bluuebunny/crossref_metadata_2025_split huggingface dataset:
Melatonin set out to ER stress signaling thwarts epithelial mesenchymal transition and peritoneal dissemination via calpain‐mediated C/EBPβ and NFκB cleavage
Authors: Wu Sheng‐Mao , Lin Wan‐Yu , Shen Chin‐Chang , Pan Hung‐Chuan , Keh‐Bin Wang , Chen Yi‐Ching , Jan Yee‐Jee , Lai De‐Wei , Tang Shu‐Ching , Tien Hsing‐Ru , Chiu Chien‐Shan , Tsai Tsung‐Chih , Lai Yi‐Liang , Sheu Meei‐Ling 
Published: October 2015

AbstractPeritoneal dissemination of tumor has high mortality and is associated with the loss of epithelial features, acquisition of motile mesenchymal morphology characteristics, and invasive properties by tumor cells. Melatonin is an endogenously produced molecule in all plant species that is known to exert antitumor activity, but to date, its underlying mechanisms and antiperitoneal metastasis efficacy is not well defined. This study determined the antiperitoneal dissemination potential of melatonin in vivo and assessed its association with the inhibition of epithelial‐to‐mesenchymal transition (EMT) signaling mechanism by endoplasmic reticulum (ER) stress, which may be a major molecular mechanism of melatonin against cancer. The results demonstrate that melatonin inhibited peritoneal metastasis in vivo and activated ER stress in Cignal ERSE Reporter Assay, organelle structure in transmission electron microscopy images, calpain activity, and protein biomarkers like p‐elf2α. Moreover, the overexpression of transcription factor C/EBPβ in gastric cancer interacted with NFκB and further regulates COX‐2 expression. These were dissociated and downregulated by melatonin, as proven by immunofluorescence imaging, immunoprecipitation, EMSA, and ChIP assay. Melatonin or gene silencing of C/EBPβ decreased the EMT protein markers (E‐cadherin, Snail, and Slug) and Wnt/beta‐catenin activity by Topflash activity, and increased ER stress markers. In an animal study, the results of melatonin therapy were consistent with those of in vitro findings and attenuated systemic proangiogenesis factor production. In conclusion, C/EBPβ and NFκB inhibition by melatonin may impede both gastric tumor growth and peritoneal dissemination by inducing ER stress and inhibiting EMT.
Do Rural Patients in Canada Underutilize Preventive Care for Myocardial Infarction?
Authors: Cohen Deborah , Manuel Douglas G. , Sanmartin Claudia 
Published: October 2015

AbstractPurposeThe objective of this study was to explore Canadian rural‐urban differences in the use of primary and secondary preventive diagnostic services for acute myocardial infarction (AMI)—a condition that is amenable to primary health care prevention efforts.MethodsWe examined primary and secondary preventive care services utilized 2 years prior to a patient's first AMI in a cohort of 30,491 patients in Ontario, Canada, from 2010 to 2012. Using logistic regression, rural‐urban differences in lipid testing, glucose testing, stress testing, electrocardiograms, and echocardiograms in middle‐age and senior patients were examined.FindingsThe odds of rural patients receiving care for primary preventive screening were more than 50% lower than the odds for urban patients, with rural seniors being the most affected. Lipid testing: middle‐age OR 0.519 (95% CI, 0.469‐0.574), senior OR 0.422 (0.386‐0.460); glucose testing: middle‐age OR 0.471 (0.426‐0.521), senior OR 0.359 (0.328‐0.394). The odds of rural patients receiving secondary preventive diagnostic care were also lower than the odds for urban patients, but differences between the age groups were not as apparent. Stress testing: middle‐age OR 0.745 (95%CI, 0.642‐0.866), senior OR 0.726 (0.643‐0.820); electrocardiogram: middle‐age OR 0.815 (0.737‐0.901), senior OR 0.724 (0.659‐0.795); echocardiogram: middle‐age OR 0.755 (0.655‐0.869), senior OR 0.746 (0.681‐0.818).ConclusionsStudy results support ongoing concerns related to health care for rural Canadians by demonstrating underutilization of AMI preventive diagnostic care among rural patients. Rural seniors are most at risk. These results have implications for rural health care as well as seniors’ health policy in Canada.
The present and future disease burden of hepatitis C virus infections with today's treatment paradigm – volume 3
Authors: Sibley A. , Han K. H. , Abourached A. , Lesmana L. A. , Makara M. , Jafri W. , Salupere R. , Assiri A. M. , Goldis A. , Abaalkhail F. , Abbas Z. , Abdou A. , Al Braiki F. , Al Hosani F. , Al Jaberi K. , Al Khatry M. , Al Mulla M. A. , Al Quraishi H. , Al Rifai A. , Al Serkal Y. , Alam A. , Alavian S. M. , Alashgar H. I. , Alawadhi S. , Al‐Dabal L. , Aldins P. , Alfaleh F. Z. , Alghamdi A. S. , Al‐Hakeem R. , Aljumah A. A. , Almessabi A. , Alqutub A. N. , Alswat K. A. , Altraif I. , Alzaabi M. , Andrea N. , Babatin M. A. , Baqir A. , Barakat M. T. , Bergmann O. M. , Bizri A. R. , Blach S. , Chaudhry A. , Choi M. S. , Diab T. , Djauzi S. , El Hassan E. S. , El Khoury S. , Estes C. , Fakhry S. , Farooqi J. I. , Fridjonsdottir H. , Gani R. A. , Ghafoor Khan A. , Gheorghe L. , Gottfredsson M. , Gregorcic S. , Gunter J. , Hajarizadeh B. , Hamid S. , Hasan I. , Hashim A. , Horvath G. , Hunyady B. , Husni R. , Jeruma A. , Jonasson J. G. , Karlsdottir B. , Kim D. Y. , Kim Y. S. , Koutoubi Z. , Liakina V. , Lim Y. S. , Löve A. , Maimets M. , Malekzadeh R. , Matičič M. , Memon M. S. , Merat S. , Mokhbat J. E. , Mourad F. H. , Muljono D. H. , Nawaz A. , Nugrahini N. , Olafsson S. , Priohutomo S. , Qureshi H. , Rassam P. , Razavi H. , Razavi‐Shearer D. , Razavi‐Shearer K. , Rozentale B. , Sadik M. , Saeed K. , Salamat A. , Sanai F. M. , Sanityoso Sulaiman A. , Sayegh R. A. , Sharara A. I. , Siddiq M. , Siddiqui A. M. , Sigmundsdottir G. , Sigurdardottir B. , Speiciene D. , Sulaiman A. , Sultan M. A. , Taha M. , Tanaka J. , Tarifi H. , Tayyab G. , Tolmane I. , Ud din M. , Umar M. , Valantinas J. , Videčnik‐Zorman J. , Yaghi C. , Yunihastuti E. , Yusuf M. A. , Zuberi B. F. , Schmelzer J. D. 
Published: October 2015

SummaryThe total number, morbidity and mortality attributed to viraemic hepatitis C virus (HCV) infections change over time making it difficult to compare reported estimates from different years. Models were developed for 15 countries to quantify and characterize the viraemic population and forecast the changes in the infected population and the corresponding disease burden from 2014 to 2030. With the exception of Iceland, Iran, Latvia and Pakistan, the total number of viraemic HCV infections is expected to decline from 2014 to 2030, but the associated morbidity and mortality are expected to increase in all countries except for Japan and South Korea. In the latter two countries, mortality due to an ageing population will drive down prevalence, morbidity and mortality. On the other hand, both countries have already experienced a rapid increase in HCV‐related mortality and morbidity. HCV‐related morbidity and mortality are projected to increase between 2014 and 2030 in all other countries as result of an ageing HCV‐infected population. Thus, although the total number of HCV countries is expected to decline in most countries studied, the associated disease burden is expected to increase. The current treatment paradigm is inadequate if large reductions in HCV‐related morbidity and mortality are to be achieved.
DHN melanin biosynthesis in the plant pathogenic fungus Botrytis cinerea is based on two developmentally regulated key enzyme (PKS)‐encoding genes
Authors: Schumacher Julia 
Published: October 2015

SummaryBotrytis cinerea is the causal agent of gray mold disease in various plant species and produces grayish macroconidia and/or black sclerotia at the end of the infection cycle. It has been suggested that the pigmentation is due to the accumulation of 1,8‐dihydroxynaphthalene (DHN) melanin. To unravel its basis and regulation, the putative melanogenic and regulatory genes were identified and functionally characterized. Unlike other DHN melanin‐producing fungi, B. cinerea and other Leotiomycetes contain two key enzyme (PKS)‐encoding enzymes. Bcpks12 and bcpks13 are developmentally regulated and are required for melanogenesis in sclerotia and conidia respectively. BcYGH1 converts the BcPKS13 product and contributes thereby to conidial melanogenesis. In contrast, enzymes acting downstream in conversion of the PKS products (BcBRN2, BcSCD1 and BcBRN1) are required for both, sclerotial and conidial melanogenesis, suggesting that DHN melanogenesis in B. cinerea follows a non‐linear pathway that is rather unusual for secondary metabolic pathways. Regulation of the melanogenic genes involves three pathway‐specific transcription factors (TFs) that are clustered with bcpks12 or bcpks13 and other developmental regulators such as light‐responsive TFs. Melanogenic genes are dispensable in vegetative mycelia for proper growth and virulence. However, DHN melanin is considered to contribute to the longevity of the reproduction structures.
Transcriptome changes in STSV2‐infected Sulfolobus islandicus REY15A undergoing continuous CRISPR spacer acquisition
Authors: León‐Sobrino Carlos , Kot Witold P. , Garrett Roger A. 
Published: October 2015

SummaryA transcriptome study was performed on Sulfolobus islandicus REY15A actively undergoing CRISPR spacer acquisition from the crenarchaeal monocaudavirus STSV2 in rich and basal media over a 6 day period. Spacer acquisition preceded strong host growth retardation, altered transcriptional activity of four different CRISPR‐Cas modules and changes in viral copy numbers, and with significant differences in the two media. Transcript levels of proteins involved in the cell cycle were reduced, whereas those of DNA replication, DNA repair, transcriptional regulation and some antitoxin–toxin pairs and transposases were unchanged or enhanced. Antisense RNAs were implicated in the transcriptional regulation of adaptation and interference modules of the type I‐A CRISPR‐Cas system, and evidence was found for the occurrence of functional co‐ordination between the single CRISPR‐Cas adaptation module and the functionally diverse interference modules.
Civil society, radicalism and the rediscovery of mythic nationalism
Authors: Molnár Virág 
Published: October 2015

AbstractThe article argues that contrary to the widely held view that traces the recent rise of illiberalism inHungary andEasternEurope to a weak civil society, the past decade has witnessed a surge of civil society activism. But rather than working exclusively towards strengthening and complementing liberal political institutions, civil society has also provided fertile soil to the spread of right‐wing populism, radicalism and xenophobia. The analysis suggests that civil society organisations have in fact played an important role in the right‐wing radicalisation of contemporaryHungarian politics. Conservative civic groups have been instrumental in reinvigorating the symbolic vocabulary of a mythic nationalism that was widespread at the turn of the nineteenth and twentieth century as well as in the 1930s. The resurrection of nationalist, irredentist and anti‐Semitic symbols and paraphernalia (e.g. greaterHungary car stickers) has been a major vehicle for increasing the public visibility and political impact of these groups. The article shows through case studies of specific organisations how this seemingly anachronistic symbolic repertoire has found new resonance in contemporaryHungarian public life.
Catherine of Siena and the New Evangelization
Authors: Cahall Perry J. 
Published: October 2015

AbstractThis article shows the relevance of past ages to the current project of the new evangelization. In particular, it presents St. Catherine of Siena as an example of the intuition that saints throughout the history of the Church have had regarding how to undertake the process of evangelization. The concept of the “new evangelization” is outlined by referring to the writings and speeches of Pope St. John Paul II, Pope Benedict XVI, and Pope Francis. While covering the basic features of the new evangelization, Saint Catherine's life and insights are presented as an example of how to accomplish the project of the new evangelization.
Osteoprotegerin and zoledronate bone effects during orthodontic tooth movement
Authors: Fernández‐González F. J. , López‐Caballo J. L. , Cañigral A. , Menéndez‐Díaz I. , Brizuela A. , de Cos F. J. , Cobo T. , Vega J. A. 
Published: October 2015

Structured AbstractObjectivesTo assess the effects of local delivery of recombinant fusion protein osteoprotegerin (OPG‐Fc) and bisphosphonate zoledronate on bone and periodontal ligament in a rat tooth movement model.Materials and methodsMaxillary first molars of 36 male Sprague–Dawley rats were displaced mesially using a calibrated spring connected to an anterior mini‐screw. Two different drugs were used: a single dose of Zoledronate (16 μg) and a twice‐weekly dose of OPG‐Fc (5.0 mg/kg) were injected. Tooth movement was measured on scanned plaster casts. Structural and immunohistochemical analysis of the orthodontic‐induced changes in bone included receptor activator of nuclear factor ĸ (RANK), Runx, type 1 collagen, matrix metalloproteinases (MMPs) 2 and 9, tissue inhibitors of metalloproteinases (TIMPs) 1 and 2, and vimentin.ResultsBoth groups showed a reduction in mesial molar displacement. Animals receiving OPG‐Fc demonstrated only 52%, 31%, and 21% of the total mesial molar displacement compared to control rats at 7, 14, and 21 days, respectively (*p < 0.001). For rats receiving zoledronate tooth displacement decreased significantly with 52%, 46% and 30%, respectively (*p < 0.001). At 14 and 21 days, OPG‐Fc group showed significantly less molar displacement than the zoledronate group (*p < 0.001). RANK, Runx, vimentin, MMP‐9 and tissues‐inhibitor metalloproteinase 1 immunoreactivity were reduced in zoledronate treated animals and even more in OPG treated animals.ConclusionLocal delivery of OPG‐Fc or zoledronate inhibits bone resorption and therefore tooth movement. OPG‐Fc was more effective than zoledronate in blocking the action of osteoclasts.
The Impact of Duration of Atrial Fibrillation Recurrences on Measures of Health‐Related Quality of Life and Symptoms
Authors: KOCHHÄUSER SIMON , JOZA JACQUELINE , ESSEBAG VIDAL , PROIETTI RICCARDO , KOEHLER JODI , TSANG BERNICE , WULFFHART ZAEV , PANTANO ALFREDO , KHAYKIN YAARIV , ZIEGLER PAUL D. , VERMA ATUL 
Published: October 2015

BackgroundLittle is known about the relationship between daily atrial fibrillation (AF) burden and quality of life (QOL). We sought to determine the influence of atrial tachycardia (AT) or AF burden on measures of QOL and symptoms.Methods and ResultsWe retrospectively analyzed patients with dual‐chamber pacemakers from the Atrial Septal Pacing Efficacy Clinical Trial (ASPECT), Atrial Therapy Efficacy and Safety Trial (ATTEST), and aTRial arrhythmias dEtected by implaNted Device diagnostics Study (TRENDS) trials. All patients underwent at least one QOL evaluation. We predefined four AF burden groups: no AT/AF (group 1), ≤30 minutes (group 2), 30 minutes–2 hours (group 3), and >2 hours (group 4) per day. We compared QOL measures using the 12‐item Short‐Form Health Survey (SF‐12; standard 4 week recall) and the AF Symptom Checklist (SC) severity and frequency between groups 2–4 to those in group 1. A total of 798 patients were analyzed (age 72 ± 11 years, 447 male [56%]). SC frequency and severity and SF‐12 physical and mental scores worsened significantly when patients in group 4 were compared to patients with no AF. There were no statistically significant differences for any of the measures when comparing group 2 or 3 patients to group 1. By linear regression, only the 2‐hour‐cutoff had a significant impact on QOL as measured by SC frequency (+3.15, P < 0.001), severity (+3.23, P < 0.001), SF‐12 physical score (−2.42, P = 0.013), and SF‐12 mental score (−2.11, P = 0.021).ConclusionA daily AT/AF burden of more than 2 hours had significant impact on QOL. This might influence the choice of appropriate cut‐off points to determine the success of an AF treatment.
I Can't Relax! You're Driving me Quasi!
Authors: Ingram Stephen 
Published: October 2015

AbstractRobust Realists think that there are irreducible, non‐natural, and mind‐independent moral properties. Quasi‐Realists and Relaxed Realists think the same, but interpret these commitments differently. Robust Realists interpret them as metaphysical commitments, to be defended by metaphysical argument. Quasi‐Realists and Relaxed Realists say that they can only be interpreted as moral commitments. These theories thus pose a serious threat to Robust Realism, for they apparently undermine the very possibility of articulating the robust metaphysical commitments of this theory. I clarify and respond to this threat, showing that there is in fact space to develop and defend a robust moral ontology.
Keeping it Real: Intentional Inexistents, Fineness‐of‐Grain, and the Dilemma for Extrinsic Higher‐Order Representational Theories
Authors: Picciuto Vincent 
Published: October 2015

AbstractAccording to the standard argument from targetless higher‐order representations, the possibility of such representations presents a dilemma for higher‐order theorists. In this article I argue that there are two theoretically well‐motivated replies to the standard argument. Consequently, the standard argument against higher‐order theories fails. I then go on to argue that while certain versions of higher‐order theory can adequately respond to the standard argument, they both, nevertheless, fail to explain the fineness‐of‐grain that phenomenally conscious experience appears to have.
Associative Virtues and Hume's Narrow Circle
Authors: Frykholm Erin 
Published: October 2015

AbstractThis article offers a straightforward reading of Hume's ‘narrow circle’ – the boundary employed to define those with whom we sympathize in assessing an agent's moral character – that follows from a more careful look at his account of virtue. Hume employs a principle that can be understood as a virtue ethical equivalent of associative obligation, which thereby delimits the boundaries of this circle. This reading avoids concerns about unjustified partiality, moral blind spots, and demandingness, and shows a clear path for reaching uniform moral judgments; it also offers a new perspective on virtue of interest for contemporary virtue ethics.
Actin Polymerization: An Event Regulated by Tyrosine Phosphorylation During Buffalo Sperm Capacitation
Authors: Naresh S , Atreja SK 
Published: October 2015

ContentsIn the female reproductive tract, the spermatozoa undergo a series of physiological and biochemical changes, prior to gaining the ability to fertilize, that result to capacitation. However, the actin polymerization and protein tyrosine phosphorylation are the two necessary steps for capacitation. In this study, we have demonstrated the actin polymerization and established the correlation between protein tyrosine phosphorylation and actin reorganization during in vitro capacitation in buffalo (Bubalus bubalis) spermatozoa. Indirect immunofluorescence and Western blot techniques were used to detect actin polymerization and tyrosine phosphorylation. The time‐dependent fluorimetric studies revealed that the actin polymerization starts from the tail region and progressed towards the head region of spermatozoa during capacitation. The lysophosphatidyl choline (LPC)‐induced acrosome reaction (AR) stimulated quick actin depolymerization. The inhibitor cytochalasin D (CD) blocked the in vitro capacitation by inhibiting the actin polymerization. In addition, we also performed different inhibitor (Genistein, H‐89, PD9809 and GF‐109) and enhancer (dbcAMP, H2O2 and vanadate) studies on actin tyrosine phosphorylation and actin polymerization. The inhibitors of tyrosine phosphorylation inhibit actin tyrosine phosphorylation and polymerization, whereas enhancers of tyrosine phosphorylation stimulate F‐actin formation and tyrosine phosphorylation. These observations suggest that the tyrosine phosphorylation regulates the actin polymerization, and both are coupled processes during capacitation of buffalo spermatozoa.
Dependence Modelling with Regular Vine Copula Models: A Case-Study for Car Crash Simulation Data
Authors: Schepsmeier Ulf , Czado Claudia 
Published: October 2015

SummaryThe analysis of car crash output parameters such as firewall intrusion points assist the overall engineering process. Such data are nowadays collected from many numerical simulations and it is not possible for the engineer to analyse this growing amount of data by hand. Therefore, data mining and statistical methods are needed. Here, we propose to use the flexible class of regular vine (R-vine) copulas for modelling the dependence between such output variables. R-vine copulas are multivariate copulas constructed hierarchically from bivariate copulas as building blocks. We introduce the concept of such constructions and their graphical tree representation. Applied to simulated frontal crash data of a Ford Taurus such graphs help us to illustrate the dependence structure among different firewall intrusion locations. The big advantage of R-vines compared with standard approaches such as the multivariate normal distribution or the multivariate Gaussian copula is the ability to model asymmetries and dependence in the tails. Our application demonstrates the strong potential of R-vines in the engineering context and opens further application areas.
The New Cultural Conflict, Polarization, and Representation in the Swiss Party System, 1975–2011
Authors: Bornschier Simon 
Published: October 2015

AbstractParty relationships in the Swiss party system have become substantially more antagonistic over the past decades. This article analyzes the actors and ideologies that have triggered the emergence of a polarizing cultural antagonism, and shows that this conflict is not primarily about Switzerland's relationship with Europe. The implications of the emergence of the new cultural conflict for democracy are far from clear. Using an innovative approach to measure the congruence between voter preferences and party positions, I show that the representation of citizens’ interests along the cultural dimension has improved significantly since the 1970s. The concomitant polarization of the economic dimension has not altered the quality of representation, on the other hand. I conclude by discussing the trade‐offs between the political articulation of a traditionalist‐communitarian conception of community that clearly resonates with an important part of the Swiss populace, and other components of liberal democracy.
Identification of a novel HLA‐B*15 variant, B*15:367, using sequence‐based typing in a Korean woman
Authors: Ham J. Y. , Yoon C. E. , Moon J. H. , Won D. I. , Suh J. S. 
Published: October 2015

AbstractNew allele, B*15:367, differs from B*15:11:01 by a single nucleotide exchange at codon 222 (GAG→AAG).