and colorectal cancer, a less favorable stage distribution.
Conclusions: Longer times to diagnostic testing after an abnormal screening test can decrease screening effectiveness, but the impact varies substantially by cancer type.
Impact: Understanding the impact of time to diagnostic testing on screening effectiveness can help inform quality improvement efforts. Cancer Epidemiol Biomarkers Prev; 27(2); 158–64. ©2017 AACR.
Effect of Mammography Screening on Mortality by Histological Grade
Authors: Tabar Laszlo , Chen Tony Hsiu-Hsi , Yen Amy Ming-Fang , Chen Sam Li-Sheng , Fann Jean Ching-Yuan , Chiu Sherry Yueh-Hsia , Ku May M.S. , Wu Wendy Yi-Ying , Hsu Chen-Yang , Chen Yu-Ying , Beckmann Kerri , Smith Robert A. , Duffy Stephen W. 
Published: November 2017

AbstractBackground: It has been asserted that mammography screening preferentially benefits those with less aggressive cancers, with lesser or no impact on more rapidly progressing and therefore more life-threatening tumors.Methods: We utilized data from the Swedish Two-County Trial, which randomized 77,080 women ages 40 to 74 to invitation to screening and 55,985 for usual care. We tabulated cancers by histologic grade and then compared mortality from cancers specific to histologic grade between the invited and control group using Poisson regression, with specific interest in the effect on mortality from grade 3 cancers. We used incidence-based mortality from tumors diagnosed within the screening phase of the trial. Finally, we cross-tabulated grade with tumor size and node status, to assess downstaging within tumor grades.Results: There was a major reduction in mortality from grade 3 tumors (RR = 0.65; 95% CI, 0.53–0.80; P &lt; 0.001), and more deaths prevented from grade 3 tumors (n = 95) than grade 1 and 2 tumors combined (n = 48) in the invited group. The proportions of tumors ≥15 mm or larger and node-positive tumors were substantially reduced in the grade 3 tumors in the invited group.Conclusions: The combination of prevention of tumors progressing to grade 3 and detection at smaller sizes and lesser rates of lymph node metastases within grade 3 tumors results in a substantial number of deaths from grade 3 cancers being prevented by invitation to mammographic screening.Impact: Mammography screening prevents deaths from aggressive cancers. Cancer Epidemiol Biomarkers Prev; 27(2); 154–7. ©2017 AACR.
Identification of Pleiotropic Cancer Susceptibility Variants from Genome-Wide Association Studies Reveals Functional Characteristics
Authors: Wu Yi-Hsuan , Graff Rebecca E. , Passarelli Michael N. , Hoffman Joshua D. , Ziv Elad , Hoffmann Thomas J. , Witte John S. 
Published: November 2017

Abstract
Background: There exists compelling evidence that some genetic variants are associated with the risk of multiple cancer sites (i.e., pleiotropy). However, the biological mechanisms through which the pleiotropic variants operate are unclear.
Methods: We obtained all cancer risk associations from the National Human Genome Research Institute-European Bioinformatics Institute GWAS Catalog, and correlated cancer risk variants were clustered into groups. Pleiotropic variant groups and genes were functionally annotated. Associations of pleiotropic cancer risk variants with noncancer traits were also obtained.
Results: We identified 1,431 associations between variants and cancer risk, comprised of 989 unique variants associated with 27 unique cancer sites. We found 20 pleiotropic variant groups (2.1%) composed of 33 variants (3.3%), including novel pleiotropic variants rs3777204 and rs56219066 located in the ELL2 gene. Relative to single-cancer risk variants, pleiotropic variants were more likely to be in genes (89.0% vs. 65.3%, P = 2.2 × 10−16), and to have somewhat larger risk allele frequencies (median RAF = 0.49 versus 0.39, P = 0.046). The 27 genes to which the pleiotropic variants mapped were suggestive for enrichment in response to radiation and hypoxia, alpha-linolenic acid metabolism, cell cycle, and extension of telomeres. In addition, we observed that 8 of 33 pleiotropic cancer risk variants were associated with 16 traits other than cancer.
Conclusions: This study identified and functionally characterized genetic variants showing pleiotropy for cancer risk.
Impact: Our findings suggest biological pathways common to different cancers and other diseases, and provide a basis for the study of genetic testing for multiple cancers and repurposing cancer treatments. Cancer Epidemiol Biomarkers Prev; 27(1); 75–85. ©2017 AACR.
A Role for CXCR4 in Peritoneal and Hematogenous Ovarian Cancer Dissemination
Authors: Figueras Agnès , Alsina-Sanchís Elisenda , Lahiguera Álvaro , Abreu Manuel , Muinelo-Romay Laura , Moreno-Bueno Gema , Casanovas Oriol , Graupera Mariona , Matias-Guiu Xavier , Vidal August , Villanueva Alberto , Viñals Francesc 
Published: November 2017

AbstractEpithelial ovarian cancer is characterized by a low recovery rate because the disease is typically diagnosed at an advanced stage, by which time most patients (80%) already exhibit disseminated neoplasia. The cytokine receptor CXCR4 has been implicated in the development of metastasis in various tumor types. Using a patient-derived tissue macroarray and mRNA expression analysis, we observed high CXCR4 levels in high-grade serous epithelial ovarian carcinomas, the most metastatic tumor, compared with those in endometrioid carcinomas. CXCR4 inhibition by treatment with the CXCR4 antagonist AMD3100 or by expression of shRNA anti-CXCR4 similarly inhibited angiogenesis in several models of ovarian carcinomas orthotopically grown in nude mice, but the effect on tumor growth was correlated with the levels of CXCR4 expression. Moreover, CXCR4 inhibition completely blocked dissemination and metastasis. This effect was associated with reduced levels of active Src, active ERKs, the inhibition of EMT transition, and block of hematogenous ovarian cancer dissemination decreasing circulating human tumoral cells (CTC). In tumors, CXCR4-expressing cells also had more mesenchymal characteristics. In conclusion, our results indicate that CXCR4 expression confers a proinvasive phenotype to ovarian carcinoma cells. Thus, anti-CXCR4 therapy is a possible agent for a complementary treatment of advanced disseminated epithelial high-grade serous ovarian cancer patients. Mol Cancer Ther; 17(2); 532–43. ©2017 AACR.
Found in Translation: How Preclinical Research Is Guiding the Clinical Development of the BCL2-Selective Inhibitor Venetoclax
Authors: Leverson Joel D. , Sampath Deepak , Souers Andrew J. , Rosenberg Saul H. , Fairbrother Wayne J. , Amiot Martine , Konopleva Marina , Letai Anthony 
Published: November 2017

Abstract
Since the discovery of apoptosis as a form of programmed cell death, targeting the apoptosis pathway to induce cancer cell death has been a high-priority goal for cancer therapy. After decades of effort, drug-discovery scientists have succeeded in generating small-molecule inhibitors of antiapoptotic BCL2 family proteins. Innovative medicinal chemistry and structure-based drug design, coupled with a strong fundamental understanding of BCL2 biology, were essential to the development of BH3 mimetics such as the BCL2-selective inhibitor venetoclax. We review a number of preclinical studies that have deepened our understanding of BCL2 biology and facilitated the clinical development of venetoclax.
Significance: Basic research into the pathways governing programmed cell death have paved the way for the discovery of apoptosis-inducing agents such as venetoclax, a BCL2-selective inhibitor that was recently approved by the FDA and the European Medicines Agency. Preclinical studies aimed at identifying BCL2-dependent tumor types have translated well into the clinic thus far and will likely continue to inform the clinical development of venetoclax and other BCL2 family inhibitors. Cancer Discov; 7(12); 1376–93. ©2017 AACR.
Rethinking Secrecy in Religion
Authors: MacGillavry David William 
Published: November 2017

AbstractSecrecy is often studied as a social phenomenon in which certain information is concealed from a targeted audience out of fear of the repercussions, if this information were to fall into the wrong hands. It is therefore surprising that people are relatively willing to share their secrets with others. Traditionally, this behaviour has been explained on the bases of the assumption that people are naturally inclined to reveal their secrets. However, new evidence from the cognitive sciences and social psychology calls this assumption, and thus the theories of secrecy which rely on it, into question. In this article I present a re-interpretation of secrecy in light of this new evidence and evaluate what implications this holds for the study of secrecy in religion.
Forms of Justice in Aeschylus’ Eumenides
Authors: Dugdale Eric , Gerstbauer Loramy 
Published: November 2017

Abstract
In this article, we explore the forms of justice presented in Aeschylus’ Eumenides. Most scholarship hitherto has focused on the shift from retaliatory justice to trial by court of law enacted in the play. However, the verdict pronounced in Orestes’ favor does not bring about resolution, but rather threatens to destabilize the polis, as the Furies redirect their anger against Athens. Indeed, the play can be seen as a study in the limitations of criminal justice. Our article examines the resolution of the conflict in the post-trial phase of the play in the light of principles and practices of modern restorative justice. Such comparison is not intended as arguing for correspondence. Rather, the aim is to understand more fully the dynamics of Athena’s intervention by analyzing it against key elements of restorative justice.
Is There a Polis in Euripides’ Medea?
Authors: Perris Simon 
Published: November 2017

Abstract
The polis is a dominant force in scholarship on Greek tragedy, including Euripides’ Medea. This paper addresses the question of whether there is, in fact, a polis (i.e. a Greek-style city-state) in the play.
The polis proper does not often feature in tragedy. Euripides’ Corinth, like many urban centres in tragedy, is a generic palatial settlement ruled by a king. It is not a community of citizens. Creon is a non-constitutional absolute hereditary monarch, and it is a commonplace of tragedy that absolute sole role is antithetical to the idea of the polis.
Medea is exiled, not ostracised; she is never a metic. Her relationships and actions are governed by elite xenia, not citizenship. Thus, though ‘political’ interpretations of Medea are all to the good, polis-centric interpretations become much less attractive once one observes the almost complete absence of the polis from the play.
Health literacy, self-care agency, health status and social support among elderly Chinese nursing home residents
Authors: Liu Yong-bing , Xue Ling-ling , Xue Hui-ping , Hou Ping 
Published: November 2017

Objective: The purpose of this study was to evaluate the relationship between health literacy, self-care agency, social support and health status among elderly Chinese nursing home residents in Xinjiang. Design: Participants were selected using a stratified cluster random sampling design. Setting: The study was conducted from September 2011 to June 2012 in 44 nursing homes in four cities of Xinjiang, China. Methods: A total of 1,452 participants aged between 60 and 99 years met the study inclusion criteria. Data were collected using the Chinese Citizen Health Literacy Questionnaire, the Exercise of Self-Care Agency Scale, the Social Support Rating Scale, the Short Form 36 Health Survey Questionnaire and the Activities of Daily Living Scale. Subsequently, 1,452 questionnaires were distributed with a response rate of 96.14% (1,396 of 1,452). Results: Path analysis with structural equation modelling was used to test a hypothesised model linking health literacy to self-care agency, social support and health status. The optimal fitted model indicated that pathways linking health literacy to health status consisted of one direct path (path coefficient = .074) and three indirect paths (path coefficient = .194), with a total path coefficient of health literacy to health status being .268. Conclusion: Improving health literacy may enable older adults to more appropriately use self-care agency and social support as part of health promotion. The outcomes of this study suggest that to enhance the effects of health promotion interventions, health professionals should aim at raising the health literacy levels of elderly people in China.
The impact of students with left-behind experiences on childhood: The relationship between negative life events and depression among college students in China
Authors: Han Li , Zhao Sheng-yu , Pan Xuan-ying , Liao Chuan-Jing 
Published: November 2017

Background: The number of left-behind children in rural China has increased dramatically over the last decade. It is reported that about 21.88% of child population with an estimated number of 61 million are left-behind children whose parents leave them to work in cities. We conducted a cross-sectional study to explore the impacts of left-behind experience (LBE) on college students’ depression and other influencing factors. Aim: This study discusses the mediation effect of self-esteem together with psychological resilience on college students with depression and negative life events of left-behind. The study also discusses the regulation effect of LBE. Methods: A total of 788 college students were selected from three universities in Sichuan and Chongqing (367 with LBEs, 421 without LBEs). Adolescent Self-Rating Life Events Check List (ASLEC), Self-Esteem Scale (SES), Resilience Scale of Chinese Adolescent (RSCA) and Self-Rating Depression Scale (SDS) were used to measure the negative life events, self-esteem, psychological resilience and depression, respectively. Bootstrap program was used to test the mediation effect, and multiple-group analysis was used to examine the regulation effect for LBE. Results: Scores of ASLEC for the college students with LBEs were higher than those without LBEs (8.59 ± 3.57) vs (7.06 ± 3.38), p < .001). The scores of LBE, ASLEC and SDS were positively correlated with the college students with LBEs ( r = .21 to .29, p < .01), while the scores of RSCA and SES were negatively correlated ( r = −.30 to −.59, p < .01). The mediation effect of college students’ self-esteem and psychological resilience between negative life events and depression was significant (mediating effect = .08, .13, .07; p < .01). Thus, the college students’ self-esteem and psychological resilience on negative life events had strong mediation effect on depression. The test of Bootstrap showed that the mediation effect of self-esteem and psychological resilience was significant (95% confidence interval (CI) = [0.04–0.76]). The LBE had regulation effect on college students’ self-esteem and psychological resilience. (The constraint model fitting degree of variation is Δχ2 = 2,120.68, Δ df = 8, p < .001.) The self-esteem and psychological resilience of college students with LBEs can be used to mediate the relation between negative life events and depression, whereas those without LBEs cannot. Conclusion: Self-esteem and psychological resilience fully mediates college students’ negative life events and depression, which is regulated by their previous LBEs.
‘A2 is Normal’ – Thai Secondary School English Teachers’ Encounters with the CEFR
Authors: Franz Jens , Teo Adisa 
Published: November 2017

Thailand has seen several English language curriculum reforms over the last 20 years, all of which were found to have failed to lift Thai students’ standard of English language proficiency across all levels of study. In 2014, the Thai Ministry of Education announced the introduction of the Common European Framework of Reference for Languages (CEFR), in combination with Communicative Language Teaching (CLT), as its latest policy to improve the standard of English learning and teaching in Thailand’s schools. The establishment of the ASEAN Economic Community (AEC) in 2015 and concerns about the economic competitiveness of the Thai labour force were provided as the underlying rationale for this policy change. This case study, using Grounded Theory Methodology combining semi-structured in-depth interviews, a questionnaire and document analysis, addresses the question of how this education policy change was experienced and perceived by English language teachers at state secondary schools across four provinces in the south of Thailand. A marked divergence in individual teachers’ knowledge and appreciation of the policy plans was observed, with the majority of respondents displaying indifference to and ignorance of the policy. The Ministry had in 2015 tested all civil servant English teachers in a CEFR-referenced online placement test, where 94% had failed to reach the targeted proficiency level of B2. Consequently, the framework was perceived primarily as an English proficiency test for teachers, a European assessment scale which had been applied to them, but which had had no further application to either classroom teaching or student assessment. These findings are framed in the wider context of curriculum reform and English language teaching in Thailand. Comparisons with other English curriculum reform policies based on the CEFR are made, and the emphasis on testing teachers’ language proficiency is reflected upon through the wider debate on language teacher proficiency.