bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Correlative Study of Splenic Parasite Score and Peripheral Blood Parasite Load Estimation by Quantitative PCR in Visceral Leishmaniasis
Authors: Sudarshan Medhavi , Singh Toolika , Chakravarty Jaya , Sundar Shyam 
Published: September 2015

ABSTRACTParasitological diagnosis of visceral leishmaniasis (VL) by splenic smear is highly sensitive, but it is associated with the risk of severe hemorrhage. In this study, the diagnosis of VL using quantitative PCR (qPCR) in peripheral blood was evaluated in 100 patients with VL. Blood parasitemia ranged from 5 to 93,688 leishmania parasite genomes/ml of blood and positively correlated with splenic score (P< 0.0001;r2= 0.58). Therefore, quantification of parasite genomes by qPCR can replace invasive procedures for diagnostic and prognostic evaluations.
Core Genome Multilocus Sequence Typing Scheme for High-Resolution Typing of Enterococcus faecium
Authors: de Been Mark , Pinholt Mette , Top Janetta , Bletz Stefan , Mellmann Alexander , van Schaik Willem , Brouwer Ellen , Rogers Malbert , Kraat Yvette , Bonten Marc , Corander Jukka , Westh Henrik , Harmsen Dag , Willems Rob J. L. 
Published: September 2015

ABSTRACT

Enterococcus faecium
, a common inhabitant of the human gut, has emerged in the last 2 decades as an important multidrug-resistant nosocomial pathogen. Since the start of the 21st century, multilocus sequence typing (MLST) has been used to study the molecular epidemiology of
E. faecium
. However, due to the use of a small number of genes, the resolution of MLST is limited. Whole-genome sequencing (WGS) now allows for high-resolution tracing of outbreaks, but current WGS-based approaches lack standardization, rendering them less suitable for interlaboratory prospective surveillance. To overcome this limitation, we developed a core genome MLST (cgMLST) scheme for
E. faecium
. cgMLST transfers genome-wide single nucleotide polymorphism (SNP) diversity into a standardized and portable allele numbering system that is far less computationally intensive than SNP-based analysis of WGS data. The
E. faecium
cgMLST scheme was built using 40 genome sequences that represented the diversity of the species. The scheme consists of 1,423 cgMLST target genes. To test the performance of the scheme, we performed WGS analysis of 103 outbreak isolates from five different hospitals in the Netherlands, Denmark, and Germany. The cgMLST scheme performed well in distinguishing between epidemiologically related and unrelated isolates, even between those that had the same sequence type (ST), which denotes the higher discriminatory power of this cgMLST scheme over that of conventional MLST. We also show that in terms of resolution, the performance of the
E. faecium
cgMLST scheme is equivalent to that of an SNP-based approach. In conclusion, the cgMLST scheme developed in this study facilitates rapid, standardized, and high-resolution tracing of
E. faecium
outbreaks.
Rotavirus Controls Activation of the 2′-5′-Oligoadenylate Synthetase/RNase L Pathway Using at Least Two Distinct Mechanisms
Authors: Sánchez-Tacuba Liliana , Rojas Margarito , Arias Carlos F. , López Susana 
Published: September 2015

ABSTRACTThe innate immune response is the first line of defense of the host cell against a viral infection. In turn, viruses have evolved a wide variety of strategies to hide from, and to directly antagonize, the host innate immune pathways. One of these pathways is the 2′-5′-oligoadenylate synthetase (OAS)/RNase L pathway. OAS is activated by double-stranded RNA (dsRNA) to produce 2′-5′ oligoadenylates, which are the activators of RNase L; this enzyme degrades viral and cellular RNAs, restricting viral infection. It has been recently found that the carboxy-terminal domain (CTD) of rotavirus VP3 has a 2′-5′-phosphodiesterase (PDE) activity that is able to functionally substitute for the PDE activity of the mouse hepatitis virus ns2 protein. This particular phosphodiesterase cleaves the 2′-5′-phosphodiester bond of the oligoadenylates, antagonizing the OAS/RNase L pathway. However, whether this activity of VP3 is relevant during the replication cycle of rotavirus is not known. Here, we demonstrate that after rotavirus infection the OAS/RNase L complex becomes activated; however, the virus is able to control its activity using at least two distinct mechanisms. A virus-cell interaction that occurs during or before rotavirus endocytosis triggers a signal that prevents the early activation of RNase L, while later on the control is taken by the newly synthesized VP3. Cosilencing the expression of VP3 and RNase L in infected cells yields viral infectious particles at levels similar to those obtained in control infected cells, where no genes were silenced, suggesting that the capping activity of VP3 is not essential for the formation of infectious viral particles.IMPORTANCERotaviruses represent an important cause of severe gastroenteritis in the young of many animal species, including humans. In this work, we have found that the OAS/RNase L pathway is activated during rotavirus infection, but the virus uses two different strategies to prevent the deleterious effects of this innate immune response of the cell. Early during virus entry, the initial interactions of the viral particle with the cell result in the inhibition of RNase L activity during the first hours of the infection. Later on, once viral proteins are synthesized, the phosphodiesterase activity of VP3 degrades the cellular 2′-5′-oligoadenylates, which are potent activators of RNase L, preventing its activation. This work demonstrates that the OAS/RNase L pathway plays an important role during infection and that the phosphodiesterase activity of VP3 is relevant during the replication cycle of the virus.
Early Vertebrate Evolution of the Host Restriction Factor Tetherin
Authors: Heusinger Elena , Kluge Silvia F. , Kirchhoff Frank , Sauter Daniel 
Published: September 2015

ABSTRACT

Tetherin is an interferon-inducible restriction factor targeting a broad range of enveloped viruses. Its antiviral activity depends on an unusual topology comprising an N-terminal transmembrane domain (TMD) followed by an extracellular coiled-coil region and a C-terminal glycosylphosphatidylinositol (GPI) anchor. One of the two membrane anchors is inserted into assembling virions, while the other remains in the plasma membrane of the infected cell. Thus, tetherin entraps budding viruses by physically bridging viral and cellular membranes. Although tetherin restricts the release of a large variety of diverse human and animal viruses, only mammalian orthologs have been described to date. Here, we examined the evolutionary origin of this protein and demonstrate that tetherin orthologs are also found in fish, reptiles, and birds. Notably, alligator tetherin efficiently blocks the release of retroviral particles. Thus, tetherin emerged early during vertebrate evolution and acquired its antiviral activity before the mammal/reptile divergence. Although there is only limited sequence homology, all orthologs share the typical topology. Two unrelated proteins of the slime mold
Dictyostelium discoideum
also adopt a tetherin-like configuration with an N-terminal TMD and a C-terminal GPI anchor. However, these proteins showed no evidence for convergent evolution and failed to inhibit virion release. In summary, our findings demonstrate that tetherin emerged at least 450 million years ago and is more widespread than previously anticipated. The early evolution of antiviral activity together with the high topology conservation but low sequence homology suggests that restriction of virus release is the primary function of tetherin.

IMPORTANCE
The continuous arms race with viruses has driven the evolution of a variety of cell-intrinsic immunity factors that inhibit different steps of the viral replication cycle. One of these restriction factors, tetherin, inhibits the release of newly formed progeny virions from infected cells. Although tetherin targets a broad range of enveloped viruses, including retro-, filo-, herpes-, and arenaviruses, the evolutionary origin of this restriction factor and its antiviral activity remained obscure. Here, we examined diverse vertebrate genomes for genes encoding cellular proteins that share with tetherin the highly unusual combination of an N-terminal transmembrane domain and a C-terminal glycosylphosphatidylinositol anchor. We show that tetherin orthologs are found in fish, reptiles, and birds and demonstrate that alligator tetherin efficiently inhibits the release of retroviral particles. Our findings identify tetherin as an evolutionarily ancient restriction factor and provide new important insights into the continuous arms race between viruses and their hosts.
Proteus mirabilisand Urinary Tract Infections
Authors: Schaffer Jessica N. , Pearson Melanie M. 
Published: September 2015

ABSTRACTProteus mirabilisis a Gram-negative bacterium and is well known for its ability to robustly swarm across surfaces in a striking bulls’-eye pattern. Clinically, this organism is most frequently a pathogen of the urinary tract, particularly in patients undergoing long-term catheterization. This review coversP. mirabiliswith a focus on urinary tract infections (UTI), including disease models, vaccine development efforts, and clinical perspectives. Flagella-mediated motility, both swimming and swarming, is a central facet of this organism. The regulation of this complex process and its contribution to virulence is discussed, along with the type VI-secretion system-dependent intra-strain competition, which occurs during swarming.P. mirabilisuses a diverse set of virulence factors to access and colonize the host urinary tract, including urease and stone formation, fimbriae and other adhesins, iron and zinc acquisition, proteases and toxins, biofilm formation, and regulation of pathogenesis. While significant advances in this field have been made, challenges remain to combatting complicated UTI and decipheringP. mirabilispathogenesis.
Injection therapies for lateral epicondylalgia: a systematic review and Bayesian network meta-analysis
Authors: Dong Wei , Goost Hans , Lin Xiang-Bo , Burger Christof , Paul Christian , Wang Zeng-Li , Kong Fan-Lin , Welle Kristian , Jiang Zhi-Chao , Kabir Koroush 
Published: September 2015

BackgroundThere are many injection therapies for lateral epicondylalgia but there has been no previous comprehensive comparison, based on the Bayesian method.MethodsThe MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched for appropriate literature. The outcome measurement was the pain score. Direct comparisons were performed using the pairwise meta-analysis, and network meta-analysis, based on a Bayesian model, was used to calculate the results of all of the potentially possible comparisons and rank probabilities. A sensitivity analysis was performed by excluding low-quality studies. The inconsistency of the model was assessed by means of the node-splitting method. Metaregression was used to assess the relationship between the sample size and the treatment effect.ResultsAll of the injection treatments showed a trend towards better effects than placebo. Additionally, the peppering technique did not add additional benefits when combined with other treatments. No significant changes were observed by excluding low-quality studies in the sensitivity analysis. No significant inconsistencies were found according to the inconsistency analysis, and metaregression revealed that the sample size was not associated with the treatment effects.ConclusionsSome commonly used injection therapies can be considered treatment candidates for lateral epicondylalgia, such as botulinum toxin, platelet-rich plasma and autologous blood injection, but corticosteroid is not recommended. Hyaluronate injection and prolotherapy might be more effective, but their superiority must be confirmed by more research. The peppering technique is not helpful in injection therapies.
The prevalence and significance of a short QT interval in 18 825 low-risk individuals including athletes
Authors: Dhutia Harshil , Malhotra Aneil , Parpia Sameer , Gabus Vincent , Finocchiaro Gherardo , Mellor Greg , Merghani Ahmed , Millar Lynne , Narain Rajay , Sheikh Nabeel , Behr Elijah R , Papadakis Michael , Sharma Sanjay 
Published: September 2015

ObjectivesThe short QT syndrome is a cardiac channelopathy characterised by accelerated repolarisation which manifests as a short QT interval on the ECG. The definition of a short QT interval is debated, ranging from <390 to ≤320 ms, and its clinical significance in healthy young individuals is unknown. We assessed the prevalence and medium-term significance of an isolated short QT interval in a diverse young British population.MethodsBetween 2005 and 2013, 18 825 apparently healthy people aged 14–35 years underwent cardiovascular evaluation with history, physical examination and ECG. QT intervals were measured by cardiologists using 4 recommended guidelines (Seattle 2013, Heart Rhythm Society 2013, European Society of Cardiology 2010 and American Heart Association 2009).ResultsThe prevalence of a short QT interval was 0.1% (26 patients, ≤320 ms), 0.2% (44 patients, ≤330 ms), 7.9% (1478 patients, <380 ms), 15.8% (2973 patients, <390 ms). Male gender and Afro-Caribbean ethnicity had the strongest association with short QT intervals. Athletes had shorter QT intervals than non-athletes but athletic status did not predict short QT intervals. Individuals with short QT intervals ≤320 ms did not report syncope or a sinister family history, and during a follow-up period of 5.3±1.2 years, there were no deaths in this group.ConclusionsThe prevalence of a short QT interval depends on the recommended cut-off value. Even at values ≤320 ms, there was an excellent medium-term prognosis among 14 people followed. We conclude that a definition of ≤320 ms is realistic to prevent overdiagnosis and excessive investigations.
Internet-based cognitive behavioural therapy for adults with tinnitus in the UK: study protocol for a randomised controlled trial
Authors: Beukes Eldré W , Manchaiah Vinaya , Allen Peter M , Baguley David M , Andersson Gerhard 
Published: September 2015

IntroductionTinnitus is one of the most distressing hearing-related symptoms. Innovative ways of managing tinnitus distress and the related healthcare burden of treating tinnitus are required. An internet-based cognitive behavioural therapy (iCBT) intervention has been developed in Sweden to improve access to evidence-based tinnitus treatments. This study aims to determine the feasibility and effectiveness of iCBT in reducing the impact associated with tinnitus, in the UK. It, furthermore, aims to establish whether there are subgroups of tinnitus sufferers for whom this iCBT intervention may be more suitable.Methods and analysisA two-armed randomised control trial—with a 1-year follow-up design—will be used to evaluate the effectiveness of iCBT on tinnitus distress. A delayed treatment design using a weekly check-in control group will be used. 70 participants will be randomly assigned to each group by an independent researcher by using a computer-generated randomisation schedule, and after being prestratified for age and tinnitus severity. They will undergo the iCBT e-health intervention online together with audiological therapeutic support. The main outcome measure is the Tinnitus Functional Index. Process evaluation of the intervention will also be conducted. Data analysis will be in accordance with Consolidated Standards of Reporting Trials guidelines.Ethics and disseminationEthical approval has been granted. If this intervention proves effective, it may be possible that at least some tinnitus sufferers can be managed though an iCBT e-learning treatment programme. This would be cost effective and potentially will free up services for those with more severe problems that need face-to-face treatment.Trial registration numberClinicalTrials.gov;NCT02370810, date 05/03/2015.
Securing All intraVenous devices Effectively in hospitalised patients—the SAVE trial: study protocol for a multicentre randomised controlled trial
Authors: Rickard Claire M , Marsh Nicole , Webster Joan , Playford E Geoffrey , McGrail Matthew R , Larsen Emily , Keogh Samantha , McMillan David , Whitty Jennifer A , Choudhury Md Abu , Dunster Kimble R , Reynolds Heather , Marshall Andrea , Crilly Julia , Young Jeanine , Thom Ogilvie , Gowardman John , Corley Amanda , Fraser John F 
Published: September 2015

IntroductionOver 70% of all hospital admissions have a peripheral intravenous device (PIV) inserted; however, the failure rate of PIVs is unacceptably high, with up to 69% of these devices failing before treatment is complete. Failure can be due to dislodgement, phlebitis, occlusion/infiltration and/or infection. This results in interrupted medical therapy; painful phlebitis and reinsertions; increased hospital length of stay, morbidity and mortality from infections; and wasted medical/nursing time. Appropriate PIV dressing and securement may prevent many cases of PIV failure, but little comparative data exist regarding the efficacy of various PIV dressing and securement methods. This trial will investigate the clinical and cost-effectiveness of 4 methods of PIV dressing and securement in preventing PIV failure.Methods and analysisA multicentre, parallel group, superiority randomised controlled trial with 4 arms, 3 experimental groups (tissue adhesive, bordered polyurethane dressing, sutureless securement device) and 1 control (standard polyurethane dressing) is planned. There will be a 3-year recruitment of 1708 adult patients, with allocation concealment until randomisation by a centralised web-based service. The primary outcome is PIV failure which includes any of: dislodgement, occlusion/infiltration, phlebitis and infection. Secondary outcomes include: types of PIV failure, PIV dwell time, costs, device colonisation, skin colonisation, patient and staff satisfaction. Relative incidence rates of device failure per 100 devices and per 1000 device days with 95% CIs will summarise the impact of each dressing, and test differences between groups. Kaplan-Meier survival curves (with log-rank Mantel-Cox test) will compare device failure over time. p Values of <0.05 will be considered significant. Secondary end points will be compared between groups using parametric or non-parametric techniques appropriate to level of measurement.Ethics and disseminationEthical approval has been received from Queensland Health (HREC/11/QRCH/152) and Griffith University (NRS/46/11/HREC). Results will be published according to the CONSORT statement and presented at relevant conferences.Trial registration numberAustralian New Zealand Clinical Trial Registry (ACTRN); 12611000769987.
Preventing Australian football injuries with a targeted neuromuscular control exercise programme: comparative injury rates from a training intervention delivered in a clustered randomised controlled trial
Authors: Finch Caroline F , Twomey Dara M , Fortington Lauren V , Doyle Tim L A , Elliott Bruce C , Akram Muhammad , Lloyd David G 
Published: September 2015

BackgroundExercise-based training programmes are commonly used to prevent sports injuries but programme effectiveness within community men's team sport is largely unknown.ObjectiveTo present the intention-to-treat analysis of injury outcomes from a clustered randomised controlled trial in community Australian football.MethodsPlayers from 18 male, non-elite, community Australian football clubs across two states were randomly allocated to either a neuromuscular control (NMC) (intervention n=679 players) or standard-practice (control n=885 players) exercise training programme delivered as part of regular team training sessions (2× weekly for 8-week preseason and 18-week regular-season). All game-related injuries and hours of game participation were recorded. Generalised estimating equations, adjusted for clustering (club unit), were used to compute injury incidence rates (IIRs) for all injuries, lower limb injuries (LLIs) and knee injuries sustained during games. The IIRs were compared across groups with cluster-adjusted Injury Rate Ratios (IRRs).ResultsOverall, 773 game injuries were recorded. The lower limb was the most frequent body region injured, accounting for 50% of injuries overall, 96 (12%) of which were knee injuries. The NMC players had a reduced LLI rate compared with control players (IRR: 0.78 (95% CI 0.56 to 1.08), p=0.14.) The knee IIR was also reduced for NMC compared with control players (IRR: 0.50 (95% CI 0.24 to 1.05), p=0.07).ConclusionsThese intention-to-treat results indicate that positive outcomes can be achieved from targeted training programmes for reducing knee and LLI injury rates in men's community sport. While not statistically significant, reducing the knee injury rate by 50% and the LLI rate by 22% is still a clinically important outcome. Further injury reductions could be achieved with improved training attendance and participation in the programme.
Volumetric and dynamic uncertainty modelling in Block 22, offshore Trinidad and Tobago
Authors: Kimber R. N. , Curtis M. D. , Boundy F. O. , Diamond P. H. , Uwaga A. O. 
Published: September 2015

Block 22, located offshore in the North Coast Marine Area (NCMA) of Trinidad and Tobago, contains the Cassra gas accumulation discovered by the Cassra-1 and Cassra-2 wells. Both wells encountered dry, biogenic gas in early Pliocene, shoreface–shelfal sandstone reservoirs.
A best-practice modelling methodology is documented to capture a range of subsurface uncertainties for use in reservoir simulation to generate production profiles in support of pre-development project planning. Calibration of a sequence stratigraphic interpretation from seismic with core data was instrumental in generating a depositional model, within which sedimentary facies could be stochastically distributed and used to constrain the population of petrophysical properties.
Static geological uncertainties were modelled using an uncertainty workflow methodology in commercial three-dimensional (3D) geomodelling software, resulting in multiple, static model realizations and probabilistic GIIP (Gas Initially In Place) distributions for Cassra and some nearby prospects. The multi-regional model required careful selection of realizations for reservoir simulation, based on a ranking scheme that combined GIIP, GRV (gross rock volume) and net:gross (net to gross ratio), and not simply P90–P50–P10 percentiles from the global distribution.
The reservoir simulation phase included a dynamic uncertainty workflow using commercial experimental design modelling software. By including dynamic uncertainties such as horizontal/vertical permeability and well productivity in the workflow, a more objectively defined suite of production profile predictions was achieved.