bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vaccinia Virus C9 Ankyrin Repeat/F-Box Protein Is a Newly Identified Antagonist of the Type I Interferon-Induced Antiviral State
Authors: Liu Ruikang , Moss Bernard 
Published: February 2018

ABSTRACTType I interferons (IFNs) induce expression of more than 300 cellular genes that provide protection against viruses and other pathogens. For survival, viruses evolved defenses to prevent the IFN response or counteract the IFN-induced antiviral state. However, because viruses and cells coevolved, the dynamic relationship between virus and host is difficult to discern. In the present study, we demonstrated that vaccinia virus with a large deletion near the left end of the genome had a diminished ability to replicate in cells that had been pretreated with beta interferon (IFN-β), suggesting that one or more of the missing 17 open reading frames (ORFs) encode an antagonist of the IFN-induced antiviral state. By systematically deleting groups of ORFs and then individual ORFs, the C9L gene was shown to be required for IFN resistance. Replication of the C9L deletion mutant (vΔC9) was impaired in human cells that had been pretreated with IFN-β. Expression of viral early genes occurred, but subsequent events, including genome uncoating, genome replication, and postreplicative gene expression, were inhibited. Expression of the C9 protein occurred prior to genome replication, consistent with an early role in counteracting the IFN-induced antiviral state. C9 contains six ankyrin repeat motifs and a near C-terminal F-box. Mass spectrometry and immunoblotting identified host proteins that copurified with a functional epitope-tagged C9. The most abundant proteins were components of the SCF (CUL1, SKP1, F-box) and signalosome/deneddylation complexes, which interact with each other, suggesting a possible role in proteolysis of one or more interferon-induced proteins.IMPORTANCEPoxviruses comprise a family of large DNA viruses that replicate in the cytoplasm of vertebrate and insect hosts and cause human and zoonotic diseases. In most cases the primary infection is moderated by innate immune defenses. Vertebrates, including fish, amphibians, reptiles, birds, and mammals, all produce type I interferon homologs. In humans, interferon stimulates the synthesis of more than 300 proteins thought to have roles in host defense. Conversely, viruses have evolved means to thwart the host defenses. We are attempting to deconstruct the established virus-host relationship in order to better understand the molecular mechanisms involved. In the present study, we identified a vaccinia virus gene that prevents interferon-mediated inhibition of very early stages of viral replication and is conserved in orthopoxviruses. The viral protein was shown to interact with host proteins involved in proteolysis, suggesting that vaccinia virus may subvert the cellular apparatus for its own defense.
Maraviroc Is Associated with Latent HIV-1 Reactivation through NF-κB Activation in Resting CD4+T Cells from HIV-Infected Individuals on Suppressive Antiretroviral Therapy
Authors: Madrid-Elena Nadia , García-Bermejo María Laura , Serrano-Villar Sergio , Díaz-de Santiago Alberto , Sastre Beatriz , Gutiérrez Carolina , Dronda Fernando , Coronel Díaz María , Domínguez Ester , López-Huertas María Rosa , Hernández-Novoa Beatriz , Moreno Santiago 
Published: February 2018

ABSTRACTMaraviroc is a CCR5 antagonist used in the treatment of HIV-1 infection. We and others have suggested that maraviroc could reactivate latent HIV-1. To test the latency-reversing potential of maraviroc and the mechanisms involved, we performed a phase II, single-center, open-label study in which maraviroc was administered for 10 days to 20 HIV-1-infected individuals on suppressive antiretroviral therapy (EudraCT registration no. 2012-003215-66). All patients completed full maraviroc dosing and follow-up. The primary endpoint was to study whether maraviroc may reactivate HIV-1 latency, eliciting signaling pathways involved in the viral reactivation. An increase in HIV-1 transcription in resting CD4+T cells, estimated by levels of HIV-1 unspliced RNA, was observed. Moreover, activation of the NF-κB transcription factor was observed in these cells. To elucidate the mechanism of NF-κB activation by maraviroc, we have evaluated in HeLa P4 C5 cells, which stably express CCR5, whether maraviroc could be acting as a partial CCR5 agonist, with no other mechanisms or pathways involved. Our results show that maraviroc can induce NF-κB activity and that NF-κB targets gene expression by CCR5 binding, since the use of TAK779, a CCR5 inhibitor, blocked NF-κB activation and functionality. Taking the results together, we show that maraviroc may have a role in the activation of latent virus transcription through the activation of NF-κB as a result of binding CCR5. Our results strongly support a novel use of maraviroc as a potential latency reversal agent in HIV-1-infected patients.IMPORTANCEHIV-1 persistence in a small pool of long-lived latently infected resting CD4+T cells is a major barrier to viral eradication in HIV-1-infected patients on antiretroviral therapy. A potential strategy to cure HIV-1-infection is the use of latency-reversing agents to eliminate the reservoirs established in resting CD4+T cells. As no drug has been shown to be completely effective so far, the search for new drugs and combinations remains a priority for HIV cure. We examined the ability of maraviroc, a CCR5 antagonist used as an antiretroviral drug, to activate latent HIV-1 in infected individuals on antiretroviral therapy. The study showed that maraviroc can activate NF-κB and, subsequently, induce latent HIV-1-transcription in resting CD4+T cells from HIV-1-infected individuals on suppressive antiretroviral therapy. Additional interventions will be needed to eliminate latent HIV-1 infection. Our results suggest that maraviroc may be a new latency-reversing agent to interfere with HIV-1 persistence during antiretroviral therapy.
A Functional Link between RNA Replication and Virion Assembly in the Potyvirus
Plum Pox Virus
Authors: Gallo Araiz , Valli Adrian , Calvo María , García Juan Antonio 
Published: February 2018

ABSTRACT

Accurate assembly of viral particles in the potyvirus
Plum pox virus
(PPV) has been shown to depend on the contribution of the multifunctional viral protein HCPro. In this study, we show that other viral factors, in addition to the capsid protein (CP) and HCPro, are necessary for the formation of stable PPV virions. The CP produced in
Nicotiana benthamiana
leaves from a subviral RNA termed LONG, which expresses a truncated polyprotein that lacks P1 and HCPro, together with HCPro supplied
in trans
, was assembled into virus-like particles and remained stable after
in vitro
incubation. In contrast, deletions in multiple regions of the LONG coding sequence prevented the CP stabilization mediated by HCPro. In particular, we demonstrated that the first 178 amino acids of P3, but not a specific nucleotide sequence coding for them, are required for CP stability and proper assembly of PPV particles. Using a sequential coagroinfiltration assay, we observed that the subviral LONG RNA replicates and locally spreads in
N. benthamiana
leaves expressing an RNA silencing suppressor. The analysis of the effect of both point and deletion mutations affecting RNA replication in LONG and full-length PPV demonstrated that this process is essential for the assembly of stable viral particles. Interestingly, in spite of this requirement, the CP produced by a nonreplicating viral RNA can be stably assembled into virions as long as it is coexpressed with a replication-proficient RNA. Altogether, these results highlight the importance of coupling encapsidation to other viral processes to secure a successful infection.

IMPORTANCE
Viruses of the family
Potyviridae
are among the most dangerous threats for basically every important crop, and such socioeconomical relevance has made them a subject of many research studies. In spite of this, very little is currently known about proteins and processes controlling viral genome encapsidation by the coat protein. In the case of
Plum pox virus
(genus
Potyvirus
), for instance, we have previously shown that the multitasking viral factor HCPro plays a role in the production of stable virions. Here, by using this potyvirus as a model, we move further to show that additional factors are also necessary for the efficient production of potyviral particles. More importantly, a comprehensive screening for such factors led us to the identification of a functional link between virus replication and packaging, unraveling a previously unknown connection of these two key events of the potyviral infection cycle.
Incidence and determinants of tuberculosis infection among adult patients with HIV attending HIV care in north-east Ethiopia: a retrospective cohort study
Authors: Ahmed Ausman , Mekonnen Desalew , Shiferaw Atsede M , Belayneh Fanuel , Yenit Melaku K 
Published: February 2018

ObjectiveThis study assessed the incidence of tuberculosis (TB) and its predictors among adults living with HIV/AIDS in government health facilities in north-east Ethiopia.SettingA 5-year retrospective cohort study was conducted from May to June 2015 on 451 adult HIV/AIDS-infected individuals who enrolled in the HIV care clinics of government health facilities in north-east Ethiopia.ParticipantsA total of 451 HIV-infected adults who newly enrolled in the adult HIV care clinic from 1 July 2010 with complete information were followed until May 2015.Primary outcome measureThe primary outcome was the proportion of patients diagnosed with TB or the TB incidence rate.Secondary outcome measureThe incidence of TB was investigated in relation to years of follow-up.ResultsA total of 451 charts with complete information were followed for 1377.41 person-years (PY) of observation. The overall incidence density of TB was 8.6 per 100 PYof observation. Previous TB disease (adjusted HR (AHR) 3.65, 95% CI 1.97 to 6.73), being bedridden (AHR 5.45, 95% CI 1.16 to 25.49), being underweight (body mass index (BMI) <18.5 kg/m2) (AHR 2.53, 95 % CI 1.27 to 5.05), taking isoniazid preventive therapy (IPT) (AHR 0.14, 95% CI 0.05 to 0.39), haemoglobin below 11 g/dL (AHR 2.31, 95% CI 1.35 to 3.93), and being in WHO clinical stages III and IV (AHR 2.84, 95% CI 1.11 to 7.27; AHR 3.07, 95% CI 1.08 to 8.75, respectively) were significant for the incidence of TB.ConclusionThe incidence of TB among adults living with HIV/AIDS in the first 3 years of follow-up was higher compared with that of subsequent years. Previous TB disease, no IPT, low BMI and haemoglobin level, advanced WHO clinical stage, and bedridden condition were the determinants of the incidence of TB. Therefore, addressing the significant predictors and improving TB/HIV collaborative activities should be strengthened in the study setting.
Correlates of intensity-specific physical activity in children aged 9–11 years: a multilevel analysis of UK data from the International Study of Childhood Obesity, Lifestyle and the Environment
Authors: Wilkie Hannah J , Standage Martyn , Gillison Fiona B , Cumming Sean P , Katzmarzyk Peter T 
Published: February 2018

ObjectivesPhysical activity (PA) can provide numerous physical and psychological health gains, yet a low proportion of children in England are sufficiently active to accrue benefit. Analysing the correlates of PA from a socioecological perspective may help to identify factors that promote versus discourage PA. The purpose of the present study was to: (1) assess the relationships between a wide range of potential correlates and intensity-specific PA and (2) explore which correlates are associated with meeting government PA guidelines.Design, setting and participantsCross-sectional study on children aged 9–11 years from the South West of England (n=425; 183 males).Outcome measuresA mixture of self-reported and objective measures (eg, body mass index (BMI), accelerometer-derived PA, self-reported sport participation, etc) were collected from child participants, parents and school teachers. After adjusting for covariates (ie, age, sex and accelerometer wear time), multilevel modelling techniques were employed to examine the relationships between potential correlates and light-intensity, moderate-intensity and vigorous-intensity PA, as measured with an ActiGraph GT3X+ accelerometer. Generalised linear mixed modelling was used to analyse the correlates associated with government-recommended levels of PA.ResultsComputer use shared a negative association whereas parent support for PA showed a positive relationship with light-intensity PA. In terms of moderate-intensity PA, computer use and BMI z-score shared a negative association whereas positive relationships were found for sport participation, active transport and for outdoor time after school. Children at schools with 25%–49% of pupils attending school sport/PA clubs did more moderate-intensity PA than those attending schools with lower participation rates. For vigorous-intensity PA, a negative relationship was observed for BMI z-score, and positive associations for self-efficacy, active transport, parent support and the presence of crossing guards on routes to school. Correlates associated with meeting the PA guidelines were BMI z-score (negative), sport participation, active transport and outdoor time after school (all positive).ConclusionResults demonstrate that factors pertaining to the individual, home and school environment may play an important role in understanding the correlates of differing PA intensities in children.Trial registration numberNCT01722500.
Portuguese version of a stress and well-being evaluation tool (ASSET)at the workplace: validation of the psychometric properties
Authors: Heitor dos Santos Maria João , Moreira Sérgio , Carreiras Joana , Cooper Cary , Smeed Matthew , Reis Maria de Fátima , Pereira Miguel José 
Published: February 2018

ObjectiveThe main objective of this work was to translate the English version of ASSET (A Shortened Stress Evaluation Tool) into the Portuguese version and to validate its psychometric properties. Additionally, this work tested the convergent validity of the instrument.MethodsThe translation and retroversion were conducted by experts and submitted to the authors for approval. Within an observational, cross-sectional study, regarding mental health at the workplace, ASSET together with other scales was applied to a sample of 405 participants. The psychometric validity of the subscales was studied using confirmatory factorial analysis.ResultsThe factorial structure of ASSET is globally supported by the results, with the Perceptions of Your Job and Attitudes Towards your Organisation subscales requiring slight adjustments in the item structure and the Your Health subscales replicating the original structure. The convergent validity also supports the ASSET, showing that all subscales are significantly correlated with variables used to test convergence.ConclusionsGlobally, the results constitute an important contribution to ASSET and open the possibility of its usage among Portuguese-speaking countries. The results provide an evidence on the validity of the instrument and, in particular, of the mental and physical health subscales.
Scoping review on the use of socially assistive robot technology in elderly care
Authors: Abdi Jordan , Al-Hindawi Ahmed , Ng Tiffany , Vizcaychipi Marcela P 
Published: February 2018

ObjectiveWith an elderly population that is set to more than double by 2050 worldwide, there will be an increased demand for elderly care. This poses several impediments in the delivery of high-quality health and social care. Socially assistive robot (SAR) technology could assume new roles in health and social care to meet this higher demand. This review qualitatively examines the literature on the use of SAR in elderly care and aims to establish the roles this technology may play in the future.DesignScoping review.Data sourcesSearch of CINAHL, Cochrane Library, Embase, MEDLINE, PsychINFO and Scopus databases was conducted, complemented with a free search using Google Scholar and reference harvesting. All publications went through a selection process, which involved sequentially reviewing the title, abstract and full text of the publication. No limitations regarding date of publication were imposed, and only English publications were taken into account. The main search was conducted in March 2016, and the latest search was conducted in September 2017.Eligibility criteriaThe inclusion criteria consist of elderly participants, any elderly healthcare facility, humanoid and pet robots and all social interaction types with the robot. Exclusions were acceptability studies, technical reports of robots and publications surrounding physically or surgically assistive robots.ResultsIn total, 61 final publications were included in the review, describing 33 studies and including 1574 participants and 11 robots. 28 of the 33 papers report positive findings. Five roles of SAR were identified: affective therapy, cognitive training, social facilitator, companionship and physiological therapy.ConclusionsAlthough many positive outcomes were reported, a large proportion of the studies have methodological issues, which limit the utility of the results. Nonetheless, the reported value of SAR in elderly care does warrant further investigation. Future studies should endeavour to validate the roles demonstrated in this review.Systematic review registrationNIHR 58672.
Does industry-sponsored education foster overdiagnosis and overtreatment of depression, osteoporosis and over­active bladder syndrome? An Australian cohort study
Authors: Mintzes Barbara , Swandari Swestika , Fabbri Alice , Grundy Quinn , Moynihan Ray , Bero Lisa 
Published: February 2018

ObjectivesTo investigate patterns of industry-sponsored educational events that focus on specific health conditions for which there are concerns about overdiagnosis and overtreatment.Design and settingThis retrospective cohort study examines publicly reported industry-sponsored events in Australia from October 2011 to September 2015 for three conditions potentially subject to overdiagnosis and overtreatment: depression, osteoporosis and overactive bladder. We used a database of transparency reports to identify events with a focus on depression, osteoporosis and overactive bladder and compared these with other sponsored events. We hypothesised that companies marketing treatments for each condition would sponsor related events and that target audiences would mainly work in primary care, reflecting a broad patient population.Main outcome measuresEvent and attendee characteristics, sponsoring companies, related marketed treatments, cost-effectiveness ratings and dispensing rates.ResultsOver the study period, we identified 1567 events focusing on depression, 1375 on osteoporosis and 190 on overactive bladder (total n=3132, with 96 660 attendees). These events were attended by primary care doctors more often than sponsored events without a focus on these three conditions: relative risk (RR)=3.06 (95% CI 2.81 to 3.32) for depression, RR=1.48 (95% CI 1.41 to 1.55) for osteoporosis and RR=2.59 (95% CI 2.09 to 3.21) for overactive bladder. Servier, which markets agomelatine and AstraZeneca (quetiapine) sponsored 51.2% and 23.0% of depression events, respectively. Amgen and GlaxoSmithKline, which co-market denosumab, sponsored 49.5% of osteoporosis events and Astellas and Commonwealth Serum Laboratories (CSL) (mirabegron and solifenacin) sponsored 80.5% of overactive bladder events.ConclusionsThis 4-year overview of industry-sponsored events on three overdiagnosed and overtreated conditions found that primary care clinicians were often targeted, dinner was often provided and that a few companies sponsored most events. In most cases, sponsors’ products are not cost-effective choices for the specified condition. This pattern highlights the need for professional education to be free of commercial sponsorship.
Does exposure to simulated patient cases improve accuracy of clinicians’ predictive value estimates of diagnostic test results? A within-subjects experiment at St Michael’s Hospital, Toronto, Canada
Authors: Armstrong Bonnie , Spaniol Julia , Persaud Nav 
Published: February 2018

ObjectiveClinicians often overestimate the probability of a disease given a positive test result (positive predictive value; PPV) and the probability of no disease given a negative test result (negative predictive value; NPV). The purpose of this study was to investigate whether experiencing simulated patient cases (ie, an ‘experience format’) would promote more accurate PPV and NPV estimates compared with a numerical format.DesignParticipants were presented with information about three diagnostic tests for the same fictitious disease and were asked to estimate the PPV and NPV of each test. Tests varied with respect to sensitivity and specificity. Information about each test was presented once in the numerical format and once in the experience format. The study used a 2 (format: numerical vs experience) × 3 (diagnostic test: gold standard vs low sensitivity vs low specificity) within-subjects design.SettingThe study was completed online, via Qualtrics (Provo, Utah, USA).Participants50 physicians (12 clinicians and 38 residents) from the Department of Family and Community Medicine at St Michael’s Hospital in Toronto, Canada, completed the study. All participants had completed at least 1 year of residency.ResultsEstimation accuracy was quantified by the mean absolute error (MAE; absolute difference between estimate and true predictive value). PPV estimation errors were larger in the numerical format (MAE=32.6%, 95% CI 26.8% to 38.4%) compared with the experience format (MAE=15.9%, 95% CI 11.8% to 20.0%,d=0.697, P<0.001). Likewise, NPV estimation errors were larger in the numerical format (MAE=24.4%, 95% CI 14.5% to 34.3%) than in the experience format (MAE=11.0%, 95% CI 6.5% to 15.5%,d=0.303, P=0.015).ConclusionsExposure to simulated patient cases promotes accurate estimation of predictive values in clinicians. This finding carries implications for diagnostic training and practice.
Clinician, patient and general public beliefs about diagnostic imaging for low back pain: protocol for a qualitative evidence synthesis
Authors: Traeger Adrian C , Reed Benjamin J , O’Connor Denise A , Hoffmann Tammy C , Machado Gustavo C , Bonner Carissa , Maher Chris G , Buchbinder Rachelle 
Published: February 2018

IntroductionLittle is known about how to reduce unnecessary imaging for low back pain. Understanding clinician, patient and general public beliefs about imaging is critical to developing strategies to reduce overuse.ObjectiveTo synthesise qualitative research that has explored clinician, patient or general public beliefs about diagnostic imaging for low back pain.Methods and analysisWe will perform a qualitative evidence synthesis of relevant qualitative research exploring clinician, patient and general public beliefs about diagnostic imaging for low back pain. Exclusions will be studies not using qualitative methods and studies not published in English. Studies will be identified using sensitive search strategies in MEDLINE, EMBASE, CINAHL, AMED and PsycINFO. Two reviewers will independently apply inclusion and exclusion criteria, extract data, and use the Critical Appraisal Skills Programme quality assessment tool to assess the quality of included studies. To synthesise the data we will use a narrative synthesis approach that involves developing a theoretical model, conducting a preliminary synthesis, exploring relations in the data, and providing a structured summary. We will code the data using NVivo. At least two reviewers will independently apply the thematic framework to extracted data. Confidence in synthesis findings will be evaluated using the GRADE Confidence in the Evidence from Reviews of Qualitative Research tool.Ethics and disseminationEthical approval is not required to conduct this review. We will publish the results in a peer-reviewed journal.PROSPERO registration numberCRD42017076047.