bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improved Diagnosis of Infection Associated with Osteosynthesis by Use of Sonication of Fracture Fixation Implants
Authors: Yano Maysa Harumi , Klautau Giselle Burlamaqui , da Silva Cely Barreto , Nigro Stanley , Avanzi Osmar , Mercadante Marcelo Tomanink , Salles Mauro Jose Costa 
Published: September 2014

ABSTRACT

Previous studies have shown that sonication fluid cultures from removed orthopedic devices improved the microbiological diagnosis of orthopedic implant-associated infections; however, few of these investigations have applied sonication to the removed fracture fixation devices to evaluate its utility for the diagnosis of osteosynthesis-associated infection (OAI). We compared sonication fluid to conventional tissue cultures from 180 subjects with different sizes of plates and screws (
n
= 156), spinal implants (
n
= 26), and intramedullary nails (
n
= 3), of whom 125 and 55 subjects had OAI and noninfected osteosynthesis (NIO), respectively. The sensitivity for detecting OAI was 90.4% for sonication fluid culture and 56.8% for periprosthetic tissue cultures (
P
< 0.05), and the specificities were 90.9% and 96.4%, respectively. Sonication fluid culture detected more pathogens than peri-implant tissue culture (113 versus 71;
P
< 0.001), while polymicrobial infections were diagnosed by sonication fluid cultures and tissue cultures in 20.8% and 8% (
P
< 0.001), respectively. Microbiological diagnosis was achieved exclusively by sonication fluid cultures for 47 (90.4%) subjects, and among them, 18 (38.3%) had previously received antibiotics, whereas in five (9.6%) infected subjects, tissue culture was positive and the sonication fluid culture was negative. Among 39 (31.2%) OAI cases receiving antibiotics, the identification of the organisms occurred in 38.5% and 82.1% of the tissue and sonication fluid cultures, respectively (
P
< 0.049). We demonstrated that sonication fluid culture from removed osteosyntheses has the potential for improving the microbiological diagnosis of OAI.
Epididymitis Caused by Coxsackievirus A6 in Association with Hand, Foot, and Mouth Disease
Authors: Vuorinen Tytti , Österback Riikka , Kuisma Jani , Ylipalosaari Pekka 
Published: September 2014

ABSTRACT
Coxsackievirus A6 (CV-A6) caused hand, foot, and mouth disease (HFMD) with a unique manifestation of epididymitis. The patient underwent operation due to suspicion of testicular torsion. Epididymitis was diagnosed by ultrasound examination. Enterovirus was detected from epididymal fluid by PCR and typed by partial sequencing of viral protein 1 as CV-A6.
Amino Acid Changes in the Influenza A Virus PA Protein That Attenuate Avian H5N1 Viruses in Mammals
Authors: Fan Shufang , Hatta Masato , Kim Jin Hyun , Le Mai Quynh , Neumann Gabriele , Kawaoka Yoshihiro 
Published: September 2014

ABSTRACT

The influenza viral polymerase complex affects host tropism and pathogenicity. In particular, several amino acids in the PB2 polymerase subunit are essential for the efficient replication of avian influenza viruses in mammals. The PA polymerase subunit also contributes to host range and pathogenicity. Here, we report that the PA proteins of several highly pathogenic avian H5N1 viruses have attenuating properties in mammalian cells and that the attenuating phenotype is conferred by strain-specific amino acid changes. Specifically, lysine at position 185 of A/duck/Vietnam/TY165/2010 (TY165; H5N1) PA induced strongly attenuating effects
in vitro
and
in vivo
. More importantly, the introduction of the arginine residue commonly found at this position in PA significantly increased the viral polymerase activity of TY165 in mammalian cells and its virulence and pathogenicity in mice. These findings demonstrate that the PA protein plays an important role in influenza virulence and pathogenicity.

IMPORTANCE
Highly pathogenic influenza viruses of the H5N1 subtype cause severe respiratory infections in humans, which have resulted in death in nearly two-thirds of the patients with laboratory-confirmed cases. We found that the viral PA polymerase subunit of several H5N1 viruses possesses amino acid changes that attenuate virus replication in mammalian cells (yet the H5N1 viruses possessing these mutations are highly pathogenic in mice). Specifically, we found that an arginine-to-lysine substitution at position 185 of an H5N1 virus PA protein significantly affected that virus's virulence and pathogenicity in mice. The PA protein thus plays a role in the pathogenicity of highly pathogenic H5N1 influenza viruses.
Elephant Endotheliotropic Herpesviruses EEHV1A, EEHV1B, and EEHV2 from Cases of Hemorrhagic Disease Are Highly Diverged from Other Mammalian Herpesviruses and May Form a New Subfamily
Authors: Richman Laura K. , Zong Jian-Chao , Latimer Erin M. , Lock Justin , Fleischer Robert C. , Heaggans Sarah Y. , Hayward Gary S. 
Published: September 2014

ABSTRACT

A family of novel endotheliotropic herpesviruses (EEHVs) assigned to the genus
Proboscivirus
have been identified as the cause of fatal hemorrhagic disease in 70 young Asian elephants worldwide. Although EEHV cannot be grown in cell culture, we have determined a total of 378 kb of viral genomic DNA sequence directly from clinical tissue samples from six lethal cases and two survivors. Overall, the data obtained encompass 57 genes, including orthologues of 32 core genes common to all herpesviruses, 14 genes found in some other herpesviruses, plus 10 novel genes, including a single large putative transcriptional regulatory protein (ORF-L). On the basis of differences in gene content and organization plus phylogenetic analyses of conserved core proteins that have just 20% to 50% or less identity to orthologues in other herpesviruses, we propose that EEHV1A, EEHV1B, and EEHV2 could be considered a new
Deltaherpesvirinae
subfamily of mammalian herpesviruses that evolved as an intermediate branch between the
Betaherpesvirinae
and
Gammaherpesvirinae
. Unlike cytomegaloviruses, EEHV genomes encode ribonucleotide kinase B subunit (RRB), thymidine kinase (TK), and UL9-like origin binding protein (OBP) proteins and have an alphaherpesvirus-like dyad symmetry Ori-Lyt domain. They also differ from all known betaherpesviruses by having a 40-kb large-scale inversion of core gene blocks I, II, and III. EEHV1 and EEHV2 DNA differ uniformly by more than 25%, but EEHV1 clusters into two major subgroups designated EEHV1A and EEHV1B with ancient partially chimeric features. Whereas large segments are nearly identical, three nonadjacent loci totaling 15 kb diverge by between 21 and 37%. One strain of EEHV1B analyzed is interpreted to be a modern partial recombinant with EEHV1A.

IMPORTANCE
Asian elephants are an endangered species whose survival is under extreme pressure in wild range countries and whose captive breeding populations in zoos are not self-sustaining. In 1999, a novel class of herpesviruses called EEHVs was discovered. These viruses have caused a rapidly lethal hemorrhagic disease in 20% of all captive Asian elephant calves born in zoos in the United States and Europe since 1980. The disease is increasingly being recognized in Asian range countries as well. These viruses cannot be grown in cell culture, but by direct PCR DNA sequence analysis from segments totaling 15 to 30% of the genomes from blood or necropsy tissue from eight different cases, we have determined that they fall into multiple types and chimeric subtypes of a novel
Proboscivirus
genus, and we propose that they should also be classified as the first examples of a new mammalian herpesvirus subfamily named the
Deltaherpesvirinae
.
Identification of Nucleotide-Level Changes Impacting Gene Content and Genome Evolution in Orthopoxviruses
Authors: Hatcher Eneida L. , Hendrickson Robert Curtis , Lefkowitz Elliot J. 
Published: September 2014

ABSTRACT

Poxviruses are composed of large double-stranded DNA (dsDNA) genomes coding for several hundred genes whose variation has supported virus adaptation to a wide variety of hosts over their long evolutionary history. Comparative genomics has suggested that the
Orthopoxvirus
genus in particular has undergone reductive evolution, with the most recent common ancestor likely possessing a gene complement consisting of all genes present in any existing modern-day orthopoxvirus species, similar to the current
Cowpox virus
species. As orthopoxviruses adapt to new environments, the selection pressure on individual genes may be altered, driving sequence divergence and possible loss of function. This is evidenced by accumulation of mutations and loss of protein-coding open reading frames (ORFs) that progress from individual missense mutations to gene truncation through the introduction of early stop mutations (ESMs), gene fragmentation, and in some cases, a total loss of the ORF. In this study, we have constructed a whole-genome alignment for representative isolates from each
Orthopoxvirus
species and used it to identify the nucleotide-level changes that have led to gene content variation. By identifying the changes that have led to ESMs, we were able to determine that short indels were the major cause of gene truncations and that the genome length is inversely proportional to the number of ESMs present. We also identified the number and types of protein functional motifs still present in truncated genes to assess their functional significance.

IMPORTANCE
This work contributes to our understanding of reductive evolution in poxviruses by identifying genomic remnants such as single nucleotide polymorphisms (SNPs) and indels left behind by evolutionary processes. Our comprehensive analysis of the genomic changes leading to gene truncation and fragmentation was able to detect some of the remnants of these evolutionary processes still present in orthopoxvirus genomes and suggests that these viruses are under continual adaptation due to changes in their environment. These results further our understanding of the evolutionary mechanisms that drive virus variation, allowing orthopoxviruses to adapt to particular environmental niches. Understanding the evolutionary history of these virus pathogens may help predict their future evolutionary potential.
DDX3 DEAD-Box RNA Helicase Is a Host Factor That Restricts Hepatitis B Virus Replication at the Transcriptional Level
Authors: Ko Chunkyu , Lee Sooyoung , Windisch Marc P. , Ryu Wang-Shick 
Published: September 2014

ABSTRACT
DDX3 is a member of the DEAD-box RNA helicase family, involved in mRNA metabolism, including transcription, splicing, and translation. We previously identified DDX3 as a hepatitis B virus (HBV) polymerase (Pol) binding protein, and by using a transient transfection, we found that DDX3 inhibits HBV replication at the posttranscriptional level, perhaps following encapsidation. To determine the exact mechanism of the inhibition, we here employed a diverse HBV experimental system. Inconsistently, we found that DDX3-mediated inhibition occurs at the level of transcription. By using tetracycline-inducible HBV-producing cells, we observed that lentivirus-mediated DDX3 expression led to a reduced level of HBV RNAs. Importantly, knockdown of DDX3 by short hairpin RNA resulted in augmentation of HBV RNAs in two distinct HBV replication systems: (i) tetracycline-inducible HBV-producing cells and (ii) constitutive HBV-producing HepG2.2.15 cells. Moreover, DDX3 knockdown in HBV-susceptible HepG2-NTCP cells, where covalently closed circular DNA (cccDNA) serves as the template for viral transcription, resulted in increased HBV RNAs, validating that transcription regulation by DDX3 occurs on a physiological template. Overall, our results demonstrate that DDX3 represents an intrinsic host antiviral factor that restricts HBV transcription.

IMPORTANCE
Upon entry into host cells, viruses encounter host factors that restrict viral infection. During evolution, viruses have acquired the ability to subvert cellular factors that adversely affect their replication. Such host factors include TRIM5α and APOBEC3G, which were discovered in retroviruses. The discovery of host restriction factors provided deeper insight into the innate immune response and viral pathogenesis, leading to better understanding of host-virus interactions. In contrast to the case with retroviruses, little is known about host factors that restrict hepatitis B virus (HBV), a virus distantly related to retroviruses. DDX3 DEAD box RNA helicase is best characterized as an RNA helicase involved in RNA metabolism, such as RNA processing and translation. Here, we show that DDX3 inhibits HBV infection at the level of viral transcription.
Drift of the HIV-1 Envelope Glycoprotein gp120 toward Increased Neutralization Resistance over the Course of the Epidemic: a Comprehensive Study Using the Most Potent and Broadly Neutralizing Monoclonal Antibodies
Authors: Bouvin-Pley M. , Morgand M. , Meyer L. , Goujard C. , Moreau A. , Mouquet H. , Nussenzweig M. , Pace C. , Ho D. , Bjorkman P. J. , Baty D. , Chames P. , Pancera M. , Kwong P. D. , Poignard P. , Barin F. , Braibant M. 
Published: September 2014

ABSTRACT
Extending our previous analyses to the most recently described monoclonal broadly neutralizing antibodies (bNAbs), we confirmed a drift of HIV-1 clade B variants over 2 decades toward higher resistance to bNAbs targeting almost all the identified gp120-neutralizing epitopes. In contrast, the sensitivity to bNAbs targeting the gp41 membrane-proximal external region remained stable, suggesting a selective pressure on gp120 preferentially. Despite this evolution, selected combinations of bNAbs remain capable of neutralizing efficiently most of the circulating variants.
The Conserved Disulfide Bond within Domain II of Epstein-Barr Virus gH Has Divergent Roles in Membrane Fusion with Epithelial Cells and B Cells
Authors: Möhl Britta S. , Sathiyamoorthy Karthik , Jardetzky Theodore S. , Longnecker Richard 
Published: September 2014

ABSTRACT
Epstein-Barr virus (EBV) infects target cells via fusion with cellular membranes. For entry into epithelial cells, EBV requires the herpesvirus conserved core fusion machinery, composed of glycoprotein B (gB) and gH/gL. In contrast, for B cell fusion it requires gB and gH/gL with gp42 serving as a cell tropism switch. The available crystal structures for gH/gL allow the targeted analysis of structural determinants of gH to identify functional regions critical for membrane fusion. Domain II of EBV gH contains two disulfide bonds (DBs). The first is unique for EBV and closely related gammaherpesviruses. The second is conserved across the beta- and gammaherpesviruses and is positioned to stabilize a putative syntaxin-like bundle motif. To analyze the role of these DBs in membrane fusion, gH was mutated by amino acid substitution of the DB cysteines. Mutation of the EBV-specific DB resulted in diminished gH/gL cell surface expression that correlated with diminished B cell and epithelial cell fusion. In contrast, mutation of the conserved DB resulted in wild-type-like B cell fusion, whereas epithelial cell fusion was greatly reduced. The gH mutants bound well to gp42 but had diminished binding to epithelial cells. Tyrosine 336, located adjacent to cysteine 335 of the conserved DB, also was found to be important for DB stabilization and gH/gL function. We conclude that the conserved DB has a cell type-specific function, since it is important for the binding of gH to epithelial cells initiating epithelial cell fusion but not for fusion with B cells and gp42 binding.

IMPORTANCE
EBV predominantly infects epithelial and B cells in humans, which can result in EBV-associated cancers, such as Burkitt and Hodgkin lymphoma, as well as nasopharyngeal carcinoma. EBV is also associated with a variety of lymphoproliferative disorders, typically of B cell origin, observed in immunosuppressed individuals, such as posttransplant or HIV/AIDS patients. The gH/gL complex plays an essential but still poorly characterized role as an important determinant for EBV cell tropism. In the current studies, we found that mutants in the DB C278/C335 and the neighboring tyrosine 336 have cell type-specific functional deficits with selective decreases in epithelial cell, but not B cell, binding and fusion. The present study brings new insights into the gH function as a determinant for epithelial cell tropism during herpesvirus-induced membrane fusion and highlights a specific gH motif required for epithelial cell fusion.
Duration and breaks in sedentary behaviour: accelerometer data from 1566 community-dwelling older men (British Regional Heart Study)
Authors: Jefferis Barbara J , Sartini Claudio , Shiroma Eric , Whincup Peter H , Wannamethee S Goya , Lee I-Min 
Published: September 2014

BackgroundSedentary behaviours are increasingly recognised as raising the risk of cardiovascular disease events, diabetes and mortality, independently of physical activity levels. However, little is known about patterns of sedentary behaviour in older adults.MethodsCross-sectional study of 1566/3137 (50% response) men aged 71–91 years from a UK population-based cohort study. Men wore a GT3x accelerometer over the hip for 1 week in 2010–2011. Mean daily minutes of sedentary behaviours, percentage of day in sedentary behaviours, sedentary bouts and breaks were calculated and summarised by health and demographic characteristics.Results1403 ambulatory men aged 78.4 years (SD=4.6 years) with ≥600 min of accelerometer wear on ≥3 days had complete data on covariables. Men spent on average 618 min (SD=83), or 72% of their day in sedentary behaviours (<100 counts/min). On average, men accumulated 72 spells of sedentary behaviours per day, with 7 breaks in each sedentary hour. Men had on average 5.1 sedentary bouts of ≥30 min, which accounted for 43% of sedentary time, and 1.4 bouts of ≥60 min, which accounted for 19% of daily sedentary time. Men who were over 80 years old, obese, depressed and had multiple chronic conditions accumulated more sedentary time and spent more time in longer sedentary bouts.ConclusionsOlder men spend nearly three quarters of their day in sedentary behaviours, mostly accumulated in short bouts, although bouts lasting ≥30 min accounted for nearly half of the sedentary time each day. Men with medical risk factors were more likely to also display sedentary behaviour.
Predicting risk of hospitalisation or death: a retrospective population-based analysis
Authors: Louis Daniel Z , Robeson Mary , McAna John , Maio Vittorio , Keith Scott W , Liu Mengdan , Gonnella Joseph S , Grilli Roberto 
Published: September 2014

ObjectivesDevelop predictive models using an administrative healthcare database that provide information for Patient-Centred Medical Homes to proactively identify patients at risk of hospitalisation for conditions that may be impacted through improved patient care.DesignRetrospective healthcare utilisation analysis with multivariate logistic regression models.DataA population-based longitudinal database of residents served by the Emilia-Romagna, Italy, health service in the years 2004–2012 including demographic information and utilisation of health services by 3 726 380 people aged ≥18 years.Outcome measuresModels designed to predict risk of hospitalisation or death in 2012 for problems that are potentially avoidable were developed and evaluated using the area under the receiver operating curve C-statistic, in terms of their sensitivity, specificity and positive predictive value, and for calibration to assess performance across levels of predicted risk.ResultsAmong the 3 726 380 adult residents of Emilia-Romagna at the end of 2011, 449 163 (12.1%) were hospitalised in 2012; 4.2% were hospitalised for the selected conditions or died in 2012 (3.6% hospitalised, 1.3% died). The C-statistic for predicting 2012 outcomes was 0.856. The model was well calibrated across categories of predicted risk. For those patients in the highest predicted risk decile group, the average predicted risk was 23.9% and the actual prevalence of hospitalisation or death was 24.2%.ConclusionsWe have developed a population-based model using a longitudinal administrative database that identifies the risk of hospitalisation for residents of the Emilia-Romagna region with a level of performance as high as, or higher than, similar models. The results of this model, along with profiles of patients identified as high risk are being provided to the physicians and other healthcare professionals associated with the Patient Centred Medical Homes to aid in planning for care management and interventions that may reduce their patients’ likelihood of a preventable, high-cost hospitalisation.
The Prevention of Delirium and Complications Associated with Surgical Treatments (PODCAST) study: protocol for an international multicentre randomised controlled trial
Authors: Avidan Michael S , Fritz Bradley A , Maybrier Hannah R , Muench Maxwell R , Escallier Krisztina E , Chen Yulong , Ben Abdallah Arbi , Veselis Robert A , Hudetz Judith A , Pagel Paul S , Noh Gyujeong , Pryor Kane , Kaiser Heiko , Arya Virendra Kumar , Pong Ryan , Jacobsohn Eric , Grocott Hilary P , Choi Stephen , Downey Robert J , Inouye Sharon K , Mashour George A 
Published: September 2014

IntroductionPostoperative delirium is one of the most common complications of major surgery, affecting 10–70% of surgical patients 60 years and older. Delirium is an acute change in cognition that manifests as poor attention and illogical thinking and is associated with longer intensive care unit (ICU) and hospital stay, long-lasting cognitive deterioration and increased mortality. Ketamine has been used as an anaesthetic drug for over 50 years and has an established safety record. Recent research suggests that, in addition to preventing acute postoperative pain, a subanaesthetic dose of intraoperative ketamine could decrease the incidence of postoperative delirium as well as other neurological and psychiatric outcomes. However, these proposed benefits of ketamine have not been tested in a large clinical trial.MethodsThe Prevention of Delirium and Complications Associated with Surgical Treatments (PODCAST) study is an international, multicentre, randomised controlled trial. 600 cardiac and major non-cardiac surgery patients will be randomised to receive ketamine (0.5 or 1 mg/kg) or placebo following anaesthetic induction and prior to surgical incision. For the primary outcome, blinded observers will assess delirium on the day of surgery (postoperative day 0) and twice daily from postoperative days 1–3 using the Confusion Assessment Method or the Confusion Assessment Method for the ICU. For the secondary outcomes, blinded observers will estimate pain using the Behavioral Pain Scale or the Behavioral Pain Scale for Non-Intubated Patients and patient self-report.Ethics and disseminationThe PODCAST trial has been approved by the ethics boards of five participating institutions; approval is ongoing at other sites. Recruitment began in February 2014 and will continue until the end of 2016. Dissemination plans include presentations at scientific conferences, scientific publications, stakeholder engagement and popular media.Registration detailsThe study is registered at clinicaltrials.gov,NCT01690988(last updated March 2014). The PODCAST trial is being conducted under the auspices of the Neurological Outcomes Network for Surgery (NEURONS).Trial registration numberNCT01690988 (last updated December 2013).