bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detection of HPV16, HPV18, p16, and E6/E7 MRNA in Nasopharyngeal Cancer: A Systematic Review and Meta-Analysis
Authors: Machado Rosalie , Khaymovich Julian , Costantino Peter David , Tham Tristan 
Published: August 2018

ABSTRACTIntroductionHuman Papilloma Virus (HPV) associated head and neck cancers, particularly oropharyngeal cancers (OPC), have a superior prognosis to HPV negative cancers. A literature review did not find any studies that analyzed HPV 16, HPV 18 DNA and p16 in the nasopharynx subsite, although it has been reported in the oropharynx. The detection of HPV DNA and p16 in the nasopharynx could have implications for the treatment of NPC. To date no one has reported the detection or concordance rates of HPV associated markers in nasopharyngeal carcinoma (NPC).MethodsA literature search was undertaken on Medline, EMBASE, Scopus, and the Cochrane Library to identify studies that used PCR and ISH for detection of HPV DNA and p16 in the nasopharynx. We included studies published between 1992 and 2017 that reported the prognostic impact of HPV DNA and/or p16, treated HPV and p16 as categorical variables with at least 10 patients who tested for p16 and/or HPV16/HPV18 DNA in NPC, irrespective of HPV status. We then collected information from many parameters, and performed a meta-analysis to produce pooled prevalence estimates and explored sources of heterogeneityResults21 studies published between 1992 and 2017 were selected for meta-analysis, with sample sizes ranging from 10 to 1328. The total (random effects) pooled detection of any HPV marker in NPC patients was 19.7% (95% CI: 12.56 to 28.00). The total (random effects) pooled detection of p16 positivity in NPC patients was 23.98% (95% CI: 14.82 to 34.54). The total (random effects) pooled detection of HPV DNA in NPC patients, detected by ISH, was 14.43% (95% CI: 10.13 to 19.33) and for HPV DNA in NPC patients including E6/E7 was 18.13% (95% CI: 11.45 to 25.94). The total (random effects) pooled detection of HPV DNA in NPC patients was 18.13% (95% CI: 11.45 to 25.94). The total (random effects) pooled detection of EBV positivity in NPC patients was 76.21% (95% CI: 66.40 to 84.80). Heterogeneity was high for all of the results. The attributable fraction of p16+ and HPV DNA+ in NPC is 0.029. The attributable fraction of EBV positive and HPV – in NPC is 0.827. The attributable fraction of EBV negative and HPV – in NPC is 0.0639. The attributable fraction of EBV negative and HPV + in NPC is 0.085. The attributable fraction of EBV positive and HPV + in NPC is 0.023. The attributable fraction of HPV positive and mRNA+ in NPC was 0.115. The attributable fraction of p16 in NPC was 0.123.DiscussionThis is the first study that contributes to the concordance and detection rates of HPV related markers in NPC.LimitationsMost of the studies included were of Asian extraction. Most of the papers also did not test for E6/E7 RNA and therefore we are unsure of the amount of active E6/E7 RNA in NPC.
Evolution of the U.S. Biological Select Agent Rathayibacter toxicus
Authors: Davis Edward W. , Tabima Javier F. , Weisberg Alexandra J. , Lopes Lucas Dantas , Wiseman Michele S. , Wiseman Michael S. , Pupko Tal , Belcher Michael S. , Sechler Aaron J. , Tancos Matt A. , Schroeder Brenda K. , Murray Timothy D. , Luster Douglas G. , Schneider William L. , Rogers Elizabeth E. , Andreote Fernando D. , Grünwald Niklaus J. , Putnam Melodie L. , Chang Jeff H. 
Published: August 2018

Rathayibacter toxicus
is a toxin-producing species found in Australia and is often fatal to grazing animals. The threat of introduction of the species into the United States led to its inclusion in the Federal Select Agent Program, which makes
R. toxicus
a highly regulated species. This work provides novel insights into the evolution of
R. toxicus
.
R. toxicus
is the only species in the genus to have acquired a CRISPR adaptive immune system to protect against bacteriophages. Results suggest that coexistence with the bacteriophage NCPPB3778 led to the massive shrinkage of the
R. toxicus
genome, species divergence, and the maintenance of low genetic diversity in extant bacterial groups. This work contributes to an understanding of the evolution and ecology of an agriculturally important species of bacteria.
Subfoveal choroidal thickness as a prognostic factor in exudative age-related macular degeneration
Authors: Kumar Jaya B , Wai Karen M , Ehlers Justin P , Singh Rishi P , Rachitskaya Aleksandra V 
Published: August 2018

AimsTo investigate the relationship between subfoveal choroidal thickness (SFCT), visual acuity (VA), optical coherence tomography (OCT) features and total anti-vascular endothelial growth factor (VEGF) treatments to determine whether SFCT serves as a prognostic factor in age-related macular degeneration (AMD).MethodsThis is a retrospective case series of 62 consecutive treatment-naive patients with exudative AMD followed for 1 year and treated with treat-and-extend or pro re nata anti-VEGF protocols. SFCT was measured at three locations using Cirrus HD-OCT (the foveal centre and 500 um nasal and temporal to the fovea) at presentation, 3, 6 and 12 months. Demographic characteristics, OCT imaging biomarkers and VA were recorded.ResultsMean SFCT at baseline was 187 µm (range: 70–361 µm). There was a trend of decreasing SFCT at 1 year (173 µm) compared with 3 months (175 µm) and baseline (188 µm) (p=0.2). There was no correlation between baseline SFCT and presence of subretinal fluid (p=0.2), intraretinal fluid (p=0.6) or subretinal hyper-reflective material (p=0.4) at baseline. The mean number of injections at 1 year was 6.6 (range: 2–12). Increased SFCT at baseline showed statistically significant correlation with a higher number of intravitreal injections at 1 year (p=0.004). Eyes with SFCT>1 SD above the mean required 50% more injections compared with others. There was no association between SFCT on presentation with baseline and 1 year VA (p=0.7 and p=0.2).ConclusionsSFCT in naïve patients with exudative AMD may be an important prognostic tool in determining treatment burden. Patients with thicker subfoveal choroid may require increased intravitreal injections.
Medication reminder applications to improve adherence in coronary heart disease: a randomised clinical trial
Authors: Santo Karla , Singleton Anna , Rogers Kris , Thiagalingam Aravinda , Chalmers John , Chow Clara K , Redfern Julie 
Published: August 2018

ObjectiveThe aim of the MEDication reminder APPs to improve medication adherence in Coronary Heart Disease Study was to evaluate the effectiveness and feasibility of using publicly available high-quality medication reminder applications (apps) to improve medication adherence compared with usual care in patients with coronary heart disease (CHD). An additional aim was to examine whether an app with additional features improved adherence further.MethodsPatients with CHD (n=163) were randomised to one of three groups: (1) usual care, (2) a basic app or (3) an advanced app with interactive/customisable features. The primary analysis compared usual care versus app use on the primary outcome of the 8-item Morisky Medication Adherence Scale (MMAS-8) at 3 months. Secondary outcomes included blood pressure and cholesterol levels.ResultsThe mean age was 57.9 years and 87.7% were male. At 3 months, patients using an app had higher adherence (mean MMAS-8 score 7.11) compared with the usual care group (mean MMAS-8 score 6.63) with a mean difference between groups of 0.47 (95% CI 0.12 to 0.82, p=0.008). There was no significant difference in patients using the basic app versus the advanced app (mean difference −0.16, 95% CI −0.56 to 0.24, p=0.428). There were no significant differences in secondary clinical outcome measures.ConclusionPatients with CHD who used medication reminder apps had better medication adherence compared with usual care, and using apps with additional features did not improve this outcome further. These data suggest medication apps are likely to help patients with chronic health conditions adhere to medicines, but further examination of whether such benefits are sustained is warranted.Clinical trial registration numberACTRN12616000661471; Results.
Statins and the risk of intracerebral haemorrhage in patients with stroke: systematic review and meta-analysis
Authors: Ziff Oliver Jonathan , Banerjee Gargi , Ambler Gareth , Werring David J 
Published: August 2018

ObjectiveWhether statins increase the risk of intracerebral haemorrhage (ICH) in patients with a previous stroke remains uncertain. This study addresses the evidence of statin therapy on ICH and other clinical outcomes in patients with previous ischaemic stroke (IS) or ICH.MethodsA systematic literature review and meta-analysis was performed in conformity with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to assess observational and randomised studies comparing statin therapy with control (placebo or no treatment) in patients with a previous ICH or IS. The risk ratios (RR) for the primary outcome (ICH) and secondary outcomes (IS, any stroke, mortality and function) were pooled using random effects meta-analysis according to stroke subtype.ResultsForty-three studies with a combined total of 317 291 patient-years of follow-up were included. In patients with previous ICH, statins had no significant impact on the pooled RR for recurrent ICH (1.04, 95% CI 0.86 to 1.25; n=23 695); however, statins were associated with significant reductions in mortality (RR 0.49, 95% CI 0.36 to 0.67; n=89 976) and poor functional outcome (RR 0.71, 95% CI 0.67 to 0.75; n=9113). In patients with previous IS, statins were associated with a non-significant increase in ICH (RR 1.36, 95% CI 0.96 to 1.91; n=103 525), but significantly lower risks of recurrent IS (RR 0.74, 95% CI 0.66 to 0.83; n=53 162), any stroke (RR 0.82, 95% CI 0.67 to 0.99; n=55 260), mortality (RR 0.68, 95% CI 0.50 to 0.92; n=74 648) and poor functional outcome (RR 0.83, 95% CI 0.76 to 0.91; n=34 700).ConclusionsIrrespective of stroke subtype, there were non-significant trends towards future ICH with statins. However, this risk was overshadowed by substantial and significant improvements in mortality and functional outcome among statin users.Trial registration numberCRD42017079863.
Sexually transmitted infections in the Delta Regional Authority: significant disparities in the 252 counties of the eight-state Delta Region Authority
Authors: Barger Alexandra C , Pearson William S , Rodriguez Christofer , Crumly David , Mueller-Luckey Georgia , Jenkins Wiley D 
Published: August 2018

ObjectiveChlamydia, gonorrhoea and syphilis (primary and secondary) are at high levels in the USA. Disparities by race, gender and sexual orientation have been characterised, but while there are indications that rural poor populations may also be at distinct risk this has been subjected to little study by comparison. The federally designated Delta Regional Authority, similar in structure to the Appalachian Regional Commission, oversees 252 counties within eight Mississippi Delta states experiencing chronic economic and health disparities. Our objective was to identify differences in infection risk between Delta Region (DR)/non-DR counties and examine how they might vary by rurality, population density, primary care access and education attainment.MethodsReported chlamydia/gonorrhoea/syphilis data were obtained from the Centers for Disease Control and Prevention AtlasPlus, county demographic data from the Area Health Resource File and rurality classifications from the Department of Agriculture. Data were subjected to analysis by t-test, χ2 and linear regression to assess geographical disparities in incidence and their association with measures of rurality, population and primary care density, and education.ResultsOverall rates for each infection were significantly higher in DR versus non-DR counties (577.8 vs 330.1/100 000 for chlamydia; 142.8 vs 61.8 for gonorrhoea; 3.6 vs 1.7 for syphilis; all P<0.001) and for nearly every infection for every individual state. DR rates for each infection were near-universally significantly increased for every level of rurality (nine levels) and population density (quintiles). Regression found that primary care and population density and HS graduation rates were significantly associated with each, though model predictive abilities were poor.ConclusionsThe nearly 10 million people living in the DR face significant disparities in the incidence of chlamydia, gonorrhoea and syphilis—in many instances a near-doubling of risk. Our findings suggest that resource-constrained areas, as measured by rurality, should be considered a priority for future intervention efforts.
The generating function for the Bessel point process and a system of coupled Painlevé V equations
Authors: Charlier Christophe , Doeraene Antoine 
Published: August 2018

We study the joint probability generating function for [Formula: see text] occupancy numbers on disjoint intervals in the Bessel point process. This generating function can be expressed as a Fredholm determinant. We obtain an expression for it in terms of a system of coupled Painlevé V equations, which are derived from a Lax pair of a Riemann–Hilbert problem. This generalizes a result of Tracy and Widom [C. A. Tracy and H. Widom, Level spacing distributions and the Bessel kernel, Commun. Math. Phys. 161(2) (1994) 289–309], which corresponds to the case [Formula: see text]. We also provide some examples and applications. In particular, several relevant quantities can be expressed in terms of the generating function, like the gap probability on a union of disjoint bounded intervals, the gap between the two smallest particles, and large [Formula: see text] asymptotics for [Formula: see text] Hankel determinants with a Laguerre weight possessing several jump discontinuities near the hard edge.
An Algorithmic Approach to Formally Verify an ECC Library
Authors: K. Keerthi , Rebeiro Chester , Hazra Aritra 
Published: August 2018

The weakest link in cryptosystems is quite often due to the implementation rather than the mathematical underpinnings. A vast majority of attacks in the recent past have targeted programming flaws and bugs to break security systems. Due to the complexity, empirically verifying such systems is practically impossible, while manual verification as well as testing do not provide adequate guarantees.
In this article, we leverage model checking techniques to prove the functional correctness of an elliptic curve cryptography (ECC) library with respect to its formal specification. We demonstrate how the huge state space of the C library can be aptly verified using a hierarchical assume-guarantee verification strategy. To test the scalability of this approach, we verify the correctness of five NIST-specified elliptic curve implementations. We also verify the newer curve25519 elliptic curve, which is finding multiple applications, due to its higher security and simpler implementation. The 192-bit NIST elliptic curve took 1 day to verify. This was the smallest curve we verified. The largest curve with a 521-bit prime field took 26 days to verify. Curve25519 took 1.5 days to verify.
Evaluation of Transperineal Magnetic Resonance Imaging/Ultrasound-Fusion Biopsy Compared to Transrectal Systematic Biopsy in the Prediction of Tumour Aggressiveness in Patients with Previously Negative Biopsy
Authors: Borkowetz Angelika , Renner Theresa , Platzek Ivan , Toma Marieta , Herout Roman , Baunacke Martin , Groeben Christer , Huber Johannes , Laniado Michael , Baretton Gustavo , Froehner Michael , Zastrow Stefan , Wirth Manfred P. 
Published: August 2018

<b><i>Objectives:</i></b> We compared the transperineal MRI/ultrasound-fusion biopsy (fusPbx) to transrectal systematic biopsy (sysPbx) in patients with previously negative biopsy and investigated the prediction of tumour aggressiveness with regard to radical prostatectomy (RP) specimen. <b><i>Material and Methods:</i></b> A total of 710 patients underwent multiparametric magnetic resonance imaging (mpMRI), which was evaluated in accordance with Prostate Imaging Reporting and Data System (PI-RADS). The maximum PI-RADS (maxPI-RADS) was defined as the highest PI-RADS of all lesions detected in mpMRI. In case of proven prostate cancer (PCa) and performed RP, tumour grading of the biopsy specimen was compared to that of the RP. Significant PCa (csPCa) was defined according to Epstein criteria. <b><i>Results:</i></b> Overall, scPCa was detected in 40% of patients. The detection rate of scPCa was 33% for fusPbx and 25% for sysPbx alone (<i>p</i> &#x3c; 0.005). Patients with a maxPI-RADS ≥3 and a prostate specific antigen (PSA)-density ≥0.2 ng/mL<sup>2</sup> harboured more csPCa than those with a PSA-density &#x3c; 0.2 ng/mL<sup>2</sup> (41% [33/81] vs. 20% [48/248]; <i>p</i> &#x3c; 0.001). Compared to the RP specimen (<i>n</i> = 140), the concordance of tumour grading was 48% (γ = 0.57), 36% (γ = 0.31) and 54% (γ = 0.6) in fusPbx, sysPbx and comPbx, respectively. <b><i>Conclusions:</i></b> The combination of fusPbx and sysPbx outperforms both biopsy modalities in patients with re-biopsy. Additionally, the PSA-density may represent a predictor for csPCa in patients with maxPI-RADS ≥3.
Controlling Complexity of Cerebral Cortex Simulations—I: CxSystem, a Flexible Cortical Simulation Framework
Authors: Andalibi Vafa , Hokkanen Henri , Vanni Simo 
Published: August 2018

Simulation of the cerebral cortex requires a combination of extensive domain-specific knowledge and efficient software. However, when the complexity of the biological system is combined with that of the software, the likelihood of coding errors increases, which slows model adjustments. Moreover, few life scientists are familiar with software engineering and would benefit from simplicity in form of a high-level abstraction of the biological model. Our primary aim was to build a scalable cortical simulation framework for personal computers. We isolated an adjustable part of the domain-specific knowledge from the software. Next, we designed a framework that reads the model parameters from comma-separated value files and creates the necessary code for Brian2 model simulation. This separation allows rapid exploration of complex cortical circuits while decreasing the likelihood of coding errors and automatically using efficient hardware devices. Next, we tested the system on a simplified version of the neocortical microcircuit proposed by Markram and colleagues ( 2015 ). Our results indicate that the framework can efficiently perform simulations using Python, C[Formula: see text], and GPU devices. The most efficient device varied with computer hardware and the duration and scale of the simulated system. The speed of Brian2 was retained despite an overlying layer of software. However, the Python and C[Formula: see text] devices inherited the single core limitation of Brian2. The CxSystem framework supports exploration of complex models on personal computers and thus has the potential to facilitate research on cortical networks and systems.
Coastal States and MPAs in ABNJ: Ensuring Consistency with the LOSC
Authors: Oude Elferink Alex G. 
Published: August 2018

Abstract
To address the question how a future instrument for areas beyond national jurisdiction (ABNJ) might give consideration to the rights and obligations of coastal States and other States in establishing marine protected areas (MPAs) in ABNJ, the current article discusses the options that have been tabled in this respect in the preparatory meetings for the intergovernmental conference that will be negotiating that instrument. In considering the current legal framework, the focus is on the United Nations Convention on the Law of the Sea (LOSC), as the new instrument is to be elaborated under the LOSC and is required to be fully consistent with it. The article analyses the relevant practice of four specific regions that have established MPAs in ABNJ. The article concludes that due regard is fundamental in addressing interactions between coastal States and other States and considers some options to provide it with specific content.
Mathematics, Mental Imagery, and Ontology: A New Interpretation of the Divided Line
Authors: Byrd Miriam 
Published: August 2018

AbstractThis paper presents a new interpretation of the objects of dianoia in Plato’s divided line, contending that they are mental images of the Forms hypothesized by the dianoetic reasoner. The paper is divided into two parts. A survey of the contemporary debate over the identity of the objects of dianoia yields three criteria a successful interpretation should meet. Then, it is argued that the mental images interpretation, in addition to proving consistent with key passages in the middle books of the Republic, better meets those criteria than do any of the three main positions.
The Lost Yiddish Translation of Sefer Shivhei ha-Besht (Ostróg 1815)
Authors: Meir Jonatan 
Published: August 2018

Abstract
Sefer Shivhei ha-Besht is considered the central collection of hagiographic tales regarding Israel Baʿal Shem Tov (c. 1700–1760). It was first printed in Hebrew in Kopys in the latter part of 1814, and includes hundreds of stories that circulated orally and were heard by the author. The work was soon translated into Yiddish with significant changes, and three such translations have survived, each one very different to the others. The first translation, published in Ostróg in 1815, was believed lost. This article offers a brief description of the recently discovered edition, discussing its uniqueness in the context of the work’s printing history and on the background of Jewish publishing in Eastern Europe.
Manuscript to Print and Print to Print: On the Transmission History of Jacob ben Asher’s Tur Orah Hayyim
Authors: Vidro Nadia 
Published: August 2018

Abstract
This article is a case study in the transition of texts from manuscript to print. It looks at all surviving manuscripts and 15th–16th-centuries printed editions of Jacob ben Asher’s ʾArbaʿah Turim, Tur Orah Hayyim. Based on a close textual investigation of Tur Orah Hayyim, chapter 428, it identifies and dates manuscript clusters, and establishes how different imprints are linked with the manuscript tradition and with each other. The article suggests that the Soncino 1490 imprint by Solomon Soncino exerted a crucial influence on the printed text of Tur Orah Hayyim. Whereas before imprints were independent and closely associated with individual manuscripts, Soncino 1490 became the archetype for all but one subsequent 15th–16th-centuries imprints, and direct dependence on manuscripts subsided.
Cicero, Philippic 2, 44–50, 78–92, 100–119
Authors: Gildenhard Ingo 
Published: August 2018

Cicero composed his incendiary Philippics only a few months after Rome was rocked by the brutal assassination of Julius Caesar. In the tumultuous aftermath of Caesar’s death, Cicero and Mark Antony found themselves on opposing sides of an increasingly bitter and dangerous battle for control. Philippic 2 was a weapon in that war.
Conceived as Cicero’s response to a verbal attack from Antony in the Senate, Philippic 2 is a rhetorical firework that ranges from abusive references to Antony’s supposedly sordid sex life to a sustained critique of what Cicero saw as Antony’s tyrannical ambitions. Vituperatively brilliant and politically committed, it is both a carefully crafted literary artefact and an explosive example of crisis rhetoric. It ultimately led to Cicero’s own gruesome death.
This course book offers a portion of the original Latin text, vocabulary aids, study questions, and an extensive commentary. Designed to stretch and stimulate readers, Ingo Gildenhard’s volume will be of particular interest to students of Latin studying for A-Level or on undergraduate courses. It extends beyond detailed linguistic analysis to encourage critical engagement with Cicero, his oratory, the politics of late-republican Rome, and the transhistorical import of Cicero’s politics of verbal (and physical) violence.