bluuebunny/crossref_metadata_2025_split huggingface dataset:
Natural Reassortants of Potentially Zoonotic Avian Influenza Viruses H5N1 and H9N2 from Egypt Display Distinct Pathogenic Phenotypes in Experimentally Infected Chickens and Ferrets
Authors: Naguib Mahmoud M. , Ulrich Reiner , Kasbohm Elisa , Eng Christine L. P. , Hoffmann Donata , Grund Christian , Beer Martin , Harder Timm C. 
Published: September 2017

ABSTRACT

The cocirculation of zoonotic highly pathogenic avian influenza virus (HPAIV) of subtype H5N1 and avian influenza virus (AIV) of subtype H9N2 among poultry in Egypt for at least 6 years should render that country a hypothetical hot spot for the emergence of reassortant, phenotypically altered viruses, yet no reassortants have been detected in Egypt. The present investigations proved that reassortants of the Egyptian H5N1 clade 2.2.1.2 virus and H9N2 virus of the G1-B lineage can be generated by coamplification in embryonated chicken eggs. Reassortants were restricted to the H5N1 subtype and acquired between two and all six of the internal segments of the H9N2 virus. Five selected plaque-purified reassortant clones expressed a broad phenotypic spectrum both
in vitro
and
in vivo
. Two groups of reassortants were characterized to have retarded growth characteristics
in vitro
compared to the H5N1 parent virus. One clone provoked reduced mortality in inoculated chickens, although the characteristics of a highly pathogenic phenotype were retained. Enhanced zoonotic properties were not predicted for any of these clones, and this prediction was confirmed by ferret inoculation experiments: neither the H5N1 parent virus nor two selected clones induced severe clinical symptoms or were transmitted to sentinel ferrets by contact. While the emergence of reassortants of Egyptian HPAIV of subtype H5N1 with internal gene segments of cocirculating H9N2 viruses is possible in principle, the spread of such viruses is expected to be governed by their fitness to outcompete the parental viruses in the field. The eventual spread of attenuated phenotypes, however, would negatively impact syndrome surveillance on poultry farms and might foster enzootic virus circulation.

IMPORTANCE
Despite almost 6 years of the continuous cocirculation of highly pathogenic avian influenza virus H5N1 and avian influenza virus H9N2 in poultry in Egypt, no reassortants of the two subtypes have been reported. Here, the principal compatibility of the two subtypes is shown by forcing the reassortment between copassaged H5N1 und H9N2 viruses in embryonated chicken eggs. The resulting reassortant viruses displayed a wide range of pathogenicity including attenuated phenotypes in chickens, but did not show enhanced zoonotic propensities in the ferret model.
Protective Humoral Immunity in the Central Nervous System Requires Peripheral CD19-Dependent Germinal Center Formation following Coronavirus Encephalomyelitis
Authors: Atkinson Jeffrey R. , Bergmann Cornelia C. 
Published: September 2017

ABSTRACTB cell subsets with phenotypes characteristic of naive, non-isotype-switched, memory (Bmem) cells and antibody-secreting cells (ASC) accumulate in various models of central nervous system (CNS) inflammation, including viral encephalomyelitis. During neurotropic coronavirus JHMV infection, infiltration of protective ASC occurs after T cell-mediated viral control and is preceded by accumulation of non-isotype-switched IgD+and IgM+B cells. However, the contribution of peripheral activation events in cervical lymph nodes (CLN) to driving humoral immune responses in the infected CNS is poorly defined. CD19, a signaling component of the B cell receptor complex, is one of multiple regulators driving B cell differentiation and germinal center (GC) formation by lowering the threshold of antigen-driven activation. JHMV-infected CD19−/−mice were thus used to determine how CD19 affects CNS recruitment of B cell subsets. Early polyclonal ASC expansion, GC formation, and virus-specific ASC were all significantly impaired in CLN of CD19−/−mice compared to wild-type (WT) mice, consistent with lower and unsustained virus-specific serum antibody (Ab). ASC were also significantly reduced in the CNS, resulting in increased infectious virus during persistence. Nevertheless, CD19 deficiency did not affect early CNS IgD+B cell accumulation. The results support the notion that CD19-independent factors drive early B cell mobilization and recruitment to the infected CNS, while delayed accumulation of virus-specific, isotype-switched ASC requires CD19-dependent GC formation in CLN. CD19 is thus essential for both sustained serum Ab and protective local Ab within the CNS following JHMV encephalomyelitis.IMPORTANCECD19 activation is known to promote GC formation and to sustain serum Ab responses following antigen immunization and viral infections. However, the contribution of CD19 in the context of CNS infections has not been evaluated. This study demonstrates that antiviral protective ASC in the CNS are dependent on CD19 activation and peripheral GC formation, while accumulation of early-recruited IgD+B cells is CD19 independent. This indicates that IgD+B cells commonly found early in the CNS do not give rise to local ASC differentiation and that only antigen-primed, peripheral GC-derived ASC infiltrate the CNS, thereby limiting potentially harmful nonspecific Ab secretion. Expanding our understanding of activation signals driving CNS migration of distinct B cell subsets during neuroinflammatory insults is critical for preventing and managing acute encephalitic infections, as well as preempting reactivation of persistent viruses during immune-suppressive therapies targeting B cells in multiple sclerosis (MS), such as rituximab and ocrelizumab.
Vertical Transmission of Hepatitis C Virus: Variable Transmission Bottleneck and Evidence of Midgestation
In Utero
Infection
Authors: Fauteux-Daniel Sébastien , Larouche Ariane , Calderon Virginie , Boulais Jonathan , Béland Chanel , Ransy Doris G. , Boucher Marc , Lamarre Valérie , Lapointe Normand , Boucoiran Isabelle , Le Campion Armelle , Soudeyns Hugo 
Published: September 2017

ABSTRACT
Hepatitis C virus (HCV) can be transmitted from mother to child during pregnancy and childbirth. However, the timing and precise biological mechanisms that are involved in this process are incompletely understood, as are the determinants that influence transmission of particular HCV variants. Here we report results of a longitudinal assessment of HCV quasispecies diversity and composition in 5 cases of vertical HCV transmission, including 3 women coinfected with human immunodeficiency virus type 1 (HIV-1). The population structure of HCV variant spectra based on E2 envelope gene sequences (nucleotide positions 1491 to 1787), including hypervariable regions 1 and 2, was characterized using next-generation sequencing and median-joining network analysis. Compatible with a loose transmission bottleneck, larger numbers of shared HCV variants were observed in the presence of maternal coinfection. Coalescent Bayesian Markov chain Monte Carlo simulations revealed median times of transmission between 24.9 weeks and 36.1 weeks of gestation, with some confidence intervals ranging into the 1st trimester, considerably earlier than previously thought. Using recombinant autologous HCV pseudoparticles, differences were uncovered in HCV-specific antibody responses between coinfected mothers and mothers infected with HCV alone, in whom generalized absence of neutralization was observed. Finally, shifts in HCV quasispecies composition were seen in children around 1 year of age, compatible with the disappearance of passively transferred maternal immunoglobulins and/or the development of HCV-specific humoral immunity. Taken together, these results provide insights into the timing, dynamics, and biologic mechanisms involved in vertical HCV transmission and inform preventative strategies.

IMPORTANCE
Although it is well established that hepatitis C virus (HCV) can be transmitted from mother to child, the manner and the moment at which transmission operates have been the subject of conjecture. By carrying out a detailed examination of viral sequences, we showed that transmission could take place comparatively early in pregnancy. In addition, we showed that when the mother also carried human immunodeficiency virus type 1 (HIV-1), many more HCV variants were shared between her and her child, suggesting that the mechanism and/or the route of transmission of HCV differed in the presence of coinfection with HIV-1. These results could explain why cesarean section is ineffective in preventing vertical HCV transmission and guide the development of interventions to avert pediatric HCV infection.
Conformational Changes in the 5′ End of the HIV-1 Genome Dependent on the Debranching Enzyme DBR1 during Early Stages of Infection
Authors: Galvis Alvaro E. , Fisher Hugh E. , Fan Hung , Camerini David 
Published: September 2017

ABSTRACT

Previous studies in our laboratory showed that the RNA debranching enzyme (DBR1) is not required for early steps in HIV cDNA formation but is necessary for synthesis of intermediate and late cDNA products. To further characterize this effect, we evaluated the topology of the 5′ end of the HIV-1 RNA genome during early infection with and without inhibition of DBR1 synthesis. Cells were transfected with DBR1 short hairpin RNA (shRNA) followed 48 h later by infection with an HIV-1-derived vector containing an RNase H-deficient reverse transcriptase (RT). RNA was isolated at several times postinfection and treated with various RNA-modifying enzymes prior to rapid amplification of 5′ cDNA ends (5′ RACE) for HIV-1 RNA and quantitative reverse transcriptase PCR (qRT-PCR). In infected cells, DBR1 knockdown inhibited detection of free HIV-1 RNA 5′ ends at all time points. The difference in detection of free HIV-1 RNA 5′ ends in infected DBR1 knockdown versus control cells was eliminated by
in vitro
incubation of infected cell RNAs with yeast or human DBR1 enzyme prior to 5′ RACE and qRT-PCR. This was dependent on the 2′-5′ phosphatase activity of DBR1, since it did not occur when we used the catalytically inactive DBR1(N85A) mutant. Finally, HIV-1 RNA from infected DBR1 knockdown cells was resistant to RNase R that degrades linear RNAs but not RNAs in circular or lariat-like conformations. These results provide evidence for formation of a lariat-like structure involving the 5′ end of HIV-1 RNA during an early step in infection and the involvement of DBR1 in resolving it.

IMPORTANCE
Our findings support a new view of the early steps in HIV genome replication. We show that the HIV genomic RNA is rapidly decapped and forms a lariat-like structure after entering a cell. The lariat-like structure is subsequently resolved by the cellular enzyme DBR1, leaving a 5′ phosphate. This pathway is similar to the formation and resolution of pre-mRNA intron lariats and therefore suggests that similar mechanisms may be used by HIV. Our work therefore opens a new area of investigation in HIV replication and may ultimately uncover new targets for inhibiting HIV replication and for preventing the development of AIDS.
Clinical and cost-effectiveness of the Lightning Process in addition to specialist medical care for paediatric chronic fatigue syndrome: randomised controlled trial
Authors: Crawley Esther M , Gaunt Daisy M , Garfield Kirsty , Hollingworth William , Sterne Jonathan A C , Beasant Lucy , Collin Simon M , Mills Nicola , Montgomery Alan A 
Published: September 2017

ObjectiveInvestigate the effectiveness and cost-effectiveness of the Lightning Process (LP) in addition to specialist medical care (SMC) compared with SMC alone, for children with chronic fatigue syndrome/myalgic encephalitis (CFS/ME).DesignPragmatic randomised controlled open trial. Participants were randomly assigned to SMC, or SMC plus the LP (SMC+LP). Randomisation was minimised by age and gender.SettingSpecialist paediatric CFS/ME service.PatientsAged 12–18 years with mild/moderate CFS/ME.Main outcome measuresThe primary outcome was the SF-36 physical function subscale (PFS) at 6 months. Secondary outcomes included the SF-36-PFS at 3 and 12 months, and pain, anxiety, depression, school attendance and cost-effectiveness from a health service perspective at 3, 6 and 12 months.ResultsWe recruited 100 participants between September 2010 and September 2013. We tested the feasibility of running the trial with a feasibility phase (29 September 2010 to 18 September 2012). The full trial was registered in June 2012 when we had determined it was a feasible study. Of the 100 participants, 51 were randomised to SMC+LP. Data from 81 participants were analysed at 6 months. Physical function (SF-36-PFS) was better in those allocated SMC+LP (adjusted difference in means 12.5 [95% CI 4.5 to 20.5], p=0.003) and this improved further at 12 months (15.1 [95% CI 5.8 to 24.4], p=0.002). At 6 months, fatigue and anxiety were reduced and at 12 months, fatigue, anxiety, depression and school attendance had improved in the SMC+LP arm. Results were similar following multiple imputation. SMC+LP was more cost-effective in the multiple imputation data set (difference in means in net monetary benefit at 12 months £1474 [95% CI £111 to £2836], p=0.03) but not for complete cases.ConclusionThe LP is effective and is probably cost-effective when provided in addition to SMC for mild/moderately affected adolescents with CFS/ME.Trial registration numberISRCTN81456207.
Products of several commutators in a Lie nilpotent associative algebra
Authors: Deryabina Galina , Krasilnikov Alexei 
Published: September 2017

Let [Formula: see text] be a field of characteristic [Formula: see text] and let [Formula: see text] be a unital associative [Formula: see text]-algebra. Define a left-normed commutator [Formula: see text] [Formula: see text] recursively by [Formula: see text], [Formula: see text] [Formula: see text]. For [Formula: see text], let [Formula: see text] be the two-sided ideal in [Formula: see text] generated by all commutators [Formula: see text] ([Formula: see text]. Define [Formula: see text]. Let [Formula: see text] be integers such that [Formula: see text], [Formula: see text]. Let [Formula: see text] be positive integers such that [Formula: see text] of them are odd and [Formula: see text] of them are even. Let [Formula: see text]. The aim of the present note is to show that, for any positive integers [Formula: see text], in general, [Formula: see text]. It is known that if [Formula: see text] (that is, if at least one of [Formula: see text] is even), then [Formula: see text] for each [Formula: see text] so our result cannot be improved if [Formula: see text]. Let [Formula: see text]. Recently, Dangovski has proved that if [Formula: see text] are any positive integers then, in general, [Formula: see text]. Since [Formula: see text], Dangovski’s result is stronger than ours if [Formula: see text] and is weaker than ours if [Formula: see text]; if [Formula: see text], then [Formula: see text] so both results coincide. It is known that if [Formula: see text] (that is, if all [Formula: see text] are odd) then, for each [Formula: see text], [Formula: see text] so in this case Dangovski’s result cannot be improved.
Rivaroxaban for Preventing Venous Thromboembolism in High-Risk Ambulatory Patients with Cancer: Rationale and Design of the CASSINI Trial
Authors: Khorana Alok , Vadhan-Raj Saroj , Kuderer Nicole , Wun Ted , Liebman Howard , Soff Gerald , Belani Chandra , O'Reilly Eileen , McBane Robert , Eikelboom John , Damaraju C.V , Beyers Karen , Dietrich Flavia , Kakkar Ajay , Riess Hanno , Peixoto Renata , Lyman Gary 
Published: September 2017

AbstractVenous thromboembolism (VTE) is a frequent complication of cancer associated with morbidity, mortality, increased hospitalizations and higher health care costs. Cancer patients at increased risk for VTE can be identified using a validated risk assessment score, and the incidence of VTE can be reduced in high-risk settings using anticoagulation. Rivaroxaban is a potent, oral, direct, factor Xa inhibitor approved for the prevention and treatment of thromboembolic events, including VTE. CASSINI is a double-blind, randomized, parallel-group, multicentre study comparing rivaroxaban with placebo in adult ambulatory patients with various cancers who are initiating systemic cancer therapy and are at high risk of VTE (Khorana score ≥ 2). Patients with primary brain tumours or those at risk for bleeding are excluded. Approximately 700 patients will be randomized 1:1 to rivaroxaban 10 mg daily or placebo for up to 6 months if there is no evidence of VTE from compression ultrasonography (CU) during screening or from routine care imaging within 30 days prior to randomization. Mandatory CU will also be performed at weeks 8 and 16 (±7 days), and at study end (±3 days). The primary efficacy hypothesis is that anticoagulation with rivaroxaban reduces the composite of objectively confirmed symptomatic or asymptomatic, lower-extremity, proximal deep-vein thrombosis (DVT); symptomatic, upper-extremity DVT; symptomatic or incidental pulmonary embolism; and VTE-related death compared with placebo. The primary safety objective is to assess major bleeding events (Clinical trial information: NCT02555878).
Predicting Major Bleeding in Ischemic Stroke Patients With Atrial Fibrillation
Authors: Hilkens Nina A. , Algra Ale , Greving Jacoba P. 
Published: September 2017

Background and Purpose—
Performance of risk scores for major bleeding in patients with atrial fibrillation and a previous transient ischemic attack or ischemic stroke is not well established. We aimed to validate risk scores for major bleeding in patients with atrial fibrillation treated with oral anticoagulants after cerebral ischemia and explore the net benefit of oral anticoagulants among bleeding risk categories.

Methods—

We analyzed 3623 patients with a history of transient ischemic attack or stroke included in the RE-LY trial (Randomized Evaluation of Long-Term Anticoagulation Therapy). We assessed performance of HEMORR
2
HAGES (hepatic or renal disease, ethanol abuse, malignancy, older age, reduced platelet count or function, hypertension [uncontrolled], anemia, genetic factors, excessive fall risk, and stroke), Shireman, HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol concomitantly), ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation), and ORBIT scores (older age, reduced haemoglobin/haematocrit/history of anaemia, bleeding history, insufficient kidney function, and treatment with antiplatelet) with C statistics and calibration plots. Net benefit of oral anticoagulants was explored by comparing risk reduction in ischemic stroke with risk increase in major bleedings on warfarin.

Results—
During 6922 person-years of follow-up, 266 patients experienced a major bleed (3.8 per 100 person-years). C statistics ranged from 0.62 (Shireman) to 0.67 (ATRIA). Calibration was poor for ATRIA and moderate for other models. The reduction in recurrent ischemic strokes on warfarin was larger than the increase in major bleeding risk, irrespective of bleeding risk category.

Conclusions—
Performance of prediction models for major bleeding in patients with cerebral ischemia and atrial fibrillation is modest but comparable with performance in patients with only atrial fibrillation. Bleeding risk scores cannot guide treatment decisions for oral anticoagulants but may still be useful to identify modifiable risk factors for bleeding. Clinical usefulness may be best for ORBIT, which is based on a limited number of easily obtainable variables and showed reasonable performance.
An investigation of postsecondary violin instructors’ remedial pedagogy: A case study
Authors: Mio Vanessa A. 
Published: September 2017

Applied violin instructors at the postsecondary level often implement remedial pedagogy with incoming first-year students in order to address technical/musical habits or deficiencies. As students strive to alter their technique, resistance to change and low self-efficacy often result. Using a descriptive qualitative multiple case study research design, 10 postsecondary violin instructors from across North America were interviewed to gain insight into their personal perspectives and experiences implementing remedial pedagogy with first-year violin students. The interview data and external data sources were analyzed through the theoretical framework of attribution theory and teacher attribution scaffolding theory. The results indicate that many participants address correction through effective communication, based on the individual physiological/psychological wellbeing of every student, their level of self-efficacy, motivation, resistance to change, and postsecondary expectations. The pedagogical expertise and applied experiences presented in this study should inform current and future violin pedagogues about how to effectively address technical/musical deficiencies so that the wellbeing of students remains a priority throughout the remedial process.
Symptomatic duodenal perforation by inferior vena cava filter
Authors: Baptista Sincos Anna PW , Sincos Igor R , Labropoulos Nicos , Donegá Bruno C , Klepacz Andrea , Aun Ricardo 
Published: September 2017

Objectives Duodenal perforation by an inferior vena cava filter is rare and life threatening. Our objective is to find out number of occurrences and compare diagnosis and treatments. Method The reference list of Malgor’s review in 2012 was considered as well as all new articles with eligible features. Search was conducted on specific databases: MEDLINE, Web of Sciences, and Literatura Latino-Americana e do Caribe em Ciências da Saúde. Results Most of the patients presented with upper abdominal pain and the use of radiologic studies was crucial for diagnosis. The most common treatment was laparotomy with filter or strut removal plus duodenum repair. However, clinical conditions of patients must be considered and the endovascular technique with endograft deployment into inferior vena cava may be an alternative. Conclusion Duodenal perforation by an inferior vena cava filter is uncommon and in high-risk surgical patients endovascular repair must be considered.
Nurses performance in clinical ethics committees and commissions: An integrative review
Authors: de Brito Gabriela Menezes Gonçalves , de Oliveira Santa Rosa Darci 
Published: September 2017

Background: The research on nursing professionals in Clinical Ethics Committees and Nursing Ethics Commissions occurs in different parts of the world; however, little information on this subject is found in the literature. Objective: This study analyzed national and international publications in relation to the participation of nursing professionals in Clinical Ethics Committees. Research design: This was an integrative review of articles published in national and international journals between 1994 and 2016 which described the participation of nursing professionals in ethics commissions. Participants and research context: A total of 35 articles were selected. Discussion and conclusion for this article: The thematic categories were the need for time to discuss ethical issues; ethics committee to reduce the moral suffering of professionals; competencies required for participation; and barriers/difficulties and facilitators for implementation/ performance. It was concluded that professionals recognize the need for ethics committees to foster discussions. However, barriers hamper operation and fundamental competencies for participation. Communication of committee activities to professionals and educational activities may be major allies to improve the functioning of these committees.