bluuebunny/crossref_metadata_2025_split huggingface dataset:
Noroviruses Co-opt the Function of Host Proteins VAPA and VAPB for Replication via a Phenylalanine–Phenylalanine-Acidic-Tract-Motif Mimic in Nonstructural Viral Protein NS1/2
Authors: McCune Broc T. , Tang Wei , Lu Jia , Eaglesham James B. , Thorne Lucy , Mayer Anne E. , Condiff Emily , Nice Timothy J. , Goodfellow Ian , Krezel Andrzej M. , Virgin Herbert W. 
Published: July 2017

ABSTRACT

The
Norovirus
genus contains important human pathogens, but the role of host pathways in norovirus replication is largely unknown. Murine noroviruses provide the opportunity to study norovirus replication in cell culture and in small animals. The human norovirus nonstructural protein NS1/2 interacts with the host protein VAMP-associated protein A (VAPA), but the significance of the NS1/2-VAPA interaction is unexplored. Here we report decreased murine norovirus replication in VAPA- and VAPB-deficient cells. We characterized the role of VAPA in detail. VAPA was required for the efficiency of a step(s) in the viral replication cycle after entry of viral RNA into the cytoplasm but before the synthesis of viral minus-sense RNA. The interaction of VAPA with viral NS1/2 proteins is conserved between murine and human noroviruses. Murine norovirus NS1/2 directly bound the major sperm protein (MSP) domain of VAPA through its NS1 domain. Mutations within NS1 that disrupted interaction with VAPA inhibited viral replication. Structural analysis revealed that the viral NS1 domain contains a mimic of the phenylalanine–phenylalanine-acidic-tract (FFAT) motif that enables host proteins to bind to the VAPA MSP domain. The NS1/2-FFAT mimic region interacted with the VAPA-MSP domain in a manner similar to that seen with bona fide host FFAT motifs. Amino acids in the FFAT mimic region of the NS1 domain that are important for viral replication are highly conserved across murine norovirus strains. Thus, VAPA interaction with a norovirus protein that functionally mimics host FFAT motifs is important for murine norovirus replication.

IMPORTANCE
Human noroviruses are a leading cause of gastroenteritis worldwide, but host factors involved in norovirus replication are incompletely understood. Murine noroviruses have been studied to define mechanisms of norovirus replication. Here we defined the importance of the interaction between the hitherto poorly studied NS1/2 norovirus protein and the VAPA host protein. The NS1/2-VAPA interaction is conserved between murine and human noroviruses and was important for early steps in murine norovirus replication. Using structure-function analysis, we found that NS1/2 contains a short sequence that molecularly mimics the FFAT motif that is found in multiple host proteins that bind VAPA. This represents to our knowledge the first example of functionally important mimicry of a host FFAT motif by a microbial protein.
A Novel Single-Cell FISH-Flow Assay Identifies Effector Memory CD4
+
T cells as a Major Niche for HIV-1 Transcription in HIV-Infected Patients
Authors: Grau-Expósito Judith , Serra-Peinado Carla , Miguel Lucia , Navarro Jordi , Curran Adrià , Burgos Joaquin , Ocaña Imma , Ribera Esteban , Torrella Ariadna , Planas Bibiana , Badía Rosa , Castellví Josep , Falcó Vicenç , Crespo Manuel , Buzon Maria J. 
Published: July 2017

ABSTRACT

Cells that actively transcribe HIV-1 have been defined as the “active viral reservoir” in HIV-infected individuals. However, important technical limitations have precluded the characterization of this specific viral reservoir during both treated and untreated HIV-1 infections. Here, we used a novel single-cell RNA fluorescence
in situ
hybridization-flow cytometry (FISH-flow) assay that requires only 15 million unfractionated peripheral blood mononuclear cells (PBMCs) to characterize the specific cell subpopulations that transcribe HIV RNA in different subsets of CD4
+
T cells. In samples from treated and untreated HIV-infected patients, effector memory CD4
+
T cells were the main cell population supporting HIV RNA transcription. The number of cells expressing HIV correlated with the plasma viral load, intracellular HIV RNA, and proviral DNA quantified by conventional methods and inversely correlated with the CD4
+
T cell count and the CD4/CD8 ratio. We also found that after
ex vivo
infection of unstimulated PBMCs, HIV-infected T cells upregulated the expression of CD32. In addition, this new methodology detected increased numbers of primary cells expressing viral transcripts and proteins after
ex vivo
viral reactivation with latency reversal agents. This RNA FISH-flow technique allows the identification of the specific cell subpopulations that support viral transcription in HIV-1-infected individuals and has the potential to provide important information on the mechanisms of viral pathogenesis, HIV persistence, and viral reactivation.

IMPORTANCE
Persons infected with HIV-1 contain several cellular viral reservoirs that preclude the complete eradication of the viral infection. Using a novel methodology, we identified effector memory CD4
+
T cells, immune cells preferentially located in inflamed tissues with potent activity against pathogens, as the main cells encompassing the transcriptionally active HIV-1 reservoir in patients on antiretroviral therapy. Importantly, the identification of such cells provides us with an important target for new therapies designed to target the hidden virus and thus to eliminate the virus from the human body. In addition, because of its ability to identify cells forming part of the viral reservoir, the assay used in this study represents an important new tool in the field of HIV pathogenesis and viral persistence.
Protective factors for social-emotional well-being of refugee children in the first three years of settlement in Australia
Authors: Zwi Karen , Woodland Lisa , Williams Katrina , Palasanthiran Pamela , Rungan Santuri , Jaffe Adam , Woolfenden Susan 
Published: July 2017

AimThis longitudinal study investigated protective factors for social-emotional well-being in refugee children in Australia.MethodsNewly arrived refugee children aged 4–15 years were recruited between 2009 and 2013 and assessments were conducted at two points, at years 2 and 3 postarrival. Social-emotional well-being was assessed using the Strengths and Difficulties Questionnaire (SDQ). Protective factors were assessed by structured interview and the Social Readjustment Rating Scale (SRRS); scores <150 reflect fewer stressful life events in the previous year.ResultsForty-three eligible refugee children were recruited. The SDQ was completed by parents in 90% and protective factor data in 80% at years 2 and 3 of follow-up. Protective factors for normal SDQ scores were: originating from Africa (p=0.01), father present on arrival (p=0.019) and family SRRS scores <150 at year 2 (p=0.045). The median number of protective factors was 4 (range 1–8). Better SDQ scores were associated with ≥4 protective factors (p<0.006). Furthermore, more protective factors increased the child’s likelihood of a stable or improved SDQ score over time (p<0.04). Modifiable protective factors likely to promote social-emotional well-being include stability in the child’s school and residence, parental employment, financial and marital stability, proximity to one’s own ethnic community and external community support.ConclusionsCumulative protective factors, some of which are potentially modifiable, can predict social-emotional well-being in newly arrived refugee children. Children with four or more protective factors are at low risk of poor social-emotional well-being.
Research protocol for platelets in out-of-hospital cardiac arrest: an observational, case-controlled, feasibility study to assess coagulation and platelet function abnormalities with ROTEM following out-of-hospital cardiac arrest (PoHCAR)
Authors: Skorko Agnieszka , Thomas Matthew , Mumford Andrew , Johnson Thomas , Griffiths Elinor , Greenwood Rosemary , Benger Jonathan 
Published: July 2017

IntroductionOut-of-hospital cardiac arrest (OHCA) has an annual incidence of approximately 60 000 in the UK. Less than 10% of those who receive resuscitation survive to hospital discharge. For OHCA of a presumed cardiac cause, the optimal antiplatelet therapy is currently unknown. Previous studies indicate that a procoagulopathic state exists postcardiac arrest which may contribute to the formation of thrombi and contribute to poor outcomes. However, the administration of antiplatelet therapies needs to be balanced against the increased risk of bleeding that these individuals face.Methods and analysisThis observational feasibility study will recruit 30 individuals who achieve return of spontaneous circulation post-OHCA, are admitted to a single tertiary centre over a 6-month period and meet Utstein cohort criteria (witnessed cardiac arrest, VF or pulseless VT and cardiac cause of arrest likely). Rotational thromboelastometry and platelet function assessment will be performed on hospital arrival, postemergency percutaneous coronary intervention (PCI) and 12 hours, 24 hours and 48 hours post-PCI. As a comparator, 30 individuals presenting to our institution with ST-segment elevation myocardial infarction and undergoing primary PCI will have the same blood sampling performed. Plasma samples will be retained and batch tested on completion of the study for levels of protein C, protein S, thrombin–antithrombin complex, thrombin, antithrombin, plasminogen activator inhibitor-1, plasmin–antiplasmin complex, d-dimer, platelet factor-4, P selectin, E selectin and prothrombin fragments 1 and 2. 30-day follow-up for complications will be undertaken.Ethics and disseminationThis study has been approved by the Wales REC 7Research Ethics Committee. The results will be submitted to peer-reviewed medical journals and suitable national and international meetings. Results will be locally disseminated via our patient and public interest group.Trial registration numberPre-results;ISRCTN34122839.
Protocol for an observational study of delirium in the post-anaesthesia care unit (PACU) as a potential predictor of subsequent postoperative delirium
Authors: Cui Victoria , Tedeschi Catherine M , Kronzer Vanessa L , McKinnon Sherry L , Avidan Michael S 
Published: July 2017

IntroductionPostoperative delirium can be a serious consequence of major surgery, associated with longer hospital stays, readmission, cognitive and functional deterioration and mortality. Delirium is an acute, reversible disorder characterised by fluctuating course, inattention, disorganised thinking and altered level of consciousness. Delirium occurring in the hours immediately following anaesthesia and delirium occurring in the postoperative period of 1–5 days have been described as distinct clinical entities. This protocol describes an observational study with the aim of determining if delirium in the first hour following tracheal tube removal is a predictor of delirium in the 5 subsequent postoperative days. Improved understanding regarding the development of postoperative delirium would improve patient care and allow more effective implementation of delirium prevention measures.Methods and analysisPatients enrolled to the Electroencephalography Guidance of Anesthesia to Alleviate Geriatric Syndromes (ENGAGES) randomised controlled trial will be eligible for this substudy. A validated delirium assessment method, the 3-min Diagnostic Confusion Assessment Method and the Richmond Agitation and Sedation Scale will be used to assess 100 patients for delirium at 30 min and 60 min following tracheal tube removal. Patients will also be assessed for delirium over postoperative days 1–5 using three validated methods, the Confusion Assessment Method (CAM), CAM for the Intensive Care Unit and structured chart review. Logistic regression analysis will then be performed to test whether immediately postoperative delirium independently predicts subsequent postoperative delirium.Ethics and disseminationThis observational substudy of ENGAGES has been approved by the ethics board of Washington University School of Medicine. Enrolment began in June 2016 and will continue until June 2017. Dissemination plans include presentations at scientific conferences and scientific publications.Trial registration numberNCT02241655.
Reasons for computerised provider order entry (CPOE)-based inpatient medication ordering errors: an observational study of voided orders
Authors: Abraham Joanna , Kannampallil Thomas G , Jarman Alan , Sharma Shivy , Rash Christine , Schiff Gordon , Galanter William 
Published: July 2017

ObjectiveMedication voiding is a computerised provider order entry (CPOE)-based discontinuation mechanism that allows clinicians to identify erroneous medication orders. We investigated the accuracy of voiding as an indicator of clinician identification and interception of a medication ordering error, and investigated reasons and root contributors for medication ordering errors.MethodUsing voided orders identified with a void alert, we conducted interviews with ordering and voiding clinicians, followed by patient chart reviews. A structured coding framework was used to qualitatively analyse the reasons for medication ordering errors. We also compared clinician-CPOE-selected (at time of voiding), clinician-reported (interview) and chart review-based reasons for voiding.ResultsWe conducted follow-up interviews on 101 voided orders. The positive predictive value (PPV) of voided orders that were medication ordering errors was 93.1% (95% CI 88.1% to 98.1%, n=94). Using chart review-based reasons as the gold standard, we found that clinician-CPOE-selected reasons were less reflective (PPV=70.2%, 95% CI 61.0% to 79.4%) than clinician-reported (interview) (PPV=86.1%, 95%CI 78.2% to 94.1%) reasons for medication ordering errors. Duplicate (n=44) and improperly composed (n=41) ordering errors were common, often caused by predefined order sets and data entry issues. A striking finding was the use of intentional violations as a mechanism to notify and seek ordering assistance from pharmacy service. Nearly half of the medication ordering errors were voided by pharmacists.DiscussionWe demonstrated that voided orders effectively captured medication ordering errors. The mismatch between clinician-CPOE-selected and the chart review-based reasons for error emphasises the need for developing standardised operational descriptions for medication ordering errors. Such standardisation can help in accurately identifying, tracking, managing and sharing erroneous orders and their root contributors between healthcare institutions, and with patient safety organisations.
Recruiting adult participants to physical activity intervention studies using sport: a systematic review
Authors: Cooke Rachel , Jones Andy 
Published: July 2017

ObjectiveTo undertake a systematic review of the effectiveness of recruitment mechanisms for engaging and retaining target participants in sports interventions to promote physical activity behaviour change in adults.DesignA narrative systematic review of published studies providing details of the effectiveness of recruitment techniques used in interventions aimed at increasing physical activity via sport in adults.Data sourcesSearches were conducted using five electronic databases, clinical trial registers, grey literature and snowballing from reference lists. All papers published in the English language were considered. The search was completed in November 2015.Eligibility criteriaAll articles providing information on the recruitment of adults into interventions involving sport and reporting physical activity or participation outcomes were included.ResultsTwenty-three studies met the inclusion criteria. The quality of recruitment reporting across included studies was generally classified as poor, lacking detailed descriptions of recruitment processes and providing insufficient reporting of recruitment outcomes. There was a distinct recruitment bias for more affluent, white, middle-aged women. Active-only recruitment techniques appeared to achieve a participant sample with more representative demographic characteristics than passive approaches.ConclusionsDue to inadequate reporting and evaluation, the mechanisms for achieving effective recruitment and engagement in sport, particularly in hard-to-reach groups, are still unclear. Independent of recruitment mode, creating an intervention and context that reflect the interests and motivations of the target audience presents a promising area. There is an urgent need for more robust evaluation design and reporting of sports interventions.
Chromoendoscopy versus narrow band imaging in UC: a prospective randomised controlled trial
Authors: Bisschops Raf , Bessissow Talat , Joseph Joseph A , Baert Filip , Ferrante Marc , Ballet Vera , Willekens Hilde , Demedts Ingrid , Geboes Karel , De Hertogh Gert , Vermeire Séverine , Rutgeerts Paul , Van Assche Gert 
Published: July 2017

BackgroundPatients with long-standing UC have an increased risk for the development of colonic neoplastic lesions. Chromoendoscopy (CE) has been proven to enhance neoplasia detection while the role of virtual chromoendoscopy (VC) is still to be defined.ObjectiveTo compare the performance of CE to VC for the detection of neoplastic lesions in patients with long-standing UC.DesignA multicentre prospective randomised controlled trial. 131 patients with long-standing UC were randomised between CE with methylene blue 0.1% (n=66) or VC with narrow band imaging (NBI) (n=65). Biopsies were taken from visible lesions and surrounding mucosa. No random biopsies were performed. The primary outcome was the difference in total number of neoplastic lesions detected in each group.ResultsThere was no significant difference between NBI and CE for neoplasia detection. Mean number of neoplastic lesions per colonoscopy was 0.47 for CE and 0.32 for NBI (p=0.992). The neoplasia detection rate was not different between CE (21.2%) and NBI (21.5%) (OR 1.02 (95% CI 0.44 to 2.35, p=0.964). Biopsies from the surrounding mucosa yielded no diagnosis or dysplasia. The per lesion neoplasia detection was 17.4% for CE and 16.3% for NBI (OR 1.09 (95% CI 0.59 to 1.99, p=0.793). The total procedural time was on average 7 min shorter in the NBI group.ConclusionCE and NBI do not differ significantly for detection of colitis-associated neoplasia. Given the longer withdrawal time for CE and easier applicability, NBI may possibly replace classical CE.Trial registration numberNCT01882205; Results.
Occupational and leisure-time physical activity and risk of disability pension: prospective data from the HUNT Study, Norway
Authors: Fimland Marius Steiro , Vie Gunnhild , Holtermann Andreas , Krokstad Steinar , Nilsen Tom Ivar Lund 
Published: July 2017

ObjectivesTo prospectively investigate the association between occupational physical activity (OPA) and disability pension due to musculoskeletal cause, mental cause or any cause. We also examined the combined association of OPA and leisure-time physical activity (LTPA) with disability pension.MethodsA population-based cohort study in Norway on 32 362 persons aged 20–65 years with questionnaire data on OPA and LTPA that were followed up for incident disability pension through the National Insurance Database. We used Cox regression to estimate adjusted HRs with 95% CIs.ResultsDuring a follow-up of 9.3 years, 3837 (12%) received disability pension. Compared with people with mostly sedentary work, those who performed much walking, much walking and lifting, and heavy physical work had HRs of 1.26 (95% CI 1.16 to 1.38), 1.44 (95% CI 1.32 to 1.58) and 1.48 (95% CI 1.33 to 1.70), respectively. These associations were stronger for disability pension due to musculoskeletal disorders, whereas there was no clear association between OPA and risk of disability pension due to mental disorders. People with high OPA and low LTPA had a HR of 1.77 (95% CI 1.58 to 1.98) for overall disability pension and HR of 2.56 (95% CI 2.10 to 3.11) for disability pension due to musculoskeletal disorders, versus low OPA and high LTPA.ConclusionsWe observed a positive association between OPA and risk of disability pension due to all causes and musculoskeletal disorders, but not for mental disorders. Physical activity during leisure time reduced some, but not all of the unfavourable effect of physically demanding work on risk of disability pension.
Scoring ultrasound synovitis in rheumatoid arthritis: a EULAR-OMERACT ultrasound taskforce-Part 2: reliability and application to multiple joints of a standardised consensus-based scoring system
Authors: Terslev Lene , Naredo Esperanza , Aegerter Philippe , Wakefield Richard J , Backhaus Marina , Balint Peter , Bruyn George A W , Iagnocco Annamaria , Jousse-Joulin Sandrine , Schmidt Wolfgang A , Szkudlarek Marcin , Conaghan Philip G , Filippucci Emilio , D'Agostino Maria Antonietta 
Published: July 2017

ObjectivesTo test the reliability of new ultrasound (US) definitions and quantification of synovial hypertrophy (SH) and power Doppler (PD) signal, separately and in combination, in a range of joints in patients with rheumatoid arthritis (RA) using the European League Against Rheumatisms–Outcomes Measures in Rheumatology (EULAR-OMERACT) combined score for PD and SH.MethodsA stepwise approach was used: (1) scoring static images of metacarpophalangeal (MCP) joints in a web-based exercise and subsequently when scanning patients; (2) scoring static images of wrist, proximal interphalangeal joints, knee and metatarsophalangeal joints in a web-based exercise and subsequently when scanning patients using different acquisitions (standardised vs usual practice). For reliability, kappa coefficients (κ) were used.ResultsScoring MCP joints in static images showed substantial intraobserver variability but good to excellent interobserver reliability. In patients, intraobserver reliability was the same for the two acquisition methods. Interobserver reliability for SH (κ=0.87) and PD (κ=0.79) and the EULAR-OMERACT combined score (κ=0.86) were better when using a ‘standardised’ scan. For the other joints, the intraobserver reliability was excellent in static images for all scores (κ=0.8–0.97) and the interobserver reliability marginally lower. When using standardised scanning in patients, the intraobserver was good (κ=0.64 for SH and the EULAR-OMERACT combined score, 0.66 for PD) and the interobserver reliability was also good especially for PD (κ range=0.41–0.92).ConclusionThe EULAR-OMERACT score demonstrated moderate-good reliability in MCP joints using a standardised scan and is equally applicable in non-MCP joints. This scoring system should underpin improved reliability and consequently the responsiveness of US in RA clinical trials.