bluuebunny/crossref_metadata_2025_split huggingface dataset:
STAT3 Regulates Lytic Activation of Kaposi's Sarcoma-Associated Herpesvirus
Authors: King Christine A. , Li Xiaofan , Barbachano-Guerrero Arturo , Bhaduri-McIntosh Sumita 
Published: September 2015

ABSTRACTLytic activation of Kaposi's sarcoma-associated herpesvirus (KSHV) from latency is a critical contributor to pathogenesis and progression of KSHV-mediated disease. Development of targeted treatment strategies and improvement of lytic-phase-directed oncolytic therapies, therefore, hinge on gaining a better understanding of latency-to-lytic-phase transition. A key observation in that regard, also common to other herpesviruses, is the partial permissiveness of latently infected cells to lytic-cycle-inducing agents. Here, we address the molecular basis of why only some KSHV-infected cells respond to lytic stimuli. Since cellular signal transducer and activator of transcription 3 (STAT3) is constitutively active in KSHV-associated cancers, KSHV activates STAT3, and STAT3 has been found to regulate lytic activation of Epstein-Barr virus (EBV)-infected cells, we asked if STAT3 contributes similarly to the life cycle of KSHV. We found that high levels of STAT3 correlate with the refractory state at the single-cell level under conditions of both spontaneous and induced lytic activation; importantly, STAT3 also regulates lytic susceptibility. Further, knockdown of STAT3 suppresses the cellular transcriptional corepressor Krüppel-associated box domain-associated protein 1 (KAP1; also known as TRIM28), and suppression of KAP1 activates lytic genes, including the viral lytic switch RTA, thereby linking STAT3 via KAP1 to regulation of the balance between lytic and latent cells. These findings, taken together with those from EBV-infected and, more recently, herpes simplex virus 1 (HSV-1)-infected cells, cement the contribution of host STAT3 to persistence of herpesviruses and simultaneously reveal an important lead to devise strategies to improve lytic-phase-directed therapies for herpesviruses.IMPORTANCELytic activation of the cancer-causing Kaposi's sarcoma-associated herpesvirus (KSHV) is vital to its life cycle and causation of disease. Like other herpesviruses, however, a substantial fraction of latently infected cells are resistant to lytic-phase-inducing stimuli. Investigating the molecular basis for this refractory state is essential for understanding how the virus persists and how it causes disease and to guide efforts to improve treatment of KSHV-mediated diseases. We found that, like two other herpesviruses, EBV and HSV-1, KSHV exploits the cellular transcription factor STAT3 to regulate the susceptibility of latently infected cells to lytic triggers. These findings highlight a common STAT3-centered strategy used by herpesviruses to maintain persistence in their hosts while also revealing a key molecule to pursue while devising methods to improve herpesvirus lytic-phase-directed therapies.
Downregulation of Toll-Like Receptor 9 Expression by Beta Human Papillomavirus 38 and Implications for Cell Cycle Control
Authors: Pacini Laura , Savini Claudia , Ghittoni Raffaella , Saidj Djamel , Lamartine Jerome , Hasan Uzma A. , Accardi Rosita , Tommasino Massimo 
Published: September 2015

ABSTRACT

Innate immunity is the first line of host defense against infections. Many oncogenic viruses can deregulate several immune-related pathways to guarantee the persistence of the infection. Here, we show that the cutaneous human papillomavirus 38 (HPV38) E6 and E7 oncoproteins suppress the expression of the double-stranded DNA sensor Toll-like receptor 9 (TLR9) in human foreskin keratinocytes (HFK), a key mediator of the antiviral innate immune host response. In particular, HPV38 E7 induces TLR9 mRNA downregulation by promoting accumulation of ΔNp73α, an antagonist of p53 and p73. Inhibition of ΔNp73α expression by antisense oligonucleotide in HPV38 E6/E7 HFK strongly rescues mRNA levels of TLR9, highlighting a key role of ΔNp73α in this event. Chromatin immunoprecipitation experiments showed that ΔNp73α is part of a negative transcriptional regulatory complex with IκB kinase beta (IKKβ) that binds to a NF-κB responsive element within the TLR9 promoter. In addition, the Polycomb protein enhancer of zeste homolog 2 (EZH2), responsible for gene expression silencing, is also recruited into the complex, leading to histone 3 trimethylation at lysine 27 (H3K27me3) in the same region of the TLR9 promoter. Ectopic expression of TLR9 in HPV38 E6/E7 cells resulted in an accumulation of the cell cycle inhibitors p21
WAF1
and p27
Kip1
, decreased CDK2-associated kinase activity, and inhibition of cellular proliferation. In summary, our data show that HPV38, similarly to other viruses with well-known oncogenic activity, can downregulate TLR9 expression. In addition, they highlight a new role for TLR9 in cell cycle regulation.

IMPORTANCE
The mucosal high-risk HPV types have been clearly associated with human carcinogenesis. Emerging lines of evidence suggest the involvement of certain cutaneous HPV types in development of skin squamous cell carcinoma, although this association is still under debate. Oncogenic viruses have evolved different strategies to hijack the host immune system in order to guarantee the persistence of the infection. Their capability to evade the immune system is as important as their ability to promote cellular transformation. Therefore, understanding the viral mechanisms involved in viral persistence is a valid tool to evaluate their potential role in human carcinogenesis. Here, we show that E6 and E7 oncoproteins from the cutaneous HPV38 downregulate the expression of the double-stranded DNA sensor TLR9 of innate immunity. We also present evidence that the HPV38-mediated downregulation of TLR9 expression, in addition to its potential impact on the innate immune response, is linked to cell cycle deregulation.
Variation in hospital rates of induction of labour: a population-based record linkage study
Authors: Nippita Tanya A , Trevena Judy A , Patterson Jillian A , Ford Jane B , Morris Jonathan M , Roberts Christine L 
Published: September 2015

ObjectivesTo examine interhospital variation in rates of induction of labour (IOL) to identify potential targets to reduce high rates of practice variation.DesignPopulation-based record linkage cohort study.SettingNew South Wales, Australia, 2010–2011.ParticipantsAll women with live births of ≥24 weeks gestation in 72 hospitals.Primary outcome measureVariation in hospital IOL rates adjusted for differences in case-mix, according to 10 mutually exclusive groups derived from the Robson caesarean section classification; groups were categorised by parity, plurality, fetal presentation, prior caesarean section and gestational age.ResultsThe overall IOL rate was 26.7% (46 922 of 175 444 maternities were induced), ranging from 9.7% to 41.2% (IQR 21.8–29.8%) between hospitals. Nulliparous and multiparous women at 39–40 weeks gestation with a singleton cephalic birth were the greatest contributors to the overall IOL rate (23.5% and 20.2% of all IOL respectively), and had persisting high unexplained variation after adjustment for case-mix (adjusted hospital IOL rates ranging from 11.8% to 44.9% and 7.1% to 40.5%, respectively). In contrast, there was little variation in interhospital IOL rates among multiparous women with a singleton cephalic birth at ≥41 weeks gestation, women with singleton non-cephalic pregnancies and women with multifetal pregnancies.Conclusions7 of the 10 groups showed high or moderate unexplained variation in interhospital IOL rates, most pronounced for women at 39–40 weeks gestation with a singleton cephalic birth. Outcomes associated with divergent practice require determination, which may guide strategies to reduce practice variation.
Atrial fibrillation care improvement collaborative
Authors: Robelia Paul , Kopecky Stephen , Thacher Tom 
Published: September 2015

AbstractAtrial fibrillation (AF) is an increasingly common cardiac arrhythmia. Many patients with new onset or recurrent AF present to the emergency department and are subsequently admitted to the hospital and seen by cardiology specialists for follow up. In an attempt to address this high utilization of acute health care resources, reduce costs, and improve patient care, our institution instituted a collaborative project between the departments of emergency medicine, cardiology, family medicine, and primary care internal medicine.The project team oversaw development of a new emergency department AF order set, encouraged utilization of a new oral anticoagulant (dabigatran), improved the primary care follow up connection, and deployed a multimodal education plan for primary care providers. Between 2012 and 2014, these interventions resulted in a 17% reduction in total AF per member per month (PMPM) cost, a 28% reduction in AF PMPM inpatient cost, and a 24% reduction in inpatient admissions for AF.
Compliance to two city convenience store ordinance requirements
Authors: Chaumont Menéndez Cammie K , Amandus Harlan E , Wu Nan , Hendricks Scott A 
Published: September 2015

BackgroundRobbery-related homicides and assaults are the leading cause of death in retail businesses. Robbery reduction approaches focus on compliance to Crime Prevention Through Environmental Design (CPTED) guidelines.PurposeWe evaluated the level of compliance to CPTED guidelines specified by convenience store safety ordinances effective in 2010 in Dallas and Houston, Texas, USA.MethodsConvenience stores were defined as businesses less than 10 000 square feet that sell grocery items. Store managers were interviewed for store ordinance requirements from August to November 2011, in a random sample of 594 (289 in Dallas, 305 in Houston) convenience stores that were open before and after the effective dates of their city's ordinance. Data were collected in 2011 and analysed in 2012–2014.ResultsOverall, 9% of stores were in full compliance, although 79% reported being registered with the police departments as compliant. Compliance was consistently significantly higher in Dallas than in Houston for many requirements and by store type. Compliance was lower among single owner-operator stores compared with corporate/franchise stores. Compliance to individual requirements was lowest for signage and visibility.ConclusionsFull compliance to the required safety measures is consistent with industry ‘best practices’ and evidence-based workplace violence prevention research findings. In Houston and Dallas compliance was higher for some CPTED requirements but not the less costly approaches that are also the more straightforward to adopt.
‘Off colour’ alpaca
Authors: Turner Andrea 
Published: September 2015

THIS series gives readers the opportunity to consider and contribute to discussion of some of the ethical dilemmas that can arise in veterinary practice. Each month, a case scenario is presented, followed by discussion of some of the issues involved.In addition, a possible way forward is suggested; however, there is rarely a cut‐and‐dried answer in such cases, and readers may wish to suggest an alternative approach. This month's dilemma, ‘“Off colour” alpaca?’, was submitted and is discussed by Andrea Turner. Readers with comments to contribute are invited to send them as soon as possible, so that they can be considered for publication in the next issue. Discussion of the dilemma ‘Billy the kid’, which was published in the July/August issue of In Practice, appears on page 431.The series is being coordinated by Siobhan Mullan, of the University of Bristol. It is hoped it will provide a framework that will help practices find solutions when facing similar dilemmas.
Specificity of the comparative skin test for bovine tuberculosis in Great Britain
Authors: Goodchild A. V. , Downs S. H. , Upton P. , Wood J. L. N. , de la Rua‐Domenech R. 
Published: September 2015

A novel method for estimating specificity of the Single Intradermal Comparative Cervical Tuberculin (SICCT) test for bovine tuberculosis (bTB) using surveillance tests results is reported. The specificity of the SICCT test at three cut‐offs was estimated from the dates, locations and skinfold measurements of all routine tests carried out in Officially TB Free (OTF) cattle herds in Great Britain (GB) between 2002 and 2008, according to their separation (by distance and time) from known infected (OTF‐withdrawn) herds. The proportion of animals that tested positive was constant (P>0.20) when the distance between tested herds and nearest infected herd exceeded 8 km. For standard cut‐off, calculated specificity was 99.98 per cent (95 per cent confidence interval ±0.004 per cent), equating to one false positive result per 5000 uninfected animals tested. For severe cut‐off it was 99.91 per cent (±0.013 per cent) and for ultrasevere cut‐off (selecting all reactors and inconclusive reactors) it was 99.87 per cent (±0.017 per cent). The estimated positive predictive value of the test averaged 91 per cent and varied by regional prevalence. This study provides further evidence of the high specificity of the SICCT test under GB conditions, suggests that over 90 per cent of cattle currently culled using this test in GB were infected, and endorses slaughter of at least these cattle for bTB control.
No Evidence of Myocardial Oxygen Deprivation in Nonischemic Heart Failure
Authors: Dass Sairia , Holloway Cameron J. , Cochlin Lowri E. , Rider Oliver J. , Mahmod Masliza , Robson Matthew , Sever Emily , Clarke Kieran , Watkins Hugh , Ashrafian Houman , Karamitsos Theodoros D. , Neubauer Stefan 
Published: September 2015

Background—
Whether the myocardium in nonischemic heart failure experiences oxygen limitation remains a long-standing controversy. We addressed this question in patients with dilated cardiomyopathy (DCM) using a dual approach. First, we tested the changes in myocardial oxygenation between rest and stress states, using oxygenation-sensitive cardiovascular magnetic resonance. Second, we sought to assess the functional consequences of oxygen limitation at rest by measuring myocardial energetics before and after short-term oxygen supplementation.

Methods and Results—

Twenty-six subjects (14 DCM and 12 normal) underwent cardiac magnetic resonance imaging at 3 Tesla to assess cardiac volumes, function, oxygenation, and first-pass perfusion (0.03 mmol/kg Gd-DTPA bolus) at stress and rest (4–6 minutes IV adenosine, 140 μg/kg per minute). Signal intensity change (SIΔ) and myocardial perfusion reserve index (MPRI) were measured from oxygenation and perfusion images, respectively. Furthermore, the effect of oxygen supplementation on resting myocardial energy metabolism was tested using
31
P MR spectroscopy, measuring PCr/ATP ratios in both groups at baseline and after 4 hours of oxygen via facemask in the DCM group. During stress, there were equivalent rises in rate pressure product in both groups (DCM, 76±15% and normal, 79±9%;
P
=0.84). MPRI was significantly reduced in DCM (1.51±0.11 versus normal 1.86±0.10;
P
=0.03). However, there was no difference in oxygenation between groups: SIΔ in DCM 17±3% versus normal 20±2% (
P
=0.38). Furthermore, at a left ventricular segmental level, there was no correlation between oxygenation-sensitive SIΔ and MPRI (
R
=0.06;
P
=0.43). Resting PCr/ATP was reduced in DCM (1.66±0.07 versus normal 2.12±0.06;
P
=0.002). With oxygen supplementation, there was no change in PCr/ATP (1.61±0.08;
P
=0.58; Δ=0.04±0.05). There was also no effect of oxygen on systolic function (ejection fraction pre oxygen, 34±1%; post oxygen, 36±2%;
P
=0.46; Δ 2±1%).

Conclusions—
Our results demonstrate dissociation between microvascular dysfunction and oxygenation in DCM, suggesting that the impairment of perfusion is not sufficient to cause deoxygenation during stress. Cardiac energetics are unaffected by oxygen supplementation, indicating the absence of relevant myocardial hypoxia at rest. Our study suggests that novel treatments for nonischemic heart failure should focus on efforts to directly target cardiomyocyte function and metabolism rather than oxygen delivery and microvascular function.
Jindou: A Musical Form Found in Southern Song  Lyric Songs
Authors: Yuanzheng Yang 
Published: September 2015

By introducing a newly-discovered manuscript copy of the lyric song anthology of the poet-musician Jiang Kui (1155–1221), this article aims to elucidate a hitherto unnoticed musical form of the genre: the jindou form. A comparison between the manuscript and all the early modern editions reveals discrepancies in the stanzaic divisions of four of Jiang’s seventeen songs for which he provided notation. Through musical analysis it is argued that the opening line of the second stanza in all the early modern editions may have been intentionally placed at the end of the first in the newly-discovered manuscript in order to remind the singer of the jindou form, in which the cadential notes of the first stanza immediately repeat at the beginning of the second. Therefore, these “unusual” stanzaic divisions are not mistakes, but indications of conventional performance practice in the Southern Song dynasty as dictated by musical factors. S’appuyant sur une copie manuscrite récemment découverte de l’anthologie de poèmes chantés du poète et musicien Jiang Kui (1155–1221), cet article s’attache à élucider une forme musicale propre à ce genre et à laquelle on n’a jamais prêté attention : la forme jindou. La comparaison entre ce manuscrit et l’ensemble des éditions de la fin de la période impériale révèle des différences dans la division strophique de quatre poèmes de Jiang sur les dix-sept pour lesquels la notation musicale est fournie. L’analyse musicale permet d’établir que le premier vers de la seconde strophe dans toutes les éditions de la fin de l’empire a été délibérément placé à la fin de la première strophe dans le nouveau manuscrit, ce afin de rappeler au chanteur la forme jindou, dans laquelle les notes cadentielles de la première strophe sont immédiatement répétées au début de la seconde. Cette division inhabituelle entre strophes n’est donc pas le résultat d’une erreur: elle signale ce qui était le mode d’exécution conventionnel, basé sur des facteurs purement musicaux, à l’époque des Song du Sud.
The Modern Formation of Early Mohism: Sun Yirang’s Exposing and Correcting the Mozi
Authors: Defoort Carine 
Published: September 2015

This essay shows the historical contingency of the currently dominant portrayal of early Mohism in the field of Chinese philosophy. It documents the emergence of this portrayal in the eighteenth and nineteenth centuries by reconstructing, first, Mozi’s supposed promotion of ten core ideas and, second, the increasingly positive appreciation of his thought after centuries of rejection. The essay focuses on the book Exposing and Correcting the Mozi (Mozi jiangu) by the Qing scholar Sun Yirang, which was a milestone in the renaissance of Mozi studies. This book not only contributed to these two changes but also documents the major steps taken by Sun’s predecessors toward the formation of the current portrayal. Cet article met en évidence la contingence historique de la représentation du moïsme ancien actuellement dominante dans le champ de la philosophie chinoise. Il décrit l’émergence de cette représentation aux xviiie et xixe siècles en reconstituant, d’abord, la prétendue promotion de dix idées essentielles par Mozi, et ensuite, l’évaluation de plus en plus positive de sa pensée après des siècles de rejet. L’auteur se concentre sur l’ouvrage Exposition et rectification du Mozi (Mozi jiangu) de Sun Yirang, un érudit de l’époque des Qing, qui a marqué un jalon dans la renaissance des études sur le Mozi. Outre qu’il a lui-même contribué à ces deux évolutions, Sun décrit les principales étapes suivies par ses prédécesseurs, débouchant sur la représentation actuelle.
Students and Dissent in Egypt
Authors: Manduchi Patrizia 
Published: September 2015

This essay aims to describe the Egyptian university movement from the birth of University in Egypt (1908) until the end of Nasser period (1970). A particular focus is provided on the political and social role that students’ opposition movements assumed during all the national events, both in the liberal-monarchic age and under the Nasser presidency. A special attention has been payed to the evolution of Islamic student organizations inside Egyptian universities.The ultimate goal is to stress, with an historical perspective, the relations between the history of universities and students movements as a part of the past and recent history of Egypt. The analysis of the history of thought, the progressive evolution of civil society, the complex articulation of political discourse, the authoritarian and repressive regimes, the censorship, is relevant to better understand the actual political Egyptian context.
„Chorwaci islamskiej wiary” – byt rzeczywisty czy twór propagandy?
Authors: Gucka Agnieszka 
Published: September 2015

The “Croats of Islamic faith” – reality or a creation of propaganda? According to the latest census, in 2001, 56, 777 Muslims live in the Republic of Croatia. The present article is an attempt to answer the following questions about these “Croats of Islamic faith” (Hrvati islamske vjeroispovjesti): Who are they? Where do they come from? And how are they socially perceived?The notion that the Bosnian Muslims are “Croats of the purest blood” was first formulated in the first half of the XIX century by Dr. Ante Starčević, the founder of the Law Party and the originator of a modern Croatian national doctrine. His views were fully adopted and accepted by the Ustasha propaganda, which claims that Bosnia and Herzegovina is the historical cradle of the Croatian state. As a result of this, local Muslims enjoyed a status which was equal to that of the Catholic community. Some propaganda gestures of the time, such as a celebration of the opening of a big mosque in downtown Zagreb, were meant to make the Bosnian Muslims accept the idea of the NDH state and induce them to enroll in the Ustasha Army. After World War II numerous Muslims, who uncritically became advocates of the Ustasha propaganda also shared the fate of Pavelic and his followers. The other Muslims who left their country before the war cultivated the infamous traditions of the NDH state, as well as the myth of an apparent Catholic-Muslim brotherhood.Following the civil war (1991–1995) thousands of Muslim refugees from Bosnia and Herzegovina returned to Croatia, and the issue of their ethnic identity caused some problems. The level of social acceptance of the Muslim community in this traditionally Catholic community, however, is insufficient given the history, and displays of religious activity such as the establishment of Islamic schools and the building of mosques, raise anxiety and a fear of Islamicization amongst many Catholic Croatians. One can observe ongoing and endless Internet debates on the issue as to whether or not the Muslims living in Croatia are true Croatians, while politicians struggle to make use of the Muslim issue for their own purposes. In reality the “Croats of Islamic faith” are simply trying to adapt themselves to the global community and are too busy with everyday matters that they seem not to notice these debates that are largely theoretical.