bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modulation of Hepatitis C Virus Genome Encapsidation by Nonstructural Protein 4B
Authors: Han Qingxia , Manna David , Belton Kerry , Cole Richard , Konan Kouacou V. 
Published: April 2013

ABSTRACT
Hepatitis C Virus (HCV) NS4B protein has many roles in HCV genome replication. Recently, our laboratory (Q. Han, J. Aligo, D. Manna, K. Belton, S. V. Chintapalli, Y. Hong, R. L. Patterson, D. B. van Rossum, and K. V. Konan, J. Virol. 85:6464–6479, 2011) and others (D. M. Jones, A. H. Patel, P. Targett-Adams, and J. McLauchlan, J. Virol. 83:2163–2177, 2009; D. Paul, I. Romero-Brey, J. Gouttenoire, S. Stoitsova, J. Krijnse-Locker, D. Moradpour, and R. Bartenschlager, J. Virol. 85:6963–6976, 2011) have also reported NS4B's function in postreplication steps. Indeed, replacement of the NS4B C-terminal domain (CTD) in the HCV JFH1 (genotype 2a [G2a]) genome with sequences from Con1 (G1b) or H77 (G1a) had a negligible impact on JFH1 genome replication but attenuated virus production. Since NS4B interacts weakly with the HCV genome, we postulated that NS4B regulates the function of host or virus proteins directly involved in HCV production. In this study, we demonstrate that the integrity of the JFH1 NS4B CTD is crucial for efficient JFH1 genome encapsidation. Further, two adaptive mutations (NS4B N216S and NS5A C465S) were identified, and introduction of these mutations into the chimera rescued virus production to various levels, suggesting a genetic interaction between the NS4B and NS5A proteins. Interestingly, cells infected with chimeric viruses displayed a markedly decreased NS5A hyperphosphorylation state (NS5A p58) relative to JFH1, and the adaptive mutations differentially rescued NS5A p58 formation. However, immunofluorescence staining indicated that the decrease in NS5A p58 did not alter NS5A colocalization with the core around lipid droplets (LDs), the site of JFH1 assembly, suggesting that NS5A fails to facilitate the transfer of HCV RNA to the capsid protein on LDs. Alternatively, NS4B's function in HCV genome encapsidation may entail more than its regulation of the NS5A phosphorylation state.
Investigation of a safety-engineered device to prevent needlestick injury: why has not StatLock stuck?
Authors: Griswold Sharon , Bonaroti Alisha , Rieder Christopher J , Erbayri John , Parsons Jessica , Nocera Romy , Hamilton Richard 
Published: April 2013

ObjectiveThis article sought to define whether an alternative safety-engineered device (SED) could help prevent needlestick injury (NSI) in healthcare workers (HCWs) who place central venous catheters (CVCs).DesignThe study involved three phases: (1) A retrospective analysis of deidentified occupational health records from our tertiary care urban US hospital to clearly identify NSI risk and rates to an HCW during invasive catheter placement; (2) 95 residents were surveyed regarding their knowledge and experience with NSIs and SEDs; (3) A random sample of six residents participated in a focus group session discussing barriers to the use of SED.SettingA single urban US tertiary care teaching hospital.ParticipantsA retrospective analysis of NSI to HCWs in a tertiary care urban US hospital was conducted over a 4-year period (July 2007–June 2011). Ninety-five residents from specialties that often place CVC during training (surgery, surgical subspecialties, internal medicine, anaesthesia and emergency medicine) were surveyed regarding their experience with NSIs and SEDs. A random sample of six residents participated in a focus group session discussing barriers to the use of SED.Results314 NSIs were identified via occupational health records. 16% (21 of 131) of NSIs occurring in residents and fellows occurred during the securement of an invasive catheter such as a CVC. If an SED device had been used, the 5.25 NSIs/year could have been avoided. Each NSI occurring in an HCW incurred at least $2723 in charges. Thus, utilisation of the SED could have saved a minimum of $57 183 over the 4-year period.ConclusionsSEDs are currently available and can be used as an alternative to sharps. If safety and efficacy can be demonstrated, then implementation of such devices can significantly reduce the number of NSIs.
How accurate are medical record data in Afghanistan's maternal health facilities? An observational validity study
Authors: Broughton Edward I , Ikram Abdul Naser , Sahak Ihsanullah 
Published: April 2013

ObjectivesImprovement activities, surveillance and research in maternal and neonatal health in Afghanistan rely heavily on medical record data. This study investigates accuracy in delivery care records from three hospitals across workshifts.DesignObservational cross-sectional study.SettingThe study was conducted in one maternity hospital, one general hospital maternity department and one provincial hospital maternity department. Researchers observed vaginal deliveries and recorded observations to later check against data recorded in patient medical records and facility registers.Outcome measuresWe determined the sensitivity, specificity, area under the receiver operator characteristics curves (AUROCs), proportions correctly classified and the tendency to make performance seem better than it actually was.Results600 observations across the three shifts and three hospitals showed high compliance with active management of the third stage of labour, measuring blood loss and uterine contraction at 30 min, cord care, drying and wrapping newborns and Apgar scores and low compliance with monitoring vital signs. Compliance with quality indicators was high and specificity was lower than sensitivity. For adverse outcomes in birth registries, specificity was higher than sensitivity. Overall AUROCs were between 0.5 and 0.6. Of 17 variables that showed biased errors, 12 made performance or outcomes seem better than they were, and five made them look worse (71% vs 29%, p=0.143). Compliance, sensitivity and specificity varied less among the three shifts than among hospitals.ConclusionsMedical record accuracy was generally poor. Errors by clinicians did not appear to follow a pattern of self-enhancement of performance. Because successful improvement activities, surveillance and research in these settings are heavily reliant on collecting accurate data on processes and outcomes of care, substantial improvement is needed in medical record accuracy.
Social network analysis of Iranian researchers on emergency medicine: a sociogram analysis
Authors: Ghafouri Hamed Basir , Mohammadhassanzadeh Hafez , Shokraneh Farhad , Vakilian Maryam , Farahmand Shervin 
Published: April 2013

BackgroundThe purpose of this study was to report interaction patterns among Iranian authors of emergency medicine using social network analysis methodology, focusing on coauthorship network.MethodsThe bibliographic data of Iranian authors on the ‘emergency medicine’ field during the years 2001–2011 were retrieved from the Science Citation Index Expanded database. Co-occurrence matrices were made by BibExcel and were imported to Ucinet and NetDraw to delineate coauthorship network. To detect structural patterns among authors, we considered some measures of social network analysis, such as density, centralisation indices, component analysis and cut-points. Lastly, subject experts separately analysed the content of papers.ResultsOf 116 papers published, the network was composed of 10 components, with the largest component having 25 authors. Using social network analysis measures, we identified science bottlenecks in knowledge sharing, hub authors and accelerators of information flow. Topic analysis showed ‘Wounds and Injuries’ as the most recent theme in all components because of existence of national registry for trauma, high burden of road traffic injuries and research priority of injuries in Iran.Conclusionsbecause of Iranian low productivity in the emergency medicine field, social network analysis seems to be a proper option for bibliometrics to identify central authors and detect knowledge structure in this field.
Use of ulipristal acetate, levonorgestrel and the copper-intrauterine device for emergency contraception following the introduction of new FSRH guidelines
Authors: Baird Aisling Susan 
Published: April 2013

ObjectivesThe UK Faculty of Sexual & Reproductive Healthcare (FSRH) has recommended that for emergency contraception (EC) the health professional should discuss individual needs and inform women of the different methods, efficacy, adverse effects, interactions, eligibility and additional contraception. In our sexual and reproductive health care service (Liverpool and Knowsley, UK), revised guidance was issued in early 2012, reflecting Faculty advice. We studied (1) how our use of EC changed, (2) which methods were offered and how this changed, (3) which method was chosen by women who were offered all three UK licensed methods of EC and (4) the appropriateness of the offer of only levonorgestrel (LNG).MethodsWe studied a total of 2989 case records in the 3 months before and 3 months following the adoption by our service of the 2011 FSRH guidance. This was a retrospective review of charts undertaken by interrogating our computerised Excelicare®system of clinical records. All EC episodes in the two 3-month periods were analysed, covering October–December 2011 and March–May 2012. Additionally, three non-probabilistic, purposeful samples of representative practitioners’ charts were examined in groups of women offered all methods [and choosing either ulipristal acetate (UPA) or LNG] or who were offered LNG only.ResultsThe use of LNG fell from 93.0% of EC issued to 76.0%; UPA use rose from 3.0% to 18.7%. In the second 3-month period, of the women offered all three methods, 54.9% chose LNG and 39.8% UPA. LNG-only offers in our judgement were clinically appropriate in 62.5% cases of such offers.ConclusionsComparing the second period with the first, more women were offered all three methods, the use of LNG fell (93.0% to 76.0%) and that of UPA increased (3.0% to 18.7%). Women were encouraged to exercise choice. However, increasing choice in our service did not lead to a wholesale change from LNG to UPA.
The significance of copper concentrations in natural gold alloy for reconnaissance exploration and understanding gold-depositing hydrothermal systems
Authors: Moles N. R. , Chapman R. J. , Warner R. B. 
Published: April 2013

Analytical studies of placer (detrital) gold grains, intended to track bedrock sources and styles of mineralization, mainly consider alloy Ag content and inclusion mineralogy to generate ‘microchemical signatures’. Occasionally Hg and Pd help discriminate gold from different sources; Cu infrequently because electron microprobes seldom detect the low concentrations. Reporting of Cu has been largely confined to gold from porphyry–epithermal environments, and this has biased subsequent interpretations of observed Cu-bearing gold alloys.
This study focuses on placer gold in the Mourne Mountains, Northern Ireland, where auriferous bedrock remains undiscovered and the complex geology is consistent with either orogenic or intrusion-related mineralization. Over 500 gold grains analysed average 0.17% Cu ranging to >1% Cu and show a wide variation in Ag content. Inclusion mineralogy mainly matches that of orogenic gold elsewhere in the host terrane; however, some signatures are suggestive of zonation within an orogenic hydrothermal mineralizing system, or possibly metamorphic-hydrothermal remobilized gold associated with subsequent intrusive activity. One locality in the study area has placer gold of a distinctive Cu-rich alloy composition containing Cu sulphide inclusions, an association noted elsewhere in gold derived from alkali Cu-Au porphyries.
Consideration of Cu-bearing gold alloys worldwide indicates that previously proposed compositional correlations with deposit type are of limited value. We show that Cu contents to at least 0.8% are permissible within orogenic gold – the first time that such compositions have been clearly ascribed to orogenic mineralization. The result is particularly important considering on-going exploration in northern Canada which employs gold grain analysis to help define exploration targets.
Seismic data conditioning and neural network-based attribute selection for enhanced fault detection
Authors: Chehrazi A. , Rahimpour-Bonab H. , Rezaee M. R. 
Published: April 2013

In this study of the Dorood oil field, offshore Iran, 3D seismic data were utilized to identify a complex fault pattern in the highly faulted and fractured Fahliyan Formation. To enhance data quality and improve attribute accuracy and detection power, a steering cube was first computed based on a sliding 3D Fourier analysis technique, using the concept of directivity. The steering cube, which contains dip and azimuth information for each trace, was utilized for calculation of dip-steered filters and attributes. We applied the dip-steered median filter to remove random noise and to enhance laterally continuous seismic events by filtering along the structural dip. Several fault identification attributes, such as dip, curvature, coherency and similarity, and a meta-attribute of a ridge enhancement filter, were extracted from dip-steered, noise-attenuated data. A supervised, fully connected multi-layer perceptron neural network was constructed to select and combine the most sensitive fault attributes. The neural network, trained at identified fault and non-fault locations, was applied to the whole seismic volume to generate a cube of fault probability.
Interpretations of major faults and fractures were integrated with geological, reservoir engineering and production data to highlight the role of these heterogeneities on dynamic reservoir properties. Faults and fractures in the Fahliyan reservoir were identified in general to have the effect of decreasing reservoir permeability. While most of the faults recognized have locally a sealing capacity effect, when the fault throws are large enough to bring into contact the Manifa and Yamama reservoirs, they act as a conduit for fluid communication and, wherever a well crosses a major fault, early water breakthrough is observable.
On the Regulation and Activation of JAK2: A Novel Hypothetical Model
Authors: Lee Tai-Sung 
Published: April 2013

Abstract
Janus kinase 2 (JAK2) is a protein tyrosine kinase central to a multitude of cellular processes. Here, a novel model of JAK2 regulation and activation is proposed. In the JAK2 dimer, instead of being auto-inhibited by its own JH2 domain, inhibition comes from the JH2 domain of the partnering JAK2 monomer. Upon ligand binding, the receptor undergoes a conformational rotation that is passed to its dimeric partner. The activation is achieved by the rotation of two JAK2 molecules, which relieves the JH1/JH2 inhibitory interface and brings two JH1 domains in proximity for the subsequent trans-phosphorylation event. This hypothetical model is consistent with most of the currently available experimental evidence and warrants further tests. Based on the proposed model, it is possible to rationalize the differential responses of JAK2 signaling involving various receptors and ligands.
Implications: The proposed model of JAK2 regulation and activation is poised to suggest potential alternative drug-discovery strategies that could impact a number of relevant diseases. Mol Cancer Res; 11(8); 811–4. ©2013 AACR.
The Acoustic Parameters of Polish Voiceless Fricatives: An Analysis of Variance
Authors: Jassem Wiktor 
Published: April 2013

Abstract
Averaged spectra of the Polish voiceless fricatives are described in terms of three central moments, and the variables are analysed using both univariate and multivariate analysis of variance. The vowel context effect is strong, but that of the (male) speaker is not. /∫/ is not distinct from /ҩ/ in this experiment, but this failure should not be a handicap in automatic speech recognition.
Molecular basis of coagulation factor V deficiency caused by the R1698W inter-domain mutation
Authors: Villoutreix Bruno , Lunghi Barbara , Livaja Ruzica , Bernardi Francesco , Dahlbäck Björn , Calzavarini Sara 
Published: April 2013

SummaryCoagulation factor V (FV) deficiency is characterised by variable bleeding phenotypes and heterogeneous mutations. To add new insights into the FV genotype-phenotype relationship, we characterised the R1698W change in the A3 domain, at the poorly investigated interface with the A2 domain. The FV R1698W mutation was responsible for a markedly reduced expression level (10% of FV-WT) and specific activity in thrombin generation (0.39). Interestingly, the FVa1698W showed rapid activity decay upon activation due to increased dissociation rate between the heavy and light chains. The importance of the size and charge of the residue at position 1698 was investigated by three additional recombinant mutants, FVR1698A, FVR1698Q, and FVR1698E. FVR1698A and FVR1698Q expression (30 and 45% of FV-WT), specific activity (both 0.57) and stability were all reduced. Noticeably, FVR1698E showed normal activity and stability despite poor expression (10% of FV-WT). These data indicate the essential role of R1698 for normal biosynthetic process and support local flexibility for positively or negatively charged residues to produce stable and functional A3-A2 domain interactions. Their experimental alteration produces a gradient of FV defects, which help to interpret the wide spectrum of phenotypes in FV-deficient patients.
Long-term treatment of deep-vein thrombosis with low-molecular-weight heparin: An update of the evidence
Authors: Townshend Grace , Hull Russell 
Published: April 2013

SummaryThis article reviews updated evidence-based knowledge on long-term treatment of deep-vein thrombosis (DVT) with low-molecular-weight heparin (LMWH) or vitamin K antagonists (VKAs). Eleven trials were identified comparing the two treatments in a broad spectrum of patients with DVT and with >100 study participants. Four comparative trials were identified in patients with cancer and DVT (in whom anticoagulation treatment is more complex and bleeding complications more frequent). In the 11 trials in broad patient populations, LMWHs were as effective as VKAs in preventing recurrent venous thromboembolism (VTE), and there were no consistent differences in the incidence of bleeding complications during long-term treatment. In patients with cancer, VTE recurrence was significantly reduced with LMWH versus VKA in two studies, while major bleeding complications did not differ between groups in any of the four trials. Current evidence-based European and American guidelines recommend LMWH over VKA for the long-term treatment of DVT in patients with cancer. LMWH and VKA are recommended over the new oral anticoagulant drugs, for which there are limited data on use in long-term treatment. Post-thrombotic syndrome (PTS), a common complication of DVT, causes considerable morbidity. Long-term use of tinzaparin reduced the risk of PTS compared with VKA in one trial, and a meta-analysis of nine studies in total demonstrated a consistently favourable effect of LMWHs versus VKA on PTS-related outcomes. Given the limited treatment options available for PTS, this suggests that LMWHs provide a useful therapeutic option in any patient particularly at risk of developing PTS.
Anticoagulation with dabigatran does not increase secondary intracerebral haemorrhage after thrombolysis in experimental cerebral ischaemia
Authors: Ploen Robert , Zorn Markus , Sun Li , Zhou Wei , Veltkamp Roland 
Published: April 2013

SummaryDabigatran etexilate (DE) has recently been introduced for stroke prevention in atrial fibrillation, but management of acute ischaemic stroke during therapy with DE is a challenge. Thrombolysis is contrain-dicated because of a presumed increased risk of intracerebral haemorrhagic complications. We studied in different ischaemia models whether DE increases secondary haemorrhage after thrombolysis. C57BL/6 mice were anticoagulated with high-dose DE or warfarin. After 2 hour (h) or 3 h transient filament MCAO, rt-PA was injected. At 24 h after MCAO, secondary haemorrhage was quantified using a macroscopic haemorrhage score and haemoglobin spectrophotometry. Post-ischaemic blood-brain-barrier (BBB) damage was assessed using Evans blue. To increase the validity of findings, the duration of anticoagulation was prolonged in mice (5 x DE over 2 days), and the effect of DE after thrombolysis was also examined in thromboembolic MCAO in rats. Pretreatment with warfarin resulted in significantly more secondary haemorrhage (mean haemorrhage score 2.6 ± 0.2) compared to non-anticoagulated animals (1.7 ± 0.3) and DE (9 mg/kg, 1.6 ± 0.3) in 2 h ischaemia. Also after a 3 h period of ischaemia, haemorrhage was more severe in animals anticoagulated with warfarin compared to 9 mg/kg DE and non-anticoagulated control. Prolonged or enteral dabigatran pretreatment led to identical results. Also, thrombolysis after thromboembolic MCAO in rats did not induce more severe bleeding in DE-treated animals. Mice pretreated with warfarin had higher BBB permeability and increased activation of matrix-metalloproteinase 9. In conclusion, DE does not increase the risk of secondary haemorrhage after thrombolysis in various rodent models of ischaemia and reperfusion. The implications of this finding for stroke patients have to be determined in the clinical setting.
Cytochrome P450 2B6 and 2C9 genotype polymorphism – a possible cause of prasugrel low responsiveness
Authors: Franken Cora , Kaiser Andreas , Krüger Jan , Overbeck Kristina , Mügge Andreas , Neubauer Horst 
Published: April 2013

SummaryThe cytochrome P450 (CYP) isoenzymes are essential for the metabolic activation of the prodrug prasugrel. Little is known about the impact of polymorphism of these isoenzymes on the prevalence of prasugrel low responsiveness (PLR) in patients with coronary artery disease. We investigated the frequency of PLR and the question whether PLR is associated with decreased/non-function polymorphisms of the CYP isoenzymes (2C9*2, 2C9*3, 2C19*2, 2C19*3, and 2B6*6). Our study included 355 patients who underwent percutaneous coronary stenting. The patients were initially treated with either prasugrel (n=90; 60/10 mg: loading/daily maintenance dose) or 600/75 mg clopidogrel hydrogensulfate (n=265) in combination with 500/100 mg acetylsalicylic acid (ASA). Platelet function was tested by impedance aggregometry 48 hours after taking the loading dose. Prasugrel achieved on the average significantly higher levels of platelet inhibition as compared to clopidogrel (mean 27.3 U vs 41.2 U). The frequencies of low response for prasugrel, clopidogrel and ASA were 9.8%, 35.1% and 14.9%, respectively. We identified only body mass index to be associated with PLR. PLR was not caused by a loss of ADP P2Y12-receptor function. Half of the patients with PLR were carriers of the reducedfunction allele CYP2B6*6, and 41.7% had the genetic variant CYP2C9*2. The allele CYP2C9*3 was detected in three patients with PLR (25%) and two patients with PLR (16.7%) carried the gene variant CYP2C19*2. In conclusion, the rate of low responders was significantly lower among patients treated with prasugrel than with clopidogrel. PLR are more often carriers of CYP2C9*2 (50% in PLR) than when compared to the prevalence described in literature. Also, there is a trend to an increased frequency of CYP2B6*6 in PLR. In conclusion, CYP2B6 and CYP2C9 polymorphisms seem to be associated with prasugrel low-response.